US20050107694A1 - Method and system for ultrasonic tagging of fluorescence - Google Patents

Method and system for ultrasonic tagging of fluorescence Download PDF

Info

Publication number
US20050107694A1
US20050107694A1 US10/714,734 US71473403A US2005107694A1 US 20050107694 A1 US20050107694 A1 US 20050107694A1 US 71473403 A US71473403 A US 71473403A US 2005107694 A1 US2005107694 A1 US 2005107694A1
Authority
US
United States
Prior art keywords
scattering medium
ultrasonic
light
system
method
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/714,734
Inventor
Floribertus Jansen
Peter Lorraine
Stephen Lomnes
Pavel Fomitchov
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
General Electric Co
Original Assignee
General Electric Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by General Electric Co filed Critical General Electric Co
Priority to US10/714,734 priority Critical patent/US20050107694A1/en
Assigned to GENERAL ELECTRIC COMPANY reassignment GENERAL ELECTRIC COMPANY ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: JANSEN, FLORIBERTUS HEUKENSFELDT, FOMITCHOV, PAVEL ALEXEYEVICH, LOMNES, STEPHEN JOHNSON, LORRAINE, PETER WILLIAM
Publication of US20050107694A1 publication Critical patent/US20050107694A1/en
Application status is Abandoned legal-status Critical

Links

Images

Classifications

    • 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
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/645Specially adapted constructive features of fluorimeters
    • G01N21/6456Spatial resolved fluorescence measurements; Imaging
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/0048Detecting, measuring or recording by applying mechanical forces or stimuli
    • A61B5/0051Detecting, measuring or recording by applying mechanical forces or stimuli by applying vibrations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/0059Detecting, measuring or recording for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082Detecting, measuring or recording for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0091Detecting, measuring or recording for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for mammography
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/43Detecting, measuring or recording for evaluating the reproductive systems
    • A61B5/4306Detecting, measuring or recording for evaluating the reproductive systems for evaluating the female reproductive systems, e.g. gynaecological evaluations
    • A61B5/4312Breast evaluation or disorder diagnosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/001Preparation for luminescence or biological staining
    • A61K49/0013Luminescence
    • A61K49/0017Fluorescence in vivo
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/001Preparation for luminescence or biological staining
    • A61K49/0013Luminescence
    • A61K49/0017Fluorescence in vivo
    • A61K49/0019Fluorescence in vivo characterised by the fluorescent group
    • A61K49/0021Fluorescence in vivo characterised by the fluorescent group the fluorescent group being a small organic molecule
    • A61K49/0032Methine dyes, e.g. cyanine dyes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/001Preparation for luminescence or biological staining
    • A61K49/0013Luminescence
    • A61K49/0017Fluorescence in vivo
    • A61K49/0019Fluorescence in vivo characterised by the fluorescent group
    • A61K49/0021Fluorescence in vivo characterised by the fluorescent group the fluorescent group being a small organic molecule
    • A61K49/0032Methine dyes, e.g. cyanine dyes
    • A61K49/0034Indocyanine green, i.e. ICG, cardiogreen
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y10/00Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y20/00Nanooptics, e.g. quantum optics or photonic crystals
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • 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
    • G01N21/1717Systems in which incident light is modified in accordance with the properties of the material investigated with a modulation of one or more physical properties of the sample during the optical investigation, e.g. electro-reflectance
    • 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
    • G01N21/4795Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
    • 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
    • G01N21/1717Systems in which incident light is modified in accordance with the properties of the material investigated with a modulation of one or more physical properties of the sample during the optical investigation, e.g. electro-reflectance
    • G01N2021/1729Piezomodulation
    • 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
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6428Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G01N2021/6439Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks

Abstract

A method and system for localization of fluorescence in a scattering medium such as a biological tissue are provided. In comparison to other optical imaging techniques, this disclosure provides for improved spatial resolution, decreased computational time for reconstructions, and allows anatomical and functional imaging simultaneously. The method including the steps of illuminating the scattering medium with an excitation light to excite the fluorescence; modulating a portion of the emitted light from the fluorescence within the scattering medium using an ultrasonically induced variation of material properties of the scattering medium such as the refractive index; detecting the modulated optical signal at a surface of the scattering medium; and reconstructing a spatial distribution of the fluorescence in the scattering medium from the detected signal.

