EP1307135A4 - Systems and methods for providing information concerning chromophores in physiological media - Google Patents

Systems and methods for providing information concerning chromophores in physiological media

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Publication number
EP1307135A4
EP1307135A4 EP20010959449 EP01959449A EP1307135A4 EP 1307135 A4 EP1307135 A4 EP 1307135A4 EP 20010959449 EP20010959449 EP 20010959449 EP 01959449 A EP01959449 A EP 01959449A EP 1307135 A4 EP1307135 A4 EP 1307135A4
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wave
ofthe
scanning
optical
member
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EP20010959449
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German (de)
French (fr)
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EP1307135A2 (en )
Inventor
Xuefeng Cheng
Xiaorong Xu
Shuoming Zhou
Lai Wang
Ming Wang
Feng Li
Guobao Hu
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PHOTONIFY TECHNOLOGIES Inc
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PHOTONIFY TECHNOLOGIES INC
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0233Special features of optical sensors or probes classified in A61B5/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0233Special features of optical sensors or probes classified in A61B5/00
    • A61B2562/0242Special features of optical sensors or probes classified in A61B5/00 for varying or adjusting the optical path length in the tissue
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/04Arrangements of multiple sensors of the same type
    • A61B2562/043Arrangements of multiple sensors of the same type in a linear array
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/04Arrangements of multiple sensors of the same type
    • A61B2562/046Arrangements of multiple sensors of the same type in a matrix array
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
    • A61B5/14552Details of sensors specially adapted therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
    • A61B5/14553Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases specially adapted for cerebral tissue
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/41Detecting, measuring or recording for evaluating the immune or lymphatic systems
    • A61B5/413Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/314Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
    • G01N2021/3144Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths for oxymetry
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infra-red light
    • G01N21/359Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infra-red light using near infra-red light
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47Scattering, i.e. diffuse reflection
    • G01N21/49Scattering, i.e. diffuse reflection within a body or fluid

Abstract

The present invention generally relates to systems and methods for providing information about chromophores in physiological media. More particularly, the invention relates to non-invasive systems and methods for determining absolute values of oxygenated and/or deoxygenated hemoglobins and their ratios in a physiological medium. The system generally includes a portable probe having a source module (122) for irradiating into the medium electromagnetic radiation, a detector module (124) detecting radiation from a target area in the medium, and a processing module (140) determining the absolute values of the chromophore concentrations and the ratios thereof based on input and output parameters of the source and detector modules. In one aspect, the invention provides a solution for unknown parameters of the chromophores in a medium using a novel processing algorithm. In another aspect, the invention concerns a portable unit for performing the requisite measurements, which unit includes a movable member having one or more radiation sources and one or more radiation detectors, and an actuator designed to cause the member to move along predetermined curvilinear paths. Properties of the chromophores are measured for individual voxels defined along each motion path, and/or cross-voxels defined at the intersection of voxels along different motion paths. These measured values are then used in a preferred embodiment to generate two- or three-dimensional images of the distribution of chromophores or their properties. In other aspects, the invention includes various patterns for the optimal distribution of sources and detectors for the optical probe, and self-calibrating operation of the probe substantially in real-time.

Description

SYSTEMS AND METHODS FOR PROVIDING INFORMATION CONCERNING CHROMOPHORES IN PHYSIOLOGICAL MEDIA

FIELD OF THE INVENTION

The present invention generally relates to systems and methods for: (i) providing information regarding spatial and/or temporal distribution of chromophores or their properties in various physiological media and or (ii) determining absolute values of various properties of various physiological media, such as concentrations of oxygenated and deoxygenated hemoglobins (and/or their ratios). More particularly, the present invention relates to non-invasive self-calibrating optical imaging systems and optical probes equipped with movable sensor assemblies and real-time image construction algorithms and the methods thereof. The sensor assemblies may include symmetrically arranged optical sensors such as wave sources and/or detectors. The present invention is applicable to optical imaging systems and/or optical probes whose operation is based on wave equations such as the Beer-Lambert equation, modified Beer-Lambert equation, photon diffusion equation, and their equivalents. The present invention also relates to apparatuses and methods for obtaining the aforementioned absolute values by solving the wave equations mentioned immediately before.

BACKGROUND OF THE INVENTION

Mathematical Foundation

Near-infrared spectroscopy has been used to non-invasively measure various physiological properties in animal and human subjects. The basic principle underlying the near-infrared spectroscopy is that a physiological media such as tissues and cells include a variety of light-absorbing and/or light-scattering chromophores which can interact with electromagnetic waves transmitted thereto and traveling therethrough. Physiological tissues include various highly scattering chromophores to the near infrared waves with relatively low absorption. Many substances in a physiological medium may interact or interfere with the near-infrared light waves that propagate therethrough. For example, human tissues and cells include numerous chromophores such as water, cytochromes, lipids and among which, deoxygenated and oxygenated hemoglobins are the most dominant chromophores in the spectrum range of 600 nm to 900 nm. Therefore, the near-infrared spectroscope has been applied to measure oxygen levels in the physiological media in terms of tissue hemoglobin oxygen saturation ("oxygen saturation" hereinafter). Technical background for the near- infrared spectroscopy and diffuse optical imaging has been discussed in, e.g., Neuman, M. R., "Pulse Oximetry: Physical Principles, Technical Realization and Present Limitations," Adv. Exp. Med. Biol., vol. 220, ρ.135-144, 1987 and Severinghaus, J. W., "History and Recent Developments in Pulse Oximetry," Scan. J. Clin. and Lab. Investigations, vol. 53, p.105-111, 1993. Various techniques have been developed for the near-infrared spectroscopy, including time-resolved spectroscopy (TRS), phase modulation spectroscopy (PMS), and continuous wave spectroscopy (CWS). TRS

The TRS technology is based on operational principles such as pulse-time measurements and pulse-code modulation. In particular, it measures a time delay between an entry and an exit of electromagnetic waves to and from the physiological medium. Typically, the TRS applies to the medium an impulse or pulse sequence of electromagnetic waves having a duration in the order of a few pico-seconds. Photon diffusion encodes tissue characteristics not only in the timing ofthe delayed pulse received by a detector, but also in the received intensity time profile. Therefore, instead of receiving a "clean" replica ofthe transmitted pulse, the return signals are spread out in time, and have greatly reduced amplitudes. Accordingly, the TRS measures the intensity ofthe return signals over a finite period of time, which is long enough to detect an entire portion ofthe delayed return signals. Based on such shape changes and amplitude attenuation ofthe input impulse or pulse, different times of arrival of photons and the mean time delay between the light (or wave) source and detector are used to obtain the tissue absorption and tissue scattering through, e.g., deconvolution ofthe return signals, ^formation on the tissues traversed (such as optical pathlengfhs and their changes) is then readily obtained. Details ofthe TRS technology are provided, for example, in D.A. Boas et al., Proc. Natl. Acad. Sci., vol. 91, p. 4887 (1994); R.P. Spencer and G. Weber, Ann. (N.Y.) Acad. Sci., vol. 158, p. 3631 (1996); and J. Sipior et al., Rev. Sci. Instrum., vol. 68, p. 2666 (1997), all of which are incorporated herein by reference for background. PMS

The PMS technology employs phase-modulated electromagnetic waves irradiated by the wave source and transmitted through the physiological medium. Typical examples of PMS include homodyne systems, heterodyne systems, single side-band systems, and other systems based on transmitter-receiver cross-coupling and phase correction algorithms. Like TRS, PMS systems monitor the intensities ofthe attenuated electromagnetic waves. In addition, it is necessary for the PMS system to measure frequency-domain parameters, such as phase shift ofthe electromagnetic waves which is independent ofthe wave intensities. Based on such time-domain and frequency-domain information, PMS systems determine spectra of an absorption coefficient and/or scattering coefficient ofthe chromophores ofthe medium, and calculate absolute values ofthe hemoglobin concentrations. Details ofthe PMS technology are provided, for example, in U.S. Pat. No. 5,820,558 and a technical article by B. Chance et al. in Rev. Sci. Instrum., vol. 69, p. 3457 (1998), both of which are incorporated herein by reference in their entirety. CWS

By contrast, CWS systems employ electromagnetic waves that are non- impulsive and not phase modulated. That is, CWS systems apply to the medium electromagnetic waves having at least substantially identical amplitude over a measurable period of time. On the detection side, CWS systems only measure intensities ofthe irradiated and detected electromagnetic waves and does not assess any frequency-domain parameters thereof. hi a homogeneous, semi-infinite model, the TRS and PMS have been generally used to obtain the spectra of absorption coefficients and reduced scattering coefficients ofthe physiological media by solving a photon diffusion equation, and to estimate concentrations ofthe oxygenated and deoxygenated hemoglobins and oxygen saturation of tissues. To the contrary, the CWS has generally been used to solve the modified Beer-Lambert equation and to calculate relative values of or changes in the concentrations ofthe oxygenated and deoxygenated hemoglobin.

Despite their capability of providing hemoglobin concentrations as well as the oxygen saturation, the major disadvantage ofthe TRS and PMS is that the equipment has to be bulky and, therefore, expensive, e.g., the TRS equipment requires a pulse generator and detector, while the PMS requires additional hardware and signal processing capabilities to determine frequency-domain parameters. The CWS may be manufactured at a lower cost because all it needs to do is perform intensity measurements, but it is generally limited in its utility, for it can estimate only the changes in the hemoglobin concentrations but not the absolute values thereof nor can it estimate the tissue oxygen saturation from such changes in the hemoglobin concentration. Accordingly, the CWS cannot provide the oxygen saturation. The prior art technology also requires a priori calibration of optical probes before their clinical application by, e.g., measuring a baseline in a reference medium or in a homogeneous region ofthe medium of a test subject. Furthermore, all prior art technologies require complicated image reconstruction algorithms to generate images of two-dimensional or three-dimensional distribution ofthe chromophore properties. Accordingly, there exists a need for more efficient, reliable, compact and relatively cheap optical imaging systems that can self-calibrate themselves without relying on external measurement or data and that can incorporate more efficient image construction algorithms capable of providing two-dimensional and/or three-dimensional images of distribution of chromophores and/or their properties on a substantially real time basis. Additionally there exists a need for optical probes capable of measuring the absolute values ofthe chromophores and/or their properties and capable of scanning a larger target area of the medium in a single measurement. There exists a need for novel CWS systems and methods for measuring absolute value of concentrations ofthe hemoglobins and the oxygen saturation in the physiological medium.

SUMMARY OF THE INVENTION

The present invention generally relates to systems and methods for: (i) providing information regarding spatial and/or temporal distribution of chromophores or their properties in various physiological media and/or (ii) determining absolute values of various properties of various physiological media, such as concentrations of oxygenated and deoxygenated hemoglobins (and/or their ratios). More particularly, the present invention relates to non-invasive self-calibrating optical imaging systems and optical probes equipped with movable sensor assemblies and real-time image construction algorithms and the methods thereof. The present invention is applicable to optical imaging systems and/or optical probes whose operation is based on wave equations such as the Beer-Lambert equation, modified Beer-Lambert equation, photon diffusion equation, and their equivalents. The present invention also relates to apparatuses and methods for obtaining the aforementioned absolute values by solving the wave equations mentioned immediately before. hi one aspect ofthe present invention, a system determines concentrations of chromophores in a physiological medium. Such a system may include a source module for irradiating into the medium at least two sets of electromagnetic radiation having different wave characteristics, a detector module for detecting electromagnetic radiation transmitted through the medium, and a processing module for determining an absolute values of at least one ofthe concentrations ofthe chromophores from electromagnetic radiation irradiated from the source module and detected by the detector module, where the determination is based on intensity measurements of continuous wave electromagnetic radiation from the source module.

The present invention also provides for systems generating images representing distribution of one or more chromophores and their properties thereof in target areas of a physiological medium. Such a system may include an optical probe having at least one wave source and at least one wave detector, where the wave source is configured to irradiate electromagnetic radiation into a first target area ofthe physiological medium, and the wave detector is configured to detect this electromagnetic radiation from the first target areas ofthe medium and to generate a first output signal in response thereto. The system may also further include a signal analyzer configured to receive and sample the first output signal to obtain a plurality of amplitude values. The amplitude values may be analyzed to determine at least one set of samples ofthe first output signal having substantially similar amplitudes. The system may further include a signal processor configured to calculate a first baseline from the first output signal, where the first baseline is representative ofthe substantially similar amplitudes determined by the analyzer. The signal processor may also provide a self-calibrated first output signal by manipulating the first output signal and its first baseline, where the first baseline is a representative amplitude ofthe similar amplitudes.

The present invention also provides for methods for determining concentrations of chromophores in a physiological medium.

In another aspect ofthe present invention, a system provides information concerning distributions of hemoglobins and properties thereof in a target area of a physiological medium. Such a system may include a movable member having mounted thereon at least one wave source and at least one wave detector, where the at least one wave source is configured to irradiate near infrared electromagnetic radiation into the target area, and the at least one wave detector is configured to detect the near infrared radiation from the target area and to generate an output signal in response thereto. The system further may include an actuator coupled with the at least one movable member to move it with respect to the target area along at least one curvilinear path, and a processor determining a distribution of hemoglobins or properties thereof based on the output signal generated by the at least one wave detector along the at least one curvilinear path. hi another aspect ofthe present invention, the system for providing information concerning distributions of hemoglobins and properties thereof in target areas of a physiological medium may include an optical probe having a wave source and a wave detector, where the wave source is configured to irradiate near infrared electromagnetic radiation into a first target area ofthe physiological medium, and the wave detector is configured to detect this near infrared radiation from the medium and to generate a first output signal in response thereto. The system may also further include an analyzer receiving and sampling the first output signal to obtain a plurality of amplitude values. The amplitude values maybe analyzed to determine at least one set of samples ofthe first output signal having substantially similar amplitudes. The system may further include a signal processor configured to calculate a first baseline from the first output signal, where the first baseline is representative ofthe substantially similar amplitudes determined by the analyzer. The signal processor may also provide a self-calibrated first output signal by manipulating the first output signal and its first baseline.

In yet another aspect ofthe present invention, methods for obtaining a calibrated output signal from an optical imaging system having an optical probe with at least one wave source configured to irradiate near infrared electromagnetic radiation into target areas of a physiological medium and at least one wave detector generating output signal in response to near infrared electromagnetic radiation detected thereby, are provided for. Another aspect ofthe present invention includes an optical probe that is capable of generating images representing a distribution of hemoglobins or their properties in target areas of a physiological medium. The optical probe includes a plurality of wave source and wave detectors. The wave sources are configured to irradiate near-infrared electromagnetic radiation in the medium, and the wave detectors are configured to detect near infrared electromagnetic radiation and generate output signals in response to such detection. Embodiments of the present invention may include one or more of the following features.

A plurality of symmetrically disposed scanning units, each having a first wave source, a second wave source, a first wave detector and a second wave detector. The first wave source is disposed closer to the first wave detector than the second wave detector. The second wave source is disposed closer to the second wave detector than the first wave detector. The first near distance between the first wave source and the first wave detector is substantially similar to a second near-distance between the second wave source and the second wave detector. The first far-distance between the first wave source and second wave detector is substantially similar to the second far distance between said second wave source and first wave detector. The first and second wave source are configured to generate out put signals in response to detection of near-infrared electromagnetic radiation irradiated by at least one ofthe first and second wave sources. The output signals represent the optical interaction ofthe near infrared electromagnetic radiation with the hemoglobins in the target area ofthe medium. In additional embodiments, the optical probe may include four symmetric scanning units wherein a first scanning unit is identical to a fourth scanning unit and wherein a second scanning unit is identical to a third scanning unit. Each scanning unit has a first wave source, a second wave source, a first wave detector, and a second wave detector. The first and second wave sources are configured to be synchronized with the first and second wave detectors to generate output signals which represent electromagnetic interaction of said near-infrared radiation with the hemoglobins in the target areas ofthe medium. In additional embodiments, the optical probe may include at least one first wave source and at least one first wave detector define a first scanning element and at least one second wave source and at least one second wave detector define a second scanning element. The first and second scanning elements define a scanning unit in which said first and second wave sources are symmetrically disposed with respect to one of a line of symmetry and a point of symmetry, hi each ofthe scanning elements the first and second wave detectors are also symmetrically disposed with respect to the line of symmetry and the point of symmetry.

The present invention also includes, methods for generating two-dimensional or three-dimensional images of a target area of a physiological medium by an optical imaging system having an optical probe. The images represent spatial or temporal distribution of hemoglobins or their properties in the medium. The optical probe includes a plurality of wave sources and a plurality of wave detectors, the wave sources are configured to irradiate near-infrared electromagnetic radiation into the medium, and the wave detector is configured to generate output signals in response to detection of near-infrared electromagnetic radiation. The method comprises the steps of providing a plurality of scanning elements, each of which including at least one ofthe wave sources and at least one of said wave detectors. The method further includes defining a plurality of scanning units, each of which including at least two of said scanning elements and scanning the target area with one or more scanning units. The method further comprises the steps of grouping output signals generated by each of said scanning units and obtaining a set of solutions of wave equations applied to input and output parameters ofthe scanning units. The method further includes the steps of determining the distribution of at least one of hemoglobins and its properties from the set of solutions, and providing one or more images ofthe distribution. Another aspect ofthe present invention, a system for generating images representing properties of one or more chromophores in a target area of a physiological medium, includes at least one movable support coupled with an actuator and configured to move the support with respect to the target area along at least one curvilinear path. The system further includes one or more wave sources and one or more wave detectors mounted on the support to form a scanning unit having associated therewith a longitudinal axis, a scanning area and a scanning volume. The wave source(s) are configured to irradiate near- infrared electromagnetic radiation into the target area of said medium and the wave detector(s) are configured to detect near-infrared electromagnetic radiation from the target area and to generate an output signal in response such detection. The system further includes a processor for receiving the output signal and defining a plurality of voxels in the target area. The plurality of voxels have a characteristic dimension and a voxel axis. The processor determines the chromophore properties based on the output signal in the plurality of voxels and generates the images.

In additional embodiments ofthe invention, a system for generating images representing distribution of at least one hemoglobin property in a target area of a physiological medium, comprises a sensor assembly having at least one wave source and at least one wave detector. The system further includes a processor for receiving the output signal from the sensor assembly, and the processor is configured to define a plurality of voxels in the target area. To determine the hemoglobin property the processor solves a plurality of wave equations applied to input radiation from the at least one wave source and radiation detected by the at least one detector. The processor further generates images ofthe distribution of said hemoglobin property in the target area.

Additional embodiments ofthe invention include a system for generating images representing distribution of at least one property of at least one chromophore in a target area of a physiological medium, where the system comprises at least one wave source, at least one wave detector, a portable probe having at least one movable member and at least one actuator. The at least one movable member has mounted thereon at least one wave source and at least one detector, and the at least one actuator member is configured to couple with the at least one movable member to move it along one or more curvilinear paths. Another aspect ofthe invention is a system for generating information regarding the distribution of at least one property of at least one chromophore in target areas of a physiological medium, comprises at least one wave source, at least one wave detector, an optical probe including at least one movable member in which the at least one wave source and detector is disposed. The system further comprises a console coupling with the optical probe and including a processor configured to receive the output signal. The system further comprises an actuator configured to couple with the at least one movable member to move it along at least one curvilinear path, and a connector for providing at least one of electrical communication, optical communication, electric power transmission, mechanical power transmission, and data transmission between at least two ofthe optical probe, console, and actuator member. Additional embodiments may include, a system for generating information about the distribution of at least one property of at least one chromophore in target areas of a physiological medium, comprising a processor, at least two wave sources, and at least two wave detectors. The at least two of said wave sources and at least two of said wave detectors are disposed substantially along a line. Another aspect ofthe invention includes a method for generating images representing distribution of hemoglobins in a target area of a physiological medium by a portable measurement system. The system includes a movable member having mounted thereon at least one wave source and at least one wave detector to define a scanning unit having a longitudinal axis, a scanning area smaller than the target area and scanning volume therearound, the at least one wave source irradiating near-infrared electromagnetic radiation into said target area, the at least one wave detector being configured to detect near-infrared electromagnetic radiation in the target area and to generate output signal in response thereto, the system further comprising an actuator member coupling with said movable member to move it along at least one curvilinear path to scan the target area. The method comprises the steps of placing the movable member on the target area ofthe medium and positioning said scanning unit in a first region ofthe target area. The method further includes scanning the first region ofthe target area by irradiating near-infrared electromagnetic radiation and obtaining the output signal therefrom by the wave detector. The method further comprises the steps of manipulating the actuator member to move the movable member and scanning unit from the first region toward another region ofthe target area along a first curvilinear path. The method further comprises the step of defining a first set voxels from said output signal in at least one of said regions of said target area and determining voxel values corresponding to the first set of voxels, each voxel value being an average ofthe property over a voxel. The method further comprises the step of generating images representing the distribution of said hemoglobins from the first set of voxel values. Additional aspects ofthe invention may include a method for generating images representing distribution of at least one property of at least one chromophore in a target area of a physiological medium by a portable system. The system includes at least one wave source configured to irradiate electromagnetic radiation into said medium and at least one wave detector configured to detect electromagnetic radiation and to generate output signal in response thereto. The method comprises the steps of positioning the wave source and detector in said target area, defining a first set of voxels from said output signals and determining a sequence of voxel values for the first set of voxels, a voxel value representing an average of said property over a voxel. The method further comprises the steps of defining a second set of voxels from said output signals, determining a sequence of voxel values of said second voxels and constructing a first set of cross-voxels defined as the intersecting portions of at least two intersecting voxels which belong to one of said first and second sets of voxels, respectively. The method further comprises the steps of calculating cross-voxel values ofthe first set of cross- voxels from the voxel values ofthe intersecting voxels; and generating the images ofthe distribution ofthe chromophore property from the first sequence ofthe first cross-voxel values. Additional aspects ofthe mvention may include a method for generating images representing distribution of at least one property of at least one chromophore in a target area of a physiological medium by a measuring system. The system includes at least one wave source, at least one wave detector, a movable member, and an actuator member. The movable member configured to include at least one of said wave source and detector, and the actuator member operationally coupling with said movable member. The wave source and detector are configured to form a movable scanning unit which includes a longitudinal axis connecting the wave source and detector and which defines at least one of a scanning area and scanning volume there around. The actuator member is configured to generate at least one movement of at least one ofthe movable member and scanning unit along at least one curvilinear path. The method comprises the steps of placing the movable member on the target area ofthe medium, positioning the scanning unit in a first region of the target area and manipulating said actuator member to generate a first movement of at least one of said movable member and scanning unit from the first region to a second region of said target area along a first curvilinear path. The method further comprises the steps of defining a first set of first voxels from said output signals in at least a portion of said target area, determining a first sequence of first voxel values of said first voxels, each first voxel value representing a first average of said property averaged over said first voxel. The method further comprises the steps of defining a second set of second voxels from said output signals in at least a portion of said target area and determining a second sequence of second voxel values of said second voxels, each second voxel value representing a second average of said property averaged over said second voxel. The method further comprises the steps of constructing a set of cross- voxels each of which is defined as an intersecting portion of at least two intersecting voxels each of which belongs to one of said first and second sets of said first and second voxels, respectively. The method further comprises calculating a sequence of cross- voxel values of said cross- voxels directly from said voxel values of said intersecting voxels, and generating said images of said distribution of said property directly from said sequence of said cross- voxel values.

Other features and advantages ofthe invention will be apparent from the following detailed description, and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of an optical imaging system according to the present invention;

FIG. 2 A is a schematic diagram of an optical probe of an optical imaging system defining multiple scanning units according to the present invention;

FIG. 2B is a schematic diagram of an optical probe of an optical imaging system defining multiple scanning units having a source-detector arrangement which is reverse to that of FIG. 2 A according to the present invention.

FIG. 3A is schematic diagram of a sample optical system having two wave sources and two wave detectors having identical near distances and far-distances according to the present invention;

FIG. 3B is a schematic diagram of another sample optical system having two wave sources and two wave detectors having near-distances and far distances according to the present invention; FIG. 3C is a schematic diagram of yet another sample optical system having two wave sources and four wave detectors according to the present invention;

FIG. 4 is a cross-sectional top view of an exemplary scanning unit according to the present invention;

FIG. 5 is a cross-sectional top view of another exemplary scanning unit according to the present invention;

FIG. 6A is a schematic diagram of a linear scanning unit according to the present invention;

FIG. 6B is a schematic diagram of another linear scanning unit having a source-detector arrangement which is reverse to that of FIG. 6 A according to the present invention;

FIG. 6C is a schematic diagram of a square scanning unit according to the present invention;

FIG. 6D is a schematic diagram of another square scanning unit having a source-detector arrangement which is reverse to that of FIG. 6C according to the present invention;

FIG. 6E is a schematic diagram of a rectangular scanning unit according to the present invention;

FIG. 6F is a schematic diagram of a trapezoidal scanning unit according to the present invention; FIG. 6G is a schematic diagram of another trapezoidal scanning unit having a source-detector arrangement reverse to that of FIG. 6F according to the present invention; FIG. 6H is a schematic diagram of another trapezoidal scanning unit having an inverted source-detector arrangement according to the present invention;

FIG. 7 A is a schematic diagram of a quasi-linear scanning unit according to the present invention; FIG. 7B is a schematic diagram of a rectangular scanning unit according to the present invention;

FIG. 7C is a schematic diagram of a parallelogram scanning unit according to the present invention;

FIG. 8 A is a schematic diagram of a first set of scanning units ofthe optical probe of FIG. 2 A according to the present invention;

FIG. 8B is a schematic diagram of voxels and cross-voxels generated by the scanning units of FIG. 8 A and resulting voxel values and cross- voxel values according to the present invention;

FIG. 9 A is a schematic diagram of a second set of scanning units ofthe optical probe of FIG. 2 A according to the present invention;

FIG. 9B is a schematic diagram of voxels and cross-voxels generated by the scanning units of FIG. 9 A according to the present invention;

FIG. 9C is a schematic diagram of resulting voxel values and cross- voxel values of FIG. 9B according to the present invention; FIG. 10A is a schematic diagram of a third set of scanning units ofthe optical probe of FIG. 2A according to the present invention;

FIG. 1 OB is a schematic diagram of voxels and cross- voxels generated by the scanning units of FIG. 10A according to the present invention;

FIG. IOC is a schematic diagram of voxel values and cross- voxel values of FIG. 10B according to the present invention;

FIG. 11A is a schematic diagram of a fourth set of scanning units ofthe optical probe of FIG. 2 A according to the present invention;

FIG. 1 IB is a schematic diagram of voxels and cross-voxels generated by the scanning units of FIG. 11 A according to the present invention; FIG. 1 IC is a schematic diagram of voxel values and cross- voxel values of

FIG. 1 IB according to the present invention;

FIG. 12 is a schematic diagram ofthe voxels of FIGs. 8 through 11 and cross- voxels therefrom according to the present invention;

FIG. 13A is a schematic diagram of an asymmetric scanning unit satisfying the symmetry requirement according to the present invention; FIG. 13B is a schematic diagram of another asymmetric scanning unit which satisfies the symmetry requirement according to the present invention;

FIG. 13C is a schematic diagram of yet another asymmetric scanning unit that satisfies the symmetry requirement according to the present invention; FIG. 14A is a schematic diagram of an exemplary circular optical probe of an optical imaging system according to the present invention; and

FIG. 14B is a schematic diagram of an exemplary triangular optical probe of an optical imaging system according to the present invention.

FIG. 15 is a plot of simulated values of G (i.e., a ratio of F, to F2) at different wavelengths as a function of oxygen saturation according to the present invention;

FIG. 16 is another plot of simulated values of G at different wavelengths as a function of oxygen saturation according to the present invention;

FIG. 17 is yet another plot of simulated values of G at different wavelengths as a function of oxygen saturation according to the present invention; FIG. 18 is another plot of calculated oxygen concentration versus true oxygen saturation in a medium with a different background scattering coefficient and total hemoglobin concentration according to the present invention;

FIG. 19 is a time-course plot of total hemoglobin (FfbT) concentration, oxygenated hemoglobin (FfbO) concentration, and deoxygenated hemoglobin (Ffb) concentration according to the present invention;

FIG. 20 is a time-course plot of oxygen saturation according to the present invention;

FIG. 21 is a schematic diagram of an optical imaging system according to the present invention; FIGs. 22 A and 22B are images of blood volume of normal and abnormal breast tissues, respectively, both of which are measured by the optical imaging system of FIG. 21 according to the present invention; and

FIGs. 23A and 23B are images of oxygen saturation of normal and abnormal breast tissues, respectively, both of which are measured by the optical imaging system of FIG. 21 according to the present invention.

FIG. 24A is schematic diagram of a sample optical system having two wave sources and two wave detectors having identical near distances and far-distances according to the present invention;

FIG. 24B is a schematic diagram of another sample optical system having two wave sources and two wave detectors having near-distances and far distances according to the present invention; FIG. 24C is a schematic diagram of yet another sample optical system having two wave sources and four wave detectors according to the present invention; FIG. 15 is a plot of simulated values of G (i.e., a ratio of F, to F2) at different wavelengths as a function of oxygen saturation according to the present invention; FIG. 25 is a plot of simulated values of G (i.e., a ratio of Fj to F2) at different wavelengths as a function of oxygen saturation according to the present invention;

FIG. 26 is another plot of simulated values of G at different wavelengths as a function of oxygen saturation according to the present invention;

FIG. 27 is yet another plot of simulated values of G at different wavelengths as a function of oxygen saturation according to the present invention;

FIG. 28 is another plot of calculated oxygen concentration versus true oxygen saturation in a medium with a different background scattering, coefficient and total hemoglobin concentration according to the present invention;

FIG. 29 is a time-course plot of total hemoglobin (HbT) concentration, oxygenated hemoglobin (HbO) concentration, and deoxygenated hemoglobin (Hb) concentration according to the present invention;

FIG. 30 is a time-course plot of oxygen saturation according to the present invention;

FIG. 31 is a schematic diagram of an optical imaging system according to the present invention;

FIGs. 32A and 32B are images of blood volume of normal and abnormal breast tissues, respectively, both of which are measured by the optical imaging system of FIG. 31 according to the present invention; and

FIGs. 33 A and 33B are images of oxygen saturation of normal and abnormal breast tissues, respectively, both of which are measured by the optical imaging system of FIG. 31 according to the present invention.

FIG. 34 is a schematic diagram of an exemplary scanning unit arranged for linear translations according to the present invention;

FIG. 35 is a schematic diagram of another exemplary scanning unit arranged for rotation or revolution according to the present invention;

FIG. 36 is a schematic diagram of another exemplary scanning unit arranged for simultaneous X-translation and Y-reciprocation according to the present invention;

FIG. 37 is a schematic diagram of another exemplary scanning unit arranged to generate cross- voxels or cross measurement elements according to the present invention; FIG. 38 is a schematic diagram of a mobile optical imaging system according to the present invention; FIG. 39 is a schematic diagram of an optical imaging system according to the present invention;

FIGs. 40A and 40B are images of blood volume of normal and abnormal breast tissues, respectively, both of which are measured by the optical imaging system of FIG. 39 according to the present invention; and

FIGs. 41 A and 41B are images of oxygen saturation of normal and abnormal breast tissues, respectively, both of which are measured by the optical imaging system of FIG. 39 according to the present invention.

FIGs. 42A to 42D are exemplary arrangements of wave sources and detectors of an optical imaging system according to the present invention;

FIGs. 43A and 43B are exemplary output signals generated by wave detectors according to the present invention;

FIG. 44 is a schematic diagram of a typical self-calibrating optical imaging system according to the present invention; FIGs. 45A to 45C are further exemplary output signals generated by wave detectors according to the present invention;

FIG. 46 is a schematic view of another exemplary optical imaging system according to the present invention;

FIGs. 47A and 47B are images of changes in blood volume in both normal and abnormal breast tissues, respectively, measured by the optical imaging system of FIG. 46 according to the present invention; and

FIGs. 48 A and 48B are images of oxygen saturation in normal and abnormal breast tissues, respectively, measured by the optical imaging system of FIG. 46 according to the present invention. FIG. 49 is a schematic diagram of an optical imaging system according to the present invention;

FIG. 50 is a cross-sectional top view of an exemplary scanning unit according to the present invention;

FIG. 51 is a cross-sectional top view of another exemplary scanning unit according to the present invention;

FIG. 52 is a schematic diagram ofthe scanning unit of FIG. 51 arranged for linear translation according to the present invention;

FIG. 53 is a schematic diagram of images obtained by the scanning unit of FIG. 52 according to the present invention; FIG. 54 is an example of two-dimensional spatial distribution of an output signal generated by a wave detector of FIG. 52 according to the present invention; FIG. 55 is another schematic diagram ofthe scanning unit of FIG. 51 arranged for rotation according to the present invention;

FIG. 56A is a schematic diagram ofthe scanning unit of FIG. 51 arranged for linear translation along the X-axis according to the present invention; FIG. 56B is a schematic diagram ofthe scanning unit of FIG. 51 arranged for rotation according to the present invention;

FIG. 56C is a schematic diagram ofthe scanning unit of FIG. 51 arranged for linear translation along the Y-axis according to the present invention;

FIG. 57 is a schematic diagram of images obtained by the scanning unit of FIGs. 56A to 56C according to the present invention;

FIG. 58 is another schematic diagram ofthe scanning unit of FIG. 51 arranged for simultaneous X-translation and Y-reciprocation according to the present invention;

FIG. 59 is a cross-sectional top view of yet another exemplary scanning unit according to the present invention;

FIG. 60 is a schematic diagram of a mobile optical imaging system according to the present invention;

FIG. 61 is a schematic diagram of an exemplary optical imaging system according to the present invention; FIGs. 62 A and 62B are images of blood volume of normal and abnormal breast tissues, respectively, both of which are measured by the optical imaging system of FIG. 61 according to the present invention; and

FIGs. 63 A and 63B are images of oxygen saturation of normal and abnormal breast tissues, respectively, both of which are measured by the optical imaging system of FIG. 61 according to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The following description provides various optical imaging systems arranged to provide images of two- or three-dimensional spatial or temporal distribution of properties of chromophores in a physiological medium. More particularly, the following description provides preferred aspects and embodiments ofthe optical imaging systems, the optical probes therefor equipped with movable scanning units, mobile source-detector assemblies, self-calibration algorithms for calibrating the output signals, and real-time image construction algorithms and the methods thereof. I. Apparatus In General

A. General Configuration

In one aspect ofthe present invention, an optical imaging system is provided to generate images of spatial distribution or temporal variation of one or more properties of

5 chromophores in target areas of a physiological medium using a scanning unit which has a scanning area smaller than the target area.

FIG. 1 is a schematic diagram of an optical imaging system according to the present invention. An exemplary optical imaging system 100 includes a body 110, movable member 120 having two wave sources 122 and two wave detectors 124, actuator member

10 130 coupled with and arranged to move movable member 120 with respect to body 110 along one or more curvilinear paths in the directions shown by the arrows, and imaging member 140 coupled with and arranged to receive signals from the sensors (i.e., wave sources 122 and detectors 124) and to generate images ofthe spatial or temporal distribution ofthe chromophore and/or their properties. By arranging a pre-determined number of wave

15 sources 122 and detectors 124, they define a scanning unit 125 which forms a basic source- detector arrangement for scanning the medium.

Body 110 is generally made of rigid or semi-rigid material such as plastics. As will be explained below, shape and size of body 110 may be determined according to various design criteria which may include, e.g., an area ofthe medium to be scanned and 0 examined (i.e., a "target area"), shape and size of movable member 120, characteristics of movements of movable member 120, generated by actuator member 130, and configuration of curvilinear path of movable member 120.

Body 110 includes a housing 112 substantially shaped as a rectangle and is arranged to receive movable member 120 therein. In general, housing 112 is shaped and 5 sized substantially larger than movable member 120 so that movable member 120 can move along different portions of housing 112. As will be discussed below, the area of housing 112 generally corresponds to a "target area" ofthe medium that is to be scanned by sensors 122, 124 disposed at movable body (or sensor assembly) 120. Configuration of body 110 is generally determined according to various design criteria, e.g., the shape and size ofthe area 0 ofthe medium to be scanned, shape and size of movable member 120, configuration ofthe curvilinear paths along which actuator member 130 moves movable member 120 across different regions or portions ofthe target area, etc. Body 110 may be made of semi-rigid or flexible material to conform to contoured surface ofthe medium.

5 B. Sources & Detectors/Scanning Element/ Scanning Unit

The following description provides source-detector arrangements or sensor arrangements for optical probes, optical imaging systems, and methods therefor to provide images of two- and/or three-dimensional spatial or temporal distribution of chromophores and/or their properties in a target area of various physiological media. More particularly, the following description provides preferred aspects and embodiments of symmetric sensor arrangements for optical probes ofthe optical imaging systems.

Arrangement of Wave Sources Movable member 120 may include one or more wave sources, each arranged to form optical coupling with the medium and to irradiate electromagnetic waves thereinto. Any wave sources may be used in the movable member to irradiate electromagnetic waves having pre-selected wavelengths, e.g., in ranges between 100 nm and 5,000 nm, 300 nm and 3,000 nm or, more particularly, in the "near-infrared range" between 500 nm and 2,500 nm. As will be explained below, typical wave sources are arranged to irradiate the near-infrared electromagnetic waves having wavelengths of about 690 nm (670-710 nm) or about 830 nm (810-850 nm). The wave sources may be arranged to emit electromagnetic waves with different wave characteristics such as, e.g., different wavelengths, phase angles, frequencies, amplitudes or harmonics. In the alternative, the wave sources may irradiate electromagnetic waves in which identical, similar or different signal waves are superposed to carrier electromagnetic waves having similar or mutually distinguishable wavelengths, frequencies, phase angles, amplitudes or harmonics. The embodiment shown in FIG. 1 has an arrangement where movable member 120 includes two wave sources 122 each of which irradiates electromagnetic waves with different wave characteristics, e.g., wavelengths of about 680 nm to 700 nm and about 820 nm to 840 nm. It is noted that the exact number ofthe wave sources included in the movable member is not critical in realizing the present invention which is described herein. For example, the movable member may include only a single wave source capable of irradiating multiple sets of electromagnetic waves having, e.g., different wave characteristics, identical or different signal waves or different or identical carrier waves, and so on. Such wave sources may be arranged to irradiate electromagnetic waves continuously, periodically or intermittently. Similarly, the movable member may include only a single wave detector that can detect the foregoing electromagnetic waves continuously, periodically, or intermittently.

Wave Detector Requirements The movable member may include at least one wave detector preferably arranged to detect electromagnetic waves and to generate output signal in response thereto. Any wave detectors may be used in this invention as long as they exhibit appropriate sensitivity to the electromagnetic waves having wavelengths in the foregoing ranges. The wave detectors or multiple wave detectors may be arranged to detect multiple sets of electromagnetic waves each set of which may have foregoing different wave characteristics. The wave detectors or multiple wave detectors may also be arranged to detect multiple sets of electromagnetic waves irradiated by multiple wave sources and to generate multiple sets of output signals accordingly. Alternatively, the movable member may also include a single wave detector which may be arranged to detect multiple sets of electromagnetic waves irradiated by multiple wave sources.

FIG. 2A is a schematic diagram of an optical probe of an optical imaging system having multiple scanning units according to the present invention. An exemplary optical imaging system includes an optical probe 120A including eight wave sources 122 (e.g., Saa, Sad, Sbfa, Sbc, Scb, Scc, Sda, and Sdd) and eight wave detectors 124 (e.g., Dab, Dac, Dba, Dbd, Dca, Dcd, Ddb, and Ddc) where optical sensors (i.e., wave sources 122 and detectors 124) are disposed on a scanning surface thereof. In general, each pair of wave source 122 and detector 124 forms a scanning element which forms a basic functional unit of optical probe 120A. In each scanning element, wave source 122 irradiates electromagnetic waves into the target area ofthe medium and wave detector 124 detects such electromagnetic waves which have interacted with (e.g., absorbed and/or scattered) and which emanate from the target area ofthe medium and then generates an output value which represents an amplitude ofthe electromagnetic waves detected thereby across the scanning element.

Instead of directly using the output values generated by each ofthe scanning elements, one or more wave sources 122 and/or detectors 124 are preferably grouped to further define a "sensor assembly," "sensor array" or "scanning unit" 125, where one or more wave detectors 124 of each scanning unit 125 are arranged to detect electromagnetic waves irradiated by one or more wave sources 122 ofthe same scanning unit so that an area ofthe medium (referred to as a "target area" hereinafter) can be scanned by the scanning unit 125. Thus, each scanning unit 125 can generate an output signal which is a collection of multiple output values each of which is generated by multiple scanning elements ofthe same scanning unit. Each scanning unit 125 is generally defined around its optical sensors 122,

124 and arranged to form an uninterrupted scanning area so that the optical property of a particular target area can be obtained by a single scanning ofthe medium by optical probe 120A. It is noted in the figure that the end portions of scanning units 125 are elongated only for illustration purposes. Configuration of scanning unit 125 and scanning area thereof is generally determined by that ofthe source-detector arrangement such as, e.g., the number of wave sources 122 and detectors 124 in each scanning unit 125, grouping or pairing of wave sources 122 and detectors 124 in each scanning element, grouping or pairing ofthe scanning elements in each scanning unit 125, geometric arrangement between sensors 122, 124, that between the scanning elements of each scanning unit 125, that between scanning units 125

5 ofthe optical probes, irradiation capacity or emission power of wave sources 122, detection sensitivity of wave detectors 124, and the like.

