WO2008112312A1 - Appareil et procédé de réduction d'espace en phase pour l'imagerie de structures fluorescentes, diffusantes et/ou absorbantes - Google Patents

Appareil et procédé de réduction d'espace en phase pour l'imagerie de structures fluorescentes, diffusantes et/ou absorbantes Download PDF

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Publication number
WO2008112312A1
WO2008112312A1 PCT/US2008/003445 US2008003445W WO2008112312A1 WO 2008112312 A1 WO2008112312 A1 WO 2008112312A1 US 2008003445 W US2008003445 W US 2008003445W WO 2008112312 A1 WO2008112312 A1 WO 2008112312A1
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Prior art keywords
light
illuminating
collimator
detecting
segments
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PCT/US2008/003445
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English (en)
Inventor
Lifan Wang
Carl Pennypacker
William Sheehan
James W. Gee, Jr.
Michael Piontek
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Geneva Medical Imaging, Llc
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Application filed by Geneva Medical Imaging, Llc filed Critical Geneva Medical Imaging, Llc
Priority to US12/450,151 priority Critical patent/US20120059254A1/en
Publication of WO2008112312A1 publication Critical patent/WO2008112312A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/04—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances
    • A61B1/043—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances for fluorescence imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0091—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for mammography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/43—Detecting, measuring or recording for evaluating the reproductive systems
    • A61B5/4306—Detecting, measuring or recording for evaluating the reproductive systems for evaluating the female reproductive systems, e.g. gynaecological evaluations
    • A61B5/4312—Breast evaluation or disorder diagnosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6814—Head
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/04—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances
    • A61B1/042—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances characterised by a proximal camera, e.g. a CCD camera
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/42—Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems

Definitions

  • the present invention is for a method and apparatus using non-hazardous sources for illumination and techniques to utilize ultraviolet, optical and/or infrared light to obtain images of biological, plant, animal, human and certain inanimate objects, using reflected, scattered, absorbed, fluoresced, (usually, but not limited to, light excited by one wavelength of light and emitting another longer wavelength of light), and/or transmitted ultraviolet, optical, and/or infrared light to compute, construct and/or form or reconstruct the image desired.
  • apparatus and methods which, we maintain, can detect different objects, such as tumors, cancer, Traumatic Brain Injury (TBF), blood clots, blood flow, and other structures and functions of clinical interest subcutaneously and non- invasively, with depth penetration of at least and/or greater than approximately one centimeter, up to say four centimeters.
  • TBF Traumatic Brain Injury
  • Differentiation from other tissues is by the scattering, transmission, and absorption characteristics, parameters that are usually different for blood, lipids, body fluids, and other subcutaneous tissues and organs, or by emitted heat or fluoresced light.
  • this device is useful in certain organic, inorganic, and non-biologic materials such as certain plastics, such as polymers, etc.
  • This device can emit ultraviolet, infrared or optical light of various frequencies and polarizations into the subject.
  • This detector works at power levels and wavelengths that are harmless to animals or humans, even with prolonged exposure.
  • TBI Traumatic Brain Injury
  • a further claim is that by carefully tuning and illuminating a potential source of interest, the tumor (including cancerous ones) may be heated momentarily (sufficiently long to accomplish the result) to about 113 degrees Fahrenheit to kill the tumor, and surrounding tissues remain much cooler and undamaged.
  • This temperature is well known, by a process called hyperthermia, to kill cancers ((see, e.g., http://www.cancer.gov/cancertopics/factsheet/ therapy/hyperthermia) for data on hyperthermia studies).
  • This apparatus includes a new device (herein termed "collimator", although this device is unique which allows this apparatus and method or system to function.
  • the collimator can be in the form of a separate illuminating collimator and a detector or detecting collimator or combined into a single illumo-detector collimator. While it is preferable to have a collimator at the upstream (with respect to photon travel) distal end (entry place) in some situations the collimator may be located further downstream or even dispensed with. Such alternatives may have somewhat degraded but yet useable performance, than when the detecting collimator is located at the distal end.
  • the methods asserted would be useful in solving underlying radiactive transfer problem of light through a confused medium, using polarization, frequency, collimation, and other possible constraints.
  • the "Phase Space" of the illuminating source is key, phase space being defined as the entry point and the velocity unit vector of incident photons.
  • An important component of our device are the collimators, which in various forms are described below.
  • the technique is designed for use with transmitted light, absorbed light, scattered or reflected light, or some combination thereof. It also applies to a wide variety of geometries between the illumination source and the detectors. Environmental background light can reduced by shielding.
  • the technique is as follows. It is well established that, for example, human bone, organs, and soft tissues are at least somewhat transparent in appropriate ultraviolet, optical and infrared frequencies (viz., certain frequencies of light can penetrate the constituents of the human body, with some efficiency). Relative to reference tissues, malignant tissues, tissues without vascularization (such as brain trauma-Traumatic Brain Injury) and others of special clinical significance have different but characteristic scattering, fluorescing (in the presence or absence of fluoresing agents) and absorption functions. Prior art has claimed methods of using different frequencies (Gee and Pennypacker Patent No. 7,158,660, which is incorporated herein by reference, Marchitto, et al, U.S. Patent No.