Description

    BACKGROUND OF THE INVENTION
  • This disclosure relates generally to medical imaging systems, and more particularly, to methods and systems for localization of fluorescent dyes in a scattering medium, e.g., biological tissue.
  • Millions of women participate in x-ray mammography each year. The specificity of this exam for radiologically dense breasts is not optimal. Suspicious lesions are subject to follow-up with other modalities such as ultrasound imaging, and ultimately are likely to be examined by biopsy. The physical discomfort and psychological impact to the women who obtain false-positive results from this screening procedure is immeasurable. The low sensitivity of the procedure gives rise to a high number of false negative results. This, in turn, leads to later stage detection of the disease and poorer patient prognostics. The rate of women having x-ray mammography screening is increasing annually, which leads to an overall earlier detection of suspect lesions. However, the increased frequency of mammography procedures, combined with the risks associated with the increased exposure to ionizing radiation brings into focus the clinical need for an alternate screening procedure that provides increased diagnostic sensitivity and specificity in radiologically dense breast tissue, that uses nonionizing radiation. One technology that shows promise for impacting this clinical challenge is Optical Imaging.
  • Optical imaging has the potential of developing into a highly sensitive modality that makes use of harmless levels of near-infrared light (NIR). Endogenous screening procedures have been proposed that use multiple wavelengths of NIR light to measure the relative levels of oxy- and deoxy-hemoglobin. This ratio has been proposed as a functional indicator for malignant tissue. Others have been working to create targeted fluorescent optical contrast agents that would selectively bind to biomarkers that are indicators of the presence of malignant tissue. The addition of targeted fluorescent contrast agents could potentially improve the diagnostic specificity of this technology. The list of variants of optical imaging technologies that are being developed for this particular clinical problem comprises continuous wave imaging (CW), time domain photon migration imaging (TDPM), frequency domain photon migration imaging (FDPM), thermo-acoustic computed tomography (TCT), and imaging with ultrasonically tagged light (UTL).
  • Continuous wave optical imaging—Continuous wave (CW) techniques involve illuminating a subject using one or more wavelengths of light and detecting the returning light at a separate location. The illumination is time-invariant. The technique boasts a low cost and complexity method for interrogating tissue for absorption, spectroscopic investigation, and for fluorescence imaging. However, the information contained within the signal is largely dominated by a signal from the most shallow portions of the tissue under investigation. This limits the usefulness of this technique for deep tissue interrogation.
  • Time domain photon migration (TDPM)—The depth limitation cited for CW techniques can be mitigated by using a short pulse of input light at one location and looking at the temporal point spread function, at a different location. This allows one to distinguish signal attributed to long times of flight from the more dominant shallow signal. The technique uses ultrashort pulsed lasers and photon detection schemes with very high temporal resolution. The instrumentation is typically more expensive as a consequence of increased hardware complexity. Because there is a physical mechanism for discriminating portions of the signal by time-of-flight, it has been possible to demonstrate reconstruction based on approximations of the Radiative Transport Equation via linearizations and iterative optimization methods. Tomography is limited due to the severely ill-posed nature of the imaging system. That is to say that even a large change of the optical properties of an interior region of interest deep in the tissue, results in only a small change in detected optical signal. It is for this reason that generating reliable maps of the optical properties has proven difficult.
  • Frequency domain photon migration (FDPM)—This techniques increases optical imaging sensitivity by illuminating the subject using sinusoidally time-varying excitation light. Information is recovered using heterodyne or homodyne techniques to measure the amplitude and phase of the output signal. These signal characteristics can provide information about the absorption and the scatter of the tissue. The technique has been used in endogenous and exogenous, single and multi-wavelength modes and can provide information for tomographic reconstruction. Like the TDPM technique, FDPM uses the Radiative Transport Equation for reconstruction.
  • Thermoacoustic computed tomography—A significantly less ill-posed technique that combines optical absorption imaging and acoustic imaging is thermoacoustic computed tomography. A NIR optical pulse is sent into the subject. The optical energy is absorbed preferentially by absorbing features (presumably, abnormalities in the tissue). The tissue which is thus heated generates a thermoacoustic shock wave. This acoustic signal is collected on the boundary of the subject and reconstructed to generate maps of optical absorption. This technique has the advantage of using acoustic techniques for detection. It provides an advantage because acoustic energy is scattered more weakly than optical energy, and the speed of sound in tissue is low enough to allow accurate triangulation of the origin of the shock wave. The modality is used to generate maps of relative optical absorption which are thought to correspond to regions of increased blood supply in the region of a malignant tumor as a result of angiogenesis.
  • Ultrasound tagging of light (UTL)—Researchers have demonstrated that it is possible to make the optical imaging problem less ill-posed by yet another combination of ultrasound and optical imaging. The strategy described here is to add a frequency “tag” to optical signals that have traveled through a known location in the tissue insonified with ultrasound. This allows an instrument to discriminate light that traveled through a location from light that has not. This phenomenon of acoustic tagging of coherent light in a scattering medium was first described by Marks, Tomlinson and Brooksby in “A comprehensive approach to beast cancer detection using light; photon localization by ultrasound modulation and tissue characterization by spectral discrimination” Proceedings of SPIE, Vol. 1888, pp. 500-510, 1993. Since that time a number of researchers have advanced the field to the point of being able to generate tomographic images that map relative absorption of the tissue. Regions of higher vasculature can be visualized using UTL. The diagnostic hypothesis hinges on the correlation of increased regional blood density to angiogenesis.
  • BREIF DESCRIPTION OF THE INVENTION
  • A method and system for localization of fluorescent dyes in a scattering medium such as a biological tissue are provided. In comparison to other optical imaging techniques, this disclosure provides for improved spatial resolution, decreased computational time for reconstruction, and allows simultaneous anatomical and functional imaging using light-emitting agents.
  • According to an aspect of the disclosure, a method for localization of fluorescence in a scattering medium is provided. The method includes the steps of illuminating the scattering medium with an excitation light to excite the fluorescence; modulating a portion of the emitted light from the fluorescence within the scattering medium using an ultrasonic pulse; detecting the modulated optical signal at the surface of the scattering medium; and reconstructing a spatial distribution of fluorescence in the scattering medium from the detected signal.
  • In another aspect of the present disclosure, a system for localization of fluorescence in a scattering medium comprises an excitation light source for illuminating the scattering medium; a fluorescent dye within a preselected region of the scattering medium for absorbing and emitting light in the NIR (near infrared) region of the light spectrum; an ultrasonic scanning system for generating ultrasonic pulses, wherein the ultrasonic pulses modulate the emitted light from the fluorescent dye; an optical detection system for detecting the modulated light; and a data processing system acquiring the detected optical signal and generating a spatial distribution of the fluorescence in the scattering medium based on the detected optical signals.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • The above and other aspects, features, and advantages of the present invention will become more apparent in light of the following detailed description when taken in conjunction with the accompanying drawings in which:
  • FIG. 1 is an exemplary system for illustrating the principle of acoustic modulation of fluorescent light;
  • FIG. 2 is a schematic diagram of an exemplary imaging system;
  • FIG. 3 is a flowchart illustrating a data processing algorithm for localizing an object of interest in a scattering medium;
  • FIG. 4 is a diagram illustrating an application of multiple excitation sources and waveforms read by multiple detectors;
  • FIG. 5 is a partial view for illustrating an embodiment for reading from multiple detector points;
  • FIG. 6 is a partial view for illustrating another embodiment for reading from multiple detectors;
  • FIG. 7 is a partial view for illustrating an application of multiple ultrasound generators;
  • FIG. 8 illustrates an embodiment of an imaging system as a hand-held device; and
  • FIG. 9 is a graph illustrating a typical signal acquired according to an embodiment of the present disclosure.
  • DETAILED DESCRIPTION OF THE INVENTION
  • Preferred embodiments of the present invention will be described hereinbelow with reference to the accompanying drawings. In the following description, well-known functions or constructions are not described in detail to avoid obscuring the invention in unnecessary detail.
  • A system and method for the localization of fluorescent dyes in a scattering medium are provided. In various embodiments of the present invention, systems and methods will be employed for localizing an object of interest, e.g., a lesion labeled with a fluorescent dye, in a scattering medium, e.g., biological tissue.
  • Referring to FIG. 1, the system 100 generally includes an optical excitation source 102 for irradiating or illuminating a scattering medium 104, including an object of interest 120, with radiant energy, e.g., light. The light excites a fluorophore contrast agent present in the object of interest 120. The system 100 further includes an ultrasonic generation system 106 for generating ultrasound pulses into the scattering medium 104 inducing an acoustic lens 108. The light emitted from the object of interest 120 is deflected by the acoustic lens 108. A detection system 110 for detecting the radiant energy, e.g., light, deflected by the acoustic lens 108 is also provided. A data processing system 112 collects data from the detection system 110 to construct an image of the scattering medium 104 and controls the overall operations of the excitation light source 102, ultrasonic generation system 106 and detection system 110, which will be described in detailed below.
  • Alternatively, the ultrasonic generation system 106 will induce the acoustic lens 108 to modulate the excitation light before it reaches the object of interest 120. The modulated light will then excite the fluorophore contrast agent in the object of interest which will emit light to be detected by the detection system 110.
  • A system and method for localizing an object of interest in a scattering medium will now be described in reference to FIGS. 2 and 3, where FIG. 2 is an exemplary imaging system and FIG. 3 is a flowchart illustrating a data processing algorithm for localizing the object of interest in the scattering medium.
  • Prior to the imaging procedure, a fluorescent optical contrast agent is introduced into a scattering medium 104, e.g., biological tissue. The fluorescent contrast agent may preferentially bind to an object of interest 120, e.g., diseased tissue, and thus may have disease or functional specificity. The fluorescent contrast agent may be one or more or a derivative of the following: Indocyanine green (ICG); a member of the Cy family of dyes; the IR-78 dye, or any other fluorophore that emits in the NIR region. The fluorescent contrast agent will absorb and emit light in the “transparency window” of biological tissue, which is between 700-900 nm where absorption of light in tissue is minimized. In other applications, it may be useful to operate anywhere in the range from 400-2000 nm for use with light emitting agents that operate in these wavelengths.
  • An optical excitation source 102 with a spectral output tuned to a maximal absorption wavelength of the fluorescent dye is used to excite the fluorescence. The excitation light source will include a light source 202 such as a laser; laser diode; light emitting diode (LED) or a lamp, e.g., halogen, incandescent, arc lamp, high intensity discharge etc. Excitation irradiation from the optical source is delivered to a surface of the biological tissue 104 using free-space optical system including a beam expander 204 to create a large illumination area that covers most of tissue surface and an optical spectral filter 206 for band pass, notch, or low pass filtering of the light to minimized the amount of excitation light in the expected emission band. Alternatively, multiple sources deliver the light via optical fiber or fiber optic bundles to form an array of localized illumination spots that may be illuminated simultaneously or in a sequence. The optical source can be operated in continuous wave (CW), intensity modulated, or pulsed mode. The frequency of intensity modulation and pulse repetition rate may be equal or fractional with respect to an ultrasonic frequency of the ultrasonic generation system 106.
  • When excitation photons reach the fluorescent dye in the object of interest 120, e.g., a lesion, localized in a volume of biological tissue, the fluorescence will re-emit optical radiation at a longer wavelength and acts as an omnidirectional optical source.