Referring once again to FIG.l, movable member 120 is generally elongated and includes a longitudinal axis 127. Movable member 120 also includes optical sensors such as wave sources 122 and detectors 124 each of which is aligned along longitudinal axis

10 127. Wave sources 122 are generally disposed at each end of movable member 120 and wave detector 124 interposed therebetween at equal distances so that electromagnetic waves emitted by wave sources 122 travel through the medium, interact with the medium, and are detected by wave detectors 124. Therefore, wave sources 122 and detectors 124 functionally form a scanning unit 125 (i.e., source-detector arrangement) that is elongated around wave

15 sources 122 and detectors 124 along longitudinal axis 127 of movable member 120 and that defines a corresponding scanning area (or scanning volume). Movable member 120 may also be made of semi-rigid or flexible material so that sensors 122, 124 may form optical coupling while conforming to the surface contour ofthe target area.

Movable member 120 may also include a scanning unit 125 extending along

2u its longitudinal axis 127. Scanning unit 125 generally refers to a functional unit from which electromagnetic waves are irradiated into the medium and by which such electromagnetic waves interacted with the medium are detected. Accordingly, configuration of scanning unit 125 and its scanning area is predominantly determined by the corresponding configuration ofthe sensor assembly and/or source-detector arrangement which is in turn determined by,

ΛJ e.g., number of wave sources or detectors, geometric arrangement therebetween, irradiation capacity or emission power ofthe wave sources, detection sensitivity ofthe wave detectors, etc. hi the embodiment shown in FIG. 1, e.g., wave sources 122 and detectors 124 define substantially elongated scanning unit 125 where wave detectors 124 are interposed between two wave sources 122 along longitudinal axis 127 thereof. Although scanning unit 125 may

30 be characterized by various dimensions (e.g., its length, width or height), a characteristic dimension of scanning unit 125 is generally the one which is orthogonal to its longitudinal axis 127 (a direction in which scanning unit 125 and movable member 120 are moved by actuator member 130). Thus, as will be explained in greater detail below, the characteristic dimension of scanning unit 125 of FIG. 1 is its width. It is appreciated that scanning unit

35

125 constitutes a portion of movable member 120 and that such scanning unit 125 preferably moves with movable member 120 by the actuator member 130. Therefore, unless otherwise specified, the terms "scanning unit" and "movable member" may be used herein interchangeably.

It is appreciated that the scanning unit may preferably define the scanning area which is continuous throughout an entire portion ofthe scanning unit so that a single measurement by the scanning unit generates the output signal covering the entire scanning area without interruption to unscanned regions. For this purpose, the wave sources and detectors are preferably spaced at distances no greater than a threshold distance thereof. Selection of an optimal spacing between the wave sources and detectors is generally a matter of choice of one skilled in the art and may be determined by several factors which may include, but not limited to, optical properties ofthe physiological medium (e.g., absorption coefficient, scattering coefficient, and the like), irradiation capacity ofthe wave sources, detection sensitivity ofthe wave detectors, number of wave sources and/or detectors, geometric arrangement therebetween, and/or operational characteristics ofthe actuator member as will be explained below.

Still referring to FIG. 2A, foregoing optical sensors 122, 124 are arranged to form a 4-by-4 sensor array on the scanning surface of optical probe 120A. Each row ofthe sensor array typically includes at least two wave sources 122 and at least two wave detectors 124 and forms a horizontally elongated scanning unit (e.g., Ha, Hb, Hc, and Hj). Similarly, each column ofthe sensor array includes two wave sources 122 and two wave detectors 124 and defines a vertically elongated scanning unit (e.g., Va, Nb, Nc, and Vπ). For example, in the first and fourth horizontal scanning units (Ha, FLJ, two wave detectors Dab-Dac and Ddb- Ddc are interposed between two wave sources Saa-Sad and Sda-Sdd, respectively. Whereas, in the second and third horizontal scanning units (Hb, Hc), two wave sources Sbb-Sbc and Scb-Scc are interposed between two wave detectors Dba-Dbd and Dca-Dcd, respectively, hi addition, in the first and fourth vertical scanning units (Na, Nj), two wave detectors Dba-Dca and Dbd-Dcd are interposed between two wave sources Saa-Sda and Sad-Sdd, respectively, whereas, in the second and third vertical scanning units (Nb, Nc), two wave sources Sbb-Scb and Sbc-Scc are interposed between two wave detectors Dab-Ddb and Dac-Ddc, respectively. The optical probes ofthe present invention may be provided with source- detector arrangements which are different from the one shown in FIG. 2A. For example, FIG. 2B is a schematic diagram of another optical probe of an optical imaging system according to the present invention. Similar to the one of FIG. 2 A, this exemplary optical probe 130A also includes eight wave sources 122 (e.g., Sab, Sac, Sba, Sbd, Sca, Scd, Sdb, and Sdc) and eight wave detectors 124 (e.g., Dm! Dad, Dbb, Dbc, Dcb, Dcc, D^, and Ddd) forming another 4x4 sensor array. However, optical sensors 122, 124 are provided in an arrangement which is completely reverse to that of FIG. 2 A. That is, the wave sources of FIG. 2 A are replaced by the wave detectors in FIG. 2B, while the wave detectors of FIG. 2A are substituted by the wave sources in FIG. 2B. As will be discussed in greater below, both optical probes 120A, 130A can provide identical or at least substantially comparable performance characteristics. It is preferred that, in each scanning unit 125 of optical probes 120A, 130A, a first wave source be disposed closer to a first wave detector than a second wave detector, and a second wave source be disposed closer to a second wave detector than a first wave detector. In addition, such wave sources and detectors are preferably arranged such that a first near-distance between the first wave source and the first wave detector be identical or substantially similar to a second near-distance between the second wave source and the second wave detector, and that a first far-distance between the first wave source and the second wave detector be identical or substantially similar to a second far-distance between the second wave source and the first wave detector. In the second horizontal scanning unit, Hb, e.g., the first wave source (Sbb) is disposed closer to the first wave detector (Dba), and the second wave source (Sbc) closer to the second wave detector (Dbd). In addition, the first near-distance between the first wave source (Sbb) and the first wave detector (Dba) can be arranged to be identical to the second near-distance between the second wave source (Sbc) and the second wave detector (Dbd). Furthermore, the first far-distance between the first wave source (Sbb) and the second wave detector (Dbd) is also arranged to be identical to the second far-distance between the second wave source (Sbc) and the first wave detector (Dba). D. Actuator Member

Referring to FIG.l actuator member 130 operationally couples with and generates movements of wave sources 122 and/or detectors 124 along at least one curvilinear path in at least one curvilinear direction. In a specific embodiment, actuator member 130 operationally couples with movable member 120 and linearly translates said movable member (along with wave sources 122 and detectors 124) from one side of body 110 to another side thereof in a direction normal to longitudinal axis 127 of movable member 120.

In this embodiment, the width of movable member 120 is substantially similar to that of housing 112. Therefore, scanning unit 125 can scan through at least a substantial portion ofthe target area while being linearly translated across the target area. Any actuating devices maybe incorporated into the optical imaging system for the purpose of generating foregoing movements. For example, a motor-gear assembly may be employed to generate rotations about a center of rotation around a pre-selected angle or to generate revolutions for a pre-selected number of turns. Alternatively, a stepper motor may be used, along with optional guiding tracks, to generate curvilinear translations, reciprocations, and combinations thereof, where examples of such curvilinear translations may be linear displacements along linear paths or non-linear translations along curved paths. The actuator member may also impart various temporal characteristics to such movements by generating, e.g., impulses (i.e., functions of δ(t)), steps (i.e., functions of u(t)), pulses, pulse trains, sinusoids, and combinations thereof. In addition, the actuator member may generate such movements continuously, periodically, and/or intermittently.

The actuator member may also generate at least two movements ofthe wave sources and/or detectors sequentially or simultaneously along at least two curvilinear paths in at least two curvilinear directions. Such movements may be along the curvilinear paths aligned to be substantially orthogonal to each other, as exemplified by the orthogonal axes ofthe Cartesian, cylindrical or spherical coordinate systems. Alternatively, the foregoing movements may take place along the identical or parallel curvilinear paths but in opposite directions, as exemplified in the reciprocating movements.

It is appreciated that the movable body, scanning unit, and actuator member may be arranged to provide various geometric arrangements between the longitudinal axis of the scanning unit and the curvilinear path ofthe movable member. For example, the scanning unit may be aligned with the actuator member in such a way that the scanning unit travels along its short axis which is orthogonal to the longitudinal axis ofthe scanning unit, rendering the curvilinear path ofthe scanning unit and/or movable member substantially orthogonal to the axis ofthe scanning unit. By the same token, the actuator member may move the scanning unit and/or movable member along the path substantially parallel with the axis ofthe scanning unit or along another path forming a pre-determined angle with the axis ofthe scanning unit. The latter option is preferred as the latter embodiment maximizes the effective scanning area ofthe scanning unit during movements ofthe movable member. Furthermore, the actuator member may generate the foregoing movements at constant speeds or at speeds varying over time or position (e.g., continuously, periodically, or and/or intermittently). An optional motion controller may be provided so that the speed of such movement may be controlled precisely according to a pre-determined pattern. Alternatively, such movement may also be controlled adaptive to various parameters such as, e.g., optical characteristics ofthe medium and/or presence or absence of abnormal regions in the target area which is signified by, e.g., abnormally high or low absorption or scattering of electromagnetic waves transmitted therethrough. Further details ofthe actuator member will be provided below in conjunction with the exemplary embodiments ofthe scanning units illustrated in FIGs. 52 through 60. E. Imaging Member

As in FIG. 1, imaging member 140 operationally couples with wave sources 122 and/or detectors 124 and is arranged to generate two- or three-dimensional images representing spatial or temporal distribution ofthe chromophores or their properties in the medium. As described in the figure, imaging member 140 typically includes a data acquisition unit 142 (i.e., signal acquisition unit or signal processor), algorithm unit 144, and image construction or image generation unit 146 (i.e., image processor). Data acquisition unit 142 is arranged to sample optical or electrical data or signals which may be related to intensity, magnitudes, amplitudes or other characteristics of electromagnetic waves irradiated by wave source 122 and detected by wave detectors 124. Data acquisition unit 142 may also monitor other system variables or parameters related with the actuator member as well as an optional control member for controlling operation of each component of optical imaging system 100. Algorithm unit 144 receives various signals or data from data acquisition unit 142 and obtains solutions ofthe multiple wave equations applied to wave sources 122 and/or detectors 124. Conventional analytical or numerical schemes may be used in algorithm unit 144 to solve a set of wave equations such as the photon diffusion equation, Beer-Lambert equation, modified Beer-Lambert equation, and their equivalents. Algorithm unit 144 may then determine the absolute or relative values ofthe chromophores or their properties directly from such solutions or by further mathematical manipulations or signal processing thereof. Image construction unit 146 processes the foregoing absolute or relative values ofthe chromophores or their properties, and provides images for the two- or three-dimensional distribution pattern ofthe chromophores or their properties in the spatial and/or temporal domain.

F. Benefits of the Present Invention The optical imaging systems ofthe present invention offer several benefits over prior art technologies such as conventional near-infrared spectroscopy, diffuse optical spectroscopy, etc. Conventional optical sensors generally define scanning units each of which allows only a single measurement in each measurement location. Therefore, when the target area is larger than the scanning area of such scanning unit, the sensor probe must be manually moved to different regions ofthe target area, and multiple measurements must be made thereat. Such procedure tends to lengthen the examination periods, not to mention unreliable images with poor resolution due to inaccurate and/or inconsistent positioning of the sensor probes on different measurement locations ofthe medium or due to inconsistent optical coupling formed at different measurement locations. In order to rectify such deficiencies, bigger sensor assemblies with a far greater number of wave sources and detectors have been developed so that they can cover a larger target area in each measurement. However, such sensor assemblies are generally bulky and more expensive. Additionally, idiosyncratic variations among the sensors jeopardizes quality ofthe optical and/or electrical output signals, thereby degrading the quality ofthe resulting images. Furthermore, conventional optical imaging technology requires a priori estimation of an baseline of output signals before scanning the target area of the medium. Considering the widely known fact that the baseline estimation constitutes a primary source of measurement errors, conventional optical imaging systems cannot be reliably used to obtain high- resolution images of a relatively large target area.

The optical imaging systems ofthe present invention can overcome such prior art deficiencies by, e.g., providing movable scanning units with only a minimal number of wave sources and detectors which can be positioned at one region (e.g., an edge) ofthe target area and sweep through different regions of a much larger target area without having to move and reposition other components ofthe system (e.g., movable member and/or optical probe ofthe imaging system) to other regions ofthe target area. Therefore, the foregoing optical imaging system can scan such large target area with the scanning unit forming the scanning area which amounts to only a fraction ofthe target area. The foregoing optical imaging systems also need fewer sensors (i.e., fewer wave sources or detectors) than their conventional counterparts. Thus, the optical probe ofthe present invention can be constructed as a light and compact article. In addition, by incorporating fewer sensors, noises attributed to idiosyncratic component variances inherent in each ofthe wave sources and detectors may also be reduced, thereby improving signal-to-noise ratios of the output signals and providing high-quality and high-resolution images therefrom. The optical imaging systems ofthe present invention may further be arranged to ensure that substantially identical optical couplings may be formed and maintained between the medium and movable wave sources and/or detectors during the movement ofthe movable member. As will be discussed below, this embodiment allows the foregoing optical imaging systems to establish a single baseline and to apply the same baseline to multiple output signals measured throughout different target areas ofthe entire medium. This embodiment further allows the use of a much simpler and more efficient image construction scheme capable of providing real-time images ofthe properties ofthe chromophores in the medium while scanning the target area ofthe test subject.

Though any analytical or numerical schemes may be used by the algorithm unit or image construction unit ofthe imaging member, an exemplary algorithm or image construction unit ofthe present invention preferably employs solution schemes disclosed in the method described below and also discussed in the copending '972 application. II. Methods

A. Mathematical Foundations

Detailed Description of the System and Method of Measuring the Absolute Oxygen Saturation The present invention relates to optical systems and methods thereof for determining absolute values of properties and/or conditions of a physiological medium. In particular, the following description provides various embodiments of optical systems and/or methods for determining the absolute values of concentrations ofthe hemoglobins (both of deoxy- and oxy-hemoglobin) and oxygen saturation (a ratio of oxy-hemoglobin concentration to total hemoglobin concentration which is a sum ofthe concentrations of deoxy-hemoglobin and oxy-hemoglobin) in a physiological medium. For these purposes, the following description provides novel methods for solving Beer-Lambert equations, generalized photon diffusion equations, and/or modified versions thereof, hi addition, the description discloses various embodiments of optical imaging systems incorporating such methods. It is appreciated that the following methods and systems based thereon may be applied to determine absolute values of concentrations, their ratios, and or volumes of other chromophores ofthe tissues and cells ofthe physiological medium.

In one aspect ofthe invention, a novel method is provided to solve the modified Beer-Lambert equation and/or the photon diffusion equation applied to an optical system including a source module and a detector module. The source module and detector module generally include, respectively, at least one wave source and at least one wave detector. However, it is generally preferred that the source and detector modules include at least two wave sources and two wave detectors, respectively.

As described hereinabove, equation (1) is the generalized governing equation for describing migration of photons or propagation of electromagnetic waves in a medium:

I = a - β - r - I- - e[ • J (1)

It is appreciated that the system parameters "γ" and "δ" may have the value of 1.0 and "σ" may be 0.0. One simplified version of equation (1) may be obtained when the parameters

"γ" and "δ" are approximated as a unity:

■L∑ (£,C,)+

I = a -β - I0 - e[ ' J (3a)

The conventional "photon diffusion equation" has the same form as equation (3a): ?.£.∑ (t,ς)+

I = S- D- - e (3b)

where "S" corresponds to "α" of equation (3 a) and generally accounts for characteristics of the wave source such as irradiation power and geometric configuration thereof, mode of optical coupling between the wave source and medium, and/or associated optical coupling loss therebetween, "D" corresponds to "β" of equation (3a) and generally accounts for characteristics ofthe wave detector such as detection sensitivity and range, mode of optical coupling between the wave detector and medium, and/or the associated coupling loss, and "A" corresponds to "δ" of equation (3 a) which maybe either a proportionality constant or a parameter associated with the wave source, wave detector, and/or medium. It is again noted that both "I0" and "I" are functions of time only and preferably independent of frequency- domain frequency-domain parameters such as frequency and phase angle of such waves. It is also appreciated that the wave sources and detectors preferably operate in the CWS mode, i.e., the wave sources irradiate non-impulsive electromagnetic waves which have at least substantially identical amplitude over a measurable period. Therefore, the most preferred profile ofthe electromagnetic waves irradiated by the wave sources is a step-function (i.e., I0 u(t)) of which the characteristics are determined solely by their intensity (i.e., IJ but not by the frequency-domain parameters. However, as long as the irradiated waves are non- impulsive, such waves can take the form of a single step (e.g., I0 u(t) - 10 u(t-t0), where t0 represents a duration longer than a temporal sensitivity threshold ofthe wave detector, hi the alternative, the irradiated waves may be a step-train comprised of a series of steps which have at least substantially identical amplitudes.

For illustration purposes, an exemplary optical system may include, e.g., two wave sources (SI and S2) each emitting electromagnetic waves of wavelength λ, and two wave detectors (DI and D2) arranged to detect at least a portion of such electromagnetic waves. Applying the photon diffusion equation (3b) to each pair ofthe wave sources and detectors ofthe exemplary optical system yields the following set of equations:

where the superscript λj denotes that various variables and parameters are determined at the wavelength of λ,.

A simple mathematical operation may eliminate at least one system parameter from the equations (4a) to (4d). For example, the source coupling factors such as S, and S2 may be canceled therefrom by taking the first ratio ofthe equation (4a) to (4b) and by taking the fourth ratio ofthe equation (4d) to (4c). Logarithms ofthe first and second ratios are then taken to yield what are conventionally termed as "optical densities" (i.e., OD\ is defined as a logarithm of 7*lfll / 7*'1B2 and OD2 2 defined as a logarithm of jk i h y S2D2 ' S2B1 /

OD =ln^£L = ln^+ (Bs λ\D2LSW2 - Bs λ mLslm)∑ ε^C, (5a) d L S\D n2 lJ2 '

OD = ln^ = lι -+ (B 2DlLS2m - BS λ 2D2LS2D2)∑ s^C, (5b)

It is appreciated that the optical densities are generally insensitive to exact modes of optical coupling between the wave source and the physiological medium. It is further appreciated that such optical densities solely depend on the intensities ofthe detected electromagnetic waves. Therefore, the optical densities are functions of time only and generally are independent of or at least substantially insensitive to the frequency-domain parameters.

Other system parameters may also be eliminated through reformulating the above equations (5 a) and (5b). For example, the terms including the detector coupling factors, D, and D2, maybe canceled by adding equation (5a) to (5b):

ODh - ODλi + OD = F __ s/'C, (6a) i where E - = (Bs λ D2LSW2 - Bs l mLSW ) + (Bs l mLS2m - Bs λ'2D2LS2D2 ) . (6b)

As manifest in equation (6b), Fλ> is primarily determined by configurations ofthe wave sources and detectors (i.e., "L's" which are predominantly "geometry-dependent" and which account for distances between each pair of a wave source and a wave detector) as well as the path length factors (i.e., "B's" which are predominantly "medium-dependent" and which are determined by the optical properties ofthe physiological medium and/or electromagnetic waves). Equations (6a) and (6b) maybe applied to the physiological medium in order to obtain quantitative physiological information such as concentrations ofthe chromophores and/or their ratios. Numerous substances contained or suspended in the medium may be capable of interacting or interfering with photons or electromagnetic waves impinging or propagating therethrough. However, in many physiological media, hemoglobins such as deoxygenated and deoxy-hemoglobin (Hb) and oxygenated or oxy-hemoglobin (HbO) are the chromophores ofthe most physiological interests. Applying equations (6a) and (6b) to such physiological medium yields: ODh ■•∑ ε, C. ~ εHb[HB] + εl> bo[HbO] (7a) F1' where [Hb] and [HbO] respectively represent concentrations of Hb and HbO.

By arranging the wave sources, SI and S2, or additional wave sources, e.g., S3 and S4, to irradiate a second set of electromagnetic waves having a wavelength λ2 which is different from the wavelength λ,, a companion equation ofthe equation (7a) is obtained as follows: ^ = ∑ 8 H Ct _ s^[Hb + a oiHbO] (7b)

Accordingly, mathematical expressions of two system variables [Hb] and [HbO] can be readily derived from an algebraic system of equations (7a) and (7b) as follows:

OD*' OD

Fλ

[Hb] = Fλ pΛ pΛ2 _ pΛ2 pΛ (8a) ύHbύHbO GHbύHbO

ph OD _ F ODλ

'Hb ph Hb p

-Ht> ] = — F Pζ — — P , (8b)

° bGHbO GHbGHbO

where Fλ> = (BS' D2LS,D2 - Bs l mLSim)+ (Bs l mLS2m - B 2D2LS2D2) (8c) and F = (BS'\D2LSW2 - Bs l\mLslDi)+ (Bs l\mLS2m - B 2D2LS2D2) (8d)

Expressions of other physiological properties or indices may also be derived from the above equations. For example, oxygen saturation (SO2) is a frequently used index for diagnosis of ischemic conditions and generally defined as a ratio of concentration of oxy- hemoglobin to total concentration of hemoglobins (i.e., [HbT] = [Hb]+[HbO]): so lHb01 = IBbO]

2 [HbT] [Hb] + [HbO] J

Incorporating equations (8a) and (8b) to equation (9a) yields a following formula for the oxygen saturation as a function ofthe extinction coefficients (ε's), optical densities (OD's), and medium geometry-dependent factors, F and F :

The extinction coefficients ofthe oxy- and deoxy-hemoglobins measured at different wavelengths λ1 and λ2 can be obtained from the literature or from a separate measurement. As will be explained in greater below, the medium/geometry-dependent factors F and F can also be obtained empirically, semi-empirically or theoretically. Therefore, the absolute values ofthe concentrations ofthe deoxygenated and oxygenated hemoglobins, [Hb] and [HbO] respectively, can be obtained by plugging into the equations known values of extinction coefficients (ε's), experimentally measured optical densities (OD's), and readily obtainable values of medium/geometry-dependent factors, F1' and Fh . In addition, the absolute value ofthe tissue oxygen saturation (SO2) can also be directly determined from the absolute values of [Hb] and [HbO]. In short, the optical systems and methods ofthe present invention allow the determination ofthe absolute value ofthe hemoglobin (and other chromophores) concentrations and/or their ratios solely by measuring the intensities ofthe electromagnetic waves irradiated by the wave sources and those ofthe electromagnetic waves detected by the wave detectors.

It is noted that estimation of Fλl and F is not straightforward because the path length factors including such terms usually depend on specific types ofthe physiological medium as well as optical or energy characteristics of electromagnetic waves or photons. One way of estimating or approximating the values of Fli andE^ is to assume that F1' , F , or their ratio may only marginally depend on background optical properties and configurations ofthe wave sources and detectors. It is believed that these assumptions are fairly accurate in linear optical processes such as migration of photons or propagation of electromagnetic waves in the physiological media.

Once the correlations ofthe ratio of Fh to F with oxygen saturation is obtained for different physiological media by simply measuring the optical properties thereof, such correlations may be incorporated into equations (8a), (8b), and (9b), and the absolute values of [Hb], [HbO], and/or oxygen saturation may be obtained, hi particular, a ratio of Fh to Fh may be approximated, e.g., as a polynomial of oxygen saturation as follows:

G = ^ = ∑ ajSO2 i = a0 + alSO2 + a2SO2 2 + a3SO3+... (10)

where coefficients of each term (i.e., aQ,a a2 ,a3 ...) maybe obtained by, e.g., theoretical derivation, semi-theoretical estimation or numerical method best-fitting experimental data 10 obtained between the values of G and oxygen saturation. By incorporating the formula for G of equation (10) into equation (9b), the absolute value ofthe oxygen saturation may be obtained from known values ofthe extinction coefficients (i.e., 'Vs") and experimentally measured optical densities (i.e., "OD's") as follows:

By plugging into equation (11) the values of extinction coefficients (ε's), coefficients ofthe 20 correlation such as equation (10), and experimentally measured optical densities (OD's), Equation (11) can be generally solved numerically. However, an analytical expression for the oxygen saturation may also be obtained when only a few first terms ofthe polynomials are adopted so as to approximate G, ,i.e., the ratio of F to F . Other methods may also be applied to approximate G. For example, G may be estimated as a function of [Hb] and/or [HbO], although it is noted that the accuracy of this estimation may depend on the one-to- one correspondence between G and [Hb] and/or [HbO]. Alternatively, G may further be approximated as a constant as well. This approximation may be a reasonable assumption when F and F are relatively constant or tend to vary in proportion to each other according to different values of [Hb], [HbO], and/or oxygen saturation. In the alternative,

30 the value of "Lmn" may be varied by manipulating geometric configuration ofthe wave sources and detectors so as to render G stay constant or vary in a pre-determined manner.

Similarly, each of F1' and F may be approximated as a function of [Hb],

[HbO], and/or oxygen saturation. In the alternative, Fh and F may also be assigned

, , specific values which may best approximate the optical system and/or the physiological medium of interest. By taking the simplest approach of approximating Fh wA Fh to be a unity, the absolute values of [Hb], [HbO], and oxygen saturation may be obtained as follows: εH λ2 b0ODλ' - εHboOD [Hb = _ b*Hb_b*HbO ύHbύH*bO (12a)

ε^ ODh - ε^OD^ [Hb°^ bHbsύH>*bO ϋHb°H*bO (12b)

In this embodiment, oxygen saturation (SO2) can be determined solely by the known values ofthe extinction coefficients (ε's) and experimentally measured optical densities (OD's).

It is noted that [Hb], [HbO], and/or oxygen saturation obtained from the equations (12a) to (12c) (and/or other approximation methods described hereinabove) may be less accurate than those obtained from equations (8a), (8b), and (9b). Nevertheless, as long as the foregoing assumptions hold valid, one-to-one correlations may be expected between the true values of [Hb], [HbO], and oxygen saturation and those obtained from approximating equations (12a) to (12c). Such correlations maybe determined once the optical properties ofthe physiological medium are known. For example, extinction coefficients, absorption coefficients, and/or scattering coefficients ofthe physiological medium (or those ofthe chromophores) may be determined for [HbT] and oxygen saturation. With known optical properties, oxygen saturation may be estimated at different levels of [HbT] through simulations ofthe diffusion equations and/or through experiments.

Equations (12a) and (12b) may then be used to back-calculate [HbT], and a correction function can be calculated which correlates the calculated [HbT] with the true [HbT].

Similar or identical approach may be applied to calculate correction functions for [Hb] and/or [HbO] as well. It is noted that these methods may be applied to different physiological media (e.g., different human or animal subjects) to assess different optical properties and, therefore, to obtain different correction functions.

It is appreciated that the foregoing methods are applicable to any optical system and physiological media where migration of photons or propagation of electromagnetic waves may be reasonably described by the generalized governing equation

(1). It should be noted that the parameter eliminating step ofthe foregoing methods may be applicable regardless ofthe specific numerical values assigned to the parameters "γ" and "δ". For example, γ can be eliminated by taking ratios of equation (4a) to (4b) and equation (4d) to (4c), and δ can be eliminated by taking the ratio of Fh to Fh . In addition, the foregoing method may also be readily applicable to any modified versions ofthe governing equation (1) where the optical interaction or interference ofthe medium is described by the absorption coefficient, scattering coefficients, and/or reduced scattering coefficient ofthe chromophores and/or the medium. For example, by assigning an adequate value and unit to parameter "γ," such modified equations can be converted into equations substantially similar or identical to the governing equation (1). Therefore, it is manifest that the foregoing methods may be deemed universal for solving the governing equation (1) for the chromophore concentrations and/or their ratios.

It is further appreciated that the absolute values ofthe chromophore concentrations (or their ratios) may be obtained by variations ofthe foregoing methods. For example, the detector coupling factors, Dj and D2, may first be eliminated from equations (4a) to (4d) by taking the third ratio ofthe equation (4a) to (4c) and the fourth ratio ofthe equation (4d) to (4b) as follows:

OD = (5c)

/ lλ< S -_,

OD; = ]n- s- = ln-ξ-+ ln^+ (BX D2LSW2 - BX'2D2LS2D2)∑ εx'C, (5d)

J Slβ2 '' Si °. '

Similar to equations (5a) and (5b), this variational method yields optical densities ODx' and

ODXi which are substantially insensitive to the coupling mode between the wave detector and the medium. By adding equation (5c) to (5d), the logarithmic ratios (i.e., one ratio of intensities ofthe electromagnetic waves irradiated by the wave sources and another ratio of the source coupling factors, Sj and S2) also cancel each other, yielding:

OD \ = OD? + ODl = Fx ∑ εx> Q (6c)

where Ttf = (BS x 2mLS2Di - Bx\DXLs.m) + (Bs λ\D2LSiD2 - BS λ 2D2LS2D2) . (6d)

By applying equations (6c) and (6d) to the physiological medium including oxy- and deoxy- hemoglobins, following equation (7c) is obtained:

ODX

-pir = Σ ε C, = ε > b[Hb]+ ε+ olHbO] (7c) * 34 ' Similarly, a companion equation of equation (7c) maybe obtained by applying the second set of electromagnetic waves having a wave length λ2:

ODl

= ∑ εX2Ci = εx-b[Hb}+ ε 2 b0[HbO] (7d)

34 '

Thus, by solving equations (7c) and (7d), mathematical expressions of two system variables [Hb] and [HbO] can be obtained as follows:

where F£ =- (Bx 2'mLS2D1 - Bx\mLslD1) + (BX[D2LSW2 - BS l 2D2LS2D2) (8g)

<mQ 34 = — ■tSS2D2L,S2D2 ) [ O.)

The oxygen saturation may then be expressed as:

Other variations ofthe foregoing methods leading to equations (9b) and (9c) may also be used as long as they are designed to eliminate system parameters and to ultimately express [Hb], [HbO], and/or oxygen saturation in terms of known or measurable system variables or parameters such as, e.g., the experimentally measured optical densities, known values ofthe extinction coefficients, and/or other geometry-dependent parameters readily determined by the actual geometry ofthe source-detector arrangement.

It is further appreciated that the foregoing method ofthe present invention allows the wave sources to irradiate multiple sets of electromagnetic waves which have different wave characteristics through various different embodiments. The simplest arrangement maybe to provide two wave sources (such as SI and S2), where each source is designated to irradiate the electromagnetic waves having different wavelengths, phase angles, and/or harmonics. For example, the optical monitoring and/or imaging systems operating in the CWS mode include the wave sources preferably irradiating non-impulsive and non-phase- modulated electromagnetic waves which have at least substantially identical amplitudes over a minimal measurable period. Similarly, the wave detectors of CWS systems only perform the intensity measurement ofthe electromagnetic waves on a continuous basis. It is appreciated that such intensity measurement may also be performed on an intermittent basis as long as the wave detector can detect the waves for a period of time sufficient to detect the intensities thereof. Thus, the wave sources ofthe CWS systems do not have to irradiate continuous electromagnetic waves. Alternatively, each wave source may also be arranged to irradiate substantially identical signal waves which are, however, superimposed on different carrier waves. In yet another alternative, a single or each wave source may be arranged to irradiate multiple sets of electromagnetic waves intermittently, sequentially or simultaneously as long as different sets of electromagnetic waves can be identifiable by one or more wave detectors. Similar arrangements may also be applied to the wave detectors as well. For example, two wave detectors (DI and D2) maybe provided where each detector is designated to detect only a single set of electromagnetic waves. Alternatively, a single or each wave detector may detect multiple sets of electromagnetic waves with different wave characteristics on an intermittent, sequential or simultaneous mode. Because the foregoing systems and methods ofthe present invention allow these various arrangements, they can be readily incorporated into any conventional spectroscopy such as the TRS, PMS, and CWS. h another aspect ofthe invention, an over-determined numerical method is provided to solve the modified Beer-Lambert equation and/or the photon diffusion equation applied to an optical system including a source module and a detector module, where at least one ofthe source module and detector module may be arranged to irradiate or detect more than two sets of electromagnetic waves. By arranging an optical system to provide "more equations" than "the number of system variables" of interest, resulting extra equations may be utilized for other purposes, e.g., (i) to enhance the accuracy of estimated values of system variables (e.g., chromophore concentrations or their ratios), (ii) to determine system parameters (e.g., "αm," "βn," "γ," "Bmn," "Lmn," "δ," ' ' "σ" or other parameters such as absorption and scattering coefficients ofthe medium and or chromophores) or (iii) to provide correlations between the medium- and/or geometry-dependent parameters ofthe equations (1) or (3b) and the system variable(s) and/or other system parameters.

In the first embodiment, the extra equations may be used to obtain multiple values ofthe chromophore concentrations (and/or their ratios). It is expected that discrepancies may exist, at least to some extent, among the estimated values ofthe concentrations (and/or their ratios). Such discrepancies may be attributed to inherent idiosyncracy of each pair ofthe wave sources and detectors. Alternatively, the discrepancies may also arise from a non-homogeneous medium having regional variations in optical properties. One way of taking advantage of different values ofthe concenfrations ofthe chromophores (and/or their ratios) may be to average such values to obtain an arithmetic, geometric or logarithmic average to reduce random or systematic errors and to improve accuracy. Alternatively, each measured value may be weight-averaged by an appropriate weight function which may account for, e.g., geometric configuration ofthe wave source and detector assembly. hi the second embodiment, correlations between the medium- and/or geometry-dependent parameters ofthe equations (1) or (3b) and the chromophores concentrations (or their ratios) may be obtained from those extra equations. For example, when G (i.e., the ratio of F1' to FXl ) is approximated as a polynomial of oxygen saturation according to the equation (10), each coefficient ofthe polynomial may be assigned an initial value which is then improved by iterative techniques employing a conventional numerical fitting method. In addition, the extra equations may also be used to find the correction functions between the approximated and true values of oxygen saturation, [Hb], and/or [HbO].

Furthermore, the extra equations may also be used to estimate system parameters (e.g., "αm," "βn," "γ," "Bmn," "Lmn," "δ," " "σ," and or other system parameters such as absorption coefficients and/or scattering coefficients ofthe medium and/or chromophores). For example, a forward numerical scheme may be used to estimate absorption and reduced scattering coefficients ofthe physiological medium and/or chromophores included therein. As described hereinabove, migration of photons and propagation of electromagnetic waves in the medium can be described by the diffusion or transport equation. Assuming that the medium is semi-infinite and homogeneous, following equation may describe an intensity of electromagnetic waves detected by a j-th detector:

I^ S D' φ^r^μ) (13)

where S{ generally denotes a source coupling parameter accounting for, e.g., characteristics of an i-th wave source such as irradiation power and configuration thereof, mode of optical coupling between the i-th wave source and medium, and/or coupling loss therebetween, and where Dj is a detector coupling factor generally accounting for characteristics of a j-th wave detector, mode of optical coupling between the j-th wave detector and medium, and the associated coupling loss therebetween. A symbol "φ" represents a forward numerical model simulating measurement for a given pair of a wave source and detector. Parameters "μa" and "μs" represent, respectively, an absorption coefficient and (reduced) scattering coefficient. When the optical system includes, e.g., a total number of Ns wave sources and ND wave detectors, equation (13) can be expressed in a matrix form as follows:

I,

ffsΛ

It is appreciated that all system variables, Iy (i=l, ... Ns and j=l, ... , N s), are functions of time and preferably independent of or at least substantially insensitive to the frequency- domain parameters. Each side ofthe equation (14) is divided by the first column of each matrix:

Each row ofthe matrices of equation (15) is then divided by the first row of each matrix to yield matrices A and B:

As manifest in equation (16), both ofthe matrices A and B are functions ofthe absorption and reduced scattering coefficients and do not depend on the source- and detector-coupling parameters such as S; and D,-. Accordingly, by minimizing the difference between A and B (i.e., ), the best estimates ofthe absorption coefficient and (reduced) scattering coefficient may be numerically obtained by conventional curve-fitting methods. After estimating the absorption and reduced scattering coefficients, [Hb], [HbO], and oxygen saturation may be obtained by the following set of formulae: ph , .h _ ph ,,h

\ LHb J\ - ° ph _ p fh p μh' (17a) bHb°HbO bHb°HbO

bHbbHbO bHbbHbO

[Hb] + [HbO] εϊoμ - ε^μ + μ - εϊμ

It is noted that the foregoing over-determined method may be applied to the optical systems with at least two wave sources and three wave detectors, at least three wave sources and two wave detectors, or three wave sources and three wave detectors. In the alternative, the over-determined method may equally be applied to the optical systems where a single or each wave source or detector has the capability of irradiating or detecting multiple sets of electromagnetic waves, respectively.

It is appreciated that the foregoing over-determined method may be incorporated into any conventional numerical schemes. For example, a forward, backward or hybrid model may be applied to determine, e.g., an extinction coefficient, absorption coefficient or scattering coefficient ofthe physiological medium (or the chromophores included therein). Such models may also be applied to estimate the absolute values ofthe concentrations ofthe chromophores (and/or ratios thereof). It is noted, however, that the results obtained by such numerical models generally include errors associated therewith.

Such inherent errors may be minimized by employing numerical models with the error terms ofthe second or higher order. However, such models may have a major drawback of requiring rigorous numerical computations. Accordingly, the accuracy and efficiency of each numerical model must be considered in selecting an appropriate model.

In yet another aspect ofthe invention, an optical system is provided to solve a set of wave equations and to determine absolute values ofthe concenfrations ofthe chromophores (and/or ratios thereof) contained or suspended in a physiological medium.

An exemplary optical system may include a body, a source module including at least one wave source, a detector module having at least one wave detector, and a processing module.

The source module is supported by the body, optically couples with the physiological medium, and irradiates into the medium at least two sets of electromagnetic waves having different wave characteristics. The detector module is also supported by the body, optically couples with the medium, and detects electromagnetic waves transmitted through the medium. The processing module operatively couples with the detector module, solves a set of multiple wave equations, and determines the absolute values ofthe chromophore concentrations and/or ratios thereof.

In general, the processing module includes an algorithm which is arranged to solve the foregoing equations (1) or (3b) or their modified versions. For example, one or more ofthe foregoing methods may be incorporated into hardware or software or implemented into a microprocessor. Accordingly, the absolute values ofthe chromophore concentrations (and/or their ratios) can be calculated from, e.g., experimentally measured intensity ofthe electromagnetic waves irradiated by the wave source, experimentally measured intensity ofthe electromagnetic waves detected by the wave detector, and at least one system parameter which may account for an optical interaction or interference between the electromagnetic waves and the medium. The algorithm ofthe processing module may include one or more functions or correlations expressing the medium- and/or geometry- dependent term(s) ofthe foregoing wave equations as a function ofthe chromophore concentrations (or their ratios). The algorithm ofthe processing module may be capable of executing the over-determined method described hereinabove. In addition, the processing module and algorithm thereof may be modified to operate in the TRS and PMS modes. The source module may include at least one wave source and the detector module may include at least two wave detectors. Alternatively, the source module may include at least two wave sources while the detector module may include at least one wave detector. It is preferred, however, that the source and detector modules include, respectively, at least two wave sources and at least two wave detectors. Embodiments Using the Above Method

As described hereinabove, the foregoing methods ofthe present invention are rather insensitive to actual configuration of wave sources and detectors. Accordingly, the optical monitoring and imaging systems ofthe present invention may include any number of wave sources and/or detectors arranged in any arbitrary configuration subject only to the "symmetric requirements" ofthe copending '972 application. However, a few source- detector configurations may be preferred to obtain the absolute values ofthe chromophore concentrations (and/or their ratios) with better accuracy, reliability, and reproducibility.