  • This application asserts that measures with good detail and signal-to-noise ratios of the three-dimensional scattered pattern of light, together with data indicating scattering as a function of polarization, photon direction, fluorescing and frequency, allow a unique and restrictive reconstruction of the spatial location of scattering centers and, absorption and/or fluorescing features which are non-homogeneous ' to the embedding tissues.
  • other health-related targets are of interest, such as endoscopic internal applications, as are industrial fabrication and testing, such as discovering fracture zones or weaknesses or any strength-related compromises in, for example, carbon-epoxy or other resins or other structures.
  • the present invention also as noted above relates to the utilization of fluorescence and also extends the invention with or without fluorescence to internal endoscopic applications. Differentiation of scattering, absorbing, emitting and/or fluorescing objects by a number of measured variables is used, included spectral distribution of all forms of the light signal, polarization, spatial dependence, and other characteristics of the input emerging and radiation.
  • ICN-Green will absorb light at certain frequencies and fluoresce at a different frequency could be used to delineate the target from the environs, or vice versa, (depending upon whether the material, ICN-Green or other, is located in the target or environs). This phenomenon would be useful in situations with or without detection of any subsequent emission post exitation.
  • the range of materials that could be used is broader as there is less or little concern with damage to the subject being studied. That does not mean no concern whatsoever.
  • the method and apparatus of the present invention illuminating and detection with or without fluorescing, can be provided in external and/or internal or endoscopic applications for animate or inanimate subjects.
  • this device is useful in certain organic, inorganic, and non-biologic materials such as certain laminates and plastics, such as polymers, etc.
  • the device of the invention may emit ultraviolet, infrared or optical light of various frequencies and polarizations into the subject. By analyzing the resultant reflectance, fluorescent or other emission, transmission, absorption, and scattering by the target and intervening or imbedding media, it is possible to solve for the underlying constituents and spatial distribution in the subject media and locate the differentiated matter.
  • the fluorescing substance could be injected directly or indirectly or otherwise placed into a structure of interest or the patient, which could be a vascular structure, or activity or lack of activity, or presence or absence of fluorescing material.
  • a structure of interest or the patient which could be a vascular structure, or activity or lack of activity, or presence or absence of fluorescing material.
  • another form of providing the fluorescing material would be to take the same orally (which could be considered to be another form of injection).
  • Traumatic Brain Injury (TBI) manifests itself with less blood flow in areas of the brain injured by some external (usually) agent, such as explosive projectiles or shock waves or other explosive debris, a rock or pipe, or an auto or sports-related accident. Patients would exhibit a deficit of the usually injected blood carried fluorescing agent or lack of blood flow, using methods described below.
  • the present invention in various applications may provide images say of a depth of from or on the surface to 1 cm to as far as 4 cm below or beyond the surface, including in endoscopic applications used heretofore or in the future to detect such matters and develop images.
  • the apparatus and method used even with the fluorescent and/or endoscopic forms is inexpensive compared to say, a CAT scan device, it makes such screening or other uses possible in local hospitals, clinics, third world countries, even rural areas, airports, public arenas, sports events, doctors' offices, emergency rooms, ambulances, and trauma care centers.
  • a very high signal-to-noise ratio image can be acquired, with very little background interference.
  • the areas of interest are highlighted in the image acquired by subtraction of the two (or more) images.
  • Such approach would reduce or eliminate noise and interference from matters such as hair, bone, skull and/or other non-vascular structures in, for example, a TBI imaging.
  • a tumor including cancerous ones
  • surrounding tissues remain much cooler and undamaged.
  • a fluorescing agent and/or use of selected wavelengths of light could expedite preferential absorption of energy in the tumor or the surrounding areas, which have higher vascularization.
  • one could absorb preferentially energy in the area of interest with such a system by sending in light that absorbs much more preferentially than the surrounding flesh, hence depositing energy in the tumor much more efficiently, with no danger to the patient.
  • This apparatus may include a device, herein termed illumo-detector which, as noted can be a separate illuminator and a separate detector or a combination unit carrying out both functions.
  • the technique is designed for use with transmitted light, absorbed light, emanated light, fluorescing light, scattered light and/or reflected light, or some combination thereof. It also applies to a wide variety of geometries between the illumination source and the detector.
  • Figure 1 is a simple schematic diagram of a first embodiment apparatus of and for performing the method of the present invention.
  • Figure IA is a schematic of a laser or light, two mirror alignment checking apparatus.
  • Figure 2 is a schematic of light scattering as a function of polarization.
  • Figure 3 is a schematic of an input (illuminator) and detector portion of the apparatus of and for practicing the method of the present invention.