  • A focused ultrasonic beam is then formed using the ultrasonic generation system 106. The ultrasonic generation system may include (i) a single focused piezoelectric ultrasonic transducer (PZT) 210 coupled to an arbitrary function generator 214 and a high power RF amplifier 212; (ii) an ultrasonic scanning phased array, or (iii) a laser photoacoustic generator. The generated ultrasonic beam is transmitted into and scanned throughout the volume of the tissue. The ultrasonic generation can be performed in CW mode, or in pulsed mode using single frequency or frequency-swept tonebursts, or a short single broadband pulse. The ultrasonic beam can be configured as a single ultrasonic focal spot; an array of focal spots situated along a single line; a line focused beam oriented along optical source-to-receiver axis; superposition of two or more ultrasonic beams to form an acoustic interference pattern at the same frequency; or superposition of two or more ultrasonic beams to form an acoustic interference pattern at different frequencies.
  • The generated ultrasonic wave changes refractive index of the tissue via an elasto-optic effect. The amount of refractive index modulation depends on the acoustic pressure intensity, and the shape of the area of modified refractive index is defined by the geometry of the ultrasonic wave. The volume of tissue where this gradient of refractive index is acts as an “acoustic lens” 108 whose optical power varies in time at the ultrasonic frequency. The strongest refractive index modulation occurs in the focal point 109 of the ultrasonic beam.
  • A fraction of light emitted from the florescent dye is transmitted through the ultrasonic focal point 109 of the acoustic lens 108 and gets optically modulated at the ultrasonic frequency. The physical mechanism of the modulation is a deflection of the transmitted photon from its original direction by the acoustic lens. The strongest ultrasonic induced modulation occurs when the ultrasonic focal point is located half way between the object of interest 120 and a plane of optical detection.
  • Alternatively, the ultrasonic beam may be formed before the excitation light reaches the object of interest 120. In this situation, the excitation light will be optically modulated before it excites the fluorescence in the object of interest, and therefore, the light emitted by the fluorescence in the object of interest will be modulated at the ultrasonic frequency of the ultrasonic generation system 106.
  • When the acoustically modulated light reaches the surface of the biological tissue 104, it can be detected using the detection system 110. A variety of optical detectors can be used for the detection of ultrasonic modulated light such as: a single optical detector 234 such as a photodetector, photomultiplier tube (PMT), photodiode; arrays of photodetectors; or full field optical detectors such as charge-coupled device (CCD) cameras. The optical energy can be delivered to the detectors via free-space imaging optics such as a collection optic 230 and optical filter 232, optical fibers and/or through fiber bundles. An efficient detection of ultrasonic induced modulation requires blocking of excitation light that can be done using optical filtering techniques. One or more optical filters 232 may also be provided to reject light that is not fluorescent emission, and accept light that is fluorescent emission. The detection system 110 further includes an amplifier 236 for amplifying the detected optical signal received from detector 234 and a bandpass filter 238 for filtering the amplified signal before being sent to the data processing system 112. Preferably, the point of detection will be located at an approximately 90 degrees angle in relation to the ultrasonic transducer.
  • This optical signal, e.g., the time varying intensity of light, is acquired and stored for further processing for each position of the ultrasonic focal spot during the scan.
  • The modulated optical signal is detected using one or more of the following techniques: direct detection of the signal; a homodyne detection method wherein the gain of the optical signal is modulated at the ultrasonic frequency, and the phase between the optical gain and the ultrasound is swept over a range of angles; a heterodyne detection method wherein the gain of the optical signal is modulated at some frequency that is different that the ultrasound frequency, and the amplitude of the signal at the side lobes is measured; a shuttering detection method that integrates the optical signal at a particular phase in the ultrasonic modulation over many acoustic cycles, wherein the optical signal is then integrated at one or more different phases over many acoustic cycles, and the modulated light signal is extracted by comparison of these integrated signals; or a double cross correlation technique that performs a correlation analysis of the detected optical signal against the illumination input signal and the acoustic input signal to measure the amplitude of the signal for optimal noise rejection.
  • The data collected by the optical detectors will then be sent to the data processing system 112. It is to be understood that the data processing system 112 may be implemented in various forms of hardware, software, firmware, special purpose processors, or a combination thereof. In one embodiment, the data processing system 112 may be implemented in software as an application program tangibly embodied on a program storage device. The application program may be uploaded to, and executed by, a machine comprising any suitable architecture. Preferably, the machine is implemented on a computer platform having hardware such as one or more central processing units (CPU), a random access memory (RAM), a read only memory (ROM) and input/output (I/O) interface(s) such as a keyboard, cursor control device (e.g., a mouse) and display device. The computer platform also includes an operating system and micro instruction code. The various processes and functions described herein may either be part of the micro instruction code or part of the application program (or a combination thereof) which is executed via the operating system. In addition, various other peripheral devices may be connected to the computer platform such as an additional data storage device and a printing device.
  • It is to be further understood that, because some of the constituent system components and method steps depicted in the accompanying figures may be implemented in software, the actual connections between the system components (or the process steps) may differ depending upon the manner in which the present invention is programmed. Given the teachings of the present invention provided herein, one of ordinary skill in the related art will be able to contemplate these and similar implementations or configurations of the present invention.
  • The location of the fluorescent dye can be determined from a data set obtained during ultrasonic scan over the volume of the biological tissue. Initially in step 302, the excitation light source 102 will illuminate the scattering medium 104. A two-dimensional (2D) scanning of a volume of the scattering medium 104 will be preformed for N×M steps along an X and Y axis of the scattering medium 104. After the scattering medium is illuminated, the transducer 210 and detector 234 are moved to the j-position along the X axis (step 304) and, similarly, are moved to the i-position along the Y axis (step 306). Once the proper position is located, the transducer 230 is fired to induce the acoustic lens (step 308).
  • Detector 234 will detect an optical signal generated via the acoustical lens and the optical signal will be sent to the data processing system to acquire an ultrasonic trace (step 310). A time window is applied to the ultrasonic trace to extract a signal corresponding to an arrival of the ultrasonic wave to the focal point of the acoustic lens (step 312). Next, a fast Fourier transform (FFT) is performed on the windowed signal (step 316) and an amplitude of the signal is measured at the ultrasound frequency (step 316). The measured amplitude is then assigned a grey level of the i-j pixel of the image to be generated (step 318).
  • The method will then check if N scans have been taken along the i-position on the Y-axis (step 320). If it is less than N, the method will return to step 306, the transducer 210 and detector 234 will be move to the next position along the Y-axis and steps 308 through 318 will be repeated. Similarly, the method will then check if M scans have been taken along the j-position on the X-axis (step 322). If j is less than M, the method will return to step 304, the transducer 210 and detector 234 will be move to the next position along the X-axis and steps 308 through 318 will be repeated.
  • Referring to FIG. 4, the use of multiple illumination points and detection points is illustrated. In FIG. 4, S represents an excitation light source at a specific point on the volume and D represents a detector for acquiring an optical signal at the specified point, where an exemplary detected signal is associated with each detector. To acquire the multiple detected signals, a signal detector 234 may be utilized in conjunction with switch 550. Switch 550 will be connected to several detector point D1 through Dn which will be coupled to the detector 234 depending on a position of the switch 550, as shown in FIG. 5. Optionally, the switch will be coupled to and controlled by the data processing system 112. Alternatively, multiple detectors will be located on the surface of the scattering medium 104 and switch 660 will couple individual detectors 234 to the data processing system.
  • Similarly, to generate ultrasonic pulses at different locations and induce acoustic lens at varying angles, multiple transducers 210 may be located at multiple points and coupled to the arbitrary function generator 214 via switch 770.
  • When all the scans have been acquired, an image localizing the object of interest will be created and displayed on the display or saved to memory (step 324). This can be done using the measured amplitude of the US modulated signal and ultrasonic time-of-flight for each scan location; measured depth of modulation as a function of focal-spot-to-detector distance; or known focal-spot-to-detector geometry.
  • The reconstruction algorithm for the fluorescent optical image may be any one of the following conventional techniques: Solution by direct inversion of a linear description of the forward model; Solution by iterative optimization of a nonlinear description of the forward model; Solution by direct solution of a nonlinear description of the forward model.
  • To illustrate the principles of the present disclosure, the following experiment was preformed. A 0.1 ml of micro-molar solution of Rhodamine 6G (maximal emission ˜570 nm) was injected into a transparent gel to form a fluorescent-marked area, e.g., an object of interest, approximately 1 mm in diameter and 5 mm length. A rectangular plastic cuvette with the gel was immersed into a water tank, e.g., a scattering medium. The fluorescence was excited using frequency-doubled YAG laser (λ=532 nm, optical power 10 mW), which beam was expanded by 10× microscope objective. An immersed PZT transducer (focal length 50 mm, diameter 25 mm) was excited by 10 tonebursts of 2 MHz frequency. Focal point of the transducer was located on axis between the fluorophore and optical detector at 20 mm distance from the fluorophore. The fluorescent light was collected by 50 mm lens on an amplified Si-photodetector, e.g., a model PDA55 commercially available from Thorlabs of New Jersey. An interference band-reject optical filter with OD=6 at λ=532 nm was placed in front of the photodetector to block the excitation light. Overall optical power of the fluorescent light at the photodetector was ˜20 nW, the level of ambient light and excitation light leakage were below 1 nW. The photodetector signal was amplified by 54 dB using a broadband RF amplifier, commercially available from GE Panametrics, of Waltham, Mass., band-pass filtered, digitized and averaged 512 times by a digital oscilloscope.
  • A typical acquired waveform and its spectrum are shown in FIG. 9. This experiment demonstrates the existence of the effect of ultrasonic tagging of fluorescence. The time delay of the detected signal corresponds to an arrival time of the ultrasonic toneburst to the acoustic focal point, that was verified by small axial displacement of the transducer. The spectrum of the signal shows that the power of 2.0 MHz signal within a 5 □s time window where the detected signal is present is significantly stronger than a 2.0 MHz component in a 5 □s time window taken earlier where just noise is present. This experiment clearly demonstrates the existence of the effect of ultrasonic tagging of fluorescence in a transparent medium.
  • Referring to FIG. 8, a hand-held imaging device 800 is illustrated. The imaging device 800 includes an excitation light source for illuminating the scattering medium. Preferably, light from the excitation light source is transmitted to a surface of the scattering medium via an optical fiber 840; in this way, the source can be located remotely from the device to conserve space in the device 800.
  • The imaging device includes a phased array of ultrasonic transducers 842 for inducing an acoustical lens 108 in the scattering medium. Light modulated by the acoustical lens is preferably detected by a second optical fiber 844 coupled to a detection system for acquiring ultrasonic traces.
  • A system and method for the localization of fluorescent dyes in a scattering medium are provided. The system and method provides for increased optical image resolution; simultaneous anatomical imaging (using ultrasonic scan data) and functional imaging (using optical data); decreased optical reconstruction complexity and required computation time, while utilizing non-ionizing radiation.
  • While the disclosure has been illustrated and described in typical embodiments, it is not intended to be limited to the details shown, since various modifications and substitutions can be made without departing in any way from the spirit of the present disclosure. As such, further modifications and equivalents of the disclosure herein disclosed may occur to persons skilled in the art using no more than routine experimentation, and all such modifications and equivalents are believed to be within the spirit and scope of the disclosure as defined by the following claims.