In one exemplary embodiment, multiple wave sources and wave detectors may be arranged so that near-distances between each pair ofthe wave source and detector are at least substantially identical. For example, for the source module including a first and a second wave source and the detector module including a first and a second wave detector, a first near distance between the first wave source and the first wave detector may be arranged to be substantially similar to a second near-distance between the second wave source and the second wave detector. In addition, a first far-distance between the first wave source and the second wave detector may be arranged to be substantially similar to a second far-distance between the second wave source and the first wave detector. It is appreciated that such an embodiment is not necessary for every single pair ofthe wave sources and detectors. For example, when the source module has M wave sources and the detector module has N wave detectors (M and N are integers greater than 1), at least two of M wave sources and two of N wave detectors may be arranged so that a distance between an Mj-th wave source and an Nrth detector is substantially similar to that between an M2-th wave source and an N2-th wave detector, and that a distance between the Mrth wave source and the N2-th wave detector is substantially similar to that between the M2-th wave source and the Nj-th wave detector, where M-, and M2 are both integers between 1 and M, and where Nj and N2 are both integers between 1 and N. Such an embodiment is typically realized by the wave sources and detectors arranged substantially symmetrically, e.g., those arranged substantially linearly along a straight line. FIG. 3 A is a schematic diagram of a sample optical system having two wave sources and two wave detectors having identical near-distances and far-distances according to the present invention. It is first appreciated that the source-detector arrangement of FIG. 3 A satisfies the identical near-distance and far-distance configuration. For example, the first near-distance between the wave source Sj and detector Dj is identical or substantially similar to the second near-distance between the wave source S2 and detector D2. hi addition, the first far-distance between the wave source S! and detector D2 is identical or substantially similar to the second far-distance between the wave source S2 and detector D^ An advantage of satisfying such configurational limitation lies in the observation that electromagnetic waves are substantially uniformly transmitted, absorbed or scattered throughout the entire target area or target volume ofthe medium (refer to banana-shaped paths ofthe electromagnetic waves in the figure). Therefore, the photos or electromagnetic radiation uniformly covers all regions ofthe target area ofthe medium and, therefore, enhances the accuracy as well as reliability ofthe output signal (e.g., an improved signal-to- noise ratio) generated by the wave detector. As will be demonstrated in the following Examples, the foregoing linear arrangement ofthe wave sources and detectors has provided the absolute values ofthe concentrations of oxygenated and deoxygenated hemoglobins and oxygen saturation with great accuracies. It is also appreciated that not all wave sources and/or detectors have to be arranged linearly. For example, the wave sources and wave detectors may be arranged not linearly but substantially symmetrically with respect to a line of symmetry and/or a point of symmetry. As long as such symmetric configuration is maintained by the wave sources and wave detectors, the identical near-distance and far- distance requirements are automatically met. hi another exemplary embodiment, multiple wave sources and detectors may be arranged in an asymmetrical configuration that does not satisfy the identical near-distance and far-distance requirements. FIG. 3B is a schematic diagram of another sample optical system with two wave sources and two wave detectors having different near-distances and far-distances according to the present invention. As manifest in the figure, both the near- and far-distances ofthe source-detector pairs are different. In addition, the banana-shaped paths ofthe electromagnetic waves (see the figure) reveal that each source-detector pair covers different portions ofthe target area in different depths. Thus, such source-detector arrangement allows detection ofthe electromagnetic waves absorbed or scattered through different regions ofthe target area in different depths. hi yet another exemplary embodiment, the foregoing symmetric and asymmetric embodiments can be realized in a single wave source-detector arrangement. FIG. 3C is a schematic diagram of yet another sample optical system having two wave sources and four wave detectors according to the present invention. It is appreciated that not every source-detector pair satisfies the identical near- and far-distance configuration of FIG. 3 A. For example, although the first and fourth wave detectors (Dj and D4) as well as the second and third wave detectors (D2 and D3) have the identical near- and far-distances from the wave sources (Sj and S2), such near- and far-distances are different for the first and third wave detectors (Dλ and D3) or the second and fourth wave detectors (D2 and D4) with respect to the wave sources (S, and S2). Therefore, by selectively coupling appropriate wave source with wave detector and by irradiating and detecting the electromagnetic waves thereby, either symmetric or asymmetric source-detector arrangement can be attained. Another advantage of such an embodiment is that such a source-detector arrangement allows multiple scanning of a given target area ofthe medium. For example, the area positioned under the second wave detector (D2) can be scanned by, e.g., six different source-detector pairs such as S,-DrD2-S2, S1-D1-D3-S2, SrDrD4-S2, SrD2-D3-S2, SrD2-D4-S2, and SrD3- D4-S2. Accordingly, the accuracy ofthe resulting absolute value ofthe chromophore concentration (and ratios thereof) can be improved.

It is appreciated that the actual configuration ofthe source-detector assembly does not affect the foregoing methods of determining the absolute values ofthe chromophore concentrations and ratios thereof. For example, in all ofthe foregoing equations, the only term that depends on the actual configuration ofthe source-detector assembly is "L" or "LsiDj" representing a linear distance between an i-th wave source (Sj) and a matching j-th wave detector (Dj) which is operatively coupled to the i-th wave source so as to detect the electromagnetic waves irradiated thereby. Because the L value is predetermined by the design ofthe source-detector assembly and because other system variables or parameters do not depend upon the L value, the foregoing methods ofthe present invention can be used regardless ofthe presence or absence ofthe symmetry between the wave sources and wave detectors.

The foregoing symmetric source-detector configurations can be applied to construct two-dimensional optical probes for the CWS optical monitoring and imaging systems. In one embodiment, the symmetric wave source-detector arrangement of FIG. 3 A can be stacked in an alternating manner to form a four-by-four square or rectangular optical probe, e.g., the first and fourth rows having two wave detectors interposed between two wave sources while the second and third rows having two wave sources interposed between two wave detectors, hi another embodiment, such optical probes may be constructed to have different number of wave sources and/or detectors in the horizontal and vertical directions. For example, the arrangement of FIG. 3 A can be repeated twice to form a four-by-two probe, six times to form a four-by-six probe, and so on. h yet another embodiment, such symmetric wave source-detector aπangements may also be repeated in an angular fashion to form circular or arcuate optical probes. In addition, the repeated rows (or columns) ofthe wave sources and wave detectors may be stretched to form trapezoidal optical probes or stacked to form optical probes having parallelogram shapes. Further embodiments of such symmetric source-detector configurations and optical probes having various geometry are provided in the commonly assigned co-pending U.S. non-provisional patent application bearing serial no. 09/778,614, entitled "Optical Imaging System with Symmetric Optical Probe" filed on February 6, 2001 which is incorporated herein in its entirety by reference. It is further appreciated that two-dimensional optical probes for the CWS optical monitoring and imaging systems can also be constructed based on the foregoing asymmetric source-detector configurations. For example, the asymmetric source-detector arrangement can be repeated at any distances and/or in any order or pattern to form square, rectangular, arcuate or circular optical probes. It is noted that such asymmetric wave source- detector arrangement can be repeated (e.g., rows stacked on top ofthe others) in predetermined distances so that the repeated wave sources and detectors (e.g., a column of wave sources and detectors) satisfy the foregoing near- and far-distance requirements. The foregoing wave source-detector configurations and optical probes constructed thereby can also be made to be linearly displaced and/or to rotate one or more of the sensors (i.e., wave sources and detectors) while maintaining optical coupling between such sensors and the medium. Such an embodiment enables to scan a specific target area more than once and to provide more measurement data therefrom, e.g., by aπanging the wave sources and detectors to scan the target area at multiple speeds, along different scanning paths and/or in different scanning angles, and the like. Regardless of actual configurations ofthe source-detector arrangement, such optical probes with mobile sensor elements enable measurement ofthe absolute values ofthe chromophores and/or construction of images thereof by using fewer wave sources and detectors. Further details regarding such optical probes with mobile sensors and techniques of directly obtaining images therefrom are provided in the commonly assigned co-pending U.S. non-provisional patent application bearing serial no. 09/778,617, entitled "Optical Imaging System for Direct Image Construction" filed on February 6, 2001 which is incorporated herein in its entirety by reference. hi operation, a source module with at least one wave source and a detector module having at least one wave detector are provided to a scanning surface of an optical probe which is operatively connected to a main body of an optical system. Alternatively, the wave source and/or detector modules may be disposed in the main body and optical fibers may be provided to connect the source and detector modules to openings provided on the scanning surface ofthe optical probe. Any conventional wave sources and detectors may be used for such optical prove. It is preferred, however, that the wave sources irradiate electromagnetic waves in the near-infrared range between 500 nm and 1,200 nm or, in particular, between 600 nm and 900 nm and that the wave detectors have appropriate sensitivity to the foregoing electromagnetic waves. The optical probe is placed on a target area ofthe physiological medium, with its scanning surface disposed on the target area to form an optical coupling therebetween. The source module is activated so that at least two sets of electromagnetic waves having different wave characteristics are irradiated into the medium. The detector module then picks up different sets of electromagnetic waves irradiated by the wave source, propagated through the medium, and directed toward the wave detector. The wave detector generates electric signals which are delivered to the processing module ofthe main body ofthe optical system. Based on the experimentally measured intensities ofthe electromagnetic waves and at least one system parameter such as extinction or scattering coefficients ofthe chromophores, the processing module computes the absolute values ofthe concentration of oxygenated and deoxygenated hemoglobins or the oxygen saturation.

It is noted that the optical system according to the present invention may include an equation solving module which is operationally separate from the processing module. Such an equation solving module may include variety of numerical models designed perform one or more ofthe foregoing methods ofthe present invention. Although the foregoing disclosure has been directed toward obtaining the absolute values ofthe concentrations of oxygenated and deoxygenated hemoglobins (and/or their ratios), the foregoing optical systems and methods may be applicable to obtain the absolute values of other substances in the medium or properties thereof. For example, the systems and methods ofthe present invention may be directly applied or modified to determine the absolute values ofthe concentrations (or their ratios) of other chromophores such as lipids, cytochromes, water, and the like. Depending upon the absorption or scattering coefficients, the wavelengths ofthe electromagnetic waves maybe adjusted for better resolution. In addition, chemical compositions may be added to the medium to enhance optical interaction or interference of chromophores in the medium or to convert an non-chromatic substance ofthe medium into a chromophore.

As described hereinabove, the foregoing optical systems and methods ofthe present invention are preferred to be incorporated to the continuous wave spectroscopic technology. However, such systems and methods may readily be incorporated into the time- resolved and phase-modulation spectroscopic technologies as well.

The optical systems and methods according to the present invention find a variety of medical applications. As described above, such optical monitoring and/or imaging systems and methods may be applied to measure the absolute values of concentrations of oxygenated and deoxygenated hemoglobin and/or their ratio. Such optical systems will be beneficial in non-invasively diagnosis of ischemic conditions and/or ischemia in various organs and tissues such as, e.g., a brain (stroke), heart (ischemia) or other physiological abnormalities originating from or characterized by abnormally low concentration of oxy-hemoglobin. In addition, presence of cancerous tumors in various internal organs, breasts, and skins may be easily detected as well. Such optical systems and methods may further be applied to cells disposed in epidermis, corium, and organs such as a lung, liver, and kidney. Such optical systems and methods may also be applied to diagnose vascular occlusion during or after surgical procedures including transplantation of tissues, skins, and organs, e.g., heart, lung, liver, and kidney.

Incorporating any ofthe foregoing solution schemes into the optical probes with the foregoing symmetric source-detector arrangements ofthe present invention offers further benefits over the prior art technology. Contrary to the CWS technology allowing measurement of changes in the hemoglobin concentrations, the symmetric source-detector arrangements described herein provide a direct means for assessing spatial and/or temporal distribution ofthe "absolute values" of various chromophore properties ofthe physiological medium, including those of hemoglobins. This also allows a physician to directly assess the oxygen concentrations and oxygen saturation in tissues, cells, organs, muscles or blood of an animal and/or human subject. The foregoing symmetric source-detector arrangements also allow the physician to make direct diagnosis ofthe test subject based on the "absolute values" ofthe chromophore properties ofthe medium thereof.

The scanning units ofthe optical probes ofthe present invention can adopt various source-detector arrangements which satisfy the symmetric requirements ofthe co- pending '972 application. FIGs. 4 and 5 are examples of such symmetric scanning units, where the wave sources and detectors are arranged symmetrically in FIGs. 6 A to 6H with respect to a line of symmetry 127, whereas those are arranged symmetrically with respect to a point of symmetry 128 in FIGs. 7A to 7C. It is appreciated in the foregoing figures that the shapes and sizes ofthe wave sources and detectors are simplified and exaggerated for ease of illustration.

FIGs. 7A and 7B are schematic diagrams of linear scanning units according to the present invention. The scanning units (He and Hf) of FIGs. 6 A and 6B are identical or substantially similar to those of FIGs. 2A and 2B and, therefore, automatically satisfy the symmetry requirements ofthe identical near- and far-distances between wave sources 122 and detectors 124. It is appreciated that such scanning unit (He and Hf) can be modified without violating the foregoing symmetry requirements ofthe co-pending '972 application. For example, in the scanning unit, He, the distance between the neighboring wave source and detector may be lengthened or shortened as long as such distance does not exceed the threshold sensitivity range ofthe wave detector which may range from, e.g., several cm to 10 cm or, in particular, about 5 cm for most human and/or animal tissues. In addition, so long as the symmetry with respect to line of symmetry 127 can be maintained, the distance between wave detectors, Dab and Dac, may also be adjusted to be identical to or different from the near-distances between the adjacent wave source and detector pairs such as Saa-Dab and Dac-Sad.

FIGs. 6C and 6D are schematic diagrams of square scanning units according to the present invention. In each ofthe square scanning units, two wave sources and two wave detectors are disposed at four vertices ofthe square. In particular, as shown in the scanning unit, Sa, two wave sources, Saa and Sab, are disposed at the upper vertices ofthe square, two wave detectors, Dba and Dbb, are disposed at the lower vertices thereof, and line of symmetry 127 vertically passes through the middle ofthe square. Accordingly, the near- distance between the adjacent wave source and detector corresponds to the vertical distance between the wave source Saa (or Sab) and detector Dba (or Dbb), while the far-distance is the diagonal length connecting the wave source Saa (or Sab) and detector Dbb (or Dab). The same applies to the scanning unit, Sb, of FIG. 6D that has the source-detector arrangement which is reverse to that in FIG. 6C. As discussed above, both the near- or far-distance between the adjacent sensors may also be adjusted as long as the aforementioned sensitivity limitation is met by the wave detectors, Daa and Dab.

FIG. 6E is a schematic diagram of a rectangular scanning unit according to the present invention, where two wave sources and two wave detectors are disposed at four vertices ofthe rectangular scanning unit, Ra. Similar to the foregoing scanning units, the source-detector arrangement ofthe foregoing scanning unit may also be reversed such that the wave sources are positioned at the upper vertices ofthe rectangle, whereas the wave detectors are arranged at the lower vertices thereof. The horizontal and vertical distances between the adjacent optical sensors may further be increased or decreased as long as the foregoing sensitivity limitation ofthe wave detectors is met.

FIGs. 6F and 6G represent schematic diagrams of trapezoidal scanning units according to the present invention. In the exemplary trapezoidal scanning unit, Ta, of FIG. 6F, two wave sources, Saa and Safa, are disposed in the upper vertices ofthe frapezoid, while two wave detectors, Dba and Dbb, are disposed in the lower vertices thereof so that line of symmetry 127 passes through the middle ofthe frapezoid. More particularly, two opposing sides ofthe frapezoid are preferably arranged to have the same lengths so as to satisfy the foregoing symmetry requirements ofthe co-pending '972 application. Therefore, the near- distance is the distance between the wave source Saa (or Sab) and detector Dba (or Dbb), while the far-distance is to the diagonal length between the wave source Saa (or Sab) and detector Dbb (or Dba). The same applies to the scanning unit, Tb, of FIG. 6G, except that the sensors are reversely arranged.

FIG. 6H is a schematic diagram of yet another trapezoidal scanning unit according to the present invention, where the scanning unit, Tc, is substantially similar to those of FIGs. 6F and 6G, except that the upper vertices ofthe frapezoid are separated by a greater distance than the lower vertices thereof. As discussed above, the distances between the adjacent sensors may also be adjusted as long as two opposing sides ofthe frapezoid have equal lengths and the foregoing sensitivity limitation is met by the wave detectors.

FIG. 7 A is a schematic diagram of a quasi-linear scanning unit according to the present invention, where the scanning unit, Pa, includes two wave detectors, Dba and Dbb, disposed in the center portion thereof, where the first wave source, Saa, is disposed at the upper-right corner ofthe scanning unit, and where the second wave source, Sca, is disposed at the lower-left corner thereof, hi particular, the wave sources, Sca and Saa, are arranged at the same angle from the wave detectors, Dba and Dbb, respectively, and they are spaced apart therefrom by the same distance so that the wave sources and detectors are symmetrically arranged with respect to point of symmetry 128. Therefore, the foregoing embodiment also satisfies the symmetry requirements ofthe wave sources and detectors ofthe co-pending '972 application.

FIG. 7B is a schematic diagram of a rectangular scanning unit according to the present mvention, where a first horizontal scanning element including the sensors, Saa and Dab, is disposed over or above a second horizontal scanning element including sensors, Dba and Sab, and where such sensors 122, 124 occupy four vertices ofthe rectangle, hi this embodiment, the near-distance is the vertical distance between the wave source S^ (or wave detector Dab) and wave detector Dba (or wave source Sb ), while the far-distance corresponds to the diagonal length between the wave sources (or detectors). It is also appreciated that sensors 122, 124 may be grouped to define a first vertical scanning element (Saa and Dba) and a second vertical scanning element (Dab and Sbb). As will be described in greater detail below, the optical imaging system maybe arranged to group sensors 122, 124 to define such scanning elements. FIG. 7C shows a schematic diagram of a parallelogram scanning unit according to the present invention. The scanning unit, Pb, includes a first pair of sensors, Saa and Dab, which are disposed at two upper vertices ofthe parallelogram as well as a second pair of sensors, Dba and Sab, which are disposed at two lower vertices thereof the rectangle.

The scanning units, Pa, Rb, and/or Pb, may have source-detector arrangements which are reverse to those shown in FIGs. 7A to 7C by, e.g., substituting the wave source by the wave detector and vice versa. In addition, as far as the foregoing sensitivity limitation is met by the wave detectors, distances between the wave sources and/or detectors may also be adjusted to manipulate the shape and/or size ofthe resulting scanning unit and its scanning area. Furthermore, the near- and far-distances in each scanning unit, Pa, Rb, and Pb, may be reversed by adjusting an aspect ratio ofthe source-detector arrangement, where the aspect ratio is defined as a ratio of a length to a height of a quadrangle, h the scanning unit, Pb, of FIG. 7C, e.g., the horizontal distance between the wave source, Saa, and wave detector, Dab, maybe either a near-distance (e.g., when the aspect ratio is less than 1.0) or a far-distance (e.g., when the aspect ratio is greater than 1.0). When the aspect ratios of such scanning units approach 1.0, the distances between one wave source and two adjacent wave detectors become identical, and the symmetry requirement ofthe co-pending '972 application cannot be met. This may be contrasted with the source-detector arrangements in FIGs.6C and 6D where the foregoing symmetry requirement is met by the square scanning units, Sa and Sb. Due to the irradiation and/or sensitivity limitations ofthe wave sources and detectors, each ofthe foregoing scanning units covers only a small scanning area. Thus, as shown in FIGs. 2A and 2B, optical probe 120A ofthe optical imaging system ofthe present invention typically includes multiple scanning units on the scanning surface thereof so that optical probe 120A can scan the target area which is generally larger than the scanning areas of individual scanning units thereof. Although such scanning units can be arranged in a symmetric or asymmetric manner and in any combination and/or permutation thereof, it is preferred that multiple scanning units be arranged to share one or more wave sources and or detectors in order to increase efficiency of utilizing the finite scanning area and to enhance resolution ofthe resulting images. In other words, the optical probes or optical imaging system includes an imaging member that defines multiple scanning elements and multiple scanning units while incorporating some or all ofthe wave sources and/or detectors into more than one scanning element and/or scanning unit This aspect ofthe invention is now discussed using optical probe 120A of FIG. 2A as the exemplary embodiment. FIG. 8 A is a schematic diagram of a first set of scanning units ofthe optical probe of FIG. 2 A, and FIG. 8B is a schematic diagram of voxels and cross-voxels generated by the scanning units of FIG. 8 A, and resulting voxel values and cross-voxel values thereof according to the present invention. Optical probe 120A includes four horizontal scanning units (Ha, Hb, Hc, and Hπ) and four vertical scanning units (Na, Nb, Nc, and Nj), where each scanning unit 125 generates one or more output signals which correspond to representative values ofthe chromophores or their properties in the target area ofthe medium scanned by each scanning unit 125.

As shown in FIG. 8B, each scanning unit 125 defines a "voxel" in an image domain 200, in which each voxel in image domain 200 coπesponds to a small region ofthe target area ofthe medium in which one or more wave sources 122 irradiate electromagnetic waves into such a region and one or more wave detectors 124 detect such elecfromagnetic waves and generate output signals in response thereto. Thereafter, the imaging member of optical probe 120A or optical imaging system samples the output signal generated by wave detectors 124, solves a set of wave equations applied to wave sources 122 and detectors 124 ofthe same scanning unit 125, and determines a representative value ofthe chromophores or their properties therein. That is, the imaging member defines the scanning elements based on pre-determined groupings of wave sources 122 and detectors 124, spatially groups two or more overlapping or non-overlapping scanning elements so as to construct scanning units 125, samples the output signal generated by wave detectors 124 for each scanning unit, obtains the foregoing set of solutions from the wave equations, and calculates a voxel value per each voxel. Each voxel value is generally an area- or volume-averaged value ofthe chromophores or their properties which is generally averaged with respect to each scanning area or volume of scanning unit 125 or with respect to the area or volume of each voxel that is constructed in image domain 200. It is appreciated that the area-averaged voxel value is substantially similar or identical to the volume-averaged voxel value when wave detectors 124 have the sensitivity range covering a substantially identical thickness or depth ofthe medium throughout the entire target area.

In the embodiment shown in FIG. 8A, the horizontal scanning units, Ha, Hb, Hc, and Hd, define, in image domain 200, four parallel horizontal voxels 204a each of which is elongated in the X direction and stacked one over the other in a sequential mode. Based on the output signals generated by each ofthe horizontal scanning units, Ha, Hb, Hc, and Hd, the imaging member solves the wave equations applied to each horizontal scanning unit and determines the voxel value of ha, hb, hc, and hd for each horizontal voxel 204a, respectively. For simplicity of presentation, FIG. 8B highlights only one horizontal voxel 204a (the third from the top) which has the voxel value of hc. Similarly, the four vertical scanning units, Na, Nb, Nc, and Nd, define four vertical voxels 204b which are elongated in the Y direction, sequentially and laterally arranged side by side, and have the voxel values of va, vb, vc, and vd, respectively. For simplicity of illustration, FIG. 8B again highlights only one vertical voxel 204b having the voxel value of vd. As shown in the figure, each horizontal scanning unit shares one common optical sensor with one ofthe vertical scanning units, thereby defining cross-voxels as the overlapping regions ofthe intersecting horizontal and vertical voxels. Accordingly, optical probe 120A of FIG. 8A defines sixteen cross-voxels forming a 4x4 matrix in image domain 200, each having a separate cross-voxel value that is determined by two generally different voxel values ofthe intersecting voxels. For example, though two cross-voxels 214a, 214b are commonly defined in the top horizontal voxel, Ha, having the voxel value of ha, the cross- voxel value of cross-voxel 214a is calculated from va and ha, whereas that of cross- voxel 214b is obtained from vc and ha. In general, the cross-voxel values are calculated by, e.g., arithmetically averaging, geometrically averaging or weight-averaging individual voxel values ofthe intersecting voxels. In the alternative, one of such constituent voxel values may be selected as the cross- voxel value as well. It is noted that, other things being equal, accuracy of estimated values ofthe chromophores and/or their properties and resolution of the images ofthe distribution thereof generally depend on the size ofthe voxels, size ofthe cross-voxels, and the number of output signals or voxel values used to calculate the voxel values or cross-voxel values, respectively, hi this aspect, each ofthe square cross-voxels of FIG. 8B has the substantially identical resolution across entire image domain 200.

The optical probes ofthe present invention with the foregoing embodiment offers numerous benefits. By arranging the scanning units to share one or more common optical sensors, the optical probe requires fewer number ofthe wave sources and detectors. Accordingly, the foregoing optical probes may be provided as compact and light articles. In addition, idiosyncratic discrepancies attributed to component variances inherent in each of the optical sensors may be minimized, thereby improving accuracy and enhancing quality and resolution ofthe resulting images. Furthermore, the optical probes ofthe present invention do not need baseline measurements, which is generally mandatory in prior art optical imaging systems. Therefore, the optical probes ofthe present invention efficiently construct images and provide real-time images ofthe distribution ofthe chromophores or their properties on a substantially real time basis during scanning ofthe target area of a test subject.

In operation, optical probe 120A is placed on a target area ofthe medium with each of its optical sensors forming appropriate optical coupling therewith. Wave sources 122 are activated to irradiate electromagnetic waves into the medium and wave detectors 124 are also turned on to detect the electromagnetic waves transmitted through the medium. In order to minimize interferences and noises therefrom, wave sources 124 are preferably synchronized such that only one wave source irradiates electromagnetic waves having pre-selected wave characteristics for a pre-selected period during which other wave sources are turned off. Wave detectors 124 are also synchronized such that only those wave detectors which form the scanning elements with the firing wave source detect elecfromagnetic waves and generate output signals in response thereto. After the selected wave source completes irradiation, the same or another wave source then commences irradiation of electromagnetic waves having identical or different wave characteristics. After all source-detector pairs ofthe first scanning unit of optical probe 120A complete the foregoing irradiation and detection of electromagnetic waves, similar or identical operations are repeated for the next scanning unit of optical probe 120A. Sequence of such irradiation and/or detection generally does not affect operational characteristics of optical probe 120A and the final images representing the distribution ofthe chromophores or their properties. Selection of an optimum sequence is generally a matter of choice of one of ordinary skill in the art. The imaging member ofthe optical probe or optical imaging system samples and acquires such output signals at a pre-selected rate and/or duration for every scanning element of each scanning unit. The imaging member then processes the output signals and solves the set of wave equations applied to wave source 122 and detector 124 of each scanning element ofthe scanning unit of optical probe 120A. The resulting solutions reflect absolute or relative values ofthe chromophores or their properties in each voxel in image domain 200. The imaging member then applies another grouping of such voxel values by, e.g., identifying intersecting and/or overlapping portions of two or more foregoing voxels, constructing cross-voxels corresponding to such intersecting or overlapping voxels, constructing residual voxels corresponding to residual portions ofthe voxels after carving out the cross-voxels therefrom, and obtaining cross-voxel values for each cross-voxels. The foregoing voxel values and cross- voxel values are reorganized such that the images ofthe distribution ofthe chromophores or their properties are represented by the voxel values and cross- voxel values, hi the alternative, instead of calculating the voxel values and then averaging such to obtain the cross- voxel values for each ofthe cross-voxels, the output signals for the voxels can be averaged to yield the output signals for each cross-voxel, which are then processed by the imaging member to yield the cross- voxel value. hi general, configuration of voxels is determined by various factors such as the number of wave sources and detectors defining each scanning element and/or scanning unit, geometric arrangement of wave source and detectors in each scanning element and/or scanning unit, geometric arrangement of scanning elements in each scanning unit, emission power or irradiation capacity of wave sources, detection sensitivity of wave detectors, and the like. Thus, when the wave sources have same emission power and the wave detectors are provided with identical sensitivity, the equi-spaced source-detector arrangement of FIG. 8 A defines the horizontal and vertical voxels having substantially identical configurations and the identical cross-voxels all across the image domain. The same also applies to the configuration ofthe cross- voxels which is predominantly determined by, e.g., configuration of voxels, disposition and orientation thereof, the shapes and sizes of their overlapping portions, and the like.

Although physical configuration ofthe foregoing voxels is rather fixed by the shapes, sizes, and operational characteristics ofthe wave sources and detectors and by the geometric arrangement thereof, configuration ofthe cross-voxels may be manipulated by grouping ofthe wave sources and detectors (i.e., defining the scanning elements and/or scanning unit) as well as by grouping ofthe scanning elements (i.e., defining the scanning units). In other words, without varying the physical arrangements ofthe wave sources and detectors, the shapes and sizes ofthe cross-voxels can be adjusted and the resolution ofthe resulting images can be manipulated by grouping output signals according to a pre-selected pattern and by solving the wave equations applied to the wave sources and detectors of such scanning elements and/or scanning units. Therefore, the optical probes may be arranged to define primary scanning units as well as secondary scanning units, and generate primary as well as secondary output signals from the same target area without implementing additional optical sensors to the optical probe and without physically altering the pre-existing source- detector arrangements thereof. FIGs. 9 through 11 show various scanning units additionally defined in exemplary optical probe 120 A of FIG. 2 A, and FIG. 12 shows the resulting voxels, cross- voxels, and cross-voxel values thereof obtained by combining the voxel values which are described in FIG. 8 through 11. FIG. 9A shows a schematic diagram of a second set of scanning units ofthe optical probe of FIG. 2 A according to the present invention. FIG. 9B represents voxels and cross-voxels generated by such scanning units, while FIG. 9C shows resulting voxel values and cross-voxel values thereof according to the present invention. In this embodiment, the optical sensors arranged in intermediate regions ofthe optical probe are regrouped to form four rectangular or square scanning units, Ia, Ib, Ic, and Id. Similar to those shown in FIGs. 6C to 6E, the optical sensors of each of these intermediate scanning units, Ia, Ib, Ic, and Id, satisfy the foregoing symmetry requirements ofthe '972 application. Thus, rectangular or square voxels 205a-205d are defined in image domain 200, each having a voxel value of ia, i , ic, and id, respectively. Because the foregoing intermediate voxels 205a-205d intersect each other in the center portion of image domain 200, the imaging member can also define multiple rectangular or square cross-voxels 215a while leaving residual truncated voxels 215b therein. For example, each cross-voxel 215a is of one quarter size ofthe rectangular or square voxel 205a-205d, while the residual truncated voxels 215b have one half the size thereof. In addition, similar to the embodiment shown in FIGs. 8 A and 8B, the cross-voxel values of rectangular or square cross-voxels 215a are determined by two voxel values, i.e., their original voxel value and that of a neighboring voxel. Accordingly, optical probe 120A of FIG. 9A can provide images with higher resolution in the center portion of image domain 200. It is appreciated that the four corners 215c of image domain 200 carry neither voxel value nor the cross-voxel value, because none ofthe scanning units 204d-205d cover such regions.

FIG. 10A is a schematic diagram of a third set of scanning units ofthe optical probe of FIG. 2A according to the present invention. FIG. 10B is a schematic diagram of voxels and cross-voxels generated by the scanning units of FIG. 10A, while FIG. 10C shows another schematic diagram of resulting values for the voxels and cross-voxels of FIG. 10B according to the present invention. In this embodiment, optical probe 120A (or its imaging member) synchronizes the wave sources and detectors and defines four diamond-shaped scanning units, Ca, Cb, Cc, and Cd, therein. It is noted that these diamond-shaped scanning units correspond to the rectangular or square scanning units of FIGs. 6C to 6E which are tilted by 45°. Although each diamond-shaped scanning unit only includes optical sensors disposed at four corners ofthe diamond region and does not include any wave source or detector in its middle portion, the region ofthe target area ofthe medium corresponding to such middle portion in image domain 200 is nevertheless irradiated by wave sources 122 and scanned by each scanning element of each diamond-shaped scanning unit. Therefore, the diamond-shaped scanning units, Ca, Cb, Cc, and Cd, define a cross-shaped voxels 206a- 206d each of which has four prongs connected to a center region and each of which carries voxel value of ca, cb, cc, and cd, respectively. Each ofthe diamond-shaped scanning units further intersects two adjacent scanning units, thereby forming cross-voxels 216a while leaving out residual, non-intersecting prongs of original voxels 216b as depicted in FIGs. 10B and IOC. It is appreciated that, contrary to those of FIGs. 8 and 9, the cross-voxel values of all cross- voxels 216a of this embodiment are determined by the voxel values of three intersecting cross-shaped voxels, i.e., its own voxel value plus two other voxel values of adjacent cross-shaped voxels. As a result, cross-voxels 216a of FIG. IOC can provide the images with resolution higher than that of FIGs. 8C and 9C. Furthermore, similar to the rectangular or square scanning units, Ia, Ib, Ic, and Id, of FIG. 9 A, diamond-shaped scanning units, Ca, Cb, Cc, and Cd, do not scan four comers 216c of image domain 200 and, therefore, provide neither voxel values nor cross- voxel values for such regions. In this context, the diamond-shaped scanning units, Ca, Cb, Cc, and Cd, define cross-voxels 216a which are identical to those defined by intermediate scanning units, Ia, Ib, Ic, and Id, but whose cross- voxel values are determined by three voxel values instead of two. FIG. 1 IA is a schematic diagram of a fourth set ofthe scanning units ofthe optical probe of FIG. 2A according to the present invention. FIG. 1 IB represents a schematic diagram of voxels and cross- voxels generated by the scanning units of FIG. 11 A, while FIG. 1 IC is yet another schematic diagram of resulting values and cross-voxel values of FIG. 1 IB according to the present invention. In this embodiment, the wave sources and detectors are regrouped to define four other diamond-shaped scanning units, Da, Db, Dc, and Dd, which are identical to those, Ca, Cb, Cc, and Cd, of FIG. 10A. However, the imaging member of optical probe 120A or optical imaging system is arranged to define diamond- shaped voxels 207a-207d, each of which intersects all three other scanning units. Therefore, diamond-shaped scanning units, Da, Db, Dc, and Dd, define nine smaller diamond-shaped cross-voxels 217a-217c in the center portion of imaging domain 200 while leaving four truncated voxels 216d around comers of imaging domain 200 as shown in FIGs. 1 IB and 1 IC. hi general, all cross-voxels 217a-217c have identical shapes and sizes. It is appreciated, however, that the cross-voxel value of center cross-voxel 217c is calculated from the voxel values of all four diamond-shaped voxels 207a-207d, while the cross-voxel values of comer cross-voxels 217a and middle cross-voxels 217b are determined by two and three voxel values ofthe adjacent voxels, respectively. Thus, optical probe 120A of FIG. 11 A can provide the images with its resolution increasing concentrically from the outer to the center portion thereof. Similar to the scanning units of FIGs. 9A and 10A, the diamond- shaped scanning units, Da, Db, Dc, and Dd, do not scan four triangular comers 217e of image domain 200 either. As discussed above, the number of wave sources and detectors included in each scanning unit and geometric arrangement thereof are not necessarily dispositive ofthe shapes and sizes ofthe voxels and cross- voxels as well as ofthe resolution ofthe resulting images. Rather, accuracy of estimated values ofthe chromophore properties and resolution of the images thereof can be improved by manipulating the grouping pattern of the output signals. For example, the imaging member ofthe optical probe or optical imaging system of the present invention may combine one or more ofthe foregoing secondary scanning units of FIGs. 9 through 11 with the primary scanning units of FIG. 8A. This embodiment is generally preferred when it is desirable to obtain images with higher resolution as will be discussed in greater detail below. FIG. 12 is a schematic diagram ofthe resulting voxels and cross- voxels obtained by implementing the secondary scanning units of FIGs. 9 through 11 into those of FIG. 8 according to the present invention. As shown in FIG. 11, each quadrant of image domain 200 includes fifteen cross- voxels and/or residual voxels. Because all of the foregoing voxels and cross- voxels are constructed symmetric with respect to a center of image domain 200, only those images on the first quadrant 201 of image domain 200 is analyzed as a representative example ofthe images on entire image domain 200. Only for illustration purposes, first quadrant 201 is further divided into four sub-quadrants 201a- 201 d, where a first sub-quadrant 201a has five cross- voxels (A through E), a second sub- quadrant 201b includes four cross-voxels (F, J, H, and L), a third sub-quadrant 201c has another four cross-voxels (G, I, K, and M), and a fourth sub-quadrant 201 d includes one cross-voxel (N) as well as one truncated background voxel (O).

Because all four sub-quadrants 201a-201d have the identical area in imaging domain 200, the resolution ofthe images in each sub-quadrant 201a-201d is expected to be proportional to the number ofthe cross-voxels provided therein as well as the number of voxel values used to determine the cross-voxel values thereof. Therefore, the sub-quadrant 201a has the highest resolution, while the sub-quadrant 201 d has the lowest. This result is tabulated in Table 1 which enumerates every voxel value which are to be used to calculate each cross-voxel ofthe first quadrant 201.

Table 1

Cross-Voxel Voxel Values No.

A vc, hb, ia, ib, ca, Cb, cc, da, db, dc, dd 11

B Vc, hb, ia, ib, ca, c,,, cc, da, db, dc 10 C vc, hb, ia, ib, ca, c^,, cc, da, db 9 D vc, hb, ia, ib, ca, cb, cc, db, dc 9

E vc, hb, ia, ib, ca, cb, cc, db 8

F vc, ha, ia, cb, da, db 6

G vd, hb, ib, cb, db, dc 6

H vc, ha, ia, cb, db 5

I vd, hb, ib, cb, db 5

J Vc na' > Cbs vd, hb, ib, cb, 4

L vc, na, ιa, C),, 4

M vd, hb, ib, cb, 4

N vd, ha, db 3

O vd, ha 2

As listed in Table 1, the value of each cross- voxel is determined by multiple voxel values ranging from two voxels (for the pentagonal, comer cross- voxel "O"), three voxels (for the adjacent triangular cross-voxel "N"), and up to ten voxels (for the center diamond-shaped cross-voxel "B") and eleven voxels (for the center triangular cross-voxel

"A"). The results indicate that, without changing physical configuration of optical probes

120, the accuracy ofthe estimated chromophore properties as well as the resolution ofthe images may be adjusted solely by manipulating the grouping pattern ofthe wave sources and detectors and that ofthe output signals generated by such wave detectors.

Similarly, the accuracy ofthe estimated chromophore properties as well as . . . the resolution ofthe resulting images may readily be adjusted by controlling the number of secondary scanning units to be incorporated into the primary scanning unit. For example, only a pre-selected set(s) of secondary scanning units maybe combined with the primary scanning units of FIG. 8. Such selections may be encoded so that an operator may choose one ofthe pre-determined combinations which yield various image resolution and or which may adjust image resolutions around a specific region ofthe target area. It is appreciated that, without the voxel values (da, db, dc, and d^ ofthe diamond-shaped voxels of FIGs. 1 IB and 11C, all cross-voxels A through E in the first sub-quadrant 201a are estimated by the identical number of voxel values (i.e., seven voxels thereof), thereby yielding the identical resolution thereacross. The foregoing scanning elements and scanning units ofthe optical probe or optical imaging system ofthe present invention may be modified to provide optical probes which have different source-detector arrangements and/or configurations without departing from the scope ofthe present invention. As briefly discussed above, a single wave source may include two or more wave generators so that the wave source including multiple wave generators (referred to as "composite wave source" hereinafter) irradiate electromagnetic waves having two different wave characteristics, e.g., two different wavelengths. Such composite wave sources can be applied to any ofthe foregoing source-detector arrangements. For example, in FIG. 6B, the wave sources, Sab and Sac, ofthe scanning unit, Hf, can be arranged to irradiate near-infrared electromagnetic waves with the wavelengths of about 690 nm and 830 nm, thereby allowing a single scanning unit to generate at least two output signals that represent different optical interaction ofthe chromophores with such different electromagnetic waves.

Such composite wave sources can also be employed to provide asymmetric scanning units which can still satisfy the symmetry requirements ofthe co-pending '972 application. FIGs. 13 A to 13C are a few exemplary embodiments of such scanning units. FIG. 13 A is a schematic diagram of an asymmetric scanning unit satisfying the symmetry requirements ofthe co-pending '972 application according to the present invention. An exemplary asymmetric scanning unit, Aa, includes two wave detectors, Daa and Dac, and a composite wave source, Sab, interposed therebetween. The wave detectors, Daa and Dac, are disposed at both ends of scanning unit, Aa, while the wave source, Sab, is disposed in a middle but off-center portion ofthe scanning unit, Aa, such that the distance between the wave detector, Daa, and the composite wave source, Sab, corresponds to a first near-distance between a first wave generator and the wave detector, Daa, as well as a second near-distance between a second wave generator and the wave detector, Daa. Similarly, the distance between the wave detector, Dac, and the composite wave source, Sab, corresponds to a first far-distance between a first wave generator and the wave detector, Dac, as well as a second far-distance between a second wave generator and the wave detector, Dac. Thus, the asymmetric scanning unit, Aa, satisfies the symmetry requirements ofthe '972 application. FIG. 13B is a schematic diagram of another asymmetric scanning unit which satisfies the symmetry requirements according to the present invention, where a second asymmetric scanning unit, Ab, includes two wave sources, Saa and Sac, and a composite wave detector, Dab, interposed therebetween. Similar to the embodiment of FIG. 13 A, the wave detector, Dab, detects the elecfromagnetic waves emitted from two wave sources, Saa, and Sac, while satisfying the symmetry requirements. It is noted that the foregoing three-sensor arrangements shown in FIGs. 13A and 13B may not be as efficient as the four-sensor arrangements disclosed hereinabove. For example, the scanning units ofthe three-sensor arrangement scans the target area without overlapping any regions thereof. Therefore, such single-coverage may generally result in

5 less accurate estimated values ofthe chromophore properties as well as final images with lower resolution. However, by grouping the wave sources and detectors to form the three- and/or four-sensor source-detector arrangements, such disadvantages are readily obviated. FIG. 13C is a schematic diagram of scanning units defined by various three- and/or four- sensor source-detector arrangements according to the present invention. An optical probe

10 120 A includes two wave sources, Sab and Sad, and three wave detectors, Daa, Dac, and Dae, and defines two asymmetric scanning units, Ac, and Ad, where two three-sensor scanning units share one common wave detector, Dac. It is appreciated that the wave sources, Sab and Sad, and wave detectors, Daa and Dae, may also be grouped to define a symmetric scanning unit as well. As discussed above, the optical probe and optical imaging system ofthe 5 invention are versatile to define primary and secondary scanning units each of which may be symmetric or asymmetric.

The foregoing scanning units described in FIGs. 6A to 6H, FIGs. 7A to 7C, and FIGs. 13A to 13C may also be arranged to yield optical probes having various shapes and sizes. FIG. 14A is a schematic diagram of an exemplary circular optical probe of an 0 optical imaging system according to the present invention where the wave sources and detectors are disposed on a circular scanning surface, whereas FIG. 14B is another schematic diagram of an exemplary triangular optical probe of an optical imaging system according to the present invention where the sensors are disposed on a triangular scanning surface.