  • Figure 3A is a perspective schematic of a collimator tube (for the illuminator and/or detector) made of several sections of optical glass or fiber that has an absorbent or black coating on its outside surface and ends, with light transmitting collinear aligning small openings or pinholes in each end of the segments that can be stacked several in a tube.
  • Figure 4 is further schematic of the input or illuminating portion of the apparatus of and a method of the present invention.
  • Figure 5 is a schematic of another embodiment of an apparatus of and method for practicing the present invention, utilizing primarily reflected light suited for Traumatic Brain Injury.
  • Figure 6 is a schematic of yet another embodiment of apparatus of and method for practicing the present invention.
  • Figure 6A is a table of dimensions of the components of the present invention.
  • Figure 7 is a schematic of the collimator device of the present invention.
  • Figure 8 is a schematic of a light source using a micro mirror array (mma) to control input of light into the collimator.
  • mma micro mirror array
  • Figure 9 is a schematic side view of another embodiment of light scattering after penetrating the skull, for example, in a TBI application, and exciting a target injected with a fluorescing dye or agent.
  • Figure 10 is a schematic of an input and detector portion of the apparatus and method for practicing the present invention utilizing an illumo-detector strip in place on a patient's head.
  • Figure 11 is a schematic of another embodiment of apparatus of and method for practicing the present invention without the strip of Fig. 10.
  • Figure 12 is a graph showing the excitation and emission response for a typical fluorescing dye.
  • Figure 13 is a schematic of the application of the present invention in an endoscopic device.
  • Figure 14 is a schematic of the present invention in the form of an internal endoscope.
  • Figure 15 is a schematic diagram illustrating how using normal body pathways (e.g., colon, intestine, trachea, bronchial tubes, esophagi, open body space, etc.) the present invention in endoscopic form may detect anomalies on, in and/or up to 4 cm away from the surface of the pathway.
  • normal body pathways e.g., colon, intestine, trachea, bronchial tubes, esophagi, open body space, etc.
  • a first embodiment of apparatus 10 of and for practicing the present invention is shown. Starting from the left, it includes or comprises an input or illuminator unit 11, light source 12, optionally filters and/or polarizers 14, preferably, and a plurality of collimator tubes 16 forming an input collimator 18.
  • the light source could be photo diodes, diode lasers, or incandescent or other lighting, with or without filters, with the purpose of injecting light into the subject with phase-space reduced beams.
  • the dotted arrows 20 light leaves the light source 12 and enters and is altered in the filters/polarizers 14.
  • the collinear light 24 is to some degree reflected, scattered, absorbed and transmitted through the target 26.
  • the target 26 could be two internal object targets, a large one 28 and a smaller one 30.
  • the collinear light will cause or create shadowed areas
  • a detector portion 36 In order to collect the scattered, reflected and transmitted light, if any, a detector portion 36 is provided, and can comprise an output collimator 38 similar to collimator 18, and output filters and/or polarizers 40, similar to filters/polarizers 12 and a detector unit 42. Light from the target enters the output collimator 38, and if used the filters/polarizers 40, and then the detector unit 42.
  • the fundamental science is schematically indicated in Figure 1. From the above it is shown that light from the light source 12 is sent through the input collimator 18, which is similar to the detection or output collimator 38, which may be transformed by filters and/or polarizers 14 to collimated and/or collinear light 24.
  • the col Ii mated light 24 is incident and then propagates through the human breast or target 26.
  • Light say, laser light —traveling unscattered and collinearly is called or termed "ballistic photons" in some literature and prior art.
  • the detector 36 would be located to gather the reflected and scattered collinear light to determine the light absorbed which help characterize the object.
  • the input light source unit 11 and/or the output detectors 36 could be moved relatively radically about the target 26 and/or large and small targets 28 and 30.
  • This apparatus 10 could provide "shadow images" 32 or 34 of the targets 28 or 30.
  • More information about the basic principles is to be found in Alfano, et al, who, unlike in the present invention, try to eliminate or reduce the effect of scattered light by employing a time gate. The time gate concept is difficult if not impossible to carry out. Whereas in the Alfano, et al. prior art an attempt is made to reduce or eliminate the effect of scattered light, in the present invention scattered light is actually utilized and considered in obtaining a solution and analyzed to obtain and form the resultant image.
  • Figure 2 shows how the polarized collinear light 24 scatters.
  • Figure 3 shows another embodiment 10' generally similar to that shown in Figure 1 in an aligned position of the input unit 11', target 26, and detector unit 36. To the extent it is the same, the same reference numerals are used. To the extent, if any, it differs, different reference numerals are provided.
  • a collimator 18 in one potential embodiment of our apparatus 10' of the present invention, light 24 of a given polarization (see Fig. 2) is channeled into the subject 26, by pulsing individual optic fibers 44, which then are injected into a collimator 18 (see Fig. 3).