Claims (24)

1. A method for localization of fluorescence in a scattering medium, the method comprising the steps of:
illuminating the scattering medium with an excitation light to excite the fluorescence;
modulating a portion of the emitted light from the fluorescence within the scattering medium using an ultrasonic pulse;
detecting the modulated optical signal at a surface of the scattering medium.
2. The method as in claim 1, further comprising the step of reconstructing a spatial distribution of the fluorescence in the scattering medium from the detected signal.
3. The method as in claim 1, wherein the modulating step is performed by an ultrasonically induced gradient of refractive index.
4. The method as in claim 2, wherein the reconstructing step further comprises scanning a volume of the scattering medium with an ultrasonic beam and detecting the modulated optical signal for each scanning location.
5. The method as in claim 1, wherein the illumination with the excitation source is intensity modulated sinusoidally at a predetermined frequency.
6. The method as in claim 1, wherein the illumination with the excitation source is intensity modulated sinusoidally at time-varying frequencies.
7. The method as in claim 1, wherein the illumination with the excitation source is pulsed at a predetermined repetition rate and pulse width.
8. The method as in claim 1, wherein the illumination with the excitation source is in continuous wave mode.
9. The method as in claim 1, wherein the ultrasonically induced pressure gradient is shaped as a single ultrasonic focal spot, an array of focal spots situated along a single line, an elongated linear ultrasonic focal region oriented along an optical source-to-receiver axis, a superposition of two or more ultrasonic beams to form an acoustic interference pattern at the same frequency or a superposition of two or more ultrasonic beams at the different frequencies.
10. The method as in claim 1, wherein the detecting step of the modulated optical signal is performed by a homodyne detection method wherein a gain of the optical signal is modulated at the ultrasonic frequency, and a phase between the optical gain and the ultrasound is swept over a range of angles.
11. The method as in claim 1, wherein the detecting step of the modulated optical signal is performed by a heterodyne detection system wherein a gain of the optical signal is modulated at a frequency that is different that the ultrasound frequency, and an amplitude of the signal at the side lobes is measured.
12. The method as in claim 1, wherein the detecting step of the modulated optical signal is performed by a gated detection method that integrates the optical signal at a particular phase in the ultrasonic modulation over many acoustic cycles and integrates the optical signal at one or more different phases over many acoustic cycles, wherein the modulated optical signal can be extracted by comparison of the integrated signals.
13. The method as in claim 1, wherein the detecting step of the modulated optical signal is performed by a double cross correlation technique that performs a correlation analysis of the detected optical signal against the illumination input signal and the ultrasonic input signal to measure an amplitude of the detected signal for optimal noise rejection.
14. A method for localization of fluorescence in a scattering medium, the method comprising the steps of:
illuminating the scattering medium with an excitation light to excite the fluorescence;
modulating the excitation light using an ultrasonic pulse;
detecting a modulated optical signal emitted from the fluorescence at a surface of the scattering medium.
15. A system for localization of fluorescence in a scattering medium comprising:
an excitation light source for illuminating the scattering medium;
a fluorescent dye within a preselected region of the scattering medium for absorbing and emitting light in the NIR (near infrared) region of the light spectrum;
an ultrasonic scanning system for generating ultrasonic pulses, wherein the ultrasonic pulses modulate the emitted light from the fluorescent dye; and
an optical detection system for detecting the modulated light.
16. The system as in claim 15, further comprising a data processing system acquiring the detected optical signal and generating a spatial distribution of the fluorescence in the scattering medium based on the detected optical signals.
17. The system as in claim 15, wherein the excitation light source is a laser, laser diode, light emitting diode (LED) or a lamp.
18. The system as in claim 15, wherein the fluorescent dye is Indocyanine green (ICG), a member of the Cy family of dyes, IR-78 dye or a fluorophore that emits in the NIR region of light.
19. The system as in claim 15, wherein the ultrasonic scanning system is a single-ultrasonic transducer that is scanned over the preselected region of the scattering medium.
20. The system as in claim 15, wherein the ultrasonic scanning system is a phased array of single element ultrasonic transducers that are scanned over the preselected region of the scattering medium.
21. The system as in claim 15, wherein the optical detection system further comprises:
a light collection and delivery system for collecting light emitted;
at least one optical filter for filtering the light and allowing transmission of fluorescent emission; and
a detector for converting optical signals to electrical signals capable of being read by the data processing system.
22. The system as in claim 21, wherein the light collection and delivery system includes at least one optical fiber for delivering collected light from the scattering medium to the detector.
23. The system as in claim 21, wherein the detector is photodetector, photomultiplier tube (PMT), image intensifier, charge-coupled device or an array of photosensitive elements.
24. An imaging system for localization of a preselected object in a scattering medium comprising:
an excitation light source for illuminating the scattering medium;
a fluorescent dye injected into the preselected object for absorbing and emitting light in the NIR (near infrared) region of the light spectrum;
an ultrasonic scanning system for generating ultrasonic pulses, wherein the ultrasonic pulses modulate the emitted light from the fluorescent dye;
an optical detection system for detecting the modulated light; and
a data processing system acquiring the detected optical signal and generating a spatial distribution of the preselected object in the scattering medium based on the detected optical signals.
US10/714,734 2003-11-17 2003-11-17 Method and system for ultrasonic tagging of fluorescence Abandoned US20050107694A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US10/714,734 US20050107694A1 (en) 2003-11-17 2003-11-17 Method and system for ultrasonic tagging of fluorescence

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US10/714,734 US20050107694A1 (en) 2003-11-17 2003-11-17 Method and system for ultrasonic tagging of fluorescence
PCT/US2004/038599 WO2005050180A1 (en) 2003-11-17 2004-11-17 Method and system for ultrasonic tagging of fluorescence
EP04819176A EP1709427A1 (en) 2003-11-17 2004-11-17 Method and system for ultrasonic tagging of fluorescence
US11/254,266 US8103329B2 (en) 2003-11-17 2005-10-20 System and method for imaging based on ultrasonic tagging of light

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/254,266 Continuation-In-Part US8103329B2 (en) 2003-11-17 2005-10-20 System and method for imaging based on ultrasonic tagging of light

Publications (1)