A circular optical probe 140 of FIG. 14A includes nine wave sources λ to 5 S9) and twenty wave detectors (Dj to D16) on its circular scanning surface. Depending on requisite resolution, an imaging member may group these sensors and define a variety of scanning units therefrom. For example, the imaging member may define linear scanning units (e.g., SrD3-D5-S5, S5-D9-D10-S6, SrD3-D14-S9, SrD5-D12-S9, S3-D18-D19-S7, and the like), rectangular and/or trapezoidal scanning units (e.g., S2-D3-S5-D7, S2-S3-D10-D7, SrDr 0 DrS,, SrD2-D6-S8, SrD2-D13-S8, SJ-D^-D^-S,,, SrD6-D13-S9, and the like), and so on. In addition, asymmetric scanning units may further be defined across the scanning surface as well. Similarly, an exemplary triangular optical probe 150 includes six wave sources (Sx to S6) and nine wave detectors (Dj to D9) which maybe grouped to form linear, quasi-linear, rectangular, square, trapezoidal or parallelogram scanning units in addition to asymmetric 5 scanning unit. By combining primary scanning units with secondary scanning units and by processing the output signals generated by the wave detectors of such scanning units, the imaging member ofthe optical probe or optical imaging system can provide the images of two- and/or three distribution ofthe chromophores and/or their properties meeting requisite image resolution. It is manifest from FIGs. 14A and 14B that additional wave sources and detectors are disposed inside the scanning units for which such additional wave sources do not irradiate electromagnetic waves and for which such wave detectors do not generate any output signals.

Although the foregoing disclosure ofthe invention is mainly directed to the images of spatial distribution ofthe chromophore properties, the optical probes and optical imaging system ofthe present invention may also be applied to generate images of temporal distribution thereof. For example, the optical probe may be arranged to scan a substantially same target area ofthe medium over a certain time interval. By obtaining the differences in the output signals detected at different time intervals in the same target area, the imaging member calculates temporal changes in the chromophore properties in the target area and generates the images ofthe temporal distribution of such properties. In the alternative, the temporal changes in the chromophore properties may be determined and their images may be provided from spatial distributions of such chromophore properties obtained in different time frames. For example, the scanning units ofthe optical probe may repeat scanning of the target area and calculate the temporal distribution pattern ofthe chromophore property. It is noted that the temporal changes and their distribution usually relate to relative changes in the chromophore properties. However, once the absolute values of such chromophore properties are determined in any reference time frame, preceding or subsequent changes in such properties can be readily converted to the absolute values thereof and vice versa. "

It is noted that the foregoing optical probes and optical imaging systems of the present invention may also be arranged to provide values for the temporal changes in blood or water volume in the target area ofthe medium. In an exemplary embodiment for calculating such temporal changes in blood volume in a target area of a human subject, the concentration of oxygenated hemoglobin, [HbO], and that of deoxygenated hemoglobin, [Hb], are calculated by a set of equations (la) and (lb) or by another set of equations (2a) and (2b). Once [Hb] and [HbO] are obtained, the sum (i.e., total hemoglobin concentration, [HbT], which is the sum of [Hb] and [HbO]) is obtained. By obtaining the output signals from the wave detectors positioned in the same target area over time, changes in the total hemoglobin concentration can be obtained. By assuming that hematocrit of blood (i.e., the volume percentage ofthe red blood cells in blood) flowing in and out ofthe target area is maintained at a constant level over time, temporal changes in the blood volume in the target area are directly calculated in terms of temporal changes in [HbT] in the target area, h the alternative, temporal changes in [Hb] and [HbO] may be calculated from the equations (6a) and (6b) and temporal changes in [HbT] is then obtained as the sum of changes in [Hb] and [HbO] in the target area.

It is also appreciated that the optical probes and optical imaging systems of the present invention may be applied to obtain the images of three-dimensional distribution ofthe chromophore properties in the target area ofthe medium. As discussed above, the electromagnetic waves are irradiated by the wave sources and fransmitted through a target volume ofthe medium which is defined by a target area and a pre-determined thickness (or depth) into the medium. Accordingly, a set of wave equations can be formulated for such three-dimensional target volume, and the output signals generated by the wave detectors are provided to the imaging member which then solves the wave equations with relevant initial and/or boundary conditions, where such solutions from the wave equations represent the three-dimensional distribution ofthe chromophore properties in the target volume ofthe medium. To maintain the pre-selected resolution ofthe images, the optical imaging probes and/or systems preferably include a large number of wave sources and detectors defining a larger number of voxels in the target volume ofthe medium. Suppose that an exemplary optical probe or optical imaging system includes two wave sources and four wave detectors and generates two-dimensional images of a target area at a pre-selected resolution. When a target volume is defined to have the same target area and a pre-selected thickness including N two-dimensional layers stacked one over the other, such an optical imaging system may probably be required to include about 2N wave sources and 4N wave detectors in order to maintain the same resolution for each two-dimensional layer. The number of such wave sources and detectors may be reduced, however, by generating enough secondary scanning units over the target area, preferably overlapping each other. Thus, the optical probes or optical imaging systems require fewer number of wave sources and detectors by arranging the imaging member to define and incorporate enough number of secondary scanning units. It is noted, however, that resolution of images from any optical imaging system is inherently limited by the average "free walk distance" of photons in the physiological medium that is typically about 1 mm. In addition, due to sensitivity limitation or electronic and mechanical noise inherent in almost any optical imaging system, the best-attainable resolution ofthe images may be in the range of a few millimeters or about 1 mm to 5 mm for now. Thus, the foregoing voxels and cross- voxels which have dimensions less than 1 mm to 5 mm or, more particularly, about 1 mm may not necessarily enhance resolution ofthe final images.

The foregoing optical imaging systems and optical probes ofthe invention can also be used to determine intensive properties ofthe chromophores, e.g., concentration, sum of concentrations, and/or ratios of such concentrations. The foregoing optical imaging systems and optical probes may also be used to estimate extensive chromophore properties such as volume, mass, weight, volumetric flow rate, and mass flow rate thereof.

It is appreciated that the foregoing optical imaging systems, optical probes thereof, and methods therefor maybe readily adjusted to provide images of distribution of different chromophores or properties thereof. Because different chromophores generally respond to electromagnetic waves having different wavelengths, the wave sources of such optical imaging systems and probes may be manipulated to irradiate electromagnetic waves interacting with pre-selected chromophores. For example, the near-infrared waves having wavelengths between 600 nm and 1,000 nm, e.g., about 690 nm and 830 nm are suitable to measure the distribution pattern ofthe hemoglobins and their property. However, the near- infrared waves having wavelengths between 800 nm and 1,000 nm, e.g., about 900 nm, can also be used to measure the distribution pattern of water in the medium. Selection of an optimal wavelength for detecting a particular chromophore generally depends on optical absorption and/or scattering properties ofthe chromophore, operational characteristics ofthe wave sources and/or detectors, and the like.

The foregoing optical imaging systems, optical probes, and methods ofthe present invention may be clinically applied to detect tumors or stroke conditions in human breasts, brains, and any other areas ofthe human body where the foregoing optical imaging methods such as diffuse optical tomography is applicable. The foregoing optical imaging systems and methods may also be applied to assess blood flow into and out of transplanted organs or extremities and/or autografted or allografted body parts or tissues. The foregoing optical imaging systems and methods maybe arranged to substitute, e.g., ultrasonogram, X- rays, EEG, and laser-acoustic diagnostic. Furthermore, such optical imaging systems and methods may be modified to be applicable to various physiological media with complicated photon diffusion phenomena and/or with non-flat external surface.

Examples

Following examples describe simulation and experimental results obtained by the optical systems and methods thereof according to the present invention. All simulation and experimental results indicate that the optical systems and methods thereof provide accurate predictions and/or measurements ofthe concentrations ofthe hemoglobins and the oxygen saturation. Example 1

The diffusion equation (3b) was numerically solved for optical proves with multiple wave sources and detectors arranged in various configurations. The equations were applied to a sample physiological medium such as a semi-infinite, homogeneous diffuse medium with different background optical properties. Diffuse reflectances were calculated according to an imaging source approach disclosed in an article entitled, "Boundary conditions for the diffusion equation in radiative transfer" by R.C. Haskell et al. and published in Journal of Optical Society of America, vol. 11, p. 2727-2741, 1994. Values of G (i.e., the ratio of Fk to Fh simulated at different wavelengths) were estimated at different levels of oxygen saturation (SO2) and fitted as a polynomial thereof.

FIGs. 15 to 17 are plots of G's as a function of oxygen saturation (SO2). As shown in the figures, all simulation results revealed distinct one-to-one correlations between G and oxygen saturation (SO2). In addition, all ofthe figures indicated that dependence of G upon oxygen saturation was substantially insensitive to simulated source-detector configurations and background optical properties.

Conventional curve-fitting methods, e.g., the least-squares method, were applied to numerically estimate the coefficients of polynomial equation (10) (i.e., a0 , a , , a2 , a3 ... ). For example, in a system with background reduced scattering coefficient of 10 cm"1 and total hemoglobin concentration of 10"4 mol liter irradiated by the electromagnetic waves having wavelengths of 780 nm and 830 nm, following polynomial equation was obtained and found to satisfactorily approximated the relation between G and oxygen saturation (SO2): ph

G = = 0.728 + 0.399 • SO2 + 0.064 • SO2 2 + 0.067 • SO,3 (18)

Fλ

Example 2

Further simulations were performed in a system with the background scattering of 7 cm"1 and the total hemoglobin concentration of 2 10"4 mol/liter. hi the simulations, oxygen saturation (SO2) was varied from 0 to 100%. FIG. 18 is a plot of calculated oxygen saturation contrasted against true oxygen saturation. Although the background properties used to find the correlation between G and oxygen saturation were quite different, the estimated oxygen concentration was accurate with a systematic error of about a few percent.

Example 3

An exemplary optical system was prepared and hemoglobin concentrations and the oxygen saturation were monitored before and after occlusion of arteries of an extremity in a human subject, hi this Example was used the optical system of FIG. 3A including two wave sources and two wave detectors arranged in a linear fashion. Two wave detectors were linearly disposed and separated by 6 mm. Two wave sources were disposed outside of each wave detector so that the left wave source was disposed at the left side ofthe left wave detector at a distance of 9 mm, and the right wave source disposed at the right side ofthe right wave detector at a distance of 9 mm. Accordingly, each pair ofthe wave sources and detectors had identical near-distances and far-distances.

The wave sources had an outer diameter of 2 mm and included laser diodes (model HL6738MG and HL8325G, both available from Thorlabs, Inc., Newton, NJ) for irradiating electromagnetic waves with wavelengths 690 nm and 830 nm, respectively. Photo-detectors (model OPT202, available from Barr-Brown, Tucson, AZ) were used as the wave detectors.

A cuff was placed around the upper arm and the optical probe was disposed at the fore arm. After the subject was stabilized, cuff pressure was increased to about 160 mmHg in about 35 seconds, held at the same level for about 40 seconds, and then released to the atmospheric level. Absolute concentrations of total hemoglobin, oxygenated hemoglobin, and deoxygenated hemoglobin were monitored, and the oxygen saturation was calculated therefrom. FIG. 19 is a time-course plot of total hemoglobin (HbT) concentration, oxygenated hemoglobin (HbO) concentration, and deoxygenated hemoglobin (Hb) concentration according to the present invention, and FIG. 20 is a time-course plot of oxygen saturation according to the present invention. As shown in the figures, hemoglobin concentrations and oxygen saturation decreased sharply during the initial phase of occlusion, followed by a gradual decrease thereof. After the release, concentrations and oxygen saturation showed rapid increase. These results demonstrated that the optical systems and methods according to the present invention provided accurate predictions ofthe hemoglobin concentrations as well as the oxygen saturation. These results also showed that the optical systems possessed proper temporal response characteristics.

Further Exemplary Embodiments Using the Above Solution Scheme

Following the above method, for example, the absolute values of concentration of deoxygenated hemoglobin, [Hb], concentration of oxygenated hemoglobin,

[HbO], and oxygen saturation, SO2, are obtained by the following equations (8a) to (8d) and (9b):

[HbO] = (8b)

F ~ 2I % ) l°C)

- ~ -"S2Z>2 s2£>2 ) V°*-

where the parameters "εm" and "εjjbo" represent extinction coefficients ofthe deoxygenated and oxygenated hemoglobins, respectively, the variable "OD" is an optical density defined as a logarithmic ratio of light intensities (i.e., magnitudes or amplitudes of electromagnetic waves) detected by a wave detector, the parameter "B" is conventionally known as a path length factor, the parameter "LSiDj" is a distance between the i-th wave source and j-th wave detector, and the superscripts "λ," and "λ2" represent that a system parameter or variable is obtained by irradiating electromagnetic waves having wavelengths λ, and λ2, respectively. Alternatively, the algorithm unit or image construction unit ofthe imaging member may employ the over-determined iterative method as disclosed in the foregoing '972 application, where the absolute values of [Hb], [HbO], and SO2 are determined by the following equations (17a) to (17c), each of which corresponds to the equations (17a) through (17c) ofthe co-pending '972 application, respectively:

ph ,jh _ c-"2 „"

[Hbo} = C-Λl Λ2 _ p"- p GHbbb2HbO °HbtiiHbO <17b>

where the parameter "μa" denotes an absorption coefficient o the medium. It is noted that the imaging member ofthe present invention may be arranged to receive the output signals generated by the wave detectors and to calculate optical densities which may be supplied to the algorithm unit or image construction unit. Once the absolute values of or their changes

5 in the concenfrations ofthe hemoglobins are determined, the imaging member generates images representing two- or three-dimensional spatial and/or temporal distributions ofthe hemoglobins by employing a real-time image construction technique as will be discussed in greater detail below (also discussed in commonly assigned copending non-provisional U.S. Patent Application bearing Serial No. (N/A), entitled "Optical Imaging Systems for Direct

10 Image Construction" which has been filed on February 5, 2001, and which is incorporated herein in its entirety by reference).

In the alternative, changes in the hemoglobins distribution are determined by estimating changes in optical characteristics ofthe target area ofthe medium. For example, changes in concentrations of oxygenated and deoxygenated hemoglobins maybe calculated

15 from the differences in their extinction coefficients which are measured by electromagnetic waves having two different wavelengths. In an exemplary numerical scheme, the photon diffusion equations may be modified and solved by applying the diffusion approximation described in, e.g., Keijer et al., "Optical Diffusion in Layered Media," Applied Optics, vol. 27, p. 1820-1824 (1988) and Haskell et al, 'Boundary Conditions for Diffusion Equation in

20 Radiative Transfer," Journal of Optical Society of America, A, vol. 11, p. 2121-21 Al, 1994:

25 where the symbol "Φsc(rsu Γ DJ)" represents a normalized optical density measured by a j-th wave detector in response to an i-th wave source, the variables "rSl"and "rDj" are positions of the i-th wave source and j-th wave detector, respectively, the symbol " Aμaf " denotes tissue optical perturbation such as the changes in the absorption coefficient in an i-th voxel, the

DV parameters "M" and "N" are the number of measurements and the voxel number to be reconstructed, respectively, and the variable "Wy" is a weight function which represents the probability that a photon travels from the i-th wave source to a certain point inside the target area ofthe medium and is then detected by the j-th wave detector. The weight function, Wy, of equation (19) is defined as: 35

where the parameters "h " is the volume of a voxel, "Dphoton" represents a photon diffusion coefficient, and "v" denotes the velocity of light in the physiological medium. In addition, the variable "Φsc(rsi> )" is me normalized optical density which is defined as:

where the variable "I" represents the output signal measured by the sensor assembly which is comprised ofthe i-th wave source and j-th wave detector disposed at positions "rsi"and "rDj-," respectively, and the variable "IB " denotes a baseline ofthe output signal determined by the wave detector.

Various methods such as, e.g., the direct matrix inversion and simultaneous iterative reconstruction techniques, may be applied to solve the above set of equations (19) to (21). Once the tissue optical perturbations, " Aμ ' " and " Aμ 2 " are estimated by irradiating electromagnetic waves having two different wavelengths, λ- and λ2, respectively, changes in concentrations of oxygenated hemoglobin and deoxygenated hemoglobin can be obtained as follows:

where L is the distance between the wave source and detector and the parameters ε^b , ε 2 b , ε^λ b0 , and ε b0 are the extinction coefficients of oxygenated hemoglobin and deoxygenated hemoglobin at two different wavelengths, λ3 and λ2, respectively.

Incorporating any ofthe foregoing solution schemes ofthe '972 application into the optical imaging systems ofthe present invention offers additional benefits over the prior art optical imaging technology. Contrary to the CWS which allows measurement of changes in the hemoglobin or chromophore concentrations, the foregoing optical imaging systems provide a direct means for assessing spatial distribution or temporal variation ofthe absolute values ofthe properties ofthe hemoglobins or the chromophores ofthe physiological medium, thereby allowing the physicians to make direct diagnosis based on such absolute values ofthe hemoglobin or chromophore properties. Furthermore, as will be discussed in greater detail below, the foregoing optical imaging systems can readily be incorporated into any conventional optical imaging systems and their optical probes which may include any number of wave sources and/or detectors arranged in almost any arbitrary configurations. Therefore, the embodiments ofthe present invention discussed herein may be readily applied to construct optical imaging systems that can be customized to specific clinical applications without compromising their performance characteristics.

The optical imaging system ofthe present invention preferably determines the absolute or relative values ofthe chromophore properties by obtaining solutions of multiple wave equations by using one ofthe solution schemes disclosed in the co-pending '972 application. Accordingly, as far as the ofthe '972 application are satisfied, operational characteristics of such optical imaging systems are generally not affected by actual configuration ofthe wave sources and/or detectors. Thus, the optical imaging system ofthe present invention preferably includes any number of wave sources and/or detectors arranged in almost any configurations, subject to the foregoing symmetry requirements. However, the sensor assembly or scanning unit ofthe present invention may preferably be constructed according to a few semi-empirical rules which are expected to provide enhanced accuracy, reliability, and/or reproducibility ofthe estimated absolute or relative values ofthe chromophore properties. Such exemplary design rales are: (1) each scanning unit preferably includes at least two wave sources and at least two wave detectors; and (2) the distances between the wave source and detector may not exceed a threshold sensitivity range ofthe wave detector which may range from, e.g., several to 10 cm or, in particular, about 5 cm for most human and animal tissues. FIGs. 4 and 5 describe a few exemplary embodiments of the scanning units constructed according to the foregoing design rules.

FIG. 4 is a cross-sectional top view of an exemplary movable member and scanning unit thereof according to the present invention. Contrary to conventional source- detector arrangements where each wave source is surrounded by multiple wave detectors or vice versa, scanning unit 125 of FIG. 4 is defined by two wave sources 122 (i.e., SI and S2) each of which is disposed along longitudinal axis 127 thereof. Scanning unit 125 further includes two wave detectors 124 (i.e., DI and D2) which are interposed between two wave sources 122 along the same axis 127 and spaced at substantially equal distances therefrom. Therefore, scanning unit 125 defines the scanning area elongated along the same axis 127 and having a characteristic width which may be determined by, e.g., irradiation capacity or emission power of wave sources 122, sensitivity or detection range of wave detectors 124, optical characteristics ofthe medium, and the like. It is appreciated that scanning unit 125 of FIG. 4 does satisfy the symmetry requirements ofthe co-pending '972 application, i.e., the wave sources and detectors are arranged to maintain substantially identical near- and far-distances therebetween during the movement ofthe movable member and/or scanning unit. For example, a first near-distance between the wave source SI and wave detector DI is substantially similar or identical to a second near-distance between the wave source S2 and wave detector D2. In addition, a first far-distance between the wave source SI and wave detector D2 is substantially similar or identical to a second far-distance between the wave source S2 and wave detector DI. The major advantage of this symmetric arrangement lies in the fact that electromagnetic waves are substantially uniformly transmitted, absorbed, and/or scattered throughout the entire area or volume ofthe target area ofthe medium. Accordingly, such scanning unit can provide uniform coverage ofthe target area and, therefore, improve accuracy and reliability ofthe output signals (e.g., improved signal-to-noise ratios thereof), and enhance the resolution of the images constructed therefrom. It is also appreciated that scanning unit 125 of FIG. 4 has the source-detector arrangement which is substantially contrary to the general norms for constructing optical probes ofthe conventional optical imaging equipment. For example, conventional optical probes generally include a large number of wave sources and detectors which are distributed uniformly over a two-dimensional scanning field. Accordingly, the area ofthe medium that can be scanned thereby in a single measurement is at best as large as to the scanning field of the probes. To the contrary, the optical imaging system ofthe present invention includes significantly fewer wave sources and detectors which are aligned substantially along an axis (e.g., longitudinal axis) ofthe movable member in a substantially one-dimensional fashion. This linear arrangement would be a fatal drawback for the conventional probes, because the scanning area defined by the linearly aligned sensors may only amount to a narrow strip. However, by arranging the actuator member to generate various movements ofthe scanning unit, the foregoing optical imaging system can cover the target area which may be significantly larger than the scanning area and may cover every region ofthe target area. Accordingly, the foregoing linear scanning unit ofthe optical imaging system ofthe present invention can be significantly narrower than the target area ofthe medium. Further benefits and advantages of such embodiment will be discussed in greater detail below.

FIG. 5 is a cross-sectional top view of another exemplary movable member and its scanning unit according to the present invention. Scanning unit 125 includes two wave sources 122 (SI and S2) disposed along longitudinal axis 127 thereof and four wave detectors 124 (DI to D4) each of which is interposed between two wave sources 122 and aligned along the same axis 127 at substantially equal distances. The embodiment of FIG. 5 is different from that of FIG. 4 in a few aspects. First of all, it is manifest that scanning unit 125 of FIG. 5 does not necessarily satisfy the near- and far-distance configuration of FIG. 4. For example, although the first and fourth wave detectors (DI and D4) and the second and third wave detectors (D2 and D3) satisfy the symmetric requirements disclosed in the co- pending '972 application, the near- and far-distances are different for the first and third wave detectors (DI and D3) and for the second and fourth wave detectors (D2 and D4). In addition, the banana-shaped paths (see the figure) of electromagnetic waves also reveal that each pair of wave source 122 and detector 124 covers different portions ofthe target area and, therefore, generates the output signals by detecting electromagnetic waves absorbed and scattered in different extent through different portions ofthe medium. However, by interposing all four wave detectors 124 between two wave sources 122 at equal distances, the entire target area ofthe medium may be substantially uniformly covered by the source- detector assembly of FIG. 5 along the thickness and/or depth ofthe medium. Accordingly, scanning unit 125 of FIG. 5 can also provide relatively unifoπn coverage ofthe medium throughout the entire scanning area or scanning volume. In addition, scanning unit 125 of FIG. 5 can provide a longer scanning area because it includes more wave detectors 124 and, therefore, can extend farther along axis 127 than the one in FIG. 4 and can cover the longer and possibly wider region ofthe target area per each measurement. Thus, an abnormality in the medium may be more easily detected with such longer scanning unit 125 by, e.g., comparing the output signals generated by wave detectors 124 that can cover the longer and possibly wider scanning area. As an example, a sudden increase or reduction in the output signals may imply that an abnormality such as a tumor having greater or less extinction or absorption coefficients may exist along the elongated scanning area or volume defined by a pair ofthe wave source and detector responsible for that curved output signal. Furthermore, because the output signals generated by scanning unit 125 cover a longer and possibly wider scanmng area, imaging member 140 can provide a more reliable baseline ofthe output signal and, therefore, perform more accurate self-calibration ofthe output signals. Details of such self-calibration procedure will be provided below, e.g., in conjunction with FIG. 45C. Variations of the Exemplary Embodiments The source-detector arrangement may also be modified to provide scanning units having different configurations without departing from the scope ofthe invention. For example, the scanning unit may include three or more wave sources (or detectors), where at least two or all of wave sources (or detectors) may be disposed substantially linearly along the longitudinal axis ofthe scanning unit. The wave detectors (or sources) may further be interposed between two or more wave sources (or detectors) along the same axis ofthe scanning unit or along the longitudinal axis ofthe movable member. Alternatively, the scanning unit may include at least two wave sources (or detectors), where the first wave source (or detector) is disposed on one side across the axis ofthe scanning unit, while the second wave source (or detector) is disposed on the other side across the axis. Such wave sources (or detectors) may be disposed symmetrically with respect to the axis ofthe scanning unit or longitudinal axis ofthe movable member, or with respect to a point of symmetry disposed in the scanning unit as well.

In another aspect ofthe present invention, an optical imaging system may include at least one wave source and at least one wave detector, each of which couples with a body which may be arranged stationary or mobile. Such optical imaging systems may be arranged substantially similar to those of FIG. 1, e.g., including the foregoing body 110, at least one sensor assembly (corresponding to movable member 120 of FIG. 1) having at least one wave source 122 and at least one wave detector 124, an actuator member 130 for generating at least one ofthe foregoing movements of at least one ofthe body 110 and movable member 120 relative to the target area, and an imaging member 140 for receiving signals from the sensor assembly 120 and for generating the images ofthe chromophore property and/or distribution thereof. Actuation

In one embodiment, the body is arranged to be movable with respect to the target area, while the sensor assembly is fixedly coupled to a scanning surface ofthe body. Because the wave source and detector are fixedly coupled with the body and maintains a constant geometric arrangement therebetween, the actuator member moves the body so that a single movement ofthe body results in the movement ofthe sensor assembly and body in unison. This embodiment is useful for its simple mechanical construction and enhanced mechanical support attained by the fixed coupling between the sensor assembly and body. In another embodiment, the actuator member generates separate movements ofthe sensor assembly and the body so that each ofthe sensor assembly and the body can move with respect to the other while moving itself with respect to the target area as well. Despite complicated design and control requirements, this embodiment is advantageous in providing the sensor assembly with greater flexibility in scanning different regions ofthe target area along the meticulous and variety of curvilinear movement paths ofthe sensor assembly and/or the body.

Other embodiments pertaining to the foregoing optical imaging systems may also be applied to this aspect ofthe present invention of FIG. 4. For example, the actuator member may generate one or more movements continuously, intermittently or periodically. The actuator member may also generate such movement at constant speeds or at speeds varying over time and/or position over the target area. In the alternative, the actuator member may further be arranged to generate such movements simultaneously or sequentially.

Use of a Connector

In yet another aspect ofthe invention, an optical imaging system includes at least one ofthe foregoing wave sources, at least one ofthe foregoing wave detectors, an actuator member, at least one optical probe including a movable member, a console (or main body), and a connector member. In general, the actuator member generates at least one movement ofthe wave source, wave detector, and/or movable member along at least one curvilinear path. The connector member provides various communications between the optical probe and console. For example, the connector member may include power lines and/or electrical wire to deliver electric power and/or to transmit analog or digital data. The connector member may include optical pathways such as fiber optic products to transmit electromagnetic waves or optical signals between the probe and console. Furthermore, the connector member may provide mechanical support between the probe and the console or transmit translating, rotating, revolving or reciprocating power generated by the actuator member to the movable member through power transmission pathways such as a flexible power cable or universal joint.

In one embodiment, the movable member ofthe optical probe includes at least one ofthe wave source and detector. Electric power may be supplied by an internal power mechanism ofthe optical probe or from the console through the connector member. The actuator member may be implemented to or disposed in the optical probe to move at least one ofthe wave source and detector, or maybe disposed in the console where the franslational, rotational, revolving or reciprocating power may be transmitted to the movable member through the connector member. Similarly, some or an entire portion ofthe imaging member may be disposed at either ofthe optical probe and console.

In another embodiment, the console may include at least one ofthe wave source and at least one ofthe wave detectors. The movable member ofthe optical probe includes minimum instrumentation only to the extent that the movable member receives elecfromagnetic waves from the wave source ofthe console and transmits such waves into the target area ofthe medium and that the movable member detects the elecfromagnetic waves from the target area and transmits the foregoing waves toward the wave detector of the console. In one exemplary embodiment, the movable member may define two apertures on its scanning surface. A first optical fiber is disposed between the wave source and the first aperture, and the second optical fiber is disposed between the wave detector and the second aperture. By arranging the first and second apertures to form appropriate optical couplings with the medium, the target area may be indirectly scanned by the wave source and wave detector disposed at the console or through the optical pathways ofthe connector member. Similar to the foregoing embodiment, electric power may be supplied to the optical probe by its own internal power mechanism or from an external or main power mechanism ofthe console through the connector member. The actuator member may be disposed in the optical probe to move at least one ofthe first and second apertures over different regions ofthe target area or different target areas ofthe physiological medium. Alternatively, the actuator member may be disposed in the console so that franslational, rotational, revolving or reciprocating power generated thereby may be mechanically fransmitted to the movable member through the connector member. Similarly, the imaging member may be disposed at either ofthe optical probe and console. An Optional User Screen

In any ofthe foregoing embodiments, an optional screen may be provided to the optical probe so as to allow an operator to view raw images (e.g., images of distribution patterns of system variables such as the output signals generated by the wave detector), processed images (e.g., images of distribution patterns of functions or solutions obtained by processing the raw signal), and/or final images (e.g., images ofthe chromophore property and its distribution). Alternatively, when the imaging member is disposed at the console, the optical probe may include a data transmission unit to transmit the data to the imaging member on a real time, intermittent or periodic basis. The optical probe may also include a memory unit or storage member to temporarily or permanently store various signals. Benefits of Such Variation

The foregoing embodiments of this aspect ofthe invention offer benefits over the prior art technologies. First of all, bulky or heavy components such as a power supply, wave generator (such as a lamp, laser source or drive, and the like), photo-detector, detector drive, and/or circuit boards, may be included in the console, while only essential elements (e.g., optical apertures and optical fibers) are disposed in the portable probe. Thus, the movable member can maintain a compact size and light weight. Secondly, because the foregoing optical probes need fewer components, idiosyncratic errors due to component variances may also be minimized. Thirdly, the foregoing optical probe may be constructed as a semi-portable article wearable by a patient for continuous or periodic monitoring and imaging ofthe chromophore properties ofthe target area ofthe patient. Use of a Portable Probe hi a further aspect ofthe invention, an optical imaging system includes at least one portable probe and a console (or main body). The portable probe includes at least one movable member and an actuator member both of which are identical or substantially similar to those described hereinabove. For example, the movable member includes at least one ofthe foregoing wave sources and detectors, and the actuator member generates at least one movement ofthe movable member along at least one curvilinear direction. The console is generally arranged to include at least a portion ofthe imaging member.

In one embodiment, the portable probe and console operationally connect to each other via a connector member providing the foregoing communications therebetween. In another embodiment, the portable probe may be provided as a separate article which is physically detachable from the console. Such portable probe preferably includes at least one wave source, at least one wave detector, an actuator member such as a miniature motor assembly, and an internal power mechanism capable of supplying electric power to the above components ofthe portable probe. In addition, the portable probe may include either a data storage unit or data transmission unit so that the data may be temporarily stored or telemetrically fransmitted to the console. The portable probe may include a separate imaging member so as to generate two or three-dimensional raw images, processed images, or final images ofthe chromophore or their properties in the target area. The internal power mechanism may preferably be rechargeable and capable of sustaining operation ofthe portable probe for a pre-deteπnined period. The primary advantage of this embodiment lies in the fact that such portable probe can be worn by a patient or even be implanted inside the patient for constant or periodic monitoring and/or imaging of various target areas. Linear Arrangement of Sources & Detectors Li yet another aspect ofthe invention, an optical imaging system may include two or more wave sources and two or more wave detectors, where at least two ofthe wave sources and at least two ofthe wave detectors are disposed substantially linearly along a line which passes through, e.g., each ofthe wave sources and detectors.

It is noted that the linear arrangement ofthe wave sources and detectors generally results in the scanning unit substantially elongated along the line and having the scanning area which is also elongated and which is much narrower than the target area. By allowing the actuator member to generate the foregoing movements ofthe wave sources and/or detectors, the optical imaging system ofthe present invention enables the smaller scanning unit thereof to scan the entire target area. Benefits of Linear Arrangement

The foregoing aspect ofthe invention offers numerous additional benefits. Prior art optical imaging machines typically rely on a single, large probe designed to cover the target area. Accordingly, the prior art probe has to include a large number of wave sources and detectors distributed on its sensing surface. By incorporating a large number of wave sources and detectors, the prior art technology suffers from various disadvantages. For example, such probe is generally big and bulky. Thus, unless the probe is arranged to conform to the curvature ofthe target area, some wave sources and/or detectors may be subject to poor optical coupling with the contoured target area. Even if such probe may be provided with a conforming surface, such target-specific probe may find limited utility. In addition, the output signals and final images generated thereby may include a significant amount of noise attributed to the idiosyncratic component variances among the sensors. To the contrary, the optical imaging system ofthe present invention typically defines the scanning unit comprising fewer sensors many or all of which may be linearly aligned along the longitudinal axis ofthe scanning unit. Therefore, the scanning unit shaped as a naπow sensor strip can more easily conform to the contour ofthe target area. By arranging the actuator member to translate and/or rotate the scanning unit to the different regions ofthe target area, the foregoing optical imaging system may scan the entire scanning area with a much smaller scanning unit while maintaining excellent consistent optical couplings with the target area. The foregoing optical imaging system also requires fewer wave sources or detectors, thereby reducing manufacturing cost and thereby minimizing the noises attributed to the idiosyncratic component variances.

An Exemplary Scanning Unit

As discussed hereinabove, actuator members generate movements ofthe scanning unit to cover the target area ofthe medium which is substantially larger than the scanning area ofthe scanning unit. Following figures illustrate typical arrangements ofthe actuator member designed to generate various movements ofthe movable member. For the illustration purposes, the embodiment shown in FIG.5 has been selected as the exemplary scanning unit throughout FIGs. 52 through 58.

FIG. 52 is a schematic diagram ofthe scanning unit of FIG. 5 arranged for linear translations according to the present invention. As described hereinabove, movable member 120 includes two wave sources 122 and four equi-spaced wave detectors 124 that are interposed between wave sources 122. In a preferred embodiment, the wave sources 122 and wave detectors 124 are identical. Thus, scanning unit 125 is defined to have a substantially elongated shape and to extend along a longitudinal axis thereof. Stationary body 110 is preferably sized to be slightly larger than the desired target area ofthe medium so that body 110 may cover the entire target area. In this embodiment, body 110 has a rectangular (or square) shape to accommodate positioning (i.e., to accommodate the length or height of scanning unit 125) and movement of elongated scanning unit 125. Actuating member 130 such as a stepper motor assembly linearly translates scanning unit 125 along a linear path which is aligned to be substantially parallel with an upper and lower sides of rectangular (or square) body 110. It is noted that at least a portion of body 110 may form a dead area or blind spot where scanning unit 125 cannot make any reliable measurements. Such dead area is generally confined to portions adjacent to comers or edges of body 110. The size (or width)of the dead area may depend on, e.g., a distance between an edge of body 110 and wave sources 122. Because the dead area generally wastes valuable real estate of body 110, it is preferably minimized by conforming the shape of body 110 to the size and

5 shape of scanning unit 125 as well as to the curvilinear paths ofthe movements of scanning unit 125.

To generate high-precision movements ofthe scanning unit, the stationary body 110 may include one or more guiding tracks 160 which define the path ofthe linear translation. It is noted that guiding track 1 0 is disposed inside the housing of body 110 so

10 that the presence of guiding track 160 does not interfere with movement of scanning unit 125 across different regions ofthe target area. Alternatively, stationary body 110 maybe provided with barriers 170 along the edges thereof so that movements of scanning unit 125 may be confined inside the region bordered by such barriers 170 and that positioning or movement ofthe scanning unit beyond barriers 170 may be prevented.

1 The actuator member may linearly translate the scanning unit at a preselected speed of franslation. Alternatively, the actuating member may be provided with a control feature so that a user (i.e., a physician) may manipulate the movable member (or scanning unit) to move at an appropriate speed, to move along a desired guiding track, and/or to have a recess between different movements ofthe scanning unit along different

20 curvilinear paths. It is appreciated that, other factors being equal, the speed ofthe scanning unit generally adversely affects accuracy ofthe estimated values ofthe chromophore properties as well as the resolution ofthe final images thereof. Accordingly, the actuating member maybe arranged to allow an operator to select an optimal speed ofthe scanning unit which may be determined based on several factors including, but not limited to,

25 configuration ofthe scanning unit or movable member, desirable resolution ofthe final images, frequency responses of each component ofthe optical imaging system, optical properties ofthe medium, size ofthe target area, and the like.

Referring to FIG. 1, in operation, movable member 120 is positioned in its starting position which is generally adjacent to one side of body 110, e.g., a bottom portion

30 114 or a side of housing 112. Body 110 of optical imaging system 100 is placed on the medium so that scanning unit 125 of movable member 120 is positioned in a first region of the target area to form optical coupling therewith. Wave sources 122 and detectors 124 are activated so that electromagnetic waves are emitted into and detected from the target area. Actuator member 130 is activated to translate movable member 120 substantially linearly

35 from bottom 114 of housing 112 to a top 116 thereof in an upward direction which is normal to longitudinal axis 127 of movable member 120. During the upward linear translation, scanning unit 125 scans each region ofthe target area and wave detectors 124 generate output signals which are representative ofthe optical properties, spatial or temporal distribution, ofthe chromophores or their properties in each region ofthe target area. Once

5 movable member 120 reaches top portion 116 of body 110, actuator member 130 moves movable member 120 back to its starting position (i.e., bottom portion 114) along the same path but in an opposite direction. During the downward linear translation, scanning unit 125 again sweeps through the similar or different regions ofthe same target area and wave detectors 124 generate the output signals. The foregoing scanning procedure may be

10 completed after movable member 120 finishes the foregoing reciprocation across the target area.

Referring to FIG. 34, body 110 also includes a linear guiding track 118 extending across an entire length of housing 112. Movable member 120 is movably disposed on guiding track 118 and guided thereby during the linear translation of movable

15 member 120. It is noted that guiding track 118 is disposed inside housing 112 so that the presence of guiding track 118 does not interfere with movement of scanning unit 125 across different regions ofthe target area. Actuator member 130 such as a stepper motor assembly generates linear franslational movement of scanning unit 125 along the linear path aligned substantially parallel with a top 116 and a bottom 114 of rectangular body 110. It is noted 0 that at least a portion of body 110 may form a dead area or blind spot where scanning unit 125 cannot make any reliable measurements. In general, such dead area is confined to regions adjacent to edges and/or comers of body 110, and the size ofthe dead area generally depends on, e.g., a distance from an edge or comer of body 110 to wave sources 122 or detectors 124. Because the dead area generally wastes valuable real estate of body 110, it is

^ 9J5 preferably minimized by, e.g., conforming the shape of body 110 to the size and shape of scanning unit 125 as well as its curvilinear movement paths.

As in FIG 52, in operation, movable member 120 is placed on a desired target area ofthe medium and scanning unit 125 is positioned in a first region ofthe target area which is generally adjacent to one side ofthe rectangular target area so that wave sources

30 122 and detectors 124 can form optical couplings with the first region ofthe target area.

Actuator member 130 is activated to linearly translate scanning unit 125 away from the first region toward a second region ofthe target area such as an adjacent or opposing side ofthe rectangular target area. Wave sources 122 and detectors 124 are manipulated to maintain the optical couplings with the medium during the linear translation of scanning unit 125 so

35 that wave detectors 124 can continuously generate the output signal during the translation. The imaging member receives and samples the output signal as well as other signals representing the system variables or parameters (e.g., optical density signals, solution signals, distribution signals, image signals, and the like). The imaging member removes high-frequency noise from the output signals and determines a sequence of representative values ofthe chromophore property for a set of measurement elements (termed as "voxels" hereinafter and discussed in conjunction with FIGs. 4B and 6D) formed by scanning unit 125. Once scanning unit 125 reaches the opposing side ofthe target area, scanning unit 125 is translated back from the second region toward the starting first region ofthe target area. The imaging member determines another sequence of representative values ofthe chromophore property for the same or different set of voxels during this second movement. Depending on the requisite resolution ofthe final images, this translation may be repeated for a pre-determined period of time or for a pre-selected number of repetitions. After completing the scanning process, the imaging member reorganizes multiple sequences ofthe representative values, provides a two-dimensional spatial distribution ofthe chromophore properties, and generates the final images of a spatial distribution thereof over the target area.

FIG. 53 is a schematic diagram of images obtained by the scanning unit of FIG. 5 which is linearly translated across the target area according to the present invention. As manifest in the figure, the entire target area is divided into a series of elements, i.e., the "voxels," where each elongated voxel 151 extends along a voxel axis 153 throughout a substantial or entire height ofthe target area. Voxels 151 are sequentially arranged in a voxel direction which is substantially parallel with the curvilinear path of movable member 120. It is appreciated that voxels 151 denoted as a, b, c, and h cover homogeneous regions ofthe target area (i.e., regions without any abnormalities), while voxels 151 designated as d, e, f, and g include such abnormalities therein.