  • the collimator 18 could be constructed of plurality fiber optic or glass rods segments 48 with non-reflecting (absorbing or black) outer surfaces (cylindrical surface 50 and ends 52) formed as by coating thereon.
  • the ends 52 have small openings or pin holes (say of 0.01 mm to 1 mm diameter or approximately 0.00008 mm 2 to 0.8 mm 2 area) in both ends of each segment 50, with a plurality or several segments, say 5-10, stacked to form the collimator.
  • manufacturing and aligning an opening of about 0.1 mm in diameter or length and width might be suitable, which is an area of about 0.01 mm 2 to 0.008 mm 2 , depending on whether of a square or round cross-section.
  • the rod segments 48 can be of any cross section but are preferably round or square and have ends cut and polished at right angles.
  • the pin holes 54 are generally in the center and collinear so as to pass light from one segment 48 to the next so that light can travel from the source to the target and is collinear when it hits the target or received by the detectors.
  • the various segments 48 may be placed in a collinear tube 16'.
  • a micro mirror array could also be used and would comprise a means for illuminating one or several selected collimator tubes 16 or 16' at a time with the other tubes dark.
  • This construction reduces the phase space of the input beam 24 - that is, the beam enters the subject 26 or 26' with small angular scatter and known (e.g., Cartesian coordinates x,y,z polar coordinates R 5 O, Phi) entry location on the subject. Then, the output light and including scattered, reflected and transmitted light, is measured by the detector across as many angles as necessary to attain adequate detection, say to capture 80% or more of the total scattered light or of sufficient data to attain adequate detection. Light from off the target is again made collinear and optionally filtered and polarized and received at the detector 42.
  • this detected light will depend on the direction of the incoming light and the polarization of the beam.
  • Figure 2 shows the simple case of a dipole scattering, where the length of the arrows indicate the scattering of light. No light is scattered in a direction parallel to the "dipole moment represented by the black dots".
  • illuminating the target with a second, but different polarized light, and then subtracting the two polarizations yields an informative map of scattered light. This scattered light can then be subtracted from the original image. The result defines in greater clarity details of the object of interest.
  • Fig. 2 is a schematic of the behavior of light scattering as a function of polarization for an exemplary case: light polarized in the plane of the paper and perpendicular to the direction of motion of the photon. Light is scattered preferentially in angles not lying in the direction of the dipole moment, in the simple case proportional to the sin 2 of the angle between the dipole moment beam and the observer.
  • a co-alignment mechanism 66 (shown in Fig. IA) to align the input collimator and output or detector collimator, say comprising a small laser 68 with mirrors connected to the body of the input and detecting collimators 11 or 18 and 36 or 38 could be used to maintain and measure the alignment of the input and output collimators, say by reflecting the laser beam onto an aligning target 76. If the light is off the target 76, the system 11 or 18 or 36 or 38 are out of alignment. Good alignment is necessary to be sure the diminution of the light at the detector is due to scattering by the main target 26 or 26' or objects therein and not misalignment.
  • unpolarized light is channeled into the target, then light is measured with polarization sensitive detectors at many locations around the subject, say to capture 40% to 100%, and preferably 80% or more of the total scattered light or of sufficient data to attain adequate detection.
  • polarization sensitive detectors at many locations around the subject, say to capture 40% to 100%, and preferably 80% or more of the total scattered light or of sufficient data to attain adequate detection.
  • Polarizations can be changed by rotating polarizers, or swapping in different filters, and done uniformly across the collimator. This behavior allows the underlying target structure to be elucidated.
  • phase space reducer mechanism 10 and 11 can be turned on, and the unhealthy object preferentially absorbs light, and is heated to about 113 degrees Fahrenheit or somewhat higher, within a range of plus 5 degrees Fahrenheit, which kills the cancer cells ("Hyperthermia"). Tissues around the cancer do not receive or absorb as much energy, and reach lower temperatures (under 113 degrees Fahrenheit), and hence will not be damaged. It is believed that this cellular altering heating could be accomplished with a power source (light) of 25 watt output or less.
  • the plurality of illuminating sources will be dispersed about the target so that the target or unhealthy object can be brought to the necessary temperature.
  • the phases of light incident on the illumo-detector could be constructed, after some model of the subject is constructed, to cancel out so some degree scattering and reflection off of material in the beam, as the heating beam moves to the tumor. This is through the well- known methods of adaptive optics (see e.g., http://en.wikipedia.org/wiki/Adaptive/ optics.com).
  • the phases may be adjusted by a deformable mirror, such as shown in Figure 1 in the above internet reference.
  • a fifth use of these embodiments would allow the object to heat up by preferential absorption of light, and then the object could be discerned by the well-known method of thermal imaging, which can acquire different images at different wave lengths, say, 10 micron and 5 microns.
  • our device consists of a (probably movable) two-dimensional focal plane of detectors 36 and 42, with sensitivity ranging from ultraviolet or optical frequencies to the infrared.