Publication Number Publication Date
US20050107694A1 true US20050107694A1 (en) 2005-05-19

Family

ID=34574043

Family Applications (2)

Application Number Title Priority Date Filing Date
US10/714,734 Abandoned US20050107694A1 (en) 2003-11-17 2003-11-17 Method and system for ultrasonic tagging of fluorescence
US11/254,266 Active 2027-07-25 US8103329B2 (en) 2003-11-17 2005-10-20 System and method for imaging based on ultrasonic tagging of light

Family Applications After (1)

Application Number Title Priority Date Filing Date
US11/254,266 Active 2027-07-25 US8103329B2 (en) 2003-11-17 2005-10-20 System and method for imaging based on ultrasonic tagging of light

Country Status (3)

Country Link
US (2) US20050107694A1 (en)
EP (1) EP1709427A1 (en)
WO (1) WO2005050180A1 (en)

Cited By (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050256403A1 (en) * 2004-05-12 2005-11-17 Fomitchov Pavel A Method and apparatus for imaging of tissue using multi-wavelength ultrasonic tagging of light
EP1602381A1 (en) * 2004-05-14 2005-12-07 General Electric Company Contrast agent for combined modality imaging and methods and systems thereof
US20060184049A1 (en) * 2005-01-26 2006-08-17 Fuji Photo Film Co., Ltd. Apparatus for acquiring tomographic image formed by ultrasound-modulated fluorescence
WO2007100937A2 (en) * 2006-01-19 2007-09-07 The Regents Of The University Of Michigan System and method for spectroscopic photoacoustic tomography
WO2008005554A2 (en) * 2006-07-06 2008-01-10 University Of Connecticut Method and apparatus for medical imaging using near-infrared optical tomography, fluorence tomography combined with ultrasound
US20080077002A1 (en) * 2004-09-10 2008-03-27 Koninklijke Philips Electronics, N.V. Compounds and Methods for Combined Optical-Ultrasound Imaging
US20080123083A1 (en) * 2006-11-29 2008-05-29 The Regents Of The University Of Michigan System and Method for Photoacoustic Guided Diffuse Optical Imaging
US20080173093A1 (en) * 2007-01-18 2008-07-24 The Regents Of The University Of Michigan System and method for photoacoustic tomography of joints
US20080221647A1 (en) * 2007-02-23 2008-09-11 The Regents Of The University Of Michigan System and method for monitoring photodynamic therapy
US20080221447A1 (en) * 2007-03-08 2008-09-11 Olympus Medical Systems Corp. Medical apparatus obtaining information indicative of internal state of an object based on interaction between sound waves and light
US20090103096A1 (en) * 2004-12-30 2009-04-23 Art, Advanced Research Technologies Inc. Method for determining optical properties of turbid media
WO2009064753A1 (en) * 2007-11-12 2009-05-22 Cornell University Non-imaging, weakly focused fluorescence emission apparatus and methods
US20090227997A1 (en) * 2006-01-19 2009-09-10 The Regents Of The University Of Michigan System and method for photoacoustic imaging and monitoring of laser therapy
US20100094134A1 (en) * 2008-10-14 2010-04-15 The University Of Connecticut Method and apparatus for medical imaging using near-infrared optical tomography combined with photoacoustic and ultrasound guidance
US20110017217A1 (en) * 2007-08-06 2011-01-27 University Of Rochester Medical apparatuses incorporating dyes
US20110071402A1 (en) * 2009-09-24 2011-03-24 Canon Kabushiki Kaisha Apparatus and method for irradiating a medium
US7926975B2 (en) 2007-12-21 2011-04-19 Altair Engineering, Inc. Light distribution using a light emitting diode assembly
US7938562B2 (en) 2008-10-24 2011-05-10 Altair Engineering, Inc. Lighting including integral communication apparatus
US20110112391A1 (en) * 2008-07-11 2011-05-12 Canon Kabushiki Kaisha Photoacoustic measurement apparatus
US7946729B2 (en) 2008-07-31 2011-05-24 Altair Engineering, Inc. Fluorescent tube replacement having longitudinally oriented LEDs
US7976196B2 (en) 2008-07-09 2011-07-12 Altair Engineering, Inc. Method of forming LED-based light and resulting LED-based light
US20110239766A1 (en) * 2008-12-11 2011-10-06 Canon Kabushiki Kaisha Photoacoustic imaging apparatus and photoacoustic imaging method
US8118447B2 (en) 2007-12-20 2012-02-21 Altair Engineering, Inc. LED lighting apparatus with swivel connection
WO2012075860A1 (en) * 2010-12-09 2012-06-14 深圳大学 Fluorescence endoscopic imaging method and system
US8214084B2 (en) 2008-10-24 2012-07-03 Ilumisys, Inc. Integration of LED lighting with building controls
US8256924B2 (en) 2008-09-15 2012-09-04 Ilumisys, Inc. LED-based light having rapidly oscillating LEDs
US8299695B2 (en) 2009-06-02 2012-10-30 Ilumisys, Inc. Screw-in LED bulb comprising a base having outwardly projecting nodes
US8324817B2 (en) 2008-10-24 2012-12-04 Ilumisys, Inc. Light and light sensor
US8330381B2 (en) 2009-05-14 2012-12-11 Ilumisys, Inc. Electronic circuit for DC conversion of fluorescent lighting ballast
US8360599B2 (en) 2008-05-23 2013-01-29 Ilumisys, Inc. Electric shock resistant L.E.D. based light
US8362710B2 (en) 2009-01-21 2013-01-29 Ilumisys, Inc. Direct AC-to-DC converter for passive component minimization and universal operation of LED arrays
US8421366B2 (en) 2009-06-23 2013-04-16 Ilumisys, Inc. Illumination device including LEDs and a switching power control system
US8444292B2 (en) 2008-10-24 2013-05-21 Ilumisys, Inc. End cap substitute for LED-based tube replacement light
US8454193B2 (en) 2010-07-08 2013-06-04 Ilumisys, Inc. Independent modules for LED fluorescent light tube replacement
US8523394B2 (en) 2010-10-29 2013-09-03 Ilumisys, Inc. Mechanisms for reducing risk of shock during installation of light tube
US8541958B2 (en) 2010-03-26 2013-09-24 Ilumisys, Inc. LED light with thermoelectric generator
US8540401B2 (en) 2010-03-26 2013-09-24 Ilumisys, Inc. LED bulb with internal heat dissipating structures
US8556452B2 (en) 2009-01-15 2013-10-15 Ilumisys, Inc. LED lens
US8596813B2 (en) 2010-07-12 2013-12-03 Ilumisys, Inc. Circuit board mount for LED light tube
US8653984B2 (en) 2008-10-24 2014-02-18 Ilumisys, Inc. Integration of LED lighting control with emergency notification systems
US8664880B2 (en) 2009-01-21 2014-03-04 Ilumisys, Inc. Ballast/line detection circuit for fluorescent replacement lamps
US8674626B2 (en) 2008-09-02 2014-03-18 Ilumisys, Inc. LED lamp failure alerting system
US8870415B2 (en) 2010-12-09 2014-10-28 Ilumisys, Inc. LED fluorescent tube replacement light with reduced shock hazard
US8901823B2 (en) 2008-10-24 2014-12-02 Ilumisys, Inc. Light and light sensor
US8917442B2 (en) 2012-09-20 2014-12-23 Elwha Llc Focusing electromagnetic radiation within a turbid medium using ultrasonic modulation
US9057493B2 (en) 2010-03-26 2015-06-16 Ilumisys, Inc. LED light tube with dual sided light distribution
US9072171B2 (en) 2011-08-24 2015-06-30 Ilumisys, Inc. Circuit board mount for LED light
US9163794B2 (en) 2012-07-06 2015-10-20 Ilumisys, Inc. Power supply assembly for LED-based light tube
US9184518B2 (en) 2012-03-02 2015-11-10 Ilumisys, Inc. Electrical connector header for an LED-based light
US9232896B2 (en) 2012-09-20 2016-01-12 Elwha Llc Focusing electromagnetic radiation within a turbid medium using ultrasonic modulation
US9271367B2 (en) 2012-07-09 2016-02-23 Ilumisys, Inc. System and method for controlling operation of an LED-based light
US9267650B2 (en) 2013-10-09 2016-02-23 Ilumisys, Inc. Lens for an LED-based light
US9285084B2 (en) 2013-03-14 2016-03-15 Ilumisys, Inc. Diffusers for LED-based lights
US9510400B2 (en) 2014-05-13 2016-11-29 Ilumisys, Inc. User input systems for an LED-based light
US9574717B2 (en) 2014-01-22 2017-02-21 Ilumisys, Inc. LED-based light with addressed LEDs
US10161568B2 (en) 2015-06-01 2018-12-25 Ilumisys, Inc. LED-based light with canted outer walls
US10278247B2 (en) 2017-09-22 2019-04-30 Ilumisys, Inc. System and method for controlling operation of an LED-based light