Each voxel 151 represents a small region ofthe target area ofthe medium where the imaging member samples the output signal generated by wave detectors 124 and determines a representative value (termed as "voxel value" hereinafter) ofthe chromophore property by solving wave equations applied to the wave sources and detectors which define the corresponding voxel. For example, the foregoing equations (1), (2), and/or (6) can be applied to calculate absolute or relative values of concenfrations ofthe hemoglobins and/or oxygen saturation spatially averaged over each ofthe voxels. That is, the imaging module spatially groups the output signal generated by wave detectors 124 for each voxel 151, and calculates the spatial average values of such chromophore properties of each voxel 151. It is appreciated that the area-averaged voxel value can be substantially similar or identical to the volume-averaged voxel value as long as wave detectors 124 have the sensitivity range covering a substantially identical depth ofthe medium throughout the entire target area. Each voxel 151 generally has identical voxel height throughout the entire target area. For example, when scanning unit 125 is moved along a linear path (or rotated about a center of rotation with a pre-selected radius), the voxel height corresponds to an

5 effective height of scanning unit 125 that is measured along the direction orthogonal to the curvilinear path of movable member 120. However, by moving scanning unit 125 along a curved path or two or more different linear paths, voxels 151 may have various voxel heights. It is preferred, however, that voxels 151 have the identical height throughout the entire target area so that data acquisition and processing procedures may be performed by

10 simpler electric circuitry and/or algorithms.

When scanning unit 125 moves along a path which is orthogonal to its longitudinal axis 127, scanning unit 125 can provide a maximum scanning height, h such embodiment, the voxel height is substantially identical to a height of scanning unit 125 and, in addition, voxel axis 153 becomes substantially parallel with axis 127 of scanning unit

15 125. Furthermore, because voxels 151 are sequentially arranged by scanning unit 125 during its movement, multiple voxels 151 are sequentially arranged side-by-side along the curvilinear path of movable member 110.

Contrary to the voxel height and voxel axis determined by the physical configurations of voxels 151, the voxel width constitutes the characteristic dimension of 0 voxels 151 and, therefore, maybe manipulated according to various criteria including, but not limited to, resolution ofthe final images, mechanical and electrical characteristics of various parts of optical imaging system 100, and the like. It is appreciated that the voxel width maybe a direct indicator ofthe resolution ofthe final images, because the imaging member is arranged to determine the representative value ofthe chromophore property per 5 each voxel 151 and to generate the final images based thereupon. For example, in a high- resolution imaging mode, the imaging member calculates each ofthe foregoing spatially averaged voxel values at every pre-selected distance along the curvilinear path of movable member 110. Such distance may be manipulated to be less than the width of scanning unit 125 by, e.g., increasing the sampling rate ofthe data acquisition unit, so that each scanning area of scanning unit 125 may include two or more voxels 151. To the contrary, in a low- resolution imaging mode, the imaging member may be arranged to determine each ofthe above spatial averaged voxel values at a greater distance along the curvilinear path of movable member 120. Accordingly, each scanning area may be only a fraction of a voxel

125 or, conversely, each voxel 151 may have the width enough to encompass therein one or 5 more scanmng areas of scanning unit 125. It is noted that geometric configuration of voxels 151 is determined by a concerted operation ofthe scanning unit, actuator member, and/or imaging member. Thus, the voxel configuration, in particular, the characteristic dimension of voxels 151 maybe manipulated by adjusting operational characteristics of any ofthe scanning unit, actuator member, and imaging member. For example, by selecting the desired number ofthe wave sources and detectors ofthe scanning unit and by depositing them based on a pre-selected geometric arrangement, each or all ofthe voxels may be arranged to have pre-selected shapes and sizes. The actuator member may be adjusted to vary the speed of movement of the scanning unit and the contour ofthe curvilinear path, each of which may result in the voxels having various sizes and/or orientations. The imaging member may also be adjusted to receive and sample the output signals at a fixed, variable or adaptive sampling rate, the imaging member may further be manipulated to define multiple scanning units ofthe wave sources and detectors by grouping such sensors in a variety of configurations. Thus, it is generally a matter of selection of one skilled in the art to manipulate and synchronize the scanning unit, actuator member, and imaging member in order to generate the voxels having optimum shapes and sizes and arranged along the pre-selected path.

FIG. 54 is an example of a two-dimensional spatial distribution of an output signal generated by a wave detector of FIG. 5 which is linearly translated across the target area according to the present invention. In the figure, the ordinate represents magnitude or amplitude ofthe output signal generated by wave detectors 125 and the abscissa represents a position of scanning unit 125 along the path ofthe linear translation or a distance of travel thereof. A two-dimensional distribution of an exemplary output signal 150 manifests that the target area may include at least two distinct portions each of which exhibits different optical characteristics. In a first portion 152, e.g., output signal 150 is substantially flat and maintains substantially identical magnitudes. This portion 152 generally corresponds to the regions a, b, c, and h ofthe rectangular target area of FIG. 53 and represents the starting and end positions of scanning unit 125. To the contrary, in a second portion 154 interposed between the region a, b, and c and the region h, output signal 150 is relatively curved and has smaller magnitudes which vary according to the position along the target area. This may indicate that an abnormality such as a tumor may exist in second portion 154 ofthe target area. As will be discussed below, identifying such first and second portions 152, 154 of output signal 150 constitutes a basis of calculating a baseline of output signal 150 and of self-calibrating such output signal 150 for the optical imaging system. It is appreciated that second, curved portion 154 of output signal 150 may have the magnitudes greater than those of first, flat portion 152 when output signal 150 therein has a reversed polarity, when the abnormality has different optical characteristics during various developmental stages, and the like.

As in FIG. 34, wave sources 122 and detectors 124 are then moved to the starting position in the same region ofthe target area or to an adjacent different region ofthe target area, and scan the region by irradiating electromagnetic waves thereinto, by detecting electromagnetic waves therefrom, and by generating another set of output signals. After completing the scanning process, the imaging member removes the high frequency noise from the output signals, reorganizes the voxels to provide two-dimensional or three- dimensional spatial or temporal distribution ofthe chromophore properties, and generates the images ofthe spatial and/or temporal distribution of such over at least a substantial portion ofthe target area. When different sets of voxels are formed in different voxel directions, the imaging member may construct cross-voxels each of which is defined as an intersecting or overlapping portion of such voxels.

Regardless of whether the movable member performs only the forward linear franslation or the reciprocation, the imaging member can generate cross-voxels in the image domain. For example, during the linear translation, the imaging member can define a series of vertical voxels sequentially along the X-axis at each ofthe measurement locations using the output signals generated by the scanning units comprised of S DrD4-S2 and SrD2-D3- S2. After the linear franslation is completed, the imaging member can also define a series of auxiliary horizontal voxels sequentially along the Y-axis. In other words, by assuming that the target area is at steady-state during the franslation, the imaging member may regroup the wave sources and detectors to form auxiliary scanning units. For example, the wave source S, in positions A and D is grouped with the wave detector Dj in positions B and C, thereby forming a scanning unit comprised of Sj (in A)-Dl (in B)-Dj (in Q-Sj (in D). hi addition, other auxiliary scanning units may also be defined, e.g., Sj (in A)-D2 (in B)-D2 (in Q-Sj (in D), S, (in A)-D2 (in B)-D3 (in C)-S2 (in D), S, (in A)-D, (in B)-D3 (in C)-S2 (in D), D4 (in A)- S2 (in B)-S2 (in C)-D4 (in D), etc. It is appreciated that the foregoing auxiliary scanning units all satisfy the symmetry requirements ofthe co-pending '972 application. In case such symmetry should not be required, the imaging member can further define non-symmetric scanning units, e.g., Sj (in A)-D1 (in B)-D1 (in C)-S2 (in D), etc Once the foregoing horizontal and vertical voxels are defined in the image domain, the imaging member can also define cross- voxels by identifying vertical voxels intersecting with horizontal voxels. The imaging member can also calculate cross-voxel values from the voxel values ofthe intersecting vertical and horizontal voxels. Further details regarding the voxels and cross- voxels and their values are disclosed in a commonly assigned co-pending U.S. Application bearing Serial No. (N/A), entitled "Optical Imaging System for Direct Image Construction" and another commonly assigned co-pending U.S. Application bearing Serial No. (N/A) entitled "Optical Imaging System with Symmetric Optical Probe," both of which have been filed on February 5, 2001 and both of which are incorporated herein in their entirety by reference. It is noted that the cross-voxels may also be defined by moving the scanning unit or movable member along at least two non-parallel curvilinear paths. For example, in the embodiment shown in FIG. 34, the actuator member linearly translates the scanning unit in the X-direction. After the imaging member defines a series of vertical voxels sequentially along the X-direction, the actuator member then rotates the movable member about a pre-selected angle, e.g., 90° clockwise, and linearly translates the scanning unit or movable member upwardly. The imaging member then defines a series of horizontal voxels sequentially along the Y-direction. By identifying intersecting regions ofthe vertical and horizontal voxels in the target area, the imaging member constructs the cross-voxels in the image domain.

Rotational Translation

FIG. 55 is another schematic diagram ofthe scanning unit of FIG. 5 arranged for rotation or revolution according to the present invention. The actuating member is generally arranged to rotate scanning unit 125 about a pre-selected center of location which is, e.g., its mid-point 129. Accordingly, rotations or revolutions of such scanning unit 125 cover an arcuate or circular scanning area having a radius which is substantially identical to one half length of scanning unit 125. Body 110 is generally shaped and sized as an arc or circle so as to accommodate the shape and size ofthe scanning area defined by scanning unit 125 and to minimize formation ofthe dead areas thereon.

The actuator member maybe arranged to generate different types of rotations or revolutions ofthe scanning unit. For example, the actuator member may rotate the scanning unit about the center of rotation provided adjacent to one ofthe edges thereof. Rotations or revolutions of such scanning unit result in an arcuate or a circular scanning area having a diameter which is greater than the half-length ofthe scanning unit, or a diameter which is twice the length ofthe scanning unit. Alternatively, the actuator member may be arranged to generate two or more movements, rendering the scanning unit define the scanning area comprised of a combination of arcuate and circular areas with different radii and/or different centers of rotation. In addition, the actuator member may also be arranged to manipulate the scanning unit to combine such arcuate or circular movements with linear translations. When it is desired to provide such scanning areas, an optional controller may be provided so as to fine-control the movements ofthe actuator member along the multiple, pre-selected curvilinear paths. Multiple Movements of the Scanning Unit

As described above, the actuator member may generate at least two different movements ofthe movable member along at least two different curvilinear paths and/or in at least two different curvilinear directions. Such movements may be tailored to satisfy a preselected geometric arrangement therebetween. For example, at least a portion of one curvilinear path (or direction) may be substantially transverse to at least a portion ofthe

5 other curvilinear path (or direction). Such paths may be arranged to be orthogonal to each other as exemplified by the axes ofthe conventional Cartesian, cylindrical or spherical coordinate systems, hi particular, when the target area has a substantially polygonal shape, the actuator member may move the movable member along a first curvilinear path from a first side toward a second opposing side ofthe target area, to move or reposition it along a

10 second curvilinear path from the second side to the third side thereof, and then to move it along the third curvilinear path from the third side toward the first or other side of such polygonal target area. hi an embodiment of FIGs. 56A to 56C and 57, the actuator member is arranged to generate multiple movements ofthe scanning unit, e.g., linear translation ofthe

15 scanning unit (along with the movable member) along the X-axis ofthe Cartesian coordinate system and clockwise rotation thereof by 90°, followed by another linear translation thereof along the Y-axis. FIGs. 56A, 56B, and 56C are respectively schematic diagrams ofthe scanning unit of FIG. 5 arranged for such X-translation, 90° rotation, and Y-translation according to the present invention. The optical imaging systems incorporating the

20 embodiment of FIGs. 56A to 56C are substantially identical to those of FIG. 52A, except ' that the actuator member may move moveable member 120 (e.g., linear translation thereof) independent ofthe rotation of body 110.

In operation, the actuator member is initialized to position body 110 at its first configuration. Body 110 is placed on the medium to cover at least a substantial portion

25 ofthe target area, and movable member 120 (along with its scanning unit 125) is positioned in a first region ofthe target area which is adjacent to one vertical side ofthe rectangular target area. Wave sources 122 and detectors 124 are carefully positioned to form optical coupling with the first region ofthe target area so that wave sources 122 can effectively irradiate electromagnetic waves into the first region ofthe target area and wave detectors

30 124 can generate the output signal from the first region thereof.

In FIG. 56A, the actuator member (not shown) linearly translates movable member 120 away from the first region ofthe target area toward an opposing second region along the X-axis (X-translation). Wave sources 122 and detectors 124 are manipulated to maintain the optical couplings with the medium so that wave detectors 124 can generate the

35 output signals representing spatial distribution ofthe chromophore property during the X- franslation. By appropriately manipulating and synchronizing scanning unit 125 with the actuator member, the imaging member (not shown) may sample the output signal at a preselected rate. Thus, a set of vertically-extending voxels 161 is defined sequentially along the curvilinear path of scanning unit 125. Because longitudinal axis 127 of scanning unit 125 extends along the Y-axis, voxels 161 also extend along the Y-axis (thus, "Y-extended

5 voxels'), have the height substantially similar to that of scanning unit 125, and have the width which is detennined by the speed ofthe X-translation and the sampling rate ofthe data acquisition unit ofthe imaging member. In addition, because the linear translation path of scanning unit 125 is parallel with the X-axis, Y-extended voxels are sequentially arranged along the X-axis. By solving the wave equations based on the spatially averaged output

10 signal in each of theY-extended voxels, the imaging member calculates the voxel value for each Y-extended voxel.

Once movable member 120 reaches the opposing vertical side ofthe target area or the vicinity thereof, the actuator member may reposition body 110 to its second configuration by rotating body 110 by 90° in the clockwise direction, as in FIG. 56B, about

15 the center of location disposed at a center of body 110. Such body rotation of 90° results in repositioning movable member 120 (along with scanning unit 125) on or along the upper side ofthe rectangular target area. The imaging member is synchronized with body 110 and/or the actuator member so as not to sample the output signals during this body rotation. In FIG. 56C, the actuator member linearly translates movable member 120

20 (along with scanning unit 125) from the upper side toward an opposing lower side ofthe target area downwardly along the Y-axis (Y-franslation). During the Y-translation, wave sources 122 and detectors 124 are also manipulated to maintain the optical couplings with the medium so that the imaging member can sample the output signal generated by wave detector 124 at a pre-selected rate. Therefore, another set of horizontally-extending voxels

25 163 is defined sequentially along the curvilinear path of scanning unit 125. Because longitudinal axis 127 of scanning unit 125 is aligned with the X-axis, a set of horizontally- extended voxels 163 are formed along the X-axis (thus, "X-extended voxels'), hi addition, because the linear translation path of scanning unit 125 is aligned with the Y-axis, the X- extended voxels are sequentially arranged side by side along the Y-axis. By solving the

30 wave equations based on the spatially averaged output signal in each ofthe X-extended voxels, the imaging member calculates the voxel value for each X-extended voxel.

Once movable member 120 (and scanning unit 125) reaches the opposing side ofthe rectangular target area, the scanning process may be terminated. The imaging member then defines a set of cross- voxels 165 by identifying overlapping or intersecting regions between the Y-extended voxels 161 and X-extended voxels 163, and calculates a sequence of cross- voxel values of cross- voxels 165 directly from the voxel values for each pair of Y-extended voxel 161 and X-extended voxel 163 intersecting at each cross-voxel 165. Based on the cross-voxel values, the imaging member produces images of two- or three-dimensional spatial distribution ofthe properties ofthe chromophore over at least a substantial portion ofthe target area.

FIG. 57 is a schematic diagram of images obtained by the scanning unit of FIG. 5 sequentially X-translated, rotated, and Y-translated across the target area according to the present invention. As discussed above, the imaging member defines two orthogonal sets of voxels 161, 163 which intersect each other and define cross-voxels 165. Because each cross- voxel 165 is substantially smaller than Y-extended and X-extended voxels 161, 163, the imaging member can generate high-resolution images ofthe spatial and/or temporal distribution ofthe absolute values ofthe chromophore property.

In general, the characteristic dimensions of voxels 161, 163 such as widths of vertically Y-extended voxels 161 and/or heights of horizontal X-extended voxels 163 may be adjusted by manipulating the speed ofthe X-translation and Y-translation, respectively, by controlling sampling rate ofthe output signal, etc. Accordingly, by maintaining the same franslational speed during the X- and Y-translations, widths and heights of cross- voxels 165 may become identical, resulting in the square cross-voxels. In the alternative, by employing different speeds during each ofthe X- and Y- translations and/or by temporally varying such speeds, cross- voxels 161 may have rectangular shapes with different sizes. Thereby, the resolution ofthe images may be controlled manually or adaptively as well. For example, the speeds of linear translation (or any other movements) may be reduced to obtain smaller rectangular or square cross-voxels from which the imaging member may provide the final images having improved accuracy and enhanced resolution. The characteristic dimensions may similarly be adjusted by manipulating the sampling rate ofthe output signals by the imaging member.

It is noted that various embodiments may be employed to provide multiple movements ofthe movable member over the target area. For example, one or more actuator members may be used to provide different movements ofthe movable member, scanning unit, and/or sensors, in different directions, e.g., by operating each actuator member to generate a specific movement along a specific curvilinear path and/or by operating a single actuator member which can guide the movable member along different guiding tracks for different curvilinear paths. Although these embodiments may allow meticulous control of the movement ofthe movable member, they generally require more parts and more elaborate control algorithms. In the alternative, as shown in FIGs. 56A through 56C, the optical imaging system may include a movable body to which both ofthe actuator member and movable member may be fixedly coupled. By arranging the actuator member to generate a movement ofthe movable member with respect to the movable body and to generate another movement ofthe movable body with respect to the target area which is substantially independent ofthe movement ofthe movable member, a single actuator member can generate different movements ofthe movable member along many different curvilinear paths. In addition, the movements ofthe movable member and movable body may be synchronized to produce a pre-selected movement ofthe scanning unit over different regions ofthe target area.

Simultaneous Different Movement of the Scanning Unit/Movable Member

In another aspect ofthe invention, an optical imaging system includes an actuator member arranged to directly create cross-voxels by generating at least two different movements of a movable member (and/or its scanning unit) simultaneously. This aspect of the invention is described by an exemplary embodiment illustrated in FIG. 58. FIG. 58 shows a schematic diagram ofthe scanning unit of FIG. 5 arranged for simultaneous X-Y linear translations according to the present invention. In general, the optical imaging systems incorporating such embodiment are substantially identical to those of FIGs. 52 and 56A, except that the actuator member (not shown) of FIG. 58 is arranged to simultaneously generate a linear translation of movable member 120 along the X-axis and a reciprocation thereof along the Y-axis.

In operation, stationary (or movable) body 110 is placed on a target area of the medium and movable member 120 is positioned in a first region thereof. Wave sources 122 and detectors 124 are also positioned to form appropriate optical coupling with the first region ofthe target area and turned on to emit elecfromagnetic waves into and to detect such waves from the target area. The actuator member franslates movable member 120 along the X-axis while reciprocating movable member 120 along the Y-axis. Accordingly, movable member 120 (along with scanning unit 125) can scan the target area along a substantially sinusoidal path. In a preferred embodiment ofthe present invention, scanning unit 125 scans the target area while the imaging member samples the output signals at desirable time intervals and/or pre-selected locations over the target area. It is appreciated that the detailed configuration of such sinusoidal path (i.e., amplitude, frequency, phase angle etc.) maybe determined by the speed of X-translation as well as that of Y-reciprocation.

Once movable member 120 reaches the opposing side ofthe target area or the vicinity thereof, an operator may terminate the scanning process ofthe target area and manually move body 110 to the next target area ofthe medium for further scanning. In the alternative, the actuator member or an auxiliary motion generating member may be used to mechanically translate and/or rotate body 110 to the next target area as well.

It is noted that accuracy ofthe output signals maybe improved and image resolution may be enhanced by repeating the identical scanning process or performing different scanning processes over the same target area. For example, movable member 120 may be moved back to the starting first region ofthe target area through the backward X- translation accompanied by the Y-reciprocation thereof. The actuator member may be arranged to move movable member 120 substantially along the same sinusoidal path in the opposite direction and the imaging member may be arranged to sample the output signals at the same or similar measurement locations and at the same or similar sampling rates during the backward movement. By obtaining multiple output signals during the forward and backward movements at each ofthe voxels and averaging such signals, the signal-to-noise ratio ofthe output signals may be dramatically improved. In the alternative, the actuator member may generate different sinusoidal paths or the imaging member may sample the output signals at different locations and/or at different sampling rates. Accordingly, at least two different sets of voxels may be defined during the forward and backward movements of movable member 120 at each measurement location ofthe target area, hi addition, at least one set of cross-voxels maybe generated from multiple sets of voxels extending along different axes, enabling generation ofthe final images with enhanced resolution. In yet another alternative, more sets of voxels and cross- voxels may also be obtained by arranging body 110 as an article movable with respect to the target area. If preferred, the movable member may perform the Y-reciprocation while the movable member is moved at a slower speed or stalled at desired positions along the X-axis. Only after the entire height ofthe target area is scanned by the scanning unit, the movable member resumes the normal X- translation. This embodiment provides an advantage of allowing the smaller and shorter movable member to scan the entire target area.

Multiple sets of voxels and cross-voxels maybe obtained by adjusting or manipulating sampling pattern ofthe output signals by the imaging member. For example, regardless ofthe characteristics of curvilinear paths of movable member 120, the imaging member may be synchronized with the actuator member so that the imaging member can sample the output signals at pre-selected locations ofthe target area. Accordingly, the operator may manipulate the actuator member or imaging member to control the sampling mode ofthe output signals to adjust the shapes ofthe voxels and/or cross- voxels, thereby improving resolution ofthe final images, and so on.

The major advantage attained by the optical imaging system of FIG. 58 is that such systems only needs a minimal number ofthe wave sources and/or detectors. Contrary to the embodiments shown in FIGs. 52 through 56 where the scanning units preferably have a characteristic dimension (e.g., their height or radius) substantially identical to that ofthe target area (i.e., the height or radius thereof), the optical imaging system of FIG. 58 defines the scanning unit having the height and/or width substantially less than those ofthe target area and moves it in at least two directions across the entire portion ofthe target area, thereby scanning at least a substantial portion thereof. By reciprocating the shorter scanning unit in the vertical direction, however, the scanning unit can cover the entire height ofthe target area. By translating such scanning unit along the horizontal direction, the scanning unit can scan the entire width ofthe target as well. In this respect, the foregoing optical imaging system may even be able to employ a single source-single detector arrangement which may define the scanning unit having the scanning area only a tiny fraction ofthe target area.

It is appreciated that characteristics ofthe movement path ofthe movable member (and/or scanning unit) are not always dispositive ofthe shapes and/or sizes ofthe voxels defined thereby. For example, a sinusoidal path ofthe movable member does not necessarily yield curved voxels arranged along the sinusoidal path ofthe movable member. When the imaging member samples the output signals at a pre-selected time interval along the sinusoidal path, the voxels may have curved boundaries, varying heights and width, and may be arranged substantially along the sinusoidal path. However, if the imaging member is synchronized with the actuator member to sample the output signals at certain locations, resulting voxels may be manipulated to have substantially identical heights and widths and may be arranged in almost any desirable direction. Furthermore, when the Y-component speed ofthe movable member (i.e., Y-reciprocation speed) is maintained substantially faster than the X-component thereof (i.e., the X-translation speed), the resulting voxels may have approximately rectangular shapes. By the same token, the voxels may be arranged to be congruent squares, e.g., by synchronizing the imaging member with the actuator member such that the imaging member samples the output signals at every identical horizontal and vertical distance (i.e., identical spatial interval) which may corresponds to different time intervals in the temporal domain.

An actuator member may generate two or more different movements along two or more curvilinear paths so that the imaging member can define the voxels or measurement elements along two or more directions. For example, the embodiment in FIG. 58 allows the imaging member to define the voxels not only along the X-axis but also along the Y-axis. That is, the imaging member can define more than one set of voxels in the direction which may be orthogonal to the path ofthe linear translation. By manipulating the speeds along the X- as well as Y-axis and by synchronizing the sampling position or intervals with such movements, the shape and size ofthe voxels and cross- voxels may also be readily controlled.

It is noted that the voxels obtained by two simultaneous movements ofthe movable member roughly correspond to the cross- voxels of FIG. 57 obtained by two sequential and/or non-parallel movements ofthe movable member. This may be generalized to any movements ofthe movable member along any curvilinear paths. For example, an actuator member may rotate the movable member while linearly translating (or reciprocating) it along the radial direction. Such an arrangement generally yields a series of spiral layers along the radial direction, where each turn of a spiral layer may contain multiple arcuate voxels. Thus, by maintaining the rotational speed greater than the radial franslational speed, the spiral layers approach concentric shells each of which may include multiple arcuate voxels as well. Further details of such voxels are provided in the foregoing commonly assigned co-pending U.S. Applications entitled "Optical Imaging System for Direct hnage Construction" and "Optical Imaging System with Symmetric Optical Probe," both of which have been filed on February 5, 2001 and both if which are incorporated herein in their entirety by reference.

Cross Voxel Generation By Stationary & Mobile Source/Detectors In yet another aspect ofthe present invention, an optical imaging system is arranged to directly generate cross-voxels by incorporating at least one movable wave source and/or detectors into a movable component ofthe optical imaging system, and by incorporating at least one stationary wave detector and/or source into a stationary component thereof.

FIG. 59 is a cross-sectional top view of an exemplary scanning unit according to the present invention, in which all four wave sources 122 are disposed along the sides of a stationary body 110, whereas all three wave detectors 124 are implemented to a movable member 120. The actuator member (not shown) generates linear translation or reciprocation of a scanning unit 125 along the X-axis of target area. Therefore, wave sources 122 remain substantially stationary with respect to the target area ofthe medium, while wave detectors 124 may become movable with respect to wave sources 122 as well as the target area. The wave sources 122 and detectors 124 may define scanning units which are elongated at angles with respect to the linear movement path of movable member 120 and which change their configuration (such as their size, shapes, angles, and the like) during the movement of movable member 120.

In operation, stationary body 110 and movable member 120 are positioned in a first region ofthe target are so that wave sources 122 form stationary optical coupling with the target area, while wave detectors 124 movably form optical coupling in the first region ofthe target area. Wave sources 122 and detectors 14 are activated to irradiate and detect electromagnetic waves. The actuator member translates movable member 120 and its wave detectors 124 from one side to its opposing side ofthe target area along a linear path which generally corresponds to the X-axis ofthe target area. Depending upon the data acquisition or sampling rate ofthe imaging member (not shown), each pair of wave source 122 and

5 detector 124 forms an elongated voxel 171 at varying angles with respect to the linear translation path of movable member 120 (or the X-axis). Wave detectors 124 generate representative output signals spatially averaged over an entire area or volume of each elongated voxel 171. The imaging member receives and samples such output signals and determines voxel values for each elongated voxel 171. The imaging member also identifies

10 intersecting portions of two or more voxels and generates cross- voxels 173 thereat. Based on the voxel values ofthe intersecting voxels, the imaging member calculates cross- voxel values of each of such cross- voxels. Once movable member 120 reaches the opposing side ofthe target area or the vicinity thereof, the scanning process may be terminated and body 110 is moved to a next target area ofthe medium for further scanning of thereof. In the

15 alternative, the actuator member may be arranged to repeat the scanning process ofthe same target area along the identical or different curvilinear path.

It is appreciated that the geometric relation between stationary wave sources 122 and movable wave detectors 124 varies according to the position in the target area and therefore, scanning unit 125 generally defines extended voxels 171 which have different

20 shapes and sizes during the movement thereof. Such irregular voxels may pose complexity in obtaining a solution ofthe wave equations applied to scanning unit 125 and, therefore, they are generally less preferred to the ones with substantially identical shapes and sizes. The shape and size differences among extended voxels 171 may be minimized by various arrangements, e.g., by synchronizing the actuator member and imaging member so that the

25 data sampling may be performed at pre-selected positions ofthe target area, resulting in formation of cross- voxels having pre-determined configurations. The shapes and sizes of the cross-voxels and distribution pattern thereof may be controlled by adjusting geometric arrangements between the wave sources and detectors, by varying the speed of their movement, by manipulating the shapes ofthe curvilinear movement path ofthe scanning

30 unit, and so on. Accordingly, it is usually a matter of selection of one skilled in the art to find the optimum arrangements for the scanning unit, actuator member, and/or imaging member.

It is noted that the scanning unit of FIG. 37 generally defines angled voxels 161, 163 which change their shapes and sizes during the movement of movable member

35 120, because the geometric arrangements between stationary wave sources 122 and movable wave detectors 124 vary depending on the position of movable member 120 over the target area. Such voxels 161, 163 may require more complicated analytic or numerical schemes for obtaining solutions ofthe wave equations applied to such stationary wave sources 122 and movable wave detectors 124 and, therefore, generally not prefened to the ones which maintain substantially identical shapes and sizes. However, differences in the shapes and sizes among the angled voxels and their cross-voxels may also be compensated by various arrangements, e.g., by synchronizing the actuator member and imaging member so that the signal or data may be sampled at pre-selected positions ofthe target area, thereby defining the voxels having pre-deteπnined configurations. Configuration ofthe cross- voxels and distribution pattern thereof may also be controlled by manipulating geometric arrangements between the wave sources and detectors, by varying the speed of movement ofthe wave detectors, by manipulating the contour ofthe curvilinear movement path ofthe scanning unit, and so on. Therefore, it is generally a matter of choice of one skilled in the art to find the optimum arrangement for the scanning unit, actuator member, and/or imaging member in the foregoing embodiment. If preferred, at least one wave source may be disposed in the movable member and/or at least one wave detector maybe implemented to the stationary body. The foregoing source-detector arrangement can also be reversed, i.e., all ofthe wave sources are disposed at the movable member, while all ofthe wave detectors are disposed at the stationary body.

B. 2/3 Dimensional Image Generation of a Distribution The Embodiment

As described above, the accuracy ofthe output signals and resolution ofthe images may be enhanced by repeating the same scanning process or performing different scanning processes over the same target area. Multiple sets of cross-voxels may be constructed by, e.g., adjusting the sampling pattern ofthe imaging member or manipulating the path and/or path speed ofthe movement generated by the actuator member. It is noted that, the embodiment of FIG. 59 may also incorporate a minimal number ofthe wave sources and detectors, and their scanning units may have the heights and widths substantially less than those ofthe target area.

It is also appreciated that the foregoing optical imaging systems ofthe present invention can generate the images of two- and or three-dimensional distribution ofthe chromophore property on a substantially real time basis. Contrary to every conventional optical imaging system requiring complicated and time-consuming image reconstruction process, the foregoing optical imaging system may generate such images directly from the extended voxel values and/or cross-voxel values of such voxels and/or cross- voxels. For examples, the optical imaging systems of FIGs, 52 through 59 may include real time image construction algorithms regardless ofthe size ofthe target area, number of wave sources and detectors, detailed configuration ofthe curvilinear paths along which the movable and scanning units may travel, and the like. The foregoing optical imaging systems may be readily adjusted for variable resolutions ofthe images. For example, contrary to the prior art counterparts which require complicated readjustment ofthe equipment, the foregoing optical imaging system has only to adjust the data sampling rate, speed of movement ofthe movable member, grouping or sampling pattern ofthe wave sources and detectors, and so on. The adjustments may be made by an operator.

In another aspect ofthe invention, an optical imaging system maybe arranged to include a movable body and a movable member so as to generate images of distribution of chromophore properties in a target area of a physiological medium by moving the movable member within the target area as well as by moving the movable body over different target areas ofthe medium.

FIG. 60 shows a schematic diagram of another mobile optical imaging system according to the present invention. Such optical imaging system 200 typically includes a movable body 210, at least one movable member 220, and actuator member 230 and an imaging member 240. Movable body 210 is shaped and sized to cover at least a substantial portion of a target area ofthe medium and preferably encloses at least a portion of movable member 220. Movable body 210 typically includes at least one mobile unit 212 capable of moving movable body 210 over different target areas ofthe medium. Examples of such mobile units may include, but not limited to, wheels, rollers, caterpillars, and the like. Movable member 220 is arranged to be similar or identical to those described in the foregoing embodiments of FIGs. 1 to 3 and 52 to 58. For example, movable member 220 may include at least one wave source and at least one wave detector arranged according to any ofthe foregoing configurations. One or more actuator members 230 operationally may couple with both movable body 210 and movable member 220 to generate at least one primary movement of movable body 210 along at least one primary curvilinear path and at least one secondary movement of movable member 220 along at least one secondary curvilinear path. Actuator member 230 may also generate curvilinear translations, rotations, revolutions or reciprocations of movable body 210 and/or movable member 220 simultaneously or sequentially.

In an embodiment similar to that of FIG. 60, as shown in FIG. 38, when in operation, movable body 110 and movable member 120 are positioned in their starting positions. Movable body 110 is placed on the medium so that scanning unit 125 is positioned in a first region ofthe target area ofthe medium. Wave sources 122 and wave detectors 124 are then activated and actuator member 130 translates movable member 120 substantially linearly to adjacent regions ofthe target area. Once movable member 120 reaches the other side ofthe target area, the scanning process may be terminated or movable member 120 may be moved back to the first region ofthe target area while continuing the scanning process. After movable member 120 finishes scanning of all regions ofthe target area, moving unit 119 is activated to move the optical probe and/or entire optical imaging system to the second target area ofthe medium.

It is appreciated that an optional guiding member may be disposed on the target areas ofthe medium so that the movable member may travel thereon across multiple target areas. Such guiding member may preferably be made of flexible material or may have a structure so that its shape can conform to different contours of different target areas. For example, a ring-shaped guiding member may be provided to fit around a head or a base portion of a breast of a human subject. The movable member engages the guiding member and moves therealong while allowing the scanning unit to scan around the head or breast. By allowing the movable member to travel along the curvilinear paths ofthe guiding member with known spatial coordinates at a preferred or pre-determined speed, the optical imaging system may readily obtain a continuous two- or three-dimensional distribution of the output signals (or chromophore properties) around the head or breast, hi addition, the two-dimensional pattern may readily be combined into the three-dimensional distribution pattern without relying on image markers conventionally required by the prior art optical imaging technology. Therefore, such embodiment also contributes to real-time construction of two- or three-dimensional images ofthe chromophore properties in the medium. D. Self-Calibration Baseline Method In a further aspect ofthe invention, an optical imaging system calculates a baseline or background magnitude (referred to as the "baseline" hereinafter) of an output signal generated by wave detectors. Based on this baseline, the foregoing optical imaging system performs self-calibration ofthe wave detectors, sensor assembly, optical probe or portable probe of such systems. The self-calibrating optical imaging system may include at least one ofthe foregoing wave sources, at least one ofthe foregoing wave detectors, and an imaging member described herein.

The imaging member preferably removes high-frequency noise from the output signal by, e.g., arithmetically, weight- or ensemble-averaging the output signal, and/or processing at least a portion ofthe output signal through a low-pass filter. The imaging member is arranged to identify different portions or segments ofthe output signal, each of which exhibits different profile (e.g., flat, linear or curved) and has different (e.g., flat or varying) magnitudes. When the imaging member identifies one or more portions in which the output signal exhibits substantially flat profile and have substantially similar magnitudes, it generally indicates that regions ofthe target area conesponding to such flat portions ofthe output signal are predominantly composed of homogeneous material such as normal tissues and cells. The imaging member then calculates the baseline ofthe output signal by, e.g., arithmetically, geometrically or weight-averaging the magnitudes ofthe flat or linear portions ofthe output signal. The imaging member then calculates dimension less or normalized self-calibrated output signal such as, e.g., normalized optical density signals which are defined as ratios of difference signals between the output signal and baseline to the baseline. Such optical density signals may be supplied to the imaging member which then solves a set of wave equations applied to the wave sources and detectors, solutions of which represent the spatially averaged distribution ofthe properties ofthe chromophore in different regions ofthe target area ofthe medium.

It is preferred that the foregoing self-calibration process be performed on a substantially real-time basis. This implies that, before the movable member ofthe optical imaging system is moved from the first target area to a next one, the imaging member is preferably arranged to sample the output signals across different regions ofthe first target area, to calculate the baseline thereof, to generate normalized optical density signals, and to optionally display the output signals, optical density signals, and/or the distribution ofthe property ofthe chromophore at each ofthe voxels defined thereby. This aspect ofthe present invention offers several benefits over the prior art.

Contrary to prior art optical imaging technology requiring a priori estimation of a medium baseline in a sample medium or in a phantom, the optical imaging system ofthe present invention estimates a single baseline ofthe medium and uses that baseline throughout the entire target area and/or medium. Therefore, such optical imaging system obviates any need to estimate multiple baselines without compromising the performance thereof. In addition, the foregoing optical imaging system generates the images ofthe spatial distribution ofthe chromophore properties on a substantially real time basis. Furthermore, the probe or its sensors such as the wave sources and detectors ofthe foregoing optical imaging system do not have to be moved and positioned back and forth between the phantom and the target area. Accordingly, there is no danger of degrading the optical couplings formed between the probe and target area ofthe medium and, therefore, the resolution ofthe resulting images can be enhanced.

The flat portion ofthe output signal or, conversely, the rest ofthe output signal (i.e., non-flat or curved portion) may be identified by various arrangements. First, one or entire portion ofthe output signal (or the filtered output signal having an improved signal-to-noise ratio) may be divided into different portions according to a pre-selected threshold value. Such threshold value may be selected as a minimum cut-off value for the flat portion so that all data points ofthe flat portion may have the magnitudes equal to or greater than the threshold value. In the alternative, the threshold value may be a maximum cut-off value for the non-flat, curved portion so that all data points ofthe non-flat or curved portion must have magmtudes equal to or less than the threshold magnitude. Regardless of the nature ofthe threshold value, the output signal may vary in their magnitudes in the flat as well as non-flat portions. Thus, the imaging member may be provided with a secondary cutoff range or a range of deviation, where any data points falling out ofthe range may not be included in the flat or non-flat portion. Different methods and/or arrangements may be employed to establish the threshold value. For example, the imaging member may provide an operator with the output signals obtained across different regions ofthe target area and the operator may manually select the threshold value for the flat portion or non-flat or curved portion ofthe output signals. The threshold value may also be adaptively determined by identifying a reference value which may be a local (or global) maximum or a local (or global) minimum ofthe output signal. Once the reference value is identified, the threshold value is readily determined by a pre-selected mathematical equation, e.g., by multiplying (or dividing) the reference value by a pre-selected factor or by subtracting (or adding) a pre-selected offset from (or to) the reference value. In the alternative, the imaging member may calculate a cumulative average of multiple output signals generated by the wave detectors along the curvilinear movement paths ofthe movable member. The global cumulative average may then be utilized to establish the one or more ofthe threshold values, reference values, preselected factors, and/or pre-selected offsets.

It is appreciated that the imaging member may calculate the baselines for at least two different target areas ofthe medium. These multiple baselines (referred to as the "local baselines") may be analyzed to confirm their validity and to select the correct one which is not biased by the presence of abnormal cells or tissues. For example, when the movable member is positioned in a target area free of any abnormalities, the output signal will be flat over the entire region ofthe target area. The baseline may be easily calculated as the average ofthe entire output signal. When the target area includes both ofthe normal and abnormal cells or tissues, the imaging member will divide the output signal into at least two portions, i.e., one flat portion and the other non-flat portion, or will locate such flat portion or segment ofthe output signal. The baseline may then be calculated as the average ofthe flat portion ofthe output signal. However, when the majority portion of or entire target area is composed ofthe abnormal cells or tissues, the output signal has magnitudes greater than the maximum cut-off value or less than the minimum cut-off value, and may even exhibit a relatively flat profile across the target area. When such target area happens to be the first one to be examined or when the imaging member is arranged to adaptively establish the threshold magnitude based on the average value ofthe output signal of such target area, an operator may be misled to regard such average value as a correct baseline ofthe output signal of normal regions. Estimating at least two baselines in at least two different target areas may prevent such mis-diagnosis by allowing the operator to manually compare multiple local baselines or by arranging the imaging member to alert the operator upon finding a discrepancy between the baselines obtained from different target areas.

When the local baselines from multiple target areas are not substantially identical or exhibit deviations greater than a pre-selected value, the imaging member may obtain a representative, average or global baseline ("global baseline" hereinafter) and normalize the output signals by such global baseline. Alternatively, an operator or imaging member may select a single baseline from multiple baselines of different target areas and use it as the global baseline. In the alternative, a few selected local baselines or all local baselines may be averaged to calculate the global baseline, where multiple local baselines may be arithmetically, geometrically or weight-averaged to yield the global baseline.

When a global or composite medium image is to be made of multiple local images of multiple target areas, the imaging member may generate each local image based on local baselines of each target areas or based on a single global baseline. For example, the local images of local target areas may be constructed based on each of their local baselines obtained over target areas, and a composite medium image may be obtained by aligning multiple local images obtained by multiple local baselines. In the alternative, the global baseline may be calculated or selected upon which all local images may be based. In general, each approach has its own pros and cons. For example, when a composite image is required around a brain to identify any potential or actual stroke conditions, heterogeneous organs (such as ears, eyes, etc.) and different skull thickness around the brain may yield different local baselines in different target areas around the brain. If the global baseline is calculated from multiple local baselines and used for obtaining all local images, all image pixels will have the identical brightness-scale and/or color-scale across the entire medium. Although such composite medium image may enable a physician to make a comparative diagnosis, he or she may not be able to locate a mild stroke condition which may be hidden in one local target area and overshadowed by the global baseline having magnitude similar to or greater than the mild stroke condition. To the contrary, when the composite image is made of multiple local images each of which is based on individual local baselines, each local image may have its own brightness-scale or color-scale. Although the foregoing mild sfroke condition may not be compromised in the local image, the physician may have to analyze each local image separately.