  • a light source 11 and 12, 14 in the collimation system with the ability to change polarization as noted above and frequency as, for example, changed by filtering out (at 14 or 40) components from a general light spectrum, is the preferred light source, since such a source, when coupled to the detector and knowledge of the wavelengths and polarization, can help elucidate the scattering, transmission, and absorption properties of the underlying materials.
  • a laser or other light source can feed a micro mirror array (Fig. 8) to feed each "tube" 16 independently.
  • Data is collected for a number of incident angles between the laser (11, 12) and the target 26 so as to define the three-dimensional configuration of the target.
  • Polarization and frequency dependences are used, in order to further elucidate the structure and exact position of the underlying scattering centers (objects in the subject target (such as 28 or 30 in 26).
  • a further advantage of this method and apparatus of the present invention allows just one tube 16 of the input collimator 18 to be illuminated at a time, and hence the signal detected at the co-aligned tube on the output collimator 38 next to the two-dimensional detector 42, with explicit knowledge of the input.
  • the signal can be seen against a much smaller background, than in the case when all of the background of the whole input collimator were illuminated simultaneously.
  • multiply scattered photons have a small chance of scattering into the output (detector) collimator, most likely they will not have the same direction if they are incident on the co- aligned tube of the output collimator.
  • the target subjects are usually sources of thermal emission which may at certain wavelength regions dominate the photons collected by the detector.
  • the image subtraction technique we are proposing can efficiently remove this component, because scattered light is usually polarized whereas the thermal component is not. This concept is helpful in our system.
  • we can also do the opposite - infrared light can be preferentially absorbed by tissues, which then heats them up, and causes them to emit more thermal photons. Then, not observing or subtracting polarized components allows one to see sources of thermal emission in the subject.
  • the polarization components can be from the input light, from the scattered light, the filter on the detector, or any combinations of one or more of these.
  • Principle of Operation of Preferred Embodiments for example, infrared or optical light illuminates a portion of the human subject, e.g., a lobe of the brain or a mammary gland.
  • Such apparatus 10 could include collimators, such 38 as positioned in front of the detector, say 42. Multiply angles viewed should be such that collect approximately 80% or more of the scattered light.
  • Collimated light source say 11, which reduces the phase space of the input beam (20 to 22 to 24).
  • Individual tubes (16 of 18) can be turned on and off under control, if necessary.
  • the whole array of input tubes 16 on the collimator 18 can be turned on and off simultaneously, for example, in synchrony with the human arterial pulse or other body function to establish a reference frame for an image not affected by the arterial pulse or other body function.
  • Collimated Light Detector 36 and 42, with filters and polarization components 40 which allows phase space reduced light to be detected, hence greatly increase signal to noise for detecting the target (28 or 30 in 26), for example, cancer, etc.
  • a data analysis algorithmic scheme (to be developed) that allows recovery of the structure of the underlying scattering and absorption centers below the surface.
  • Software for image reduction and analysis (to be developed), which can reduce the algorithm and data to produce bona-fide three-dimensional maps of heterogeneous tissue structures.
  • steps 4) and 5) would be similar to data analysis and image reduction already accomplished for galaxy image obtained with the Hubbell telescope, or such as with atmospheric corrections, for large earth optical telescopes.
  • steps 4) and 5) would be similar to data analysis and image reduction already accomplished for galaxy image obtained with the Hubbell telescope, or such as with atmospheric corrections, for large earth optical telescopes.
  • steps 4) and 5) would be similar to data analysis and image reduction already accomplished for galaxy image obtained with the Hubbell telescope, or such as with atmospheric corrections, for large earth optical telescopes.
  • steps 4) and 5) would be similar to data analysis and image reduction already accomplished for galaxy image obtained with the Hubbell telescope, or such as with atmospheric corrections, for large earth optical telescopes.
  • each micro-target 28 and 30 scatters, transmits, and absorbs the light, with some efficiency.
  • the output at any point in space becomes the sum of scattered, and transmitted light from the micro-targets' combined effect on the beam, where light passing through one micro-target is in turn subjected to scattering, absorption, and transmission by the next micro target.
  • the subject is composed of a plurality of micro-targets of various scales, dimensions, and depth.
  • the target absorbs enough energy from the beam, it may heat up and preferentially emit more thermal radiation than the surrounding tissue 26A of target 26.
  • a slightly more complex case involves two point objects of different material.
  • the point objects are characterized by the coefficients (as above) of S, A, and T, and s, a, and t, respectively, situated next to each other. If they are illuminated, and S, A, T and s, a, t of each material are known, if in addition we are able to place some constraints on the geometry, then it is possible to solve for the underlying spatial distribution of the tissue in question. By incorporating more and more detectors and viewing angles, we achieve a higher resolution to smaller targets - say about one millimeter.
  • the principles are illustrated in Figure 1, showing schematically the preferred embodiment.