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101313209A (en) * 2005-11-23 2008-11-26 皇家飞利浦电子股份有限公司 A method of, system for, and medical image acquisition system for imaging an interior of a turbid medium taking into account the geometry of the turbid medium
US20070238997A1 (en) * 2006-03-29 2007-10-11 Estelle Camus Ultrasound and fluorescence imaging
JP5317449B2 (en) * 2007-09-12 2013-10-16 キヤノン株式会社 measuring device
JP5284129B2 (en) * 2008-02-06 2013-09-11 キヤノン株式会社 Imaging device, and the analysis method
WO2009116029A2 (en) * 2008-03-17 2009-09-24 Or-Nim Medical Ltd. Apparatus for non invasive optical monitoring
CN102137618B (en) * 2008-07-25 2015-06-17 健康与环境慕尼黑德国研究中心赫姆霍茨中心(有限公司) Quantitative multi-spectral opto-acoustic tomography (MSOT) of tissue biomarkers
EP2260754A1 (en) * 2009-06-10 2010-12-15 Universiteit Twente Device and method for photon absorption coefficient measurement
JP5645421B2 (en) * 2010-02-23 2014-12-24 キヤノン株式会社 Ultrasound imaging device and a delay control method
JP5641773B2 (en) * 2010-04-28 2014-12-17 キヤノン株式会社 measuring device
US8466420B2 (en) 2010-06-04 2013-06-18 General Electric Company Charge loss correction
US20120070817A1 (en) * 2010-09-20 2012-03-22 California Institute Of Technology Acoustic-assisted iterative wave form optimization for deep tissue focusing
US8712124B2 (en) 2011-06-21 2014-04-29 General Electric Company Artifact removal in nuclear images
WO2013066447A1 (en) 2011-08-01 2013-05-10 The Trustees Of Columbia University In The City Of New York Lens-free planar imager and wireless transmitter
WO2013059665A1 (en) 2011-10-19 2013-04-25 The Trustees Of Columbia University In The City Of New York Ultracompact fabry-perot array for ultracompact hyperspectral imaging
US9052180B2 (en) * 2012-01-03 2015-06-09 The Board Of Trustees Of The University Of Illinois Spatial light interference tomography
WO2013148349A1 (en) 2012-03-30 2013-10-03 The Trustees Of Columbia University In The City Of New York Graphene photonics for resonator-enhanced electro-optic devices and all-optical interactions
US9212948B2 (en) 2012-11-07 2015-12-15 The Trustees Of Columbia University In The City Of New York Lossless hyperspectral imaging
CN103207168A (en) * 2012-12-26 2013-07-17 西安交通大学 Optical reconstruction method for potential functional information of myocardial cell membranes
US9014333B2 (en) * 2012-12-31 2015-04-21 General Electric Company Image reconstruction methods for differential phase contrast X-ray imaging
EP2754388A1 (en) 2013-01-15 2014-07-16 Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH System and method for quality-enhanced high-rate optoacoustic imaging of an object
KR20160089689A (en) * 2015-01-20 2016-07-28 삼성전자주식회사 Ultrasound probe, ultrasound imaging apparatus, and controlling method for the same
US10016137B1 (en) 2017-11-22 2018-07-10 Hi Llc System and method for simultaneously detecting phase modulated optical signals
US10219700B1 (en) 2017-12-15 2019-03-05 Hi Llc Systems and methods for quasi-ballistic photon optical coherence tomography in diffusive scattering media using a lock-in camera detector

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3182292A (en) * 1961-06-29 1965-05-04 Link Division Of General Prec Noise-rejecting counter circuit
US5174298A (en) * 1987-07-03 1992-12-29 General Electric Cgr S.A. Imaging process and system for transillumination with photon frequency marking
US5212667A (en) * 1992-02-03 1993-05-18 General Electric Company Light imaging in a scattering medium, using ultrasonic probing and speckle image differencing
US5608690A (en) * 1995-03-02 1997-03-04 Acuson Corporation Transmit beamformer with frequency dependent focus
US6216540B1 (en) * 1995-06-06 2001-04-17 Robert S. Nelson High resolution device and method for imaging concealed objects within an obscuring medium
US20020043561A1 (en) * 1995-12-18 2002-04-18 Adaptive Optics Associates, Inc. Method of and system for producing digital images of objects with subtantially reduced speckle-noise patterns by illuminating said objects with spatially and/or temporally coherent-reduced planar laser illumination
US6699192B2 (en) * 2002-03-19 2004-03-02 Fuji Photo Film Co., Ltd. Ultrasonic receiving apparatus and ultrasonic imaging apparatus
US20040099815A1 (en) * 2000-07-23 2004-05-27 Sfez Bruno Gad Apparatus and method for probing light absorbing agents in biological tissues
US20040127783A1 (en) * 2002-09-26 2004-07-01 Kruger Robert A. Tissue scanner
US20060122475A1 (en) * 2003-09-12 2006-06-08 Or-Nim Medical Ltd. Method and apparatus for noninvasively monitoring parameters of a region of interest in a human body

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3037983C2 (en) * 1980-10-08 1983-03-31 Fa. Carl Zeiss, 7920 Heidenheim, De
US5203339A (en) * 1991-06-28 1993-04-20 The Government Of The United States Of America As Represented By The Secretary Of The Department Health And Human Services Method and apparatus for imaging a physical parameter in turbid media using diffuse waves
US5451785A (en) * 1994-03-18 1995-09-19 Sri International Upconverting and time-gated two-dimensional infrared transillumination imaging
US5919140A (en) * 1995-02-21 1999-07-06 Massachusetts Institute Of Technology Optical imaging using time gated scattered light
US5999836A (en) * 1995-06-06 1999-12-07 Nelson; Robert S. Enhanced high resolution breast imaging device and method utilizing non-ionizing radiation of narrow spectral bandwidth
US6091983A (en) * 1997-02-07 2000-07-18 Alfano; Robert R. Imaging of objects in turbid media based upon the preservation of polarized luminescence emitted from contrast agents
GB9712525D0 (en) * 1997-06-16 1997-08-20 Nycomed Imaging As Method
IL129398A (en) 1999-04-12 2005-05-17 Israel Atomic Energy Comm Metabolism monitoring or body organs
US6167297A (en) * 1999-05-05 2000-12-26 Benaron; David A. Detecting, localizing, and targeting internal sites in vivo using optical contrast agents
US6530944B2 (en) * 2000-02-08 2003-03-11 Rice University Optically-active nanoparticles for use in therapeutic and diagnostic methods
EP1434522B1 (en) * 2000-10-30 2010-01-13 The General Hospital Corporation Optical systems for tissue analysis
WO2003017745A2 (en) * 2001-08-23 2003-03-06 Sciperio, Inc. Architecture tool and methods of use
US7349731B2 (en) 2002-06-07 2008-03-25 Clemson University Research Foundation Reconstructed refractive index spatial maps and method with algorithm
JP5203951B2 (en) * 2005-10-14 2013-06-05 ザ ジェネラル ホスピタル コーポレイション Spectrum and frequency encoding fluorescent imaging