One way of obviating such inconvenience may be to artificially enhance the contrast between normal cells or tissues and abnormalities in each ofthe local target areas. For example, upon identifying any potential abnormalities, the imaging member may amplify the signals corresponding to such abnormalities so that the amplified signals will not be overshadowed by the magnitude ofthe global baseline. A special marker or color may be added to such enhanced images to alarm the physician as well, hi another example where a composite medium image is required around the breast, some tumors may be as large as or greater than the scanning unit ofthe optical imaging system or the target area defined thereby. As a result, at least one local image may have the local baseline which may be substantially greater or less than the baseline of normal cells or tissues. To prevent a global baseline from being biased by such abnormal baseline, the imaging member may be arranged to compare individual local baselines obtained from multiple local target areas and not to consider such biased baseline in calculating the global baseline. Although the above disclosure ofthe present invention is mainly directed to provide images of a spatial distribution ofthe chromophore property, the present invention may be applied to generate images of a temporal distribution thereof. As briefly discussed above, the scanning unit ofthe movable member maybe arranged to scan the substantially same region over time. From the differences in the output signals detected at different times over the same region ofthe medium, the imaging member may calculate temporal changes in the chromophore property ofthe region and generate images ofthe temporal distribution pattern of such property. Alternatively, the temporal distribution may be determined and its images may be provided from two or more spatial distributions of chromophore property obtained at different time frames. For example, the movable member and its scanning unit may repeat the scanning process ofthe target area and calculate the temporal distribution pattern ofthe chromophore property at each location ofthe target area. It is appreciated that the temporal changes usually relate to relative changes in the values ofthe chromophore property. However, once absolute values ofthe chromophore property may be determined at any reference time frame, preceding or subsequent changes in such property may readily be converted to the absolute values thereof and vice versa.

It is noted that the foregoing optical imaging systems, optical probes, and methods ofthe present invention may provide values for the temporal changes in blood or water volume in the target area ofthe medium, hi an exemplary embodiment of obtaining such temporal changes in blood volume in a specific target area of a human subject, the concentration of oxygenated hemoglobin, [HbO], and that of deoxygenated hemoglobin, [Hb], are calculated by a set of equations (la) and (lb) or by another set of equations (2a) and (2b). Once [Hb] and [HbO] are known, their sum (i.e., total hemoglobin concentration, [HbT], which is the sum of [Hb] and [HbO]) is also calculated. By obtaining the output signals from the wave detectors positioned in the same target area over time, changes in the total hemoglobin concentration is obtained. By assuming that hematocrit (i.e., the volume percentage ofthe red blood cells in blood) of blood flowing in and out ofthe target area is maintained at a constant level over time, temporal changes in the blood volume in the target area are directly calculated in terms of temporal changes in [HbT] in the target area. In the alternative, temporal changes in [Hb] and [HbO] may be calculated from the equations (6a) and (6b) and, therefore, temporal changes in [HbT] is obtained as the sum ofthe changes in [Hb] and [HbO] in the target area.

It is also appreciated that the optical imaging systems, optical probes, and methods ofthe present invention maybe applied to obtain the images of three-dimensional distribution ofthe chromophore properties in the target area ofthe medium. As discussed above, electromagnetic waves are irradiated by the wave sources and transmitted through a target volume ofthe medium which is defined by a target area and a pre-selected depth (or thickness) into the medium. Accordingly, a set of wave equations can be formulated for such three-dimensional target volumes. The output signals generated by the wave detectors are delivered to the imaging member which then solves the wave equations with relevant initial and/or boundary conditions, where such solutions from the wave equations represents the three-dimensional distribution ofthe chromophore property in the target volume ofthe medium. To maintain pre-selected resolution ofthe images, the optical imaging systems or probes thereof preferably include enough number of wave sources and/or detectors arranged to define a larger number of scanning units and voxels in the target volume. Suppose an exemplary optical imaging system includes two wave sources and four wave detectors, and generates the two-dimensional images of a target area with a pre-determined resolution. When a target volume is defined to have an area same as the target area and a pre-selected thickness representing N two-dimensional layers stacked one over the other, such an optical imaging system may probably be required to include approximately 2N wave sources and/or 4N wave detectors to maintain the same resolution as each of two-dimensional layers. The number of requisite wave sources and detectors may be reduced, however, by manipulating the actuator member to generate enough movements ofthe wave sources and detectors over the target area, preferably in multiple different curvilinear directions. However, the required number of wave sources and detectors is generally inversely proportional to the number or complexity ofthe movements ofthe movable member or to the sampling rate ofthe output signals by the imaging member. Accordingly, the optical imaging system may need fewer number of wave sources and detectors by arranging the actuator member to generate more movements ofthe scanning unit or by arranging the imaging member to sample the output signals at a higher rate. It is noted, however, that the fundamental resolution ofthe images obtainable by any optical imaging system is limited by the average "free walk distance" of photons in the physiological medium which is typically about 1 mm. In addition, due to sensitivity limitation and/or electronic and mechanical noise inherent in almost any optical imaging systems, the best-attainable resolution ofthe optical imaging system maybe in the range of a few millimeters or about 1 mm to 5 mm for now. Accordingly, the foregoing voxels which have the dimension less than 1 mm to 5 mm or, more particularly, about 1 mm may not necessarily enhance the resolution ofthe final images. The foregoing optical imaging systems, optical probes, and methods ofthe present invention can be used in both non-invasive and invasive procedures. For example, such optical probes may be non-invasively disposed on the target area on an external surface ofthe test subject, h the alternative, a miniaturized optical probe may be implemented onto a tip of a catheter and invasively disposed on an internal target area ofthe subject. The optical imaging systems may be used to determine intensive properties ofthe chromophores such as concentrations, sums thereof, and ratios thereof, and extensive values thereof such as volume, mass, weight, volumetric flow rate, and mass flow rate thereof. Exemplary Source Detector Arrangement FIGs. 42 A through 42D are exemplary arrangements of wave sources and wave detectors of an optical imaging system according to the present invention. The exemplary optical imaging system typically includes an optical probe having a scanning surface 120a-120d on which multiple wave sources 122 and detectors 124 (both collectively referred to as "sensors" hereinafter) are disposed.

In general, each pair of wave source 122 and detector 124 forms a scanning element representing a functional unit from which wave source 122 emits electromagnetic waves into a target area of a medium and wave detector 124 detects electromagnetic waves interacted with and emanating from the target area ofthe medium. Wave detector 124 generates a conesponding output value signal or data point signal representing an amount of the electromagnetic waves detected thereby across the scanning element. A group of wave sources 122 and detectors 124 or a group of scanning elements also defines a scanning unit 125 which generally forms an effective scanning area ofthe optical probe ofthe invention. As a result, the group of sensors 122, 124 generates an output signal corresponding to a collection of multiple output value signals or data point signals each of which is generated in its corresponding scanning element. Configuration of scanning unit 125 and its scanning area is predominantly determined by geometric arrangements of a sensor assembly and/or source-detector arrangement such as, e.g., the number of wave sources 122 and detectors 124, geometric arrangement therebetween, grouping of wave sources 122 and detectors 124 for the scanning elements and for the scanning units, irradiation capacity or emission power of wave source 122, detection sensitivity of wave detector 124, and the like. For example, in the embodiment of FIG. 42 A, two wave detectors 124 are interposed between two wave

5 sources 122, preferably at equal distances. Therefore, sensors 122, 124 define, on scanning area 120a, a "linear" scanning unit 125a that is substantially elongated along a longitudinal axis 127 thereof. In the embodiment of FIG. 42B, a row of wave sources 122 is disposed directly above a second row of wave detectors 124 in a substantially parallel fashion, and defines a substantially rectangular or square "areal" scanning unit 125b on scanning area

10 120b. The embodiment of FIG. 42C includes four parallel rows of sensors in each of which two wave detectors 124 (or sources 122) are interposed between two wave sources 122 (or detectors 124). Sensors 122, 124 form a scanning unit 125c substantially rectangular or square but substantially wider than one 125a of FIG. 42A and larger than one 125b of FIG. 42B. It is noted that, depending on the grouping ofthe sensors 122, 124, scanning unit 125c

15 of optical probe 120c can define multiple scanning units 125a, 125b which have different configurations. To the contrary, the embodiment in FIG. 42D includes wave detectors 124 disposed around wave sources 122 to define a substantially circular scanning unit 125d on its circular scanning area 120d. It is also appreciated that wave sources 122 and detectors 124 of circular scanning unit 125d maybe grouped to define foregoing "linear" scanning

20 units 125a as well as "aerial" scanning units 125b.

The wave sources ofthe present invention are generally arranged to form optical coupling with the medium and to irradiate electromagnetic waves thereinto. Any wave sources maybe employed in the optical imaging systems or optical probes thereof to irradiate electromagnetic waves having pre-selected wavelengths, e.g., in the ranges from 100 nm to 5,000 nm, from 300 nm to 3,000 nm or, in particular, in the "near-infrared" range from 500 nm to 2,500 nm. As will be described below, however, typical wave sources are arranged to irradiate near-infrared elecfromagnetic waves having wavelengths of about 690 nm or about 830 nm. The wave sources may also irradiate electromagnetic waves having different wave characteristics such as different wavelengths, phase angles, frequencies, 0 amplitudes, harmonics, etc. Alternatively, the wave sources may irradiate electromagnetic waves in which identical, similar or different signal waves are superposed on carrier waves with similar or mutually distinguishable wavelengths, frequencies, phase angles, amplitudes or harmonics, hi the embodiments of FIGs. 42 A to 42D, each wave source 122 is arranged to irradiate electromagnetic waves having two different wave lengths, e.g., about 660 nm to

35 720 nm, e.g., 690 nm, and about 810 nm to 850 nm, e.g., 830 nm. Similarly, the foregoing wave detector is preferably arranged to detect the aforementioned electromagnetic waves and to generate the output signal in response thereto. Any wave detectors may be used in the optical imaging systems or optical probes thereof as long as they have appropriate detection sensitivity to the elecfromagnetic waves having wavelengths in the foregoing ranges. The wave detector may also be constructed to detect electromagnetic waves which may have any ofthe foregoing wave characteristics. The wave detector may also detect multiple sets of elecfromagnetic waves irradiated by multiple wave sources and generate multiple output signals accordingly. Exemplary Output Signals FIGs. 43 A and 43B are exemplary output signals generated by the foregoing wave detector(s) according to the present invention. In the figures, the abscissa is an axial distance along an optical probe ofthe optical imaging system or that along the physiological medium, while the ordinate represents the amplitude ofthe output signal measured by the wave detector in the target areas ofthe medium. Each output signal is generally comprised of multiple output value signals or data point signals each corresponding to elecfromagnetic waves detected by the wave detector of each scanning element of each scanning unit. For illustrative purposes, the target area located at the far-left end ofthe medium (i.e., adjacent the origin ofthe figures) is designated as the "first" target area, while the target area at the far right end ofthe medium as the "last" target area. As illustrated in FIG. 43 A, exemplary output signal 150 exhibits relatively flat profile in the first portion or region 152a (i.e., from the first to the i-th target area) and in the second portion or region 152b (i.e., from the j-th to the M-th, last target area). In between flat regions 152a, 152b lies an upright bell-shaped portion 154a (i.e., from the (i+l)-th to the (j-l)-th target area) where the amplitudes of output signal 150 vary with respect to the axial position. Output signal 150 of FIG. 43B has a contour similar to that of FIG. 43A, except that an inverted bell-shaped portion 154b (i.e., from the (i+l)-th to the (j-l)-th target area) is interposed between two flat portions 152a, 152b.

In a medium composed of a majority of normal tissues, flat portions 152a, 152b of output signal 150 generally correspond to normal cells or tissues and, therefore, constitute a background output signal level for the medium (referred to as a "baseline" ofthe output signal hereinafter). To the contrary, upright and inverted bell-shaped portions 154a, 154b generally represent abnormal tissues or cells (e.g., tumor tissues, malignant or benign carcinoma such as fiber carcinoma, fluid sacks, and the like) at various development stages. Curved portions 154a, 154b may also represent normal anatomic tissues or cells (e.g., blood vessels, connective tissues, etc.) which have optical properties different from those ofthe background tissues or cells. In estimating concenfrations of oxygenated and deoxygenated hemoglobins, oxygen saturation, blood volume, and other chromophore properties, there exist needs for calibrating the output signals generated by the wave detectors for initializing the sensors and/or for accounting for the idiosyncratic differences in various scanning elements ofthe target areas ofthe medium. Furthermore, signal processing algorithms used in the optical imaging system generally require not the output signals themselves but ratios ofthe output signals (e.g., optical density) where the output signals are normalized or calibrated by a reference output signal. Accordingly, one aspect ofthe present invention is to provide an optical imaging system capable of performing self-calibration ofthe output signals based on the properties ofthe output signals themselves.

Exemplary Self-Calibrating OIS

FIG. 44 shows a schematic diagram of an exemplary self-calibrating optical imaging system according to the present invention for generating images of distribution of chromophores or their properties in the target area of a physiological medium. An optical imaging system 100 typically includes at least one wave source 122, at least one wave detector 124, and power source 102. Optical imaging system 100 further includes hardware (circuitry, processors or integrated circuits) or software such as a signal analyzer 160, signal processor 170, and image processor 180, each of which may be operationally coupled to the others and each of which may include one or more functional units. The Signal Analyzer

Signal analyzer 160 operationally couples with one or more sensors 122, 124 so that the signal analyzer can monitor various input and output signals which are required for generating the images ofthe distribution ofthe chromophore (or its properties) in the target area ofthe medium. For example, signal analyzer 160 includes one or more receiving units which operationally couple with wave source 122 and monitor the characteristics of electromagnetic waves irradiated thereby. Each ofthe receiving units also communicates with wave detector 124 and receives therefrom a first output signal which represents the distribution ofthe chromophore (or its properties) in a first target area ofthe medium. The receiving unit may also be arranged to receive external data, operational parameters, and/or other command or control signals supplied by an operator or encoded therein.

Signal analyzer 160 may include other functional units such as a sampling unit, threshold unit, comparison unit, selection unit, etc. The sampling unit receives the foregoing input or output signals or data from the receiving unit and samples the signals at a pre-selected frequency in an analog and/or digital mode. The threshold unit operationally couples with the sampling unit and determines a threshold or cut-off amplitude (or range) which is to be used by the subsequent functional units such as the comparison and selection units. The threshold amplitude or range may be pre-selected and encoded in the threshold unit. The threshold amplitude (or its range) may be manually supplied to the threshold unit by the operator. In the alternative, the threshold amplitude (or its range) may be calculated from the first output signal itself. For example, the threshold unit may identify one or more local maximum or minimum amplitudes ofthe first output signal measured in the first target area, to calculate an average amplitude of at least one or entire portion of such first output signal, to locate a global maximum or minimum amplitude from multiple output signals to be measured in multiple target areas over the medium. After designating such amplitude as a reference amplitude, the threshold unit may calculate the threshold amplitude, e.g., by multiplying the reference amplitude with a pre-selected factor which is generally less than 1.0, by adding thereto or subtracting therefrom another pre-selected factor, by employing a function which yields the threshold amplitude by substituting the foregoing maximum or minimum amplitudes into the function, and the like. The threshold unit may alternatively be encoded with or may include a pre-selected threshold range, receive the range from the operator, or calculate the range based on the foregoing maximum or minimum amplitudes. The comparison unit generally communicates with the threshold unit, receives the threshold amplitude or range therefrom, and compares it with the amplitudes ofthe first output signal. The selection unit receives the results from the comparison unit and selects multiple points or portions ofthe first output signal having identical or substantially similar amplitudes. More particularly, when the threshold unit is arranged to provide the threshold amplitude, the selection unit selects the points or portions ofthe first output signal having amplitudes greater (or less) than the threshold amplitude. However, when the threshold unit provides the threshold range, the selection unit selects multiple points or portions ofthe first output signal falling within (or outside) the threshold range. The Signal Processor

Signal processor 170 operationally couples with signal analyzer 160 and is arranged to "self-calibrate" the first output signal by the first baseline which is obtained from the first output signal itself. Similar to signal analyzer 160, signal processor 170 also includes functional units such as an averaging unit and calibration unit. The averaging unit averages the similar amplitudes ofthe points or portions ofthe first output signal selected by the selection unit and designates such average as the baseline ofthe first output signal. For example, the averaging unit may arithmetically, geometrically, weight- or ensemble- average the similar amplitudes ofthe foregoing points or portions. Once the first baseline is obtained from the first output signal, the calibration unit normalizes or non-dimensionalizes the first output signal by the first baseline, and provides a self-calibrated first output signal which maybe, e.g., a ratio of their amplitudes (i.e., the ratio ofthe first output signal to its first baseline to yield the optical density signals) or a ratio of their amplitude differences to the first baseline.

Image Processor Image processor 180 operationally couples with signal processor 170 and is arranged to construct the images ofthe chromophore (or its properties) based on the self- calibrated first output signal. Typical image processor 180 includes an algorithm unit and an imaging construction unit. The algorithm unit is encoded with or includes at least one solution scheme for solving a set of wave equations applied to wave source(s) 122 and detector(s) 124 arranged according to a pre-selected geometric arrangement. By supplying the algorithm unit with the self-calibrated first output signal along with other requisite initial and/or boundary conditions, the algorithm unit solves the set ofthe wave equations and provides a set of solutions representing at least one of concentrations of oxygenated or deoxygenated hemoglobins, oxygen saturation, blood volume, other intensive or extensive properties ofthe chromophores, and the like . The image construction unit then receives the set of solution signals and constructs the images ofthe spatial distribution ofthe foregoing properties ofthe chromophores. If preferred, the image construction unit may be arranged to construct the images regarding the distribution pattern ofthe first output signal, those ofthe self-calibrated first output signal itself, and the like. Benefits of Self-Calibrating Systems The foregoing optical imaging systems and methods ofthe present invention offer several benefits over the prior art optical imaging devices. One ofthe most serious problems ofthe prior art devices lies in the fact that their optical probes or sensors require a priori estimation ofthe baseline of their output signals. For example, the probes or sensors are positioned in a reference medium (e.g., a phantom) or in a reference area ofthe subject, output signals are generated by the wave detectors, and baselines are estimated based on the optical property of the reference medium or area. The probes or sensors are then moved and placed on the target area ofthe subject to be scanned thereby. It is well known in the field that such calibration method constitutes a major source of error in the resulting signals due to possible inherent differences in optical properties between the target area and reference medium or area, hi addition, repositioning the probes or sensors from the reference area to the target area frequently results in inconsistent optical coupling between the sensors and target area and between the sensors and reference medium (or area), thereby introducing additional noises thereto. The optical imaging system ofthe present invention, however, allows the operator to obtain the first output signal and first baseline thereof from the same target area without moving and or repositioning the optical probes or sensors from the first target area. Because the foregoing optical imaging system obtains the baseline from the same target area ofthe same medium under the identical optical coupling (therefore referred to as "self-calibration"), the optical imaging system ofthe present invention obviates the need for such reference measurement and, thus, eliminates the error associated with the inconsistent optical coupling, h addition, because the foregoing optical imaging systems can estimate the first output signal and its baseline from the same target area, such optical imaging system provides more accurate and reliable results. Furthermore, due to the simple data processing algorithms for estimating such baseline, the foregoing optical imaging system allows constraction ofthe images ofthe chromophore properties on a substantially real-time basis. Variations of Exemplary Embodiments

The foregoing optical imaging systems and methods thereof may be modified in various aspects without departing from the scope ofthe present invention.

First of all, it is appreciated that the exact number ofthe wave sources and detectors and geometric arrangements therebetween are not critical in realizing the present invention described herein. Accordingly, virtually any number of wave sources and wave detectors may be implemented into the optical probe or movable member ofthe optical imaging system in any geometric arrangements. For example, the movable member may include only a single wave source capable of irradiating multiple sets of elecfromagnetic waves. The self-calibrating feature ofthe present invention then applies to each scanning element formed by each pair ofthe wave source and detector which may irradiate multiple sets of electromagnetic waves having, e.g., different wave characteristics, identical or different signal waves superposed on different or identical carrier waves, and the like. The wave sources may also be arranged to irradiate such elecfromagnetic waves continuously, periodically or intermittently. As discussed in the co-pending '972 application, it is generally preferred, however, that the wave sources and detectors be arranged according to a few semi-empirical design rules which are expected to enhance accuracy, reliability, and/or reproducibility of the signal baselines as well as the estimated absolute values ofthe chromophore properties. Such exemplary design rules are: (1) the scanning unit preferably includes at least two wave sources and at least two wave detectors; and (2) the distances between any wave source and wave detector within a scanning unit do not exceed a threshold sensitivity range ofthe wave detector which may range from, e.g., several to 10 cm or, in particular, about 5 cm for most human and or animal tissues. Furthermore, the wave sources and detectors are preferably arranged to define the scanning units having continuous scanning area throughout the entire region thereof so that a single measurement by the scanning unit can generate the output signal covering the entire scanning area. For this purpose, the wave sources and detectors may be spaced at distances no greater than a threshold distance thereof. Selection ofthe optimal spacing between the wave sources and detectors is generally a matter of choice of one of ordinary skill in the art and such spacing is determined by many factors including, e.g., optical properties ofthe medium (e.g., absorption coefficient, scattering coefficient, and the like), irradiation or emission capacity ofthe wave sources, detection sensitivity ofthe wave detectors, configuration ofthe scanning elements and units, number ofthe wave sources and/or detectors in the optical probe, geometric arrangement between the wave sources and detectors, grouping ofthe wave sources and detectors in each ofthe scanning elements and each ofthe scanning units, and so on. Use of a Filter

The optical imaging system may include a filter unit to improve a signal-to- noise ratio ofthe output signals as well as that of subsequent signals including the baselines and self-calibrated output signals. Accordingly, the filter unit is preferably arranged to treat the output signals before they are processed by the signal analyzer and processor. When a single output signal is obtained for each target area (or medium), the filter unit preferably includes a low pass filter which may remove high-frequency noises from the output signals. When the optical probe is arranged to generate multiple output signals from a single target area, however, their signal-to-noise ratios may also be improved through various averaging methods, e.g., by arithmetically or geometrically averaging such multiple output signals, hi addition, the filter unit may also weight-average or ensemble-average the foregoing output signals. Such filtering operation can be performed in an analog and/or digital mode. Use of a Spline Unit The optical imaging system may also include a spline unit for smoothing out abrupt changes or jumps in the amplitudes of adjacent portions or data points ofthe output signal(s). Accordingly, the spline unit may include an interpolation algorithm or equivalent circuitry or software.

Signal Analyzer/Processor Arrangement The foregoing signal analyzer and signal processor ofthe present invention are preferably arranged to operate on a substantially real-time basis. For example, once the optical probe is positioned in the first target area and the wave detector generates the first output signal, the signal analyzer identifies the portions ofthe first output signal having similar amplitudes and the signal processor provides the self-calibrated first output signal before the optical probe is moved to or repositioned in the adjacent target area. The image processor may also be arranged to provide requisite images before moving the optical probe to other target areas as well. Therefore, the optical imaging system ofthe present invention can generate the images of two- and/or three-dimensional distribution ofthe chromophores or their properties on a substantially real time basis.

The signal analyzer ofthe present invention may also be arranged to identify different points or portions ofthe output signals using various algorithms different from the one disclosed hereinabove. For example, instead of focusing only on amplitudes of output signals, the signal analyzer may calculate and assess other features ofthe output signals, e.g., curvature ofthe output signals which may be signified by their first derivative values (or slopes), concaveness or convexity ofthe output signals assessed by the values of their second derivatives, number and locations of local maximums or minimums, and the like. For example, when the output signal shows a slight increase or decrease, identification of such point of deflection may be facilitated by analyzing the first and/or second derivative values ofthe output signal. In addition, by considering these secondary parameters along with the amplitudes ofthe output signals, different portions or segments may be identified along the output signal where each portion or segment exhibits different profiles (e.g., flat, sloped, convex or concave). In general, portions ofthe output signal with a substantially flat profile and similar amplitudes indicate that the region ofthe target area representing such portions of the output signal is predominantly composed of a homogeneous material such as normal tissues and cells. To the contrary, portions ofthe output signal having curved profile and varying amplitudes generally imply that the regions ofthe target area conesponding to such portions have optical properties different from those ofthe background ofthe medium such as the normal tissues or cells. Accordingly, such regions are more likely than not to include abnormal cells, although it may also be possible that they merely reflect normal connective structure or neurovascular tissues. Identification of a demarcation between such normal and abnormal regions may be facilitated by analyzing the first and/or second derivatives ofthe output signal as well.

The signal analyzer ofthe optical imaging system ofthe present invention is ananged to identify flat (or linear) portions ofthe output signal or, conversely, the rest ofthe output signal, i.e., non-flat or curved portions. As discussed above, the signal analyzer may compare amplitudes of each point ofthe output signal with the threshold amplitude or range. Alternatively, the signal analyzer may divide the output signal into multiple shorter segments, obtain average amplitudes for individual segments, and compare such averages with the threshold amplitude or range which in turn may be a local or global maximum or minimum amplitude thereof. Regardless ofthe nature ofthe threshold value, however, the output signal may vary in its amplitudes in the flat as well as non-flat portions. Thus, the signal analyzer may be provided with a secondary cut-off amplitude or a cut-off range of deviation so that any points ofthe output signal not satisfying the cut-off threshold values may not be included in the flat or non-flat portions. Baseline Analysis hi order to ensure accuracy of a baseline ofthe output signal obtained from a specific target area ofthe medium, other baselines maybe obtained from neighboring target areas and compared with the baseline from the specific target area. The self-calibrating optical imaging system ofthe present invention accomplishes this objective by providing algorithms and methods for determining a composite baseline when the baselines obtained from different target areas are not substantially identical throughout the medium.

FIGs. 45A to 45C are further exemplary output signals generated by wave detectors according to the present invention, where each figure represents the output signal obtained from the first, second, and third target area, respectively, and where each target area is covered by multiple scanning elements and scanning units. As shown in the figures, the output signals of FIG. 45 A and 45 C have different amplitudes but flat profiles in the first and third target areas, respectively, whereas the output signal of FIG. 45B decreases along the axial direction in the second target area. When the amplitudes ofthe output signal of FIG. 45A are not substantially different from those of FIG. 45C or the differences therebetween are within a pre-selected tolerance range, the data points ofthe output signals in FIGs. 45 A to 45C may be averaged to yield the baseline ofthe medium. However, when such differences are not negligible, FIGs. 45 A and 4C manifest that one ofthe first and third target areas maybe mainly comprised ofthe normal tissues or cells and the output signal therefrom represents a background output signal ofthe medium, whereas the other ofthe two target areas maybe composed ofthe abnormal tissues or cells and, thus, its output signal is skewed or biased upward or downward due to the presence of abnormal cells, tissues or lumps having a size enough to cover the entire first or third target area. In case the signal analyzer should be provided with a threshold amplitude or range supplied by the operator, the signal analyzer compares the data points ofthe target areas and locates the selected portion(s) ofthe output signal to be used for estimating the baseline. However, when the signal analyzer identifies the selected portions adaptively from the output signals themselves (e.g., by identifying the local or global maximum or minimums and calculating the threshold amplitudes or ranges accordingly), the signal analyzer may have to discern which data points should be used for calculating the baseline ofthe medium. In one embodiment, the baselines maybe obtained from the adjacent target areas and compared with the baseline obtained from FIGs. 45A and 45C. When the region of higher (or lower) amplitudes is constrained to one area while the region of lower (or higher) amplitudes tends to sunound the consfrained area, the region with the lower (or higher) amplitudes is more likely to be the background normal tissues or cells, whereas the region having higher (or lower) amplitudes is more likely to include the abnormal tissues, cells or lumps. Alternatively, the signal analyzer may supply the operator with different amplitude values and allow the operator to manually select the normal and/or abnormal region.

In some cases, output signals obtained from multiple different target areas may yield similar but not identical baselines. The signal analyzer may then be ananged to obtain a composite or average baseline from multiple baselines and utilize that composite baseline to normalize the output signals obtained from all target areas ofthe medium. As discussed above, such multiple baselines may be arithmetically, geometrically, weight- or ensemble-averaged. Alternatively, the signal analyzer may allow the operator to select a single baseline and to designate it as the composite baseline. Alternatively, each output signal (or a group thereof) may be normalized by the baseline calculated therefrom. When the signal processor generates the self-calibrated signals and the image processor constructs multiple local images (e.g., one per each scanning area or target area), a composite image may be made from multiple local images based on the individual baselines used in each target area (or a group thereof). This embodiment proves to be advantageous particularly when the physiological medium includes various anatomical structures having different optical properties. For example, the self-calibrating optical imaging system may scan the brain to detect potential or actual stroke conditions. Brain tissues and sunounding skull normally exhibit at least minimally different optical characteristics, and the thickness ofthe skull may vary in different parts ofthe brain. When the composite baseline is calculated from multiple baselines and used to normalize the output signals measured from different parts ofthe brain, all image pixels will have the same extent of normalization, i.e., identical brightness-scale or color-scale across the entire medium. Although such images with the uniform background level may assist a physician in making a comparative diagnosis, he or she may not be able to locate a mild stroke condition when it is overshadowed in a target area that is normalized by a baseline having a higher amplitude. To the contrary, when the images are constructed from the self-calibrated output signals based on individual baselines, each target area may have its own brightness-scale or color-scale. Thus, the mild stroke condition may not necessarily be compromised in the image but the physician may have to analyze each image separately. One way of obviating such inconvenience is to artificially enhance the contrast between the background anatomical stracture and abnormal tissues included in each target area. For example, upon identifying any possible abnormalities, the imaging member may identify the demarcation line and augment the signals conesponding to the demarcation line and/or the abnormalities such that the amplified signals will not be overshadowed by the color-scale or brightness-scale ofthe images based on the composite baseline. A special marker or color may also be added to such enhanced signal to alarm the physician as well.

It is appreciated that the foregoing anangement ofthe optical imaging system ofthe present invention maybe modified without departing from the scope ofthe invention. For example, the foregoing functional units ofthe signal analyzer, the signal processor, and the image processor may be further differentiated or combined or may be implemented into another portion ofthe optical imaging system. Such functional units may also be ananged to form different operational connection therebetween. For example, the receiving unit and sampling unit ofthe signal analyzer may be combined. Similarly, the comparison unit and selection unit ofthe signal analyzer may also be combined. The image processor may be ananged to operationally communicate with such units ofthe signal analyzer as well. Applications for Self-Calibrating Systems

The foregoing self-calibrating optical imaging systems and methods ofthe present invention may also be used to provide temporal changes in blood or fluid volume in the target area ofthe medium. As discussed in the co-pending application entitled "Optical Imaging System with Movable Scanning Unit," the concentrations ofthe oxygenated and deoxygenated hemoglobins are calculated according to one ofthe algorithms disclosed in the co-pending '972 application. Once such concentrations are obtained, their sum (i.e., total hemoglobin concentration) is also obtained. By sampling the output signals from the wave detectors positioned in the target area over time, changes in the total hemoglobin concentration is obtained. By assuming that blood hematocrit (i.e., the volume percentage ofthe red blood cells in blood) is maintained constant over time for blood flowing through the target area, temporal changes in the blood volume in such target area may be directly calculated in terms of temporal changes of hematocrit ofthe target area. In such cases, the optical imaging system may calculate the baseline ofthe output signal and provide the self- calibrated output signal as discussed above. Alternatively, the optical imaging system may also calculate multiple baselines from the same target area over time, obtain a temporally- averaged composite baseline, and provide a temporally-compensated self-calibrated output signal.

Although the foregoing disclosure ofthe present invention is mainly directed to self-calibration of optical imaging systems for providing images ofthe spatial distribution ofthe chromophore property, the present invention may also be applied to optical imaging systems for generating the images of temporal distribution thereof. For example, the optical probe may be ananged to scan a specific target area over time. From the variations in the output signals detected over different intervals in the target area, the signal analyzer and processor can establish the baseline and provide the self-calibrated first output signals over time. The image processor then constructs frames of images representing temporal changes in the chromophore property ofthe target area. Alternatively, the optical imaging system can also provide temporally-averaged baseline and temporally-compensated self-calibrated output signal as described in the foregoing paragraph. It is noted that the temporal changes ofthe chromophore properties usually relate to the relative values and, thus, do not directly provide any absolute values thereof. However, once an absolute value of such property is determined at any reference time frame, preceding or subsequent changes of such property may readily be converted to the absolute values by successively calculating the absolute values forwardly or backwardly.

The self-calibrating anangements and methods ofthe present invention may be used in optical imaging systems for obtaining images of three-dimensional distribution of the chromophore in the physiological medium. As discussed above, elecfromagnetic waves inadiated by the wave source are traveling through a target volume defined by a target area and by a pre-selected depth or thickness ofthe medium. Therefore, the wave detectors can generate multiple output signals each carrying optical information of a specific target layer ofthe medium. Once such output signals are obtained, a baseline can be estimated by the foregoing algorithms described herein. For example, a single baseline can be designated to the entire target volume. In the alternative, multiple baselines may be preferably defined at each depths or layers ofthe target volume. In case multiple baselines should be used, these baselines may be averaged or normalized with respect to each other so that resulting three- dimensional images may be constructed under a uniform gray-scale or color-grade.

Though any analytical or numerical schemes may be used to obtain solutions ofthe wave equations, an exemplary algorithm unit ofthe invention preferably incorporates solution schemes disclosed in the co-pending '972 application. For example, the absolute values of concentration of deoxygenated hemoglobin, [Hb], concentration of oxygenated hemoglobin, [HbO], and oxygen saturation, SO2, are obtained by equations (8a) to (8d) and (9b) ofthe co-pending '972 application, respectively. In the alternative, the algorithm unit may also employ the over-determined iterative method as disclosed in the foregoing '972 application, where the absolute values of [Hb], [HbO], and SO2 are determined by equations (17a) to (17c) ofthe co-pending '972 application, respectively, hi yet another alternative, changes in the chromophore properties are determined by estimating changes in optical characteristics ofthe target area ofthe medium. For example, changes in concentrations of oxygenated and deoxygenated hemoglobins may be calculated from the differences in their extinction coefficients which are in turn measured by electromagnetic waves having two different wavelengths. In an exemplary numerical scheme, the photon diffusion equations are modified based on the diffusion approximation described in, e.g., Keijer et al., "Optical Diffusion in Layered Media," Applied Optics, 2 , p.1820-1824 (1988), and Haskell et al, 'Boundary Conditions for Diffusion Equation in Radiative Transfer," Journal of Optical Society of America, A, 11, p.2727-2741, 1994. Details ofthe foregoing scheme is also provided in the co-pending '972 application, h each of these schemes, the output signals are calibrated by their baselines obtained by one ofthe foregoing methods. The wave sources and detectors ofthe optical probe ofthe optical imaging system ofthe present invention may be ananged to satisfy an embodiment disclosed in the co-pending '972 application, i.e., the wave sources and detectors are ananged to have substantially identical near- and far-distances therebetween. For example, in scanning units 125a, 125b of FIGs. 42A and 42B, a first near-distance between a first wave source and a first wave detector is substantially identical to a second near-distance between a second wave source and a second wave detector, hi addition, a first far-distance between the first wave source and the second wave detector is substantially identical to a second far-distance between the second wave source and a first wave detector. A major advantage of such symmetric anangement is that electromagnetic waves inadiated by the wave sources are substantially uniformly transmitted, absorbed, and/or scattered throughout the entire area or volume ofthe medium scanned by the scanning unit. Accordingly, such scanning unit can provide uniform coverage ofthe target area ofthe medium and, therefore, enhance accuracy and reliability ofthe output signal (e.g., an improved signal-to-noise ratio) generated by the wave detector. The foregoing self-calibrating optical imaging systems, optical probes, and methods ofthe present invention can be used in both non-invasive and invasive procedures. For example, the foregoing self-calibrating optical probes may be non-invasively disposed on the target area on an external surface ofthe test subject. Alternatively, a miniaturized self-calibrating optical probe maybe implemented in a tip of a catheter which is invasively disposed on an internal target area ofthe subject. The foregoing optical imaging systems and optical probes may also be used to determine intensive properties ofthe chromophores such as concentrations, sums of or differences in concentrations, and/or ratios thereof. The foregoing optical imaging systems and probes may further be utilized to calculate extensive chromophore properties such as volume, mass, volume, volumetric flow rate or mass flow rate. As discussed above, such chromophores may include, e.g., solvents ofthe medium, solutes dissolved in the medium, and/or other substances included in the medium, each of which interacts with electromagnetic waves transmitted through the medium. Examples of the chromophores may include, but not limited to, cytochromes, hormones, enzymes, both neuro- and chemo-fransmitters, proteins, cholesterols, apoproteins, lipids, carbohydrates, cytosomes, blood cells, cytosols, oxygenated hemoglobin, deoxygenated hemoglobin, and water. Specific examples ofthe chromophore properties may include, but not limited to, concentrations of oxygenated and deoxygenated hemoglobins, oxygen saturation, and blood volume.

E. Example

It is appreciated that the foregoing optical imaging systems, optical probes thereof, and methods therefor may be readily adjusted to provide images of distribution of different chromophores or properties thereof. Because different chromophores generally respond to electromagnetic waves having different wavelengths, the wave sources of such optical imaging systems and probes may be manipulated to inadiate elecfromagnetic waves interacting with pre-selected chromophores. For example, the near-infrared waves having wavelengths between 600 nm and 1,000 nm, e.g., about 690 nm and 830 nm are suitable to measure the distribution pattern ofthe hemoglobins and their property. However, the near- infrared waves having wavelengths between 800 nm and 1,000 nm, e.g., about 900 nm, can also be used to measure the distribution pattern of water in the medium. Selection of an optimal wavelength for detecting a particular chromophore generally depends on optical absorption and/or scattering properties ofthe chromophore, operational characteristics ofthe wave sources and/or detectors, and the like.

The foregoing optical imaging systems, optical probes, and methods ofthe present invention may be clinically applied to detect tumors or stroke conditions in human breasts, brains, and any other areas ofthe human body where the foregoing optical imaging methods such as diffuse optical tomography is applicable. The foregoing optical imaging systems and methods may also be applied to assess blood flow into and out of transplanted organs or extremities and/or autografted or allografted body parts or tissues. The foregoing optical imaging systems and methods maybe ananged to substitute, e.g., ultrasonogram, X- rays, EEG, and laser-acoustic diagnostic. Furthermore, such optical imaging systems and methods may be modified to be applicable to various physiological media with complicated photon diffusion and/or with non-flat external surface. It is further noted that the foregoing optical imaging systems, probes thereof, and methods can be applied to conventional optical imaging equipment in which the wave sources and detectors are rather stationarily disposed in their probes. It is appreciated that the optical imaging systems, optical probes thereof, and methods therefor ofthe present invention may incorporate or may be applied to other related inventions and embodiments thereof which have been disclosed in the commonly assigned co-pending U.S. application bearing Serial No. (n/a), entitled "Optical Imaging System with Movable Scanning Unit," another commonly assigned co-pending U.S. application bearing Serial No. (n/a), entitled "Self-Calibrating Optical Imaging System," another commonly assigned co-pending U.S. application bearing Serial No. (n/a), entitled "Optical Image System for Direct Image Construction," and yet another commonly assigned co-pending U.S. application bearing Serial No. (n/a), entitled "Optical Imaging System with Symmetric Optical Probe," all of which have been filed on February 6, 2001 and all of which are incorporated herein in their entirety by reference. 5 Following example describes an exemplary optical imaging system, optical probe, and methods thereof according to the present invention. The results indicated that the following exemplary optical imaging system provided reliable and accurate images of two- dimensional distribution of blood volume and oxygen saturation in the target areas ofthe human breast tissue.

10

EXAMPLE

An exemplary optical imaging system 500 was constructed to obtain images of two-dimensional distribution of blood volume and oxygen saturation in target areas of female human breasts. FIG. 61 is a schematic diagram of a prototype optical imaging 5 system according to the present invention.

Prototype optical imaging system 500 typically included a handle 501 and a main housing 505. Handle 501 was made of poly-vinylchloride (PVC) and acrylic stock, and provided with two control switches 503a, 503b for controlling operations of various components of system 500. Main housing 505 included a body 510, a movable member

20 520, an actuator member 530, an imaging member (not shown), and a pair of guiding tracks 560.

Body 510 was shaped as a substantially square block (3.075"x2.8"x2.63") and provided with barriers along its sides. Body 510 was ananged to movably couple with rectangular movable member 520 (1.5"x2.8"xl.05") designed to linearly translate along a

25 path defined by guiding tracks 560 and substantially parallel with one side of body 510.

Movable member 120 was ananged to have the source-detector anangement which was similar to that of Fig. 3(c). For example, movable member 520 included two wave sources 522, Sj and S2, each of which was capable of inadiating electromagnetic waves having different wavelengths. In particular, each wave source 522 included two laser

30 diodes, HL8325G and HL6738MG (ThorLabs, Inc., Newton, NJ), where each laser diode inadiated the electromagnetic waves with wavelengths of 690 nm and 830 nm, respectively. Movable member 520 also included four identical wave detectors 524 such as photo-diodes D1; D2, D3, and D4, (OPT202, Bun-Brown, Tucson, AZ) which were interposed substantially linearly between wave sources 522. Wave sources 522 and detectors 524 were spaced

35 substantially linearly at identical distances so that the scanning units defined by wave sources 522 and detectors 524 (e.g., a first scanning unit of S,, D,, D4, and S2 and a second scanning unit of Sl5 D2, D3, and S2) satisfied the foregoing near-end far-distance requirements or symmetry requirements ofthe co-pending '972 application.