  • the coefficients of scattering, absorption, and transmission of targets and subjects are mostly uniform within small variability among all humans and most animals. If fluorescence is involved, it is addressed further on in this application.
  • the following diagrams, Figures 3 and 4 illustrate details of the working system 10.
  • Figure 3 illustrates the make-up of one element or tube 16 of the Space Reduction System 10'.
  • the phase space reduction system could be made as mentioned on pages 11 and 12 and Fig. 3 A herein, or made by casting, for example, a molten material around a mold, then melting the mold out later to form the tube 16 with internal absorbing, black baffles 16A with openings 16B therein.
  • baffles 16A function similarly to the absorbing or black coatings applied to the outer surface ends 52, while the openings 16B function similarly to the pinholes or small openings 54 of the fiber optic rod version.
  • Figure 4 shows a two-dimensional slice through a multi-element phase-reduction system 10" with an input 11", a multiplexer light source 12' with fibers optic bundles 12A' (for simplicity only four being shown-but these could be many more), filters/polarizers 14' and collimator 18" with (four) corresponding tubes 16", that produce collinear, phase space reduced light 24'.
  • Each fiber 12A' or matrixed light source 12' of the input array 11' can be pulsed individually, and the output at the detector measured with knowledge of the spatial location and direction of the input beam.
  • Different individual elements 12 A' for the collimator 18" could be activated by mechanical or electronic means, for example by butting the input end (left end in Fig. 4) bundle of optical fibers 12A' that feeds the collimator against some array of diodes (in 12') or butting the collimator directly against some custom-fabricated diode or light array.
  • a micro mirror array MMA (see Fig. 8) could be located in 12' and used, or mechanically by triggering nano activators, for each tube or element 16".
  • This embodiment allows the device to probe for absorption in layers below the skin, without a transmission system, but measures changes in reflection.
  • Light enters the collimator 80 through fiber optics that are uniformly distributed over the subject area, which is pressed tightly against the collimator at its input end and against the skull or target 86 at its other end.
  • Arranged over the subject uniformly are "detection tubes" located in 80' that take ballistic photons (say photons with only one reflection) back through the collimator, and then feed them to the fiber optics and back to the detector 80. Areas of brain with excess or inadequate blood flows indicative of Traumatic Brain Injury, could thus be distinguished from normal brain tissue.
  • the input beam could be synchronized with the arterial (or other body structures) pulse (or other body movements/functions, e.g. breathing), in order to better isolate and delineate key vascularized (or other) structures.
  • the mathematical solution may be, for example, a global least-squares fit to a model of the scattering medium, where the only free parameters are the coefficients of the micro- targets. We believe that this may be the preferred embodiment of the algorithm.
  • a homogeneous set of micro-targets with the expected dominant biological component say fibrous tissue or fat, for mammary glands — can be the starting point for the calculation, with plausible guesses for differences between the observed and the re-constructed underlying tissue leading to the next steps of the iteration. We assert that in this way we can develop an algorithm that will converge quickly.
  • the micro-targets are all fat and have the same S, A, and T, then subtract that assumption from the observed pattern of light. Then, from the residuals in the case of one small volume of, say, cancerous cells ⁇ say s, a, and t and its characteristic pattern—a scattering and absorption pattern would be apparent from the residuals.
  • the software one manages to fit the spatial distribution of the targets and the coefficients of the residuals. One could insert into the global solution in the software a small object with the characteristics of a cancer cell into the assumed target and recalculate to find out whether any residuals exist, or make other corrections.
  • collimators are used in almost all imaging devices
  • the innovation that we are claiming is the development of a device that is able to illuminate one tube of the collimator (or multiple tubes with different frequencies or polarizations (if the interference can be discriminated)) at a time, in addition to a unique design that greatly decreases angular dispersion and input position of the input beam, and results in the detection of only a phase- space purified output beam, largely devoid of reflection, scattering, components, etc.
  • the idea is to sequence the input beam (fire off one "tube" of the collimator at a time, as needed).
  • One proposed way of doing this is to have a micro mirror array or video computer projector in front of the input collimator.
  • a micro mirror array or video computer projector in front of the input collimator.
  • the Collimator on the detector side or the whole detector/illuminator scheme can have a hole or blank spot for insertion of catheters or making marks on the target, for example.
  • FIG. 6 show a refinement of the proposed embodiment where we have now included the LCD "multiplexer" 12'" from a video projector as part of the multi-element phase-space reduction input system. Most of the time, the LCD remains opaque, and introduces no light component itself. When a tube 16'" is desired to be illuminated, the LCD mask opens up just at that exact point in the LCD mask and it becomes transparent.
  • Figure 6 is a two-dimensional slice through a multi-element phase-space reduction input system (4-elements).
  • Each fiber or matrixed light source 12'" of the input array can be pulsed individually, and its output measured with knowledge of the spatial input of the and the direction of the resultant beam.