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3182292A (en) * 1961-06-29 1965-05-04 Link Division Of General Prec Noise-rejecting counter circuit
US5174298A (en) * 1987-07-03 1992-12-29 General Electric Cgr S.A. Imaging process and system for transillumination with photon frequency marking
US5212667A (en) * 1992-02-03 1993-05-18 General Electric Company Light imaging in a scattering medium, using ultrasonic probing and speckle image differencing
US5608690A (en) * 1995-03-02 1997-03-04 Acuson Corporation Transmit beamformer with frequency dependent focus
US6216540B1 (en) * 1995-06-06 2001-04-17 Robert S. Nelson High resolution device and method for imaging concealed objects within an obscuring medium
US20020043561A1 (en) * 1995-12-18 2002-04-18 Adaptive Optics Associates, Inc. Method of and system for producing digital images of objects with subtantially reduced speckle-noise patterns by illuminating said objects with spatially and/or temporally coherent-reduced planar laser illumination
US20040099815A1 (en) * 2000-07-23 2004-05-27 Sfez Bruno Gad Apparatus and method for probing light absorbing agents in biological tissues
US6699192B2 (en) * 2002-03-19 2004-03-02 Fuji Photo Film Co., Ltd. Ultrasonic receiving apparatus and ultrasonic imaging apparatus
US20040127783A1 (en) * 2002-09-26 2004-07-01 Kruger Robert A. Tissue scanner
US20060122475A1 (en) * 2003-09-12 2006-06-08 Or-Nim Medical Ltd. Method and apparatus for noninvasively monitoring parameters of a region of interest in a human body

Cited By (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050256403A1 (en) * 2004-05-12 2005-11-17 Fomitchov Pavel A Method and apparatus for imaging of tissue using multi-wavelength ultrasonic tagging of light
US7144370B2 (en) * 2004-05-12 2006-12-05 General Electric Company Method and apparatus for imaging of tissue using multi-wavelength ultrasonic tagging of light
EP1602381A1 (en) * 2004-05-14 2005-12-07 General Electric Company Contrast agent for combined modality imaging and methods and systems thereof
US20080077002A1 (en) * 2004-09-10 2008-03-27 Koninklijke Philips Electronics, N.V. Compounds and Methods for Combined Optical-Ultrasound Imaging
US7859671B2 (en) * 2004-12-30 2010-12-28 Art, Advanced Research Technologies Inc. Method for determining optical properties of turbid media
US20090103096A1 (en) * 2004-12-30 2009-04-23 Art, Advanced Research Technologies Inc. Method for determining optical properties of turbid media
US7620445B2 (en) * 2005-01-26 2009-11-17 Fujifilm Corporation Apparatus for acquiring tomographic image formed by ultrasound-modulated fluorescence
US20060184049A1 (en) * 2005-01-26 2006-08-17 Fuji Photo Film Co., Ltd. Apparatus for acquiring tomographic image formed by ultrasound-modulated fluorescence
US20090054763A1 (en) * 2006-01-19 2009-02-26 The Regents Of The University Of Michigan System and method for spectroscopic photoacoustic tomography
WO2007100937A3 (en) * 2006-01-19 2008-07-03 Univ Michigan System and method for spectroscopic photoacoustic tomography
WO2007100937A2 (en) * 2006-01-19 2007-09-07 The Regents Of The University Of Michigan System and method for spectroscopic photoacoustic tomography
US20090227997A1 (en) * 2006-01-19 2009-09-10 The Regents Of The University Of Michigan System and method for photoacoustic imaging and monitoring of laser therapy
US8239006B2 (en) 2006-07-06 2012-08-07 The University Of Connecticut Method and apparatus for medical imaging using near-infrared optical tomography and fluorescence tomography combined with ultrasound
US20080058638A1 (en) * 2006-07-06 2008-03-06 Quing Zhu Method and apparatus for medical imaging using near-infrared optical tomography and flourescence tomography combined with ultrasound
WO2008005554A3 (en) * 2006-07-06 2008-02-21 Univ Connecticut Method and apparatus for medical imaging using near-infrared optical tomography, fluorence tomography combined with ultrasound
WO2008005554A2 (en) * 2006-07-06 2008-01-10 University Of Connecticut Method and apparatus for medical imaging using near-infrared optical tomography, fluorence tomography combined with ultrasound
WO2008067438A2 (en) * 2006-11-29 2008-06-05 The Regents Of University Of Michigan System and method for photoacoustic guided diffuse optical imaging
US20080123083A1 (en) * 2006-11-29 2008-05-29 The Regents Of The University Of Michigan System and Method for Photoacoustic Guided Diffuse Optical Imaging
WO2008067438A3 (en) * 2006-11-29 2008-07-24 Univ Michigan System and method for photoacoustic guided diffuse optical imaging
US20080173093A1 (en) * 2007-01-18 2008-07-24 The Regents Of The University Of Michigan System and method for photoacoustic tomography of joints
US20080221647A1 (en) * 2007-02-23 2008-09-11 The Regents Of The University Of Michigan System and method for monitoring photodynamic therapy
US20080221447A1 (en) * 2007-03-08 2008-09-11 Olympus Medical Systems Corp. Medical apparatus obtaining information indicative of internal state of an object based on interaction between sound waves and light
US20110017217A1 (en) * 2007-08-06 2011-01-27 University Of Rochester Medical apparatuses incorporating dyes
US20100270479A1 (en) * 2007-11-12 2010-10-28 Cornell University Non-imaging, weakly focused fluorescence emission apparatus and method
WO2009064753A1 (en) * 2007-11-12 2009-05-22 Cornell University Non-imaging, weakly focused fluorescence emission apparatus and methods
US8928025B2 (en) 2007-12-20 2015-01-06 Ilumisys, Inc. LED lighting apparatus with swivel connection
US8118447B2 (en) 2007-12-20 2012-02-21 Altair Engineering, Inc. LED lighting apparatus with swivel connection
US7926975B2 (en) 2007-12-21 2011-04-19 Altair Engineering, Inc. Light distribution using a light emitting diode assembly
US8360599B2 (en) 2008-05-23 2013-01-29 Ilumisys, Inc. Electric shock resistant L.E.D. based light
US8807785B2 (en) 2008-05-23 2014-08-19 Ilumisys, Inc. Electric shock resistant L.E.D. based light
US7976196B2 (en) 2008-07-09 2011-07-12 Altair Engineering, Inc. Method of forming LED-based light and resulting LED-based light
US20110112391A1 (en) * 2008-07-11 2011-05-12 Canon Kabushiki Kaisha Photoacoustic measurement apparatus
US10041876B2 (en) * 2008-07-11 2018-08-07 Canon Kabushiki Kaisha Photoacoustic measurement apparatus
US7946729B2 (en) 2008-07-31 2011-05-24 Altair Engineering, Inc. Fluorescent tube replacement having longitudinally oriented LEDs
US8674626B2 (en) 2008-09-02 2014-03-18 Ilumisys, Inc. LED lamp failure alerting system
US8256924B2 (en) 2008-09-15 2012-09-04 Ilumisys, Inc. LED-based light having rapidly oscillating LEDs
US20100094134A1 (en) * 2008-10-14 2010-04-15 The University Of Connecticut Method and apparatus for medical imaging using near-infrared optical tomography combined with photoacoustic and ultrasound guidance
US9585216B2 (en) 2008-10-24 2017-02-28 Ilumisys, Inc. Integration of LED lighting with building controls
US8251544B2 (en) 2008-10-24 2012-08-28 Ilumisys, Inc. Lighting including integral communication apparatus
US9353939B2 (en) 2008-10-24 2016-05-31 iLumisys, Inc Lighting including integral communication apparatus
US9635727B2 (en) 2008-10-24 2017-04-25 Ilumisys, Inc. Light and light sensor
US8324817B2 (en) 2008-10-24 2012-12-04 Ilumisys, Inc. Light and light sensor
US7938562B2 (en) 2008-10-24 2011-05-10 Altair Engineering, Inc. Lighting including integral communication apparatus
US10182480B2 (en) 2008-10-24 2019-01-15 Ilumisys, Inc. Light and light sensor
US9398661B2 (en) 2008-10-24 2016-07-19 Ilumisys, Inc. Light and light sensor
US8214084B2 (en) 2008-10-24 2012-07-03 Ilumisys, Inc. Integration of LED lighting with building controls
US10036549B2 (en) 2008-10-24 2018-07-31 Ilumisys, Inc. Lighting including integral communication apparatus
US9101026B2 (en) 2008-10-24 2015-08-04 Ilumisys, Inc. Integration of LED lighting with building controls
US8946996B2 (en) 2008-10-24 2015-02-03 Ilumisys, Inc. Light and light sensor
US8653984B2 (en) 2008-10-24 2014-02-18 Ilumisys, Inc. Integration of LED lighting control with emergency notification systems
US8901823B2 (en) 2008-10-24 2014-12-02 Ilumisys, Inc. Light and light sensor
US10176689B2 (en) 2008-10-24 2019-01-08 Ilumisys, Inc. Integration of led lighting control with emergency notification systems
US8444292B2 (en) 2008-10-24 2013-05-21 Ilumisys, Inc. End cap substitute for LED-based tube replacement light
US9032800B2 (en) * 2008-12-11 2015-05-19 Canon Kabushiki Kaisha Photoacoustic imaging apparatus and photoacoustic imaging method
US20140128718A1 (en) * 2008-12-11 2014-05-08 Canon Kabushiki Kaisha Photoacoustic imaging apparatus and photoacoustic imaging method
US20110239766A1 (en) * 2008-12-11 2011-10-06 Canon Kabushiki Kaisha Photoacoustic imaging apparatus and photoacoustic imaging method
US8556452B2 (en) 2009-01-15 2013-10-15 Ilumisys, Inc. LED lens
US8664880B2 (en) 2009-01-21 2014-03-04 Ilumisys, Inc. Ballast/line detection circuit for fluorescent replacement lamps
US8362710B2 (en) 2009-01-21 2013-01-29 Ilumisys, Inc. Direct AC-to-DC converter for passive component minimization and universal operation of LED arrays
US8330381B2 (en) 2009-05-14 2012-12-11 Ilumisys, Inc. Electronic circuit for DC conversion of fluorescent lighting ballast
US8299695B2 (en) 2009-06-02 2012-10-30 Ilumisys, Inc. Screw-in LED bulb comprising a base having outwardly projecting nodes
US8421366B2 (en) 2009-06-23 2013-04-16 Ilumisys, Inc. Illumination device including LEDs and a switching power control system
CN102510993A (en) * 2009-09-24 2012-06-20 佳能株式会社 Apparatus and method for irradiating medium
US20110071402A1 (en) * 2009-09-24 2011-03-24 Canon Kabushiki Kaisha Apparatus and method for irradiating a medium
WO2011037844A1 (en) * 2009-09-24 2011-03-31 Canon Kabushiki Kaisha Apparatus and method for irradiating a medium
US9057695B2 (en) 2009-09-24 2015-06-16 Canon Kabushiki Kaisha Apparatus and method for irradiating a scattering medium with a reconstructive wave
US8540401B2 (en) 2010-03-26 2013-09-24 Ilumisys, Inc. LED bulb with internal heat dissipating structures
US9013119B2 (en) 2010-03-26 2015-04-21 Ilumisys, Inc. LED light with thermoelectric generator
US8840282B2 (en) 2010-03-26 2014-09-23 Ilumisys, Inc. LED bulb with internal heat dissipating structures
US9057493B2 (en) 2010-03-26 2015-06-16 Ilumisys, Inc. LED light tube with dual sided light distribution
US8541958B2 (en) 2010-03-26 2013-09-24 Ilumisys, Inc. LED light with thermoelectric generator
US9395075B2 (en) 2010-03-26 2016-07-19 Ilumisys, Inc. LED bulb for incandescent bulb replacement with internal heat dissipating structures
US8454193B2 (en) 2010-07-08 2013-06-04 Ilumisys, Inc. Independent modules for LED fluorescent light tube replacement
US8596813B2 (en) 2010-07-12 2013-12-03 Ilumisys, Inc. Circuit board mount for LED light tube
US8523394B2 (en) 2010-10-29 2013-09-03 Ilumisys, Inc. Mechanisms for reducing risk of shock during installation of light tube
US8894430B2 (en) 2010-10-29 2014-11-25 Ilumisys, Inc. Mechanisms for reducing risk of shock during installation of light tube
WO2012075860A1 (en) * 2010-12-09 2012-06-14 深圳大学 Fluorescence endoscopic imaging method and system
US8870415B2 (en) 2010-12-09 2014-10-28 Ilumisys, Inc. LED fluorescent tube replacement light with reduced shock hazard
US9072171B2 (en) 2011-08-24 2015-06-30 Ilumisys, Inc. Circuit board mount for LED light
US9184518B2 (en) 2012-03-02 2015-11-10 Ilumisys, Inc. Electrical connector header for an LED-based light
US9163794B2 (en) 2012-07-06 2015-10-20 Ilumisys, Inc. Power supply assembly for LED-based light tube
US9271367B2 (en) 2012-07-09 2016-02-23 Ilumisys, Inc. System and method for controlling operation of an LED-based light
US9807842B2 (en) 2012-07-09 2017-10-31 Ilumisys, Inc. System and method for controlling operation of an LED-based light
US9232896B2 (en) 2012-09-20 2016-01-12 Elwha Llc Focusing electromagnetic radiation within a turbid medium using ultrasonic modulation
US8917442B2 (en) 2012-09-20 2014-12-23 Elwha Llc Focusing electromagnetic radiation within a turbid medium using ultrasonic modulation
US9285084B2 (en) 2013-03-14 2016-03-15 Ilumisys, Inc. Diffusers for LED-based lights
US9267650B2 (en) 2013-10-09 2016-02-23 Ilumisys, Inc. Lens for an LED-based light
US9574717B2 (en) 2014-01-22 2017-02-21 Ilumisys, Inc. LED-based light with addressed LEDs
US10260686B2 (en) 2014-01-22 2019-04-16 Ilumisys, Inc. LED-based light with addressed LEDs
US9510400B2 (en) 2014-05-13 2016-11-29 Ilumisys, Inc. User input systems for an LED-based light
US10161568B2 (en) 2015-06-01 2018-12-25 Ilumisys, Inc. LED-based light with canted outer walls
US10278247B2 (en) 2017-09-22 2019-04-30 Ilumisys, Inc. System and method for controlling operation of an LED-based light