Actuator member 530 included a high-resolution linear-actuating-type

5 stepper motor (Model 26000, Haydon Switch and Instrument, Inc., Waterbury, CT) and a motor controller (Spectrum PN 42103, Haydon Switch and Instrument, Inc.). Actuator member 530 was mounted on body 510 and movably engaged with movable member 520 so as to linearly translate movable member 520 along guiding tracks 560 fixedly positioned along the linear path and fixedly attached to main housing 505.. A pair of precision guides

10 (Model 6725K11, McMaster-Can Supply, Santa Fe Springs, CA) was used as guiding tracks 560.

The imaging member was provided inside handle 501 and included a data acquisition card (DAQCARD 1200, National Instruments, Austin, TX). Main housing 505 was made of acrylic stocks and constructed to open at its front face. Perspex Non-Glare

15 Acrylic Sheet (Liard Plastics, Santa Clara, CA) was installed on a front face 506 of housing 505 and used as a protective screen to protect wave sources 522 and detectors 524 from mechanical damages.

In operation, movable member 520 was positioned in its starting position, i.e., the far-left side of body 510. An operator turned on the main power of system 500 and

20 tuned wave sources 522 and detectors 524 by running scanning system software. A breast of a human subject was prepped and body 510 of optical imaging system 500 was positioned on the breast so that sensors 522, 524 of movable member 520 were placed in a first target area ofthe breast and formed appropriate optical coupling therewith. The first target area was scanned by clicking one control switch 503a on handle 501. Wave sources 522

25 inadiated electromagnetic waves having pre-selected wavelengths into the first target area, wave detectors 524 detected such electromagnetic waves from the first target area, and scanning had commenced. Actuator member 530 gradually translated movable member 520 linearly along one side of body 510 along guide tracks 560.

Wave sources 522 were synchronized to ignite their laser diodes in a pre- selected sequence. For example, a first laser diode ofthe wave source, Sl5 was ananged to inadiate electromagnetic waves of wavelength 690 nm and wave detectors 524 detected the waves and generated a first set of output signals in response thereto. During this first inadiation and detection period which generally lasted about 1 msec (with the duty cycle ranging from 1 : 10 to 1:1 ,000), all other laser diodes were turned off to minimize

J interference noises. After completing the inadiation and detection, the first laser diode of the wave source, S was turned off and the first laser diode ofthe wave source, S2, was turned on to inadiate electromagnetic waves ofthe same wavelength, 690 nm. Wave detectors 524 detected the waves and generated a second set of output signals accordingly. Other laser diodes were maintained at off positions during this second period of inadiation and detection as well. Similar procedures were repeated to the second laser diodes ofthe wave sources S,, and then to the second laser diode ofthe wave source S2, where both second laser diodes were ananged to sequentially inadiate electromagnetic waves having wavelengths of 830 nm.

The imaging member was also synchronized with wave sources 522 and detectors 524 and sampled the foregoing sets of output signals in a pre-selected sampling rate. In particular, the imaging member was ananged to process such output signals by defining a first and second scanning units, where the first scanning unit was comprised of the wave sources, S, and S2, and the wave detectors, O1 and D4, and the second scanning unit was made up ofthe wave sources, Sj and S2, and the wave detectors, D2 and D3. Both ofthe first and second scanning units had the source-detector anangement which satisfied the symmetry requirements ofthe co-pending '972 application. Therefore, concentrations ofthe oxygenated and deoxygenated hemoglobins were obtained by the equations (la) to (Id), and the oxygen saturation, SO2, by the equation (le). Furthermore, relative values of blood volume (i.e., temporal changes thereof) were calculated by assessing the changes in hematocrit in the target areas as discussed above.

Actuator member 530 was also synchronized with the foregoing inadiation and detection procedures so that wave sources 522 and detectors 524 scanned the entire target area or entire first region ofthe target area (i.e., inadiating elecfromagnetic waves thereinto, detecting such therefrom, and generating the output signals) before they were moved to the next adjacent region ofthe target area by actuator member 530. While actuator member 530 translated movable member 520 linearly along the pre-selected path, movable member 520 scanned successive regions ofthe target area. When movable member 520 reached the opposing end of body 510, actuator member 530 translated movable member 520 linearly to its starting position. The foregoing inadiation and detection procedures were repeated in the same or different regions ofthe target area during such backward linear movement of movable member 520 as well. After the linear reciprocation of movable member 520 ended and the scanning procedure was complete, the operator pushed the other control switch 503b to send a signal to the imaging member which started image construction process and provided two-dimensional images of spatial distribution of the oxygen saturation in the target area and the temporal changes in the blood volume therein. FIGs. 47A and 47B are two-dimensional images of blood volume in normal and abnormal breast tissues, respectively, both measured by the optical imaging system of FIG. 46. In addition, FIGs. 48A and 48B are two-dimensional images of oxygen saturation in normal and abnormal breast tissues, respectively, both measured by the optical imaging system of FIG. 46 according to the present invention. As shown in the figures, the optical imaging system provided that normal tissues had the higher oxygen saturation (e.g., over 70%) in the area with the maximum blood volume. However, the higher oxygen saturation in the conesponding area ofthe abnormal tissues was as low as 60%.

It is to be understood that, while various embodiments ofthe invention has been described in conjunction with the detailed description thereof, the foregoing is only intended to illustrate and not to limit the scope ofthe invention, which is defined by the scope ofthe appended claims. Other related embodiments, aspects, advantages, and/or modifications are within the scope ofthe following claims.