  • the collimator works as follows: Light that is going straight gets through - light that is going crooked or bounces off the walls of the tube 16 gets stopped.
  • Figure 6A list various parameters for constructing the present invention, including dimensions and wave lengths for the light source, collimators, input and output, and detectors.
  • Figure 7 shows the path (heavy arrows) of photon that is not on axis. Note the blocking stops (baffles 16A or ends 52) in the collimator tube 16 that stop photons that are reflected off of the walls. All interior walls 16A and baffles or walls are black and/or absorbing. This particular geometry mitigates against photons that reflect off of the wall or baffles from making it through the tube.
  • 3A would work in a similar manner but is easier to construct as there are no interior baffles to form, and the absorbing or black coating can be applied on the exterior, rather than on the interior of the element, the exterior being possible as the glass of section 22 would be transparent, absence the black coating.
  • a mirror array 12E could be interposed between the light source 12 and collimator 18 to control the light into the collimator such as shown in Figure 8.
  • the remainder of the input unit could be similar to that shown in Figure 1, with if desired, a filter/polarizer provided.
  • Figure 9 illustrates the use of a fluorescing agent such as ICN-Green say for cranial analysis such as in connection with TBI.
  • the collinear light 224 is to some degree reflected, scattered, absorbed and transmitted through the target 226. Such light could excite selectively, fluorescent molecules in the target of interest.
  • the present invention incorporates or utilizes fluorescing dyes or agents to help acquire the images.
  • a detector portion 236 can comprise an output collimator 238 similar to collimator 218, and output filters and/or polarizers 240, similar to filters/polarizers 212 and a detector unit 242.
  • Light from the target enters the output collimator 238, and if used the filters/polarizers 240, and then the detector unit 242.
  • the present invention can be used with fluorescing materials or dyes, if a long enough duration or time fluorescing agent would be used, one could pulse the target, and then after the pulse of exciting radiation has subsided, enable the detectors, to substantially detect only fluorescing atoms or structures, and with less background noise from scattered light.
  • Figure 9 illustrates in detail, a schematic of one embodiment of the trans-cranial imaging system.
  • This embodiment allows the device to probe for absorption and reflection in layers below the skull, without a transmission system, but measures distribution of dye, which is in the vascular system.
  • Light enters the illumo-detector 210 through fiber optics 212 that is distributed over the subject area 214, which is pressed tightly against the collimator.
  • Arranged over the subject uniformly are "detection tubes" 216 that take ballistic photons (say photons with only one reflection) through the collimator, and then feed them to the fiber optics 218 and back to the detector 220.
  • Figure 9 shows how the collinear light 224 scatters internally on an object or target containing fluorescing agent inside the human skull.
  • Figure 10 shows the details of the illumo-detector strip or unit 230, which can be placed on the patient's head.
  • light of a given polarization is "pumped" into the subject, by pulsing individual fibers 232, which then are injected via the illumo-detector strip 230.
  • the light encounters the fluorescing dye, excites radiation of a longer wavelength, and such light is recovered by the fibers 234 going to the detector 236, on the illumo-detector strip.
  • Figure 11 shows the present invention, including the light source 240, detector 242 the fluorescing agent (in patient 244) without the use of the strip of Figure 10.
  • Figure 12 illustrates emission and emitted radiation of ICN-Green, a typical fluorescing dye.
  • the light from the image without ICN-Green or other fluorescing dye which also could include light that is scattered or emitted from various objects in the beam, can then be subtracted from the image with the fluorescing dye.
  • the result (with dye less without dye or vice versa) defines in greater clarity details of the object of interest.
  • a simpler light source that uniformly or non-uniformly illuminates the target of interest, could excite the fluoresced molecules, and only light from the fluoresced molecules could be images or data acquired from such fluorescing molecules.
  • Data and images taken in the absence of the fluorescing agent could be compared to or subtracted from images that contain the fluorescing agents, so one is left with only light signals from structures of interest or the area immediately around such structures of interest.
  • point objects When dealing with fluorescing material point objects may be characterized by the coefficients of S, A, F and T, and s, a, f and t, respectively, situated next to each other (wherein S, A, T are as defined above and F and fare the fluorescing coefficient. If they are illuminated, and S, A, T and s, a, t, f of each material are known (this assumes the smaller object is the only one fluorescing), if in addition we are able to place some constraints on the geometry, then it is possible to solve for the underlying spatial distribution of the tissue in question.
  • a target that emits fluorescing light will allow greater depth and spatial resolution, as its light is emitted at a wavelength of higher transmission through the overlying material, and also the signal from such an object does not have any contribution of light from the incoming beam, allowing greater fidelity in image reconstruction.
  • a slightly different case involves one point objects one of which shines by emitting fluorescent light.
  • the point object's light scatters out of the target's body, eventually into the detector.
  • This system has the advantage of not being sensitive to light from the input of the illumo-detector, since this light is at a different wavelength than is detected, with our envisioned filters.