Also Published As

Publication number Publication date
US20060058685A1 (en) 2006-03-16
WO2005050180A1 (en) 2005-06-02
EP1709427A1 (en) 2006-10-11
US8103329B2 (en) 2012-01-24

Similar Documents

Publication Publication Date Title
EP1313396B1 (en) Photoacoustic assay and imaging system
JP3745775B2 (en) Optical techniques for examination of biological tissue
US7729750B2 (en) Method and apparatus for high resolution spatially modulated fluorescence imaging and tomography
AU2002228673B2 (en) Fluorescence-mediated molecular tomography
US5664574A (en) System for tissue examination using directional optical radiation
CN101115986B (en) Raman spectral analysis of sub-surface tissues and fluids
US5820558A (en) Optical techniques for examination of biological tissue
US7006220B2 (en) Apparatus and method for determining tissue characteristics
US6058324A (en) Examination and imaging of biological tissue
US7149567B2 (en) Near-infrared spectroscopic tissue imaging for medical applications
US8190241B2 (en) Fluorescence-mediated molecular tomography
Zacharakis et al. Fluorescent protein tomography scanner for small animal imaging
US7647091B2 (en) Method and system for free space optical tomography of diffuse media
Wang et al. A practical guide to photoacoustic tomography in the life sciences
US20040010197A1 (en) Multi-modal optical tissue diagnostic system
US6839586B2 (en) Use of multiphoton excitation through optical fibers for fluorescence spectroscopy in conjunction with optical biopsy needles and endoscopes
EP0832599B1 (en) Apparatus for non-invasive measurement of a substance
JP5808741B2 (en) Imaging apparatus and imaging method for photoacoustic imaging of small animals
US5413108A (en) Method and apparatus for mapping a tissue sample for and distinguishing different regions thereof based on luminescence measurements of cancer-indicative native fluorophor
US6304771B1 (en) Systems and methods for imaging fluorophores
EP1434522B1 (en) Optical systems for tissue analysis
EP2203733B1 (en) Confocal photoacoustic microscopy with optical lateral resolution
EP2002784B1 (en) Intravital-information imaging apparatus
US10064584B2 (en) Combined x-ray and optical tomographic imaging system
US7328059B2 (en) Imaging of light scattering tissues with fluorescent contrast agents

Legal Events

Date Code Title Description
AS Assignment

Owner name: GENERAL ELECTRIC COMPANY, NEW YORK

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:JANSEN, FLORIBERTUS HEUKENSFELDT;LORRAINE, PETER WILLIAM;LOMNES, STEPHEN JOHNSON;AND OTHERS;REEL/FRAME:014716/0535;SIGNING DATES FROM 20031114 TO 20031117