Claims

What is claimed is:
1. A system for determining concentrations of chromophores in a physiological medium, comprising: a source module for inadiating into said medium at least two sets of electromagnetic radiation having different wave characteristics; a detector module for detecting elecfromagnetic radiation transmitted through said medium; and a processing module for determining an absolute value of at least one of said concentrations of chromophores from electromagnetic radiation inadiated from the source module and detected by the detector module, wherein said determination is based on intensity measurements of continuous wave electromagnetic radiation from the source module.
2. A system according to claim 1, wherein said chromophores are hemoglobins and the processing module determines the concentration of at least one of oxygenated hemoglobin and deoxygenated hemoglobin.
3. A system according to claim 1, wherein the source and detector modules are configured to operate on a physiological medium that comprises cells of at least one of organs, tissues, and body fluids.
4. A system according to claim 3, wherein the processing module is configured to detect abnormal cells.
5. A system according to claim 4, wherein said abnormal cells are tumor cells.
6. A system according to claim 4, wherein said cells are disposed in at least one of epidermis, and corium of an internal organ including at least one of a brain, heart, lung, liver, and kidney.
7. A system according to claim 4, wherein said cells are those of a transplanted organ.
8. A system according to claim 7, wherein said transplanted organ includes at least one of a brain, heart, lung, liver, and kidney.
9. A system according to claim 1, wherein said wave characteristics include at least one of wavelength, phase angle, amplitude, harmonics and combinations thereof.
10. A system according to claim 9, wherein a first set of said electromagnetic radiation has a first wavelength and a second set of said elecfromagnetic radiation has a second wavelength, which is different from said first wavelength.
11. A system according to claim 1 , wherein a first set of said electromagnetic radiation comprises a first carrier wave and a second set of said elecfromagnetic radiation comprises a second carrier wave which has wave characteristics different from those of said first carrier wave.
12. A system according to claim 11, wherein said wave characteristics include at least one of wavelength, phase angle, amplitude, harmonic, and any combination thereof.
13. A system according to claim 1, wherein said processing module determines said absolute value using one or more parameters accounting for optical interaction properties of elecfromagnetic radiation with said medium.
14. A system according to claim 13, wherein said processing module uses a mathematical expression including a parameter dependent on one of: optical properties of said medium and configuration of said source module and detector module.
15. A system according to claim 14, wherein the mathematical expression comprises a polynomial of at least one of said concentrations and said ratios thereof.
16. A system according to claim 13, wherein said mathematical expression includes a term substantially dependent on one or more of: optical properties of said medium and configuration of said source module and detector module, which term is approximated as a constant.
17. A system according to claim 1, wherein said processing module uses the mathematical expression:
I - α β γ I0 exp {-B L δ Σ, (ε; Q) + σ}, wherein I0 is the intensity of electromagnetic waves inadiated by said source module, I is the intensity of electromagnetic waves detected by said detector module, α is a parameter associated with at least one of said source module and medium, β is a parameter associated with at least one of said detector module and medium, γ is one of a proportionality constant and a parameter associated with at least one of said source module, detector module, and medium, B is a parameter accounting for the length of an optical path of electromagnetic waves through said medium and associated with at least one of said source module, detector module, and medium, L is a parameter accounting for a distance between said source module and said detector module, δ is one of a proportionality constant and a parameter associated with at least one of said source module, detector module, and medium, ε; is a parameter accounting for an optical interaction between electromagnetic waves and an i-th chromophore in said medium, is a variable denoting concentration of said i-th chromophore, and σ is one of a proportionality constant and a parameter associated with at least one of said source module, detector module, and medium.
18. A system according to claim 17, wherein said parameter B is a path length factor.
19. A system according to claim 17, wherein said parameter ε; is at least one of a medium extinction coefficient, medium absorption coefficient, and medium scattering coefficient.
20. A system according to claim 1, wherein said source module includes at least one wave source and said detector module includes at least two wave detectors.
21. A system according to claim 1, wherein said source module includes at least two wave sources and said detector module includes at least one wave detector.
22. A system according to claim 1, wherein said source module has a first and second wave sources and said detector module has a first and second detectors.
23. A system according to claim 22, wherein said processing module uses the mathematical expression:
Imn = «m βn Y ϊo.m eXp {"Bmn Lmn δ Σ;; C;) + σ} , wherein Io m is the intensity of elecfromagnetic waves inadiated by an m-th wave source, L^ is the intensity of elecfromagnetic waves inadiated by said m-th wave source and detected by an n-th wave detector, αm is a parameter associated with at least one of said m-th wave source and medium, βn is a parameter associated with at least one of said n-th wave detector and medium, γ is one of a proportionality constant and a parameter associated with at least one of said m-th wave source, n-th wave detector, and medium, Bmn is a parameter accounting for a length of an optical path of electromagnetic waves through said medium and associated with at least one of said m-th wave source, n-th wave detector, and medium, Lmn is a parameter accounting for a distance between said m-th wave source and n-th wave detector, δ is one of a proportionality constant and a parameter associated with at least one of said m-th wave source, n-th wave detector, and medium, ε; is a parameter accounting for an optical interaction between electromagnetic waves and an i-th chromophore included in said medium, C; is a variable denoting concentration of said i-th chromophore, and σ is one of a proportionality constant and a parameter associated with at least one of said m-th wave source, n-th wave detector, and medium, wherein both of said subscripts m and n are nonzero positive integers.
24. A system according to claim 23, wherein said parameter Bmn is a path length factor associated with at least one of said m-th wave source, n-th wave detector, and medium.
25. A system according to claim 23, wherein said parameters γ and δ are approximated as unity so that said expression is simplified to lmn = α m Pno.m exp {-Bmn Lmn Σ; (Sj Q) + σ} .
26. A system according to claim 22, wherein said wave sources and wave detectors are configured so that the distance between said first wave source and said first wave detector is substantially similar to that between said second wave source and said second wave detector, and that the distance between said first wave source and said second wave detector is substantially similar to that between said second wave source and said first wave detector.
27. A system according to claim 1, wherein said source module has at least M wave sources and said detector module has at least N wave detectors, M and N being integers greater than 1, and said wave sources and wave detectors are configured such that the distance between an M,-th wave source and an Nrth detector is substantially similar to that between an M2-th wave source and an N2-th wave detector, and that the distance between said Mrth wave source and said N2-th wave detector is substantially similar to that between said M2-th wave source and said Nrth wave detector, wherein said Mj and M2 are both integers between 1 and M, and wherein said N, and N2 are both integers between 1 and N.
28. A system according to claim 1, wherein the detector module has two or more wave detectors disposed substantially along a line, and the source module has at least two wave sources that are disposed away from the line.
29. A system according to claim 1, wherein the detector module has M ≥2 wave detectors that are disposed substantially along a line.
30. A system according to claim 1, wherein said detector module has at least three wave detectors disposed substantially along a line.
31. A system for determining concenfrations of chromophores in a physiological medium, comprising: one or more sources inadiating into said medium at least two sets of near-infrared elecfromagnetic radiation having different wave characteristics; one or more detectors detecting elecfromagnetic radiation transmitted through said medium; input means for entering input parameter data; and a processing module determining absolute values of at least one of said concentrations, wherein said determination is not based on measuring phase characteristics ofthe elecfromagnetic radiation received from said one or more detectors, or the response ofthe medium to an electromagnetic impulse from said one or more sources.
32. A system for determining concentrations of chromophores in a physiological medium, comprising: at least one source for inadiating into said medium at least two sets of electromagnetic radiation having different wave characteristics; at least one detector for detecting electromagnetic radiation fransmitted through said medium; a processor coupled to the at least one detector computing one of: absolute values of said concenfrations and ratios of said concentrations, wherein said computation is based on intensity measurements of continuous wave elecfromagnetic radiation from the source module.
33. A method for determining concentrations of chromophores in a physiological medium using a measurement system having at least one wave source and at least one wave detector, wherein elecfromagnetic waves are inadiated by said at least one wave source, transmitted through the physiological medium, and detected by said at least one wave detector, the method comprising the steps of: inadiating at least two sets of electromagnetic radiation having different wave characteristics to obtain a plurality of measurements; providing a mathematical expression relating said plurality of measurements to parameters ofthe system, and parameters associated with said medium; eliminating source-dependent and detector-dependent parameters from the provided mathematical expression; and determining an absolute value of at least one of said concentrations, wherein said determination is based on intensity measurements of continuous wave electromagnetic radiation and pre-determined chromophore-dependent parameters, and is not based on measuring phase characteristics ofthe elecfromagnetic radiation received from said one or more detectors, or the response ofthe medium to an electromagnetic impulse from said one or more sources.
34. The method of claim 33, wherein the mathematical expression includes a wave equation is expressed as:
I ^ α β γ L. ex l.-B L δ ∑i fe Q + σ}, wherein I0 is the intensity of electromagnetic waves inadiated by at least one source, I is the intensity of elecfromagnetic waves detected by at least one detector, α is a parameter associated with at the least one source and the medium, β is a parameter associated with the at least one detector and the medium, γ is one of a proportionality constant and a parameter associated with at least one source, detector and medium, B is a parameter accounting for lengths of optical paths of electromagnetic waves through said medium and associated with at least one source, detector and medium, L is a parameter accounting for a distance between the source and the detector, δ is one of a proportionality constant and a parameter associated with at least one ofthe source, detector, and medium, ε; is a parameter accounting for A interaction between electromagnetic waves and an i-th chromophore in said medium, C; is a variable denoting concentration of said i-th chromophore, and σ is one of a proportionality constant and a parameter associated with at least one of said source, detector, and medium.
35. A method for determining concenfrations of chromophores in a physiological medium using a measurement system having at least one wave source and at least one wave detector by application of a wave equation having the following form: lmn = «m βn Y I0,m e*P {"Bmn Lmn δ Σ; fø C;) + σ}, wherein Io m is the intensity of electromagnetic waves inadiated by the m-th wave source, L^ is the intensity of electromagnetic waves inadiated by the m-th wave source and detected by the n-th detector, αm is a parameter associated with the m-th wave source and the medium, βn is a parameter associated with the n-th wave detector and the medium, γ is one of a proportionality parameter associated with at least one of wave source, detector, and medium, Bmn is a parameter accounting for lengths of optical paths of electromagnetic waves through said medium and associated with the m-th wave source, n-th wave detector, and the medium, Lmn is a parameter accounting for a distance between the m-th wave source and the n-th wave detector, δ is one of a proportionality parameter associated with at least one wave source, wave detector, and medium, ε; is a parameter accounting for an optical interaction between elecfromagnetic waves and an i-th chromophore in said medium, is a variable for concentration of said i-th chromophore, and σ is one of a proportionality parameter associated with a wave source, wave detector, and medium, said method comprising the steps of: inadiating a first and second set of electromagnetic radiation having different wave characteristics and measuring signals received from the medium to obtain two sets of equations relating the measured signals with unknown parameters in the wave equation; eliminating at least one ofthe parameters αm, βn, γ, δ, and σ from the wave equation using the first and second set of equations to obtain a third set of equations; obtaining an expression for an absolute value of at least one of said concentrations based on values associated with 1^,, Io m, and εi; following the step of eliminating.
36. The method of claim 35 further comprising the steps of: applying said system to said physiological medium including cells of at least one of organs, tissues, and body fluids; and measuring said absolute value of at least one of said concenfrations based on said values of I™, Io m, and ;.
37. The method of claim 36, wherein said measuring step comprises the step of: monitoring at least one of oxygenated hemoglobin concentration, deoxygenated hemoglobin concentration, and a ratio thereof.
38. The method of claim 37 further comprising the step of determining a presence of tumor cells over a finite area of said medium.
39. The method of claim 37 further comprising the step of determining a presence of an ischemic condition over a finite area of said medium.
40. The method of claim 35 further comprising the steps of applying said system to said physiological medium including transplanted cells of at least one of organs and tissues; and measuring said absolute value of at least one of said concentrations and said ratios thereof based on said L^, Io m, and ε;.
41. The method of claim 40 further comprising the step of determining the presence or absence of an ischemic condition over a finite area of said medium.
42. The method of claim 35, wherein said eliminating step comprises the step of: approximating unknown equation parameters as constants.
43. The method of claim 35, wherein said obtaining step comprises the step of inadiating said first and second set of electromagnetic radiation having at least one of different wavelengths, phase angles, amplitudes and harmonics.
44. The method according to claim 43, wherein said inadiating step comprises the steps of: applying said first set of electromagnetic radiation having a first wavelength; and applying said second set of elecfromagnetic radiation having a second wavelength, which is different from the first wavelength.
45. The method of claim 35, wherein said eliminating step comprises the step of: taking at least one first ratio of two wave equations both selected from one of said first and second sets of wave equations.
46. The method of claim 45, wherein said eliminating step comprises the step of: solving said wave equations for the same wave source with different wave detectors, thereby eliminating the parameters c , γ, and σ from said first ratio.
47. The method of claim 45, wherein said eliminating step comprises the step of: solving said wave equations for at least two different wave sources and one wave detector, thereby eliminating the parameters βn, γ, and σ from said first ratio.
48. The method of claim 45, wherein said eliminating step comprises the step of: taking at least one second ratio of two wave equations both selected from the other of said first and second sets of wave equations.
49. The method of claim 48, wherein said eliminating step comprises the step of: obtaining at least one of a sum of and a difference between said first and second ratios so as to eliminate at least one of m and βn therefrom.
50. The method of claim 35, wherein said providing step comprises the step of: o expressing a formula of said medium-dependent and said geometry-dependent parameters as a polynomial of at least one of said concentrations.
51. The method of claim 50, wherein said polynomial includes a zero-th order term. 5
52. The method of claim 35, wherein said providing step comprises the step of approximating at least one medium-dependent or geometry-dependent parameter as a constant.
0 53. A method for determining concentrations of chromophores in a physiological medium using a system having at least one wave source and at least one wave detector using a mathematical expression having the form: lmn = «m βn r I0,m e p {-Bmn Lmn δ ∑j (ε; Cj) + σ}, wherein Iom represents the intensity of electromagnetic waves inadiated by an m-th wave 5 source, L^ represents the intensity of electromagnetic waves inadiated by said m-th wave source and detected by an n-th wave detector, αm is a parameter associated with at least one of said m-th wave source and medium, βn is a parameter associated with at least one of said n-th wave detector and medium, γ is one of a proportionality constant and a parameter associated with at least one of said m-th wave source, n-th wave detector, and medium, Bmn 0 is a parameter accounting for lengths of optical paths of electromagnetic waves through said medium and associated with at least one of said m-th wave source, n-th wave detector, and medium, Lmn is a parameter accounting for a distance between said m-th wave source and n- th wave detector, δ is a one of a proportionality constant and a parameter associated with at least one of said m-th wave source, n-th wave detector, and medium, ε; is a parameter 5 accounting for an optical interaction between electromagnetic waves and an i-th chromophore in said medium, is a variable for concentration of said i-th chromophore, and σ is one of a proportionality constant and a parameter associated with at least one of said m-th source, n-th detector, and medium, said method comprising the steps of: inadiating a first and second set of electromagnetic waves having different wave characteristics and measuring signals received from the medium to obtain at least two sets of equations relating the measured signals with unknown parameters in the wave equation; eliminating at least one of αm, βn, γ, δ, and σ from the obtained wave equations; defining parameters ofthe mathematical expression including Bmn and Lmn as a function of at least one of said concentrations; and determining concenfrations of chromophores in a physiological medium.
54. The method of claim 53 further comprising the step of obtaining values of said intensities of electromagnetic waves and said extinction coefficients of said chromophores.
55. The method of claim 54 further comprising the step of obtaining the absolute value of at least one of said concentrations and said ratios thereof.
56. A system for providing information concerning distributions of hemoglobins and properties thereof in a target area of a physiological medium, comprising: movable member having mounted thereon at least one wave source and at least one wave detector, said at least one wave source configured to inadiate near-infrared electromagnetic radiation into said target area and said at least one wave detector configured to detect near-infrared elecfromagnetic radiation from the target area and to generate output signal in response thereto; an actuator coupled with the at least one movable member to move it with respect to said target area along at least one curvilinear path; and a processor determining a distribution of hemoglobins or properties thereof based on the output signal generated by the at least one wave detector along the at least one curvilinear path.
57. The system of claim 56, wherein said distribution is at least one of two-and three-dimensional distribution of said hemoglobins.
58. The system of claim 56, wherein said distribution is at least one of spatial and temporal distribution of said hemoglobins.
59. The system of claim 56, wherein said properties include the absolute values of concentration of said hemoglobins.
60. The system of claim 56, wherein said properties are relative values of said hemoglobins, said values representing at least one of spatial and temporal changes in said hemoglobins.
61. The system of claim 56, wherein said properties include at least one of concentration of said hemoglobins, a sum of at least two concentrations thereof, and a ratio thereof.
62. The system of claim 56, wherein said properties include at least one of volume, mass, weight, volumetric flow rate, and mass flow rate thereof.
63. The system of claim 56, wherein said properties include at least one of concentration of oxygenated hemoglobin, concentration of deoxygenated hemoglobin, and oxygen saturation defined as a ratio of said concentration of oxygenated hemoglobin to a sum of said concentrations of oxygenated and deoxygenated hemoglobins.
64. The system of claim 56, wherein said at least one wave source is configured to inadiate near-infrared electromagnetic radiation having different wave characteristics.
65. The system of claim 56, wherein said at least one wave detector is configured to detect near-infrared elecfromagnetic waves having different wave characteristics.
66. The system of claim 56, wherein said at least one of curvilinear path includes one of franslation, reciprocation, rotation, revolution, and a combination thereof.
67. The system of claim 56, wherein said actuator is configured to generate motion ofthe movable member at a constant speed.
68. The system of claim 56, wherein said actuator is configured to generate motion ofthe movable member at a variable speed.
69. The system of claim 56, wherein motion ofthe movable member by the actuator has temporal characteristics, which are one or more of an impulse, step, pulse, pulse train, sinusoid, and a combination thereof.
70. The system of claim 56, wherein motion ofthe movable member by the actuator is at least one of periodic, aperiodic, and intermittent.
71. The system of claim 56, wherein the movable member has a longitudinal axis and said at least one wave source and at least one detector are disposed along said longitudinal axis and are configured to form a scanning unit elongated along said longitudinal axis, said scanning unit configured to move with said movable member and to define therearound a scanning area in which said wave detector can detect near-infrared electromagnetic radiation transmitted from said target area.
72. The system of claim 71, wherein said scanning area is smaller than said target area.
73. The system of claim 71, wherein at least a portion of said curvilinear path is substantially orthogonal to said longitudinal axis ofthe movable member.
74. The system of claim 71 , wherein at least a portion of said curvilinear path of said movement substantially parallel to said longitudinal axis ofthe movable member.
75. The system of claim 71, wherein said movable member includes at least two wave detectors that are disposed substantially along said longitudinal axis.
76. The system of claim 75, wherein said movable member includes at least two wave sources disposed substantially along said longitudinal axis.
77. The system of claim 76, wherein at least two wave detectors are interposed between at least two wave sources.
78. The system of claim 77, wherein a first near-distance between a first wave source and a first wave detector is substantially similar to a second near-distance between a second wave source and a second wave detector, and wherein a first far-distance between said first wave source and said second wave detector is substantially similar to a second far- distance between said second wave source and said first wave detector.
79. The system of claim 76, wherein at least two wave sources are interposed between at least two wave detectors.
80. The system of claim 75, wherein said movable member includes at least two wave sources, a first wave source disposed on one side across said longitudinal axis and a second wave source disposed on the other side across said longitudinal axis.
81. The system of claim 80, wherein said first and second wave sources are configured to be disposed substantially symmetrically with respect to said longitudinal axis.
82. The system of claim 56, wherein said actuator is configured to generate at least two movements of said movable member along at least two curvilinear paths.
83. The system of claim 82, wherein said actuator is configured to generate sequential movements sequentially.
84. The system of claim 82, wherein said actuator is configured to generate at least a portion of a first movement and at least a portion of a second movement simultaneously.
85. The system of claim 82, wherein at least a portion of a first curvilinear path is substantially orthogonal to at least a portion of a second curvilinear path.
86. The system of claim 85, wherein at least two curvilinear paths are orthogonal axes of one ofthe Cartesian, cylindrical, and spherical coordinate systems.
87. The system of claim 56, wherein said actuator member is configured to sequentially generate at least two movements of said movable member, a first movement starting from a first portion of said target area toward a second portion thereof and a second movement starting from said second portion toward said first portion of said target area.
88. The system of claim 56, wherein said actuator member is configured to sequentially generate at least three movements of said movable member, a first movement starting from a first side of said target area toward a second side thereof, a second movement starting from said second side to a third side of said target area, and a third movement starting from said third side toward a fourth side of said target area.
89. The system of claim 88, wherein said first and third movements are substantially linear translations and said second movement is substantially rotation.
90. The system of claim 88, wherein said target area has a shape of a rectangle, wherein said first and second sides are a first pair of opposing sides of said rectangle and wherein said third and fourth sides are a second pair of opposing sides of said rectangle.
91. The system of claim 82, wherein said actuator is configured to simultaneously generate a first and second movements of said movable member along a first and second curvilinear paths, respectively, at least a portion of said first curvilinear path configured to be substantially orthogonal to at least a portion of said second curvilinear path.
92. The system of claim 91, wherein one of said first and second movements is substantially linear franslation and the other of said first and second movements is substantially reciprocation.
93. The system of claim 56, wherein said at least one wave source and at least one detector are non-invasively disposed over said target area of said medium.
94. The system of claim 56, wherein said at least one wave source and at least one detector are configured to be invasively positioned over said target area disposed inside said medium.
95. A system for generating images representing distribution of hemoglobins and properties thereof in a target area of a physiological medium, comprising: at least one sensor assembly having a wave source and a wave detector, said wave source capable of inadiating near-infrared electromagnetic radiation into said medium, and said wave detector configured to detect near-infrared electromagnetic radiation from a target area of said medium and to generate output signal in response thereto; a support member configured to support said sensor assembly; and an actuator configured to operationally couple with at least one of said sensor assembly and support member and to generate at least one movement of at least one of said sensor assembly and support member with respect to said target area along a curvilinear path; and a processor determining a distribution of hemoglobins or properties thereof based on the output signal generated by the wave detector along the at least one curvilinear path.
96. The system of claim 95, wherein said movement includes at least one of curvilinear translation, reciprocation, rotation, revolution, and a combination thereof.
97. The system of claim 95, wherein said sensor assembly fixedly couples with said support member, said actuator being configured to move both of said sensor assembly and support member with respect to said target area.
98. The system of claim 95,. wherein said sensor assembly movably couples with said support member, said actuator member being configured to move said sensor assembly with respect to said support member and the target area.
99. The system of claim 95, wherein said sensor assembly movably couples with said support member, said actuator member being configured to generate a first movement of said sensor assembly with respect to said support member and target area and to generate a second movement of said support member with respect to said target area.
100. The system of claim 99, wherein said actuator is configured to generate at least a portion of said first movement of said sensor assembly simultaneously with at least a portion of said second movement of said support member.
101. The system of claim 99, wherein said actuator member is configured to generate said first and second movements sequentially.
102. The system of claim 95, wherein said support member includes a moving unit configured to move both of said sensor assembly and support member from said target area to another target area of said medium.
103. A system for generating images representing distribution of hemoglobins or properties thereof in a target area of a physiological medium, said system having one or more wave sources configured to inadiate near-infrared electromagnetic radiation into said medium and one or more wave detectors configured to detect near-infrared elecfromagnetic radiation and to generate output signal in response thereto, said system comprising: at least one portable probe having a movable member and an actuator member, the movable member including at least one of said wave sources and at least one of said wave detectors, and said actuator member being configured to couple with said movable member and move it along at least one curvilinear path; and a console comprising a processor configured to receive output signals from the one or more detectors to determine a distribution of hemoglobins or properties thereof and to generate images of said distribution.
104. The system of claim 103 further comprising: a connector member configured to provide at least one of electrical communication, optical communication, electric power transmission, mechanical power transmission, and data transmission between said portable probe and console.
105. The system of claim 104, wherein said connector member includes at least one fiber optic article.
106. The system of claim 103, wherein said portable probe includes a rechargeable power source and forms an article detachable from said console.
107. The system of claim 106, wherein said portable probe is configured to communicate with said console telemetrically.
108. The system of claim 106, wherein said portable probe includes a memory capable of storing at least one of said output signal, a signal representing said distribution, and a signal representing said images.
109. A system for providing information about distributions of properties of hemoglobins in a target area of a physiological medium, comprising: at least one wave source configured to inadiate near-infrared electromagnetic radiation into said medium; at least one wave detector configured to generate output signal in response to near-infrared electromagnetic radiation detected thereby; and at least one optical probe including a movable member and an actuator member, said movable member including at least one of said wave source and detector, and said actuator member configured to operationally couple with said movable member and to generate at least one movement of said movable member along at least one curvilinear path.
110. The system of claim 109 further comprising: a console operationally coupling with said optical probe and including a processor receiving said output signal and determining a distribution of said properties of hemoglobins from a set of solutions of wave equations applied to input and output parameters of said wave source and wave detector, the processor being programmed to generate one or more images of said distribution.
111. An optical imaging system configured to generate images of a target area of a physiological medium, said images representing distribution of properties of hemoglobins in said target area, said optical imaging system comprising: at least two wave sources configured to emit near-infrared electromagnetic radiation into said medium; and at least two wave detectors configured to generate output signal in response to said near-infrared electromagnetic radiation detected thereby, wherein at least two of said wave sources and at least two of said wave detectors are disposed substantially along a line; and an actuator member configured to generate movement of at least one of said wave sources and detectors.
112. The system of claim 111, wherein said actuator member is configured to move all of said wave sources and detectors disposed substantially linearly along said line.
113. The system of claim 111, wherein said movement includes at least one of curvilinear translation, reciprocation, rotation, revolution, and a combination thereof.
114. A method for providing information concerning two- or three-dimensional distribution of properties of hemoglobins in a target area of a physiological medium by a measurement system, wherein said measurement system includes at least one wave source, at least one wave detector, a movable member, and an actuator member, said wave source configured to emit near-infrared elecfromagnetic radiation into said target area of said medium, said wave detector configured to generate output signal in response to said near-infrared electromagnetic radiation detected thereby, said movable member having a longitudinal axis and configured to include at least one of said wave source and detector, and said actuator member coupling with said movable member, wherein said wave source and detector are configured to form a scanning unit elongated along said longitudinal axis of said movable member and defining a scanning area therearound, and wherein said actuator member couples with said movable member and is configured to generate at least one movement of said movable member along at least one curvilinear path, said method comprising: positioning said movable member in a first region of said target area of said medium; scanning said first region by inadiating said near-infrared electromagnetic radiation thereinto by said wave source and by obtaining said output signal therefrom by said wave detector; and manipulating said actuator member to generate said movement of said movable member from said first region to a second region of said target area along at least one curvilinear path.
115. The method of claim 114 further comprising: repositioning said movable member sequentially in a plurality of target areas of said medium; and repeating said scanning and manipulating steps in each of said target areas.
116. The method of claim 114 further comprising: determining said distribution of said properties of said hemoglobins in said target area; and obtaining said images representing said distribution in said target area.
117. The method of claim 114, wherein said positioning comprises at least one of: forming optical coupling between said medium and said wave source and between said medium and said wave detector; and maintaining at least a portion of said optical couplings during said movement of said movable member.
118. The method of claim 114, wherein said manipulating comprises one of: moving said movable member at one constant speed; and moving said movable member at speeds varying with respect to at least one of time and position of said target area.
119. The method of claim 114, wherein said manipulating comprises at least one of: moving said movable member along said curvilinear path which is at least substantially orthogonal to said longitudinal axis of said movable member; moving said movable member along said curvilinear path which is at least substantially parallel with said longitudinal axis; and moving said movable member along said curvilinear path disposed at a preselected angle with respect to said longitudinal axis.
120. The method of claim 114, wherein said manipulating comprises at least one of: linearly translating said movable member along at least one linear path; translating said movable member along at least one curvilinear path; rotating said movable member about at least one center of rotation about a pre-selected angle along at least one curved path; revolving said movable member about at least one center of rotation for a pre-selected number of turns along at least one curved path; and reciprocating said movable member along at least one curvilinear path.
121. The method of claim 114, wherein said manipulating comprises : generating at least two movements of said movable member along at least two curvilinear paths.
122. The method of claim 121, wherein said generating comprises: moving said movable member along at least two curvilinear paths in at least one of a simultaneous, sequential, and intermittent mode.
123. A method for generating images representing two- or three-dimensional distribution of properties of hemoglobins in a target area of a physiological medium by an imaging system, wherein said optical imaging system includes a sensor assembly, a body, and an actuator member, said sensor assembly having at least one wave source configured to inadiate near-infrared elecfromagnetic radiation to said medium and at least one wave detector configured to generate output signal in response to near-infrared electromagnetic radiation detected thereby, said body configured to support at least a portion of said sensor assembly, and said actuator member coupling with at least one of said sensor assembly and said body and configured to generate at least one movement of at least one of said sensor assembly and said body, said method comprising: positioning said sensor assembly in a first region of said target area of said medium; scanning said first region with said sensor assembly by inadiating said near- infrared electromagnetic radiation into said first region of said medium and by generating said output signal therefrom; and causing said actuator member to generate said movement of at least one of said sensor assembly and said body from said first region toward a second region of said target area of said medium along at least one curvilinear path.
124. The method of claim 123 further comprising: fixedly coupling said sensor assembly with said body; and moving said body during said movement.
125. The method of claim 123 further comprising: movably coupling said sensor assembly with said body; and moving said sensor assembly with respect to at least one of said body and target area during said movement.
126. The method of claim 125 further comprising: generating another movement of said body by said actuator member; and moving said body with respect to said target area during said movement.
127. The method of claim 126, wherein said generating comprises one of: moving said sensor assembly and body sequentially; and moving said sensor assembly and body simultaneously.
128. A method for generating images of a target area of a physiological medium by an imaging system, said images representing two- or three-dimensional distribution of properties of hemoglobins in said target area, said method comprising the steps of: positioning at least two wave sources and at least two wave detectors in a region of said target area substantially along a line; defining a scanning unit around said wave sources and detectors, which unit has a scanning area smaller than said target area; and generating at least one movement of said wave sources and wave detectors to move at least one of said wave sources and detectors to another region of said target area.
129. The method of claim 128 further comprising: scanning said regions of said target area of said medium by inadiating said near-infrared electromagnetic radiation thereinto and by generating output signals therefrom in response to said near-infrared electromagnetic radiation detected by said wave detector.
130. The method of claim 129 further comprising: repeating said scanning step at a plurality of regions of said target area, thereby enabling said optical imaging system to scan said regions having a total area which is substantially greater than said scanning area of said scanning unit and which is' substantially identical to said target area.
131. The method of claim 130 further comprising: terminating said repeating step after a pre-selected number of repetitions.
132. The method of claim 130 further comprising: terminating said repeating step when said total area of said regions reaches a pre-selected portion of said target area.
133. An optical probe for an imaging system capable of generating images representing distribution of hemoglobins or their properties in target areas of a physiological medium, said optical probe having a plurality of wave sources and wave detectors, said wave sources configured to inadiate near-infrared electromagnetic radiation into the medium and said wave detectors configured to detect near-infrared electromagnetic radiation and to generate output signals in response thereto, said optical probe comprising: a plurality of symmetrically disposed scanning units, each having a first wave source, a second wave source, a first wave detector, and a second wave detector, said first wave source disposed closer to said first wave detector than said second wave detector and said second wave source disposed closer to said second wave detector than said first wave detector, wherein a first near-distance between said first wave source and said first wave detector is substantially similar to a second near-distance between said second wave source and said second wave detector, wherein a first far-distance between said first wave source and said second wave detector is substantially similar to a second far-distance between said second wave source and said first wave detector, and wherein said first and second wave detectors are configured to generate output signals in response to near-infrared electromagnetic radiation inadiated by at least one of said first and second wave sources and detected thereby, said output signals representing optical interaction of said near-infrared electromagnetic radiation with said hemoglobins in said target areas of said medium.
134. The optical probe of claim 133, wherein said first and second near-distances are substantially similar.
135. The optical probe of claim 133, wherein said first and second far-distances are substantially similar.
136. The optical probe of claim 133, wherein at least one of said symmetric scanning units includes an axis of symmetry with respect to which said first and second wave sources are symmetrically disposed and with respect to which said first and second wave detectors are symmetrically disposed.
137. The optical probe of claim 136, wherein at least two of said symmetric scanning units include at least one of a common wave source and a common wave detector.
138. The optical probe of claim 136, wherein said first and second wave sources and said first and second wave detectors are substantially linearly disposed.
139. The optical probe of claim 138, wherein said first and second wave sources are interposed between said first and second wave detectors.
140. The optical probe of claim 138, wherein said first and second wave detectors are interposed between said first and second wave sources.
141. The optical probe of claim 138, wherein said near-distance is about one half of said far-distance.
142. The optical probe of claim 138, wherein said optical probe includes at least one first symmetric scanning unit and at least one second symmetric scanning unit, wherein said first and second scanning units share an axis of symmetry, wherein said first scanning unit has a first anangement of said wave sources and wave detectors, and wherein said second scanning unit has said first anangement of said wave sources and detectors and is disposed below said first scanning unit.
143. The optical probe of claim 142, wherein said second scanning unit is disposed immediately below said first scanning unit.
144. The optical probe of claim 138, having at least one first symmetric scanning unit and at least one second symmetric scanning unit, wherein said first and second scanning units share an axis of symmetry, wherein said first scanning unit has a first anangement of said wave sources and wave detectors, and wherein said second scanning unit is disposed below said first scanning unit and has a second anangement of said wave sources and wave detectors that is substantially reverse to said first anangement.
145. The optical probe of claim 144, wherein said second scanning unit is disposed immediately below said first scanning unit.
146. The optical probe of claim 138, wherein said optical probe includes at least one first, second, third, and fourth symmetric scanning units each sharing an axis of symmetry with the others, wherein said first scanning unit has a first anangement of said wave sources and wave detectors, wherein said second scanning unit is disposed immediately below said first scanning unit and has a second anangement of said wave sources and wave detectors which is substantially reverse to said first anangement, wherein said third scanning unit is disposed immediately below said second scanning unit and has said second anangement, and wherein said fourth scanning unit is disposed immediately below said third scanning unit and has said first anangement.
147. The optical probe of claim 146, wherein all of said symmetric scanning units have identical shapes and sizes and define a 4x4 source-detector anangement wherein said wave sources and detectors of said symmetric scanning units are spaced at a uniform distance.
148. The optical probe of claim 147, wherein said 4x4 source-detector anangement has a shape of a quadrangle which is one of a rectangle, a square, a parallelogram, and a diamond.
149. The optical probe of claim 136, wherein said first and second wave sources and said first and second wave detectors are ananged to form four vertices of a quadrangle, said first and second wave sources disposed at two upper vertices of said quadrangle, and said first and second wave detectors disposed at two lower vertices thereof.
150. The optical probe of claim 149, wherein said quadrangle is one of a frapezoid, rectangle, and square, said frapezoid having two opposing sides of equal lengths.
151. The optical probe of claim 149, wherein said optical probe includes at least one first symmetric scanning unit and at least one second symmetric scanning units, said first and second scanning units having different axes of symmetry, said first scanning unit having a first anangement of said wave sources and detectors, and said second scanning unit disposed lateral to said first scanning unit and having said first anangement.
152. The optical probe of claim 149, wherein said optical probe includes at least one first symmetric scanning unit and at least one second symmetric scanning units, said first and second scanning units having different axes of symmetry, said first scanning unit having a first anangement of said wave sources and detectors, and said second scanning unit disposed lateral to said first scanning unit and having a second anangement of said wave sources and detectors which is substantially reverse to said first anangement.
153. The optical probe of claim 149, wherein said optical probe includes at least one first, second, third, and fourth symmetric scanning units, wherein said first scanning unit has a first anangement of said wave sources and detectors, wherein said second scanning unit is disposed lateral to said first scanning unit and has a second anangement of said wave sources and detectors which is substantially reverse to said first anangement, wherein said third scanning unit is disposed immediately below said first scanning unit and has said second anangement, and wherein said fourth scanning unit is disposed immediately below said second scanning unit and has said first anangement.
154. The optical probe of claim 136, wherein a first set of said wave sources and detectors is substantially linearly disposed and wherein a second set of said wave sources and detectors is disposed to form four vertices of a quadrangle.
155. The optical probe of claim 154, wherein said first and second sets include at least one of a common wave source and a common wave detector.
156. The optical probe of claim 133, wherein at least one of said symmetric scanning units includes a point of symmetry with respect to which said first and second wave sources are symmetrically disposed and with respect to which said first and second wave detector are symmetrically disposed.
157. The optical probe of claim 156, wherein at least two of said symmetric scanning units include at least one of a common wave source and a common wave detector.
158. The optical probe of claim 156, wherein said first and second wave sources and said first and second wave detectors are substantially linearly disposed.
159. The optical probe of claim 156, wherein said first and second wave sources and said first and second wave detectors are disposed to form four vertices of a quadrangle, wherein said first wave source and detector are disposed at two upper vertices of said quadrangle, and wherein said second wave detector and source are disposed at two lower vertices thereof.
160. The optical probe of claim 159, wherein said quadrangle is one of a rectangle and a parallelogram, said parallelogram having two sides of different lengths.
161. The optical probe of claim 133, wherein at least one of said symmetric scanning units includes at least one of a third wave source and a third wave detector.
162. The optical probe of claim 161, wherein at least one of said third wave source and detector is disposed in a substantially middle portion of said symmetric scanning unit.
163. The optical probe of claim 133, wherem at least two of said symmetric scanning units are ananged symmetrically with respect to a global axis of symmetry.
164. The optical probe of claim 163, wherein at least one of said symmetric scanning units is disposed immediately below the other of said symmetric scanning units.
165. The optical probe of claim 163, wherein at least two of said symmetric scanning units are substantially laterally ananged.
166. The optical probe of claim 133, wherein at least two of said symmetric scanning units are ananged symmetrically with respect to a global point of symmetry.
167. The optical probe of claim 166, wherein at least two of said symmetric scanning units are ananged substantially arcuately around said point of symmetry.
168. The optical probe of claim 166, wherein at least two of said symmetric scanning units are ananged substantially concentrically around said point of symmetry.
169. The optical probe of claim 133, wherein at least one of said wave sources is configured to inadiate multiple sets of electromagnetic radiation having different wave characteristics.
170. The optical probe of claim 133, wherein at least one of said wave detectors is configured to detect a plurality of sets of electromagnetic waves having different wave characteristics.
171. The optical probe of claim 133, wherein one of said wave sources is ananged to inadiate elecfromagnetic waves while at least one of said wave sources is not inadiating electromagnetic waves.
172. The optical probe of claim 133, wherein said elecfromagnetic radiation is at least one of sound waves, near-infrared rays, infrared rays, visible lights, ultraviolet rays, lasers, and photons.
173. The optical probe of claim 133, wherein said images represent at least one of two-dimensional and three-dimensional distribution of at least one of said hemoglobins and said properties thereof.
174. The optical probe of claim 133, wherein said properties represent at least one of spatial distribution and temporal variation in at least one of said hemoglobins and said properties thereof.
175. The optical probe of claim 133, wherein said properties are at least one of absolute values and relative values of at least one of said hemoglobins and said properties thereof.
176. The optical probe of claim 133, wherein said properties include at least one of concentration of deoxygenated hemoglobin, concentration of oxygenated hemoglobin, and an oxygen saturation which is a ratio of said concentration of said oxygenated hemoglobin to a sum of said concentrations of said oxygenated hemoglobin and said deoxygenated hemoglobin.
177. The optical probe of claim 133, wherein said properties are extensive properties including at least one of volume, mass, weight, volumetric flow rate, and mass flow rate of said hemoglobins.
178. An optical probe of an optical imaging system capable of generating images representing distribution of hemoglobins or their properties in target areas of a physiological medium, said optical probe including a plurality of wave sources and a plurality of wave detectors, said wave sources configured to inadiate near-infrared elecfromagnetic radiation into the medium and said wave detectors configured to detect near-infrared electromagnetic radiation and to generate output signals in response thereto, said optical probe comprising: four symmetric scam ing units wherein a first scanning unit is identical to a fourth scanning unit and wherein a second scanning unit is identical to a third scanning unit, each scanning unit having a first wave source, a second wave source, a first wave detector, and a second wave detector, wherein said first wave source is disposed closer to said first wave detector than said second wave detector and wherein said second wave source is disposed closer to said second wave detector than said first wave detector, wherein a first near-distance between said first wave source and first wave detector is ananged to be substantially similar to a second near-distance between said second wave source and second wave detector, wherein a first far-distance between said first wave source and second wave detector is ananged to be substantially similar to a second far-distance between said second wave source and first wave detector, and wherein said first and second wave sources are configured to be synchronized with said first and second wave detectors to generate output signals which represent electromagnetic interaction of said near-infrared radiation with said hemoglobins in said target areas of said medium.
179. The optical probe of claim 178, wherein all of said wave sources and all of said wave detectors of each of said scanning units are substantially linearly disposed.
180. The optical probe of claim 179, wherein said first and second wave sources are interposed between said first and second wave detectors in said first and fourth scanning units and wherein said first and second wave detectors are interposed between said first and second wave sources in said second and third scanning units.
181. An optical probe of an optical imaging system capable of generating images representing distribution of hemoglobins or their properties in target areas of a physiological medium, said optical probe comprising: a plurality of wave sources and a plurality of wave detectors, said wave sources configured to inadiate near-infrared electromagnetic radiation into the medium and said wave detectors configured to detect near-infrared electromagnetic radiation and to generate output signals in response thereto, wherein at least one first wave source and at least one first wave detector define a first scanning element in which said first wave source inadiates said near-infrared electromagnetic radiation and said first wave detector detects said waves inadiated by said first wave detector and generates a first output signal, wherein at least one second wave source and at least one second wave detector define a second scanning element in which said second wave source inadiates said near-infrared elecfromagnetic waves and said second wave detector detects said waves inadiated by said second wave detector and generates a second output signal, wherein said first and second scanning elements define a scanning unit in which said first and second wave sources are symmetrically disposed with respect to one of a line of symmetry and a point of symmetry and in each of which said first and second wave detectors are also symmetrically disposed with respect to one of said line of symmetry and said point of symmetry.
182. The optical probe of claim 181, wherein said first and second scanning units are configured to intersect each other.
183. The optical probe of claim 181 further comprising: a processor configured to receive said first and second output signals generated by said first and second wave detectors, to obtain a set of solutions of wave equations applied to input and output parameters of said first and second wave sources and to said first and second wave detectors, to determine said distribution of at least one of hemoglobins and properties thereof, and to generate said images of said distribution.
184. The optical probe of claim 183, wherein said images conespond to a plurality of voxels, wherein each of said first and second scanning units generates a plurality of first voxels and a plurality of second voxels, respectively, and wherein said processor is configured to calculate at least one first voxel value for each of said first voxels from said set of said solutions and at least one second voxel value for each of said second voxels from said set of said solutions.
185. The optical probe of claim 184, wherein said processor is configured to define a plurality of cross-voxels each of which is defined as an overlapping portion of said first and second voxels intersecting each other.
186. The optical probe of claim 185, wherein said processor is configured to calculate at least one cross- voxel value for each of said cross-voxels directly from said first and second voxel values of said intersecting first and second voxels, respectively.
187. The optical probe of claim 186, wherein each of said cross- voxel values is at least one of an arithmetic sum and arithmetic average of said first and second voxel values of said first and second voxels intersecting each other.
188. The optical probe of claim 186, wherein each of said cross-voxel values is at least one of a weighted sum and weighted average of said first and second voxel values of said first and second voxels intersecting each other.
189. A method for generating two-dimensional or three-dimensional images of a target area of a physiological medium by an optical imaging system having an optical probe, said images representing spatial or temporal distribution of hemoglobins or their properties in said medium, wherein said optical probe includes a plurality of wave sources and a plurality of wave detectors, said wave sources configured to inadiate near-infrared electromagnetic radiation into the medium, said wave detector configured to generate output signals in response to near-infrared elecfromagnetic radiation detected thereby, the method comprising the steps of: providing a plurality of scanning elements, each of which including at least one of said wave sources and at least one of said wave detectors; defining a plurality of scanning units, each of which including at least two of said scanning elements; scanning said target area with one or more scanning units; grouping output signals generated by each of said scanning units; obtaining a set of solutions of wave equations applied to input and output parameters ofthe scanning units; determining said distribution of at least one of hemoglobins and properties thereof from said set of solutions; and providing one or more images of said distribution.
190. The method of claim 189 further comprising: scanning said target area over time; determining said distribution of at least one of hemoglobins and properties thereof in said target area of said medium over time; providing said images of said distribution over time; and providing said images of changes in said distribution over time.
191. The method of claim 189 further comprising: defining a plurality of first voxels in at least one of said scanning units; determining at least one first voxel value for each of said first voxels, each of o said first voxel values representing an average value of at least one of said hemoglobins and said properties thereof; and generating said images of said distribution directly from said first voxel values.
5 192. The method of claim 191, wherein said defining comprises : controlling resolution of said images by adjusting at lease one characteristic dimension of each of said first voxels.
193. The method of claim 192, wherein said controlling comprises at least one of: 0 adjusting at least one distance between at least one of said wave sources and at least one of said wave detectors of at least one ofthe same scanning element and the same scanning unit; adjusting geometric anangement between at least one of said wave sources and at least one of said wave detectors of at least one ofthe same scanning element and the 5 same scanning unit; adjusting geometric anangement between at least two scanning elements of the same scanning unit; adjusting geometric anangement between at least two scanning units; and adjusting data sampling rate of said output signals. 0
194. The method of claim 191 further comprising: defining a plurality of second voxels in at least one of said scanning units; determining at least one second voxel value for each of said second voxels, each second voxel value representing an average value of at least one of said hemoglobins 5 and said properties thereof; and generating said images of said distribution directly from said first and second voxel values.
195. The method of claim 194 further comprising: defining a plurality of cross-voxels in at least one of said scanning units, each of said cross-voxels defined as an overlapping portion of two intersecting first and second voxels; determining at least one cross-voxel value for each of said cross-voxels, each cross-voxel value representing an average value of at least one of said hemoglobins and said properties thereof; and o generating said images of said distribution directly from said cross-voxel values and at least one of said first and second voxel values.
196. The method of claim 195, wherein said cross-voxel values are determined by at least one of: 5 adding said first and second voxel values of said intersecting first and second voxels; arithmetically averaging said first and second voxel values of said intersecting first and second voxels; adding weighted first and second voxel values of said intersecting first and 0 second voxels; and weight-averaging said first and second voxel values of said intersecting first and second voxels.
197. The method of claim 194 further comprising: 5 defining a plurality of third voxels in at least one of said scanning units; determining at least one third voxel value for each of said third voxels, each third voxel value representing an average value of at least one of said hemoglobins and said properties thereof; generating said images of said distribution directly from said first, second, 0 and third voxel values.
198. The method of claim 197 further comprising: defining a plurality of second cross- voxels in at least one of said scanning units, each of said second cross- voxels defined as an overlapping portion of two intersecting 5 first and third voxels; determining at least one second cross- voxel value for each of said second cross- vox els, each second cross-voxel value representing an average value of at least one of said hemoglobins and said properties thereof; and generating said images of said distribution based on at least one of said cross- voxel values, second cross-voxel values, first voxel values, second voxel values, and third voxel values.
199. A system for generating images representing properties of one or more chromophores in a target area of a physiological medium, comprising: at least one movable support; an actuator coupling with said at least one movable support and configured to move the support with respect to the target area along at least one curvilinear path; one or more wave sources and one or more wave detectors mounted on the support to form a scanning unit having associated therewith a longitudinal axis, a scanning area and a scanning volume, said wave source(s) configured to inadiate near-infrared electromagnetic radiation into the target area of said medium and said wave detector(s) configured to detect near-infrared electromagnetic radiation from the target area and to generate an output signal in response thereto; and a processor receiving said output signal and defining a plurality of voxels in the target area, wherein each ofthe plurality of voxels has a characteristic dimension and a voxel axis, the processor determining chromophore properties based on the output signal in the plurality of voxels and generating said images.
200. The system of claim 199, wherein the characteristic dimension ofthe plurality of voxels is one of a height, length, and width thereof, and forms a pre-selected angle with respect to said at least one curvilinear path traversed by the movable support.
201. The system of claim 199, wherein the voxel axis of each of the plurality of voxels is substantially parallel to the longitudinal axis ofthe scanning unit.
202. The system of claim 199, wherein the plurality of voxels has a height dimension which is substantially similar to a height dimension ofthe scanning unit.
203. The system of claim 199, wherein the characteristic dimension of the plurality of voxels is substantially parallel to said at least one curvilinear path fraversed by the movable support.
204. The system of claim 199, wherein the processor is configured to sample said output signal at pre-selected time intervals.
205. The system of claim 204, wherein the characteristic dimension ofthe plurality of voxel is proportional to the speed of motion ofthe movable support.
206. The system of claim 204, wherein the characteristic dimension of the plurality of voxels is proportional to the time interval between successive samplings.
207. The system of claim 199, wherein the processor is configured to determine a voxel value for each ofthe plurality of voxels and to generate an ordered sequence of determined voxel values, each voxel value representing one or more properties of hemoglobins averaged over the voxel.
208. The system of claim 207, wherein voxel values represent properties of hemoglobins averaged over at least one of said scanning area and scanning volume.
209. The system of claim 207, wherein the actuator is configured to move the support along at least two curvilinear paths, and wherem the processor is configured to define along each motion path a separate set of voxels and to determine therefrom sequences of voxel values conesponding to the separate sets of voxels.
210. The system of claim 209, wherein the processor is further configured to define a plurality of cross- voxels defined as the intersection of voxels belonging to separate sets of voxels.
211. The system of claim 210, wherein the processor is configured to determine a cross- voxel value for each of said cross- voxels and to generate a sequence of cross- voxel values from the voxel values of intersecting voxels.
212. The system of claim 211, wherein each of said cross-voxel values is at least one of an arithmetic sum, arithmetic average, geometric sum, geometric average, weighted sum, and weighted average ofthe voxel values of intersecting voxels.
213. The system of claim 211, wherein each of said cross- voxel values is at least ' one of an ensemble sum and ensemble average ofthe voxel values of intersecting voxels.
214. The system of claim 199, wherein the generated images conespond to at least one of a two-dimensional distribution and a three-dimensional distribution of said properties of chromophores.
215. The system of claim 199, wherein the generated images represent at least one of spatial distribution and temporal variation of said properties of chromophores.
216. The system of claim 199, wherein the properties is at least one of spatial distribution and temporal distribution of chromophores in the target area.
217. The system of claim 199, wherein said properties comprise at least one of intensive properties of said chromophores including concentration thereof, a sum of said concentrations, a difference of said concentrations, a ratio of said concentrations, and combinations thereof.
218. The system of claim 199, wherein the one or more chromophores comprises hemoglobins and said properties comprise at least one of extensive properties of said hemoglobins including volume, mass, volumetric flow rate, and mass flow rate thereof.
19. The system of claim 218, wherein said one or more chromophores comprises hemoglobins and said properties include at least one of concentration of oxygenated hemoglobin, concentration of deoxygenated hemoglobin, and oxygen saturation defined as a ratio of said concentration of oxygenated hemoglobin to a sum of said concentrations of deoxygenated hemoglobin and oxygenated hemoglobin.
220. The system of claim 199, wherein said elecfromagnetic radiation is at least one of sound waves, near-infrared rays, infrared rays, visible lights, ultraviolet rays, lasers, and photons.
221. The system of claim 199, wherein the longitudinal axis of the scanning unit passes through the one or more wave sources and the one or more wave detectors ofthe scanning unit.
222. The system of claim 199, wherem said one or more chromophores includes at least one a solvent of said medium, a solute dissolved in said medium, and a substance included in said medium, each of which is configured to interact with said electromagnetic waves inadiated by said wave source and transmitted through said medium.
223. The system of claim 199, wherein said one or more chromophores includes at least one of a cytochrome, cytosome, cytosol, enzyme, hormone, neurotransmitter, chemical or chemotransmitter, protein, cholesterol, apoprotein, lipid, carbohydrate, blood cell, water, and hemoglobins including oxygenated and deoxygenated hemoglobin.
224. A system for generating images representing distribution of at least one hemoglobin property in a target area of a physiological medium, comprising: a sensor assembly comprising at least one wave source and at least one wave detector, the at least one wave source configured to inadiate near-infrared electromagnetic radiation into said medium and the at least one wave detector configured to detect near- infrared elecfromagnetic radiation in the target area and to generate output signal in response thereto; an actuator coupling with the sensor assembly and configured to move the sensor assembly with respect to said target area of said medium along at least one curvilinear path; and a processor receiving output signal from the sensor assembly, the processor being configured to define a plurality of voxels in the target area, to determine said hemoglobin property by solving a plurality of wave equations applied to input radiation from the at least one wave source and radiation detected by the at least one detector, and to generate images ofthe distribution of said hemoglobin property in the target area.
225. The system of claim 224, wherein each ofthe plurality of voxels has a characteristic dimension and a voxel axis, and wherein the plurality of voxels are sequentially ananged along one or more directions conesponding to the at least one curvilinear motion path ofthe sensor assembly.
226. The system of claim 224, wherein the processor is configured to determine voxel values for the plurality of voxels and to generate a sequence of said voxel values, each voxel value representing an average ofthe at least one hemoglobin property over the voxel.
227. The system of claim 224, wherein the processor is configured to provide at least one set of cross-voxels, a cross-voxel being defined as an intersection of at least two voxels belonging to voxel sets ananged along two or more directions.
228. A system for generating images representing distribution of at least one property of at least one chromophore in a target area of a physiological medium, the system comprising: at least one wave source configured to inadiate electromagnetic radiation into said physiological medium; at least one wave detector configured to detect electromagnetic radiation in the target area and to generate output signal in response thereto; a portable probe having at least one movable member and at least one actuator, wherein the at least one movable member has mounted thereon at least one wave source and at least one detector, and the at least one actuator member is configured to couple with said at least one movable member to move it along one or more curvilinear paths; and a processor receiving output signals from the at least one detector, and providing a plurality of voxels in said target area, the processor determining said at least one property ofthe at least one chromophore by solving a plurality of wave equations applied to radiation from the at least one wave source and radiation detected by the at least one detector, and generating images of said distribution of said chromophore property.
229. A system for generating information regarding the distribution of at least one property of at least one chromophore in target areas of a physiological medium, comprising: at least one wave source configured to inadiate electromagnetic radiation into said physiological medium; at least one wave detector configured to detect electromagnetic radiation from the target area and to generate output signal in response thereto; an optical probe including at least one movable member in which at least one of said wave source and detector is disposed; a console coupling with said optical probe and including a processor configured to receive said output signal, the processor providing a plurality of voxels in portions of said target areas and determining the chromophore property by solving a plurality of wave equations applied to radiation from the at least one wave source and detected by the at least one detector, and to information about the distribution of said chromophore property in the target area; an actuator configured to couple with said at least one movable member to move it along at least one curvilinear path; and a connector for providing at least one of electrical cornmunication, optical communication, electric power transmission, mechanical power transmission, and data transmission between at least two of said optical probe, console, and actuator member.
230. A system for generating information about the distribution of at least one property of at least one chromophore in target areas of a physiological medium, comprising: at least two wave sources configured to inadiate electromagnetic radiation into said target areas of said medium; at least two wave detectors configured to generate output signals responsive to electromagnetic radiation detected from the target areas, wherein at least two of said wave sources and at least two of said wave detectors are disposed substantially along a line; and a processor configured to receive said output signal, to provide a plurality of voxels in portions of said target areas, to determine said at least one chromophore property by solving a set of wave equations applied to radiation from said at least two wave sources and detected by said at least two detectors, and to generate said infonnation about the distribution ofthe at least one chromophore property in the target area ofthe physiological medium.
231. A method for generating images representing distribution of hemoglobins in a target area of a physiological medium by a portable measurement system, the system having a movable member having mounted thereon at least one wave source and at least one wave detector to define a scanning unit having a longitudinal axis, a scanning area smaller than the target area and scanning volume therearound, the at least one wave source inadiating near-infrared elecfromagnetic radiation into said target area, the at least one wave detector being configured to detect near-infrared electromagnetic radiation in the target area and to generate output signal in response thereto, the system further comprising an actuator member coupling with said movable member to move it along at least one curvilinear path to scan the target area, the method comprising the steps of: placing said movable member on said target area of said medium; positioning said scanning unit in a first region ofthe target area; scanning said first region ofthe target area by inadiating near-infrared elecfromagnetic radiation and obtaining said output signal therefrom by said wave detector; manipulating said actuator member to move the movable member and scanning unit from said first region toward another region ofthe target area along a first curvilinear path; defining a first set voxels from said output signal in at least one of said regions of said target area; determining voxel values conesponding to the first set of voxels, each voxel value being an average of said property over a voxel; and generating images representing the distribution of said hemoglobins from said first set of voxel values.
232. The method of claim 231 further comprising the steps of: forming optical couplings between said medium and said wave source and detector; and maintaining said optical couplings during said movement of at least one of said movable member and scanning unit.
233. The method of claim 231 further comprising the steps of: aπanging of said at least one wave source and at least one wave detector substantially along a line.
234. The method of claim 231 , wherein said generating step comprises the step of: controlling resolution of said images by varying at least one dimension of said first set of voxels.
235. The method of claim 234, wherein said varying step comprises at least one of the steps of: adjusting a distance between said wave source and detector; adjusting geometric anangement between said wave source and detector; adjusting at least one of contour, length, and tortuosity of said curvilinear path of said movement of at least one of said movable member and scanning unit; adjusting a number of said movements of at least one of said movable member and said scanning unit over said target area; adjusting a speed of said movement of at least one of said movable member and scanning unit; and adjusting a sampling rate of said output signal.
236. The method of claim 231 further comprising the steps of: defining a second set of voxels in at least one different region ofthe target area; determining a voxel values associates with the second set of voxels; defining a plurality of cross- vox els defined as an intersection of at least two voxels each belonging to a different sets of voxels; obtaining cross-voxel values for said cross-voxels from the voxel values of the intersecting voxels; and generating images ofthe distribution of said hemoglobins based on the obtained cross-voxel values.
237. The method of claim 236, wherein said step of obtaining said first sequence of said first cross-voxel values comprises at least one ofthe steps of: arithmetically averaging said voxel values of said intersecting voxels; geometrically averaging said voxel values of said intersecting voxels; weight-averaging said voxel values of said intersecting voxels; and o ensemble-averaging said voxel values of said intersecting voxels.
238. The method of claim 236 further comprising the steps of: defining a third set of voxels in yet another region of said target area; determining voxel values for the third set of voxels; 5 defining a second plurality of cross-voxels defined as an intersection of at least two voxels belonging to different sets of voxels; obtaining cross-voxel values for said second set of cross- voxels from said voxel values ofthe intersecting voxels; and generating images of said distribution of hemoglobins based on the second 0 cross- voxel values.
239. The method of claim 238 further comprising the step of: generating said images of said distribution of said hemoglobins by aπanging a plurality of said sequences of said cross- voxel values, thereby improving the resolution of 5 said images.
240. A method for generating images representing distribution of at least one property of at least one chromophore in of a target area of a physiological medium by a portable system, wherein said system includes at least one wave source configured to 0 inadiate elecfromagnetic radiation into said medium and at least one wave detector configured to detect electromagnetic radiation and to generate output signal in response thereto, said method comprising the steps of: positioning said wave source and detector in said target area; defining a first set of voxels from said output signals; 5 determining a sequence of voxel values for the first set of voxels, a voxel value representing an average of said property over a voxel; defining a second set of voxels from said output signals; determining a sequence of voxel values of said second voxels; constructing a first set of cross- voxels defined as the intersecting portions of at least two intersecting voxels which belong to one of said first and second sets of voxels, respectively; calculating cross-voxel values of said first set of cross-voxels from the voxel values of said intersecting voxels; and generating said images of said distribution of said chromophore property from said first sequence of said first cross-voxel values.
241. The method of claim 240, wherein at least one of said defining steps comprises the step of defining said set of said voxels per at least one of: each pre-selected distance along said target area; each pre-selected sampling interval of said output signal; each pair of one of said wave sources and one of said wave detectors; and each scanning unit comprising at least two of said wave sources and at least two of said wave detectors.
242. The method of claim 240, wherein at least one of said defining steps comprises the step of: adjusting resolution of said images of said distribution of said property by varying at least one dimension of at least one of said voxels and cross- voxels.
243. The method of claim 240, wherein at least one of said determining steps comprises at least one ofthe steps of: averaging said property over an area of said voxel; and averaging said property over a volume of said voxel.
244. The method of claim 240, wherein said calculating step comprises at least one ofthe steps of: arithmetically averaging said voxel values of said intersecting voxels; geometrically averaging said voxel values of said intersecting voxels; weight-averaging said voxel values of said intersecting voxels; and ensemble-averaging said voxel values of said intersecting voxels.
245. A method for generating images representing distribution of at least one property of at least one chromophore in a target area of a physiological medium by a measuring system, wherein said system includes at least one wave source, at least one wave detector, a movable member, and an actuator member, said wave source configured to inadiate electromagnetic radiation into said medium, said wave detector configured to generate output signal in response to said electromagnetic radiation detected thereby, said movable member configured to include at least one of said wave source and detector, and said actuator member operationally coupling with said movable member, wherein said wave source and detector are configured to form a movable scanning unit which includes a longitudinal axis connecting said wave source and detector and which defines at least one of a scanning area and scanning volume therearound, and wherein said actuator member is configured to generate at least one movement of at least one of said movable member and scanning unit along at least one curvilinear path, said method comprising the steps of: placing said movable member on said target area of said medium; positioning said scanning unit in a first region of said target area; manipulating said actuator member to generate a first movement of at least one of said movable member and scanning unit from said first region to a second region of said target area along a first curvilinear path; defining a first set of first voxels from said output signals in at least a portion of said target area; determining a first sequence of first voxel values of said first voxels, each first voxel value representing a first average of said property averaged over said first voxel; defining a second set of second voxels from said output signals in at least a portion of said target area; determining a second sequence of second voxel values of said second voxels, each second voxel value representing a second average of said property averaged over said second voxel; constructing a set of cross-voxels each of which is defined as an intersecting portion of at least two intersecting voxels each of which belongs to one of said first and second sets of said first and second voxels, respectively; calculating a sequence of cross- voxel values of said cross- voxels directly from said voxel values of said intersecting voxels; and generating said images of said distribution of said property directly from said sequence of said cross-voxel values.
246. A system for providing information concerning distribution of hemoglobins and properties thereof in target areas of a physiological medium, comprising: an optical probe having a wave source and a wave detector, wherein said wave source is configured to inadiate near-infrared electromagnetic radiation into a first target area of said physiological medium and said wave detector is configured to detect near- infrared electromagnetic radiation from the medium and to generate a first output signal in response thereto; an analyzer receiving and sampling said first output signal to obtain a plurality of amplitude values, which are analyzed to determine at least one set of samples of said first output signal having substantially similar amplitudes; and a signal processor configured to calculate a first baseline from said first output signal, wherein said first baseline is representative of said substantially similar amplitudes determined by the analyzer, and to provide a self-calibrated first output signal by manipulating said first output signal and its first baseline.
247. The system of claim 246, wherein said optical probe has a scanning unit comprising two or more wave sources and two or more wave detectors, the scanning unit defining a scanning area therearound, which scanning area is a substantial portion of said first target area.
248. The system of claim 246, wherein said optical probe has a scanning unit comprising two or more wave sources and two or more wave detectors, the scanning unit defining a scanning area therearound, which scanning area is a fraction of said first target area.
249. The system of claim 248, wherein said optical probe has an actuator and a housing, said actuator being configured to move the scanning unit across a plurality of regions of said first target area, while said housing of said optical probe is positioned in said first target area.
250. The system of claim 249, wherein at least one of said wave detectors is configured to generate a plurality of said first output signals in said regions of said first target area.
251. The system of claim 246, wherein said signal processor is configured to provide said self-calibrated first output signal on a substantially real-time basis.
252. The system of claim 246 further comprising: an image processor configured to construct images of said distribution of hemoglobins or properties thereof in said first target area from said self-calibrated first output signals.
253. The system of claim 252, wherein said image processor is configured to construct said images on a substantially real-time basis.
254. The system of claim 252, wherein hemoglobins in said first target area are at least one of oxygenated hemoglobin and deoxygenated hemoglobin.
255. The system of claim 252, wherein said images relate to said distribution of at least one of oxygen saturation, concentration of oxygenated hemoglobin, concentration of deoxygenated hemoglobin, blood volume, and changes in blood volume in said first target area, wherein said oxygen saturation is defined as a ratio of said concentration of oxygenated hemoglobin to a sum of said concentrations of oxygenated and deoxygenated hemoglobins.
256. The system of claim 246, wherein said distribution includes at least one of spatial distribution of hemoglobins in said first target area and temporal changes in said distribution of hemoglobins in said first target area over time.
257. The system of claim 246 further comprising: a memory unit configured to store at least one of said first output signal, first baseline, and self-calibrated first output signal.
258. The system of claim 246, wherein said signal analyzer includes: a threshold unit for providing a threshold amplitude; a comparison unit for comparing amplitudes of said first output signal with a threshold amplitude; and a selection unit for identifying said plurality of samples of said first output signal having substantially similar amplitudes.
259. The system of claim 258, wherein said threshold unit is configured to receive input from an operator.
260. The system of claim 258, wherein said threshold unit is configured to calculate a reference amplitude from said first output signal and to calculate said threshold amplitude based on the reference amplitude.
261. The system of claim 260, wherein said reference amplitude is calculated from at least one of: a local maximum of said first output signal from said first target area; a local minimum of said first output signal from said first target area; an average of at least a portion of said first output signal; a global maximum of a plurality of said output signals from a plurality of said target areas of said medium; a global minimum of a plurality of said output signals from a plurality of said target areas of said medium; and a combination thereof.
262. The system of claim 260, wherein said threshold amplitude is a product of said reference amplitude and a pre-determined factor.
263. The system of claim 258, wherein said similar amplitudes of said plurality of said points are one of those greater than said threshold amplitude and those less than said threshold amplitude.
264. The system of claim 246, wherein said signal analyzer includes: a threshold unit for providing a threshold range of said amplitudes; a comparison unit for comparing said amplitudes of said first output signal with said threshold range; and a selection unit for identifying said plurality of said points of said first output signal.
265. The system of claim 264, wherein said similar amplitudes of said plurality of said points are one of those falling within said threshold range and those falling outside said threshold range.
266. The system of claim 246, wherein said signal processor includes an averaging unit for calculating said first baseline as an average of said similar amplitudes, wherein said average is one of: an arithmetic average of said similar amplitudes; a geometric average of said similar amplitudes; a weight-average of said similar amplitudes; and an ensemble-average of said similar amplitudes.
267. The system of claim 246, wherein said signal processor includes a calibration unit for providing said self-calibrated first output signal by normalizing said first output signal by said first baseline thereof.
268. The system of claim 267, wherein said self-calibrated first output signal is one of: a ratio of said first output signal to its first baseline; and a ratio of a difference between said first output signal and its first baseline to said first baseline.
269. The system of claim 246, wherein said signal analyzer includes at least one filter unit configured to improve signal-to-noise ratio of said first output signal.
270. The system of claim 269, wherein said filter unit includes at least one of: an averaging unit configured to provide at least one of an arithmetic average, geometric average, ensemble-average, and weight-average of a plurality of said first output signals from said first target area; and a low pass filter configured to remove high frequency noise from said first output signal.
271. The system of claim 246, wherein said signal analyzer further includes a confrol unit configured to store a plurality of said baselines measured in a plurality of target areas of said medium and to compare at least one of said baselines with the others thereof.
272. The system of claim 271, wherein said confrol unit is configured to provide an average of said plurality of said baselines.
278. The system of claim 271, wherein said control unit is configured to generate a signal when at least one of said baselines is at least substantially different from at least one ofthe others thereof.
279. A system for generating images representing distribution of chromophores or properties thereof in target areas of a physiological medium, said system including at least one wave source configured to inadiate electromagnetic radiation into said medium and at least one wave detector configured to detect electromagnetic radiation from said medium and to generate output signal in response thereto, said system comprising: a signal analyzer receiving and sampling a first output signal from said at least one wave detector and configured to analyze amplitudes of said first output signal, and to select a plurality of sampling points of said first output signal having substantially similar amplitudes, wherein said first output signal is representative of said distribution chromophores or properties thereof in a first target area of said medium; a signal processor configured to calculate a first baseline based on said first output signal and to provide a self-calibrated first output signal by manipulating both of said first output signal and its first baseline, where said first baseline conesponds to a representative amplitude of said similar amplitudes; and an image processor configured to construct images of said distribution of at least one of said chromophores or properties thereof from said self-calibrated first output signal.
280. An optical imaging system configured to generate images of target areas of a physiological medium, said images representing distribution of chromophores or properties thereof in said target areas, said system including at least one wave source configured to inadiate elecfromagnetic radiation into said medium and at least one wave detector configured to detect electromagnetic radiation from said medium and to generate output signal in response thereto, said system comprising: a movable member including at least one of said wave source and detector, said wave detector configured to generate a first output signal from a first target area of said medium, wherein said first output signal is representative of said distribution in a first target area of said medium; an actuator member configured to generate at least one movement of said movable member; a signal analyzer configured to receive said first output signal, to analyze amplitudes of said first output signal, and to select a plurality of points of said first output signal having substantially similar amplitudes; a signal processor configured to calculate a first baseline predominantly from said first output signal and to provide a self-calibrated first output signal by manipulating both of said first output signal and its first baseline, wherein said first baseline conesponds to a representative amplitude of said similar amplitudes; and an image processor configured to construct said images of said distribution of at least one of said chromophores and said properties thereof from said self-calibrated first output signal.
281. A system for generating images representing distribution of one or more chromophores and their properties in target areas of a physiological medium, comprising: an optical probe having at least one wave source and at least one wave detector, wherein said wave source is configured to inadiate electromagnetic radiation into a first target area of said physiological medium and wherein said wave detector is configured to detect said electromagnetic radiation from said first target area of said medium and to generate a first output signal in response thereto; a signal analyzer which is configured to receive and sample said first output signal, to analyze amplitudes of said first output signal, and to select a plurality of sample points of said first output signal having substantially similar amplitudes; and a signal processor which is configured to calculate a first baseline from said first output signal and to provide a self-calibrated first output signal by manipulating both of said first output signal and its first baseline, wherein said first baseline is a representative amplitude of said similar amplitudes.
282. A method for obtaining a calibrated output signal from an optical imaging system having an optical probe with at least one wave source configured to inadiate near- infrared electromagnetic radiation into target areas of a physiological medium and at least one wave detector generating output signal in response to near-infrared electromagnetic radiation detected thereby, the method comprising: positioning said optical probe on a first target area of said medium; generating a first output signal without moving said optical probe from said first target area; identifying at least one first portion of said first output signal, wherein the signal in said first portion has substantially similar first amplitudes; and obtaining a first baseline of said first output signal as a representative value of said substantially similar first amplitudes.
283. The method of claim 282 further comprising: normalizing said first output signal by said first baseline to provide a self- calibrated first output signal.
284. The method of claim 283, wherein said normalizing step comprises: providing a ratio signal representing a ratio of said first output signal to its first baseline.
285. The method of claim 283, wherein said normalizing step comprises: providing a difference signal representing a difference between said first output signal and its first baseline; and providing a ratio signal representing a ratio of said difference signal to said first baseline of said first output signal.
286. The method of claim 282, wherein said generating step comprises: providing movement of at least one of said wave source and detector over said first target area; and generating said first output signal during said movement.
287. The method of claim 282 further comprising: reducing noise from said first output signal prior to performing at least one of said identifying and obtaining steps.
288. The method of claim 287, wherein said reducing step comprises at least one of: arithmetically averaging a plurality said first output signals; geometrically averaging a plurality of said first output signals; weight-averaging a plurality of said first output signals; ensemble-averaging a plurality of said first output signals; and processing at least a portion of said first output signal through a low-pass filter.
289. The method of claim 282, wherein said identifying step comprises one of: selecting a threshold amplitude and identifying said first portion having said amplitudes greater than said threshold amplitude; selecting a threshold amplitude and identifying said first portion having said amplitudes less than said threshold amplitude; selecting at least one threshold range and identifying said first portion having said amplitudes falling within said threshold range; and selecting at least one threshold range and identifying said first portion having said amplitudes falling outside said threshold range.
290. The method of claim 289, wherein said selecting step comprises one of: manually selecting at least one of said threshold amplitude and range; and providing a reference amplitude and providing at least one of said threshold amplitude and range based on said reference amplitude.
291. The method of claim 290, wherein said reference amplitude is one of: a local maximum of said first output signal from said first target area; a local minimum of said first output signal from said first target area; an average of at least one portion of said first output signal; a global maximum of a plurality of said output signals from a plurality of said target areas of said medium; a global minimum of a plurality of said output signals from a plurality of said target areas of said medium; and and a combination thereof.
292. The method of claim 290, wherein said providing step comprises: multiplying said reference amplitude by a pre-selected factor to provide at least one of said threshold amplitude and range.
293. The method of claim 282, wherein said obtaining step comprises one of: arithmetically averaging said similar amplitudes; geometrically averaging said similar amplitudes; and weight-averaging said similar amplitudes.
294. The method of claim 282 further comprising: displacing said optical probe to a second target area of said medium; generating a second output signal from said second target area; and normalizing said second output signal by said first baseline of said first target area to provide a self-calibrated second output signal.
295. The method of claim 294 further comprising: repeating said displacing and generating steps of claim 43 in a plurality of said target areas of said medium.
296. The method of claim 282 further comprising: displacing said optical probe to a second target area of said medium; generating a second output signal from said second target area; identifying at least one second portion of said second output signal, wherein said second portion has substantially similar second amplitudes; and obtaining a second baseline of said second output signal as a representative value of said substantially similar second amplitudes.
297. The method of claim 296 further comprising: calculating a composite baseline by averaging said first baseline from said first target area and said second baseline from said second target area; and normalizing said first and second output signals by said composite baseline.
298. The method of claim 297, wherein said calculating step comprises one of: arithmetically averaging said baselines; weight-averaging said baselines; and selecting one of said baselines as said composite baseline.
299. A method for obtaining a calibrated output signal from an optical imaging system including an optical probe with at least one wave source and at least one wave detector, said wave source configured to inadiate near-infrared electromagnetic radiation into target areas of a physiological medium which includes a normal region and an abnormal region, said wave detector configured to generate output signal in response to said near- infrared electromagnetic radiation detected thereby, said method comprising: positioning said optical probe on a first target area of said medium; generating a first output signal without moving said optical probe from said first target area; identifying at least one first portion of said first output signal attributed to said normal region of said target area; and obtaining a first baseline of said first output signal from a representative value of said first portion of said first output signal, wherein said first portion attributed to said normal region is characterized by substantially flat profile and by substantially similar first amplitudes.
300. A method for calibrating an optical imaging system having an optical probe with at least one wave source for inadiating near-infrared elecfromagnetic radiation into target areas of a physiological medium and at least one wave detector for generating output signals in response to near-infrared electromagnetic radiation detected thereby, said method comprising: positioning said optical probe on a first target area of said medium; generating a first output signal without displacing said optical probe from said first target area; identifying at least one first portion of said first output signal having substantially similar first amplitudes before displacing said optical probe from said first target area; and obtaining a first baseline of said first output signal from a representative value of said substantially similar amplitudes before displacing said optical probe from said first target area.
301. The method of claim 300 further comprising: normalizing said first output signal by said first baseline to provide a self- calibrated first output signal on a substantially real time basis.
302. The method of claim 301 further comprising : generating at least one of images of said first output signal, images of said self-calibrated first output signal, images based on said first output signal, and images based on said self-calibrated first output signal.
EP20010959449 2000-08-04 2001-08-03 Systems and methods for providing information concerning chromophores in physiological media Ceased EP1307135A4 (en)

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US664972 1984-10-26
US22281600 true 2000-08-04 2000-08-04
US22307400 true 2000-08-04 2000-08-04
US223074P 2000-08-04
US222816P 2000-08-04
US09664972 US6597931B1 (en) 2000-09-18 2000-09-18 System and method for absolute oxygen saturation
US09778617 US20020033454A1 (en) 2000-08-04 2001-02-06 Optical imaging system with direct image construction
US778617 2001-02-06
US778613 2001-02-06
US09778618 US6516209B2 (en) 2000-08-04 2001-02-06 Self-calibrating optical imaging system
US778618 2001-02-06
US09778614 US6801648B2 (en) 2000-08-04 2001-02-06 Optical imaging system with symmetric optical probe
US09778613 US20020035317A1 (en) 2000-08-04 2001-02-06 Optical imaging system with movable scanning unit
US778614 2001-02-06
US09877515 US6587703B2 (en) 2000-09-18 2001-06-07 System and method for measuring absolute oxygen saturation
US877515 2001-06-07
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