  • wavelengths of interest for example micro-waves might be used to excite the fluorescing media or agent.
  • the target could include other materials, which have been made with small amounts of fluorescing materials, either on purpose, or added to the materials during manufacturing or for testing.
  • fluorescing materials either on purpose, or added to the materials during manufacturing or for testing.
  • light weight composite materials would show defects, such as broken fibers or other structural problems, deep in the materials. The same methods used for studying targets and surrounding areas in humans could be applied to these materials, and greatly increase the testing fidelity before, during, or after assembly into its final structure.
  • Figure 13 shows the present invention can be extended to endoscopic systems 260 and can be used with or without a fluorescing agent.
  • Another use of this system is to provide an illumo-detector element 262 of a geometry designed to be placed inside a patient 264 by the well-known methods of endoscopy (see, e.g., http://en.wikipedia.org/wiki/Endoscopy).
  • the illuminating fibers 266 are bundled together with the detector fibers 268 in an endoscopic probe 270 that can be inserted into a suitable incision, space, cavity 272 or orifice in the patient 264.
  • the illuminating fibers 266 could pulse, either individually, in groups, or simultaneously and enable the object of interest 280 that may or may not contain fluorescing dyes to be illuminated. Then, either individually or in groups, the light or fluorescently emitting light signal could be received by the detector fiber optics 268, and then either individually, in combination of fibers, or all simultaneously could form an image of the object of interest.
  • the detector may have a collimator provision at its distal end and photon entry place, or the collimator may be located in the fiber optics spaced away from the distal end, or even dispensed with.
  • the collimator located downstream from the distal end and/or placed external of the patient and/or dispensed with. With the collimator downstream many of the non centered photons (those reflected off of the outer surface of the fiber optics) would still be trapped by a downstream collimator.
  • the collimator for the illuminator is preferably at or near its discharge end, it could be placed anywhere between the light source and the end.
  • FIG 14 shows an endoscope 290 for such an application.
  • the endoscope 290 has distal end 288 of a coil 292, of illuminating and detecting fiber optics therein which includes a fish-eye wide field of view optic 294 (including fiber optics 300 for the same) enabling a field of view of about 270 degrees to enable viewing where the endoscope is looking and also its location.
  • Illuminating fiber optic are at 296 with small lenses for dispensing light over the field of view of interest.
  • Detecting fiber optics 298 are also co-parallel with fiber optics 296. In the alternative with suitable switching a single set of optic fibers could be used for all three functions (illuminating, viewing and detecting).
  • Absolute location of the endoscope can be by ultrasonic transducer 299 such as disclosed in the Silverstein et al U.S. Patent No. 4,462,408, which is hereby incorporated by reference.
  • the present invention with or without fluorescence, can form images of at considerable depth (from above, or on the surface to at least 1 cm and even to 4 cm in and beyond the surface) in tissue bone, organs, and/or through endoscopic forms of probes 310.
  • the present invention may detect tumors, cancer or other differentiated tissue or matter (say swallowed objects) 318 in tissue or organs 322 surrounding the endoscopic pathway 330 (say colon intestine, esophagi, bronchial tube, etc.) used to traverse the endoscopic probe.
  • the human or animal body 340 can be more extensively explored not only to detect differentiated tissue (tumors, cancers, etc.) 318 using naturally formed openings or spaces to insert the endoscopic probe 310 and detect matters 318 in adjacent structures, tissue or organs 322, actually hidden visually by the wall 350 of the pathway 330.
  • tissue tissue or organs 322
  • the present invention in endoscopic form one can detect anomalies or differentiated matter (tumor, cancer, etc.) above, on, in and beyond the endoscopic pathway wall.
  • endoscopic probes and methods of the present invention could be used to explore the surfaces and depths below the surface of esophagus, colon, bronchial tube and/or in any known or to be known endoscopic applications.
  • the present invention using such endoscopic probes to provide penetration and information on tissues and structures say of lcm to 4 cm into and below the surface.
  • Such probes suitably built could also have industrial applications.
  • the endoscopic applications could be used with or without fluorescing dyes and materials.
  • the power consumption for the light source and particularly the power input into the patient or material being investigated is low and less than one kilowatt, and more likely between 10 to 200 watts with about 30 watts or less being preferred. This is advantageous as no special circuits are needed to power the device.
  • a greater advantage is that the power input on a human or animal is such that there is no danger of burns, except when the collimated light (ultraviolet, visible, or infrared) is concentrated by targeting say a tumor.

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Abstract

L'invention concerne un procédé et un appareil destinés à utiliser de la lumière, y compris ultraviolette, optique et/ou infrarouge, pour détecter un corps dans un objet, comme des biomatériaux ou tissus, des tissus animaux et/ou humains. Le corps ou objet peut être rendu fluorescent par l'utilisation de teintures ou d'un agent. De la lumière est utilisée pour éclairer le corps et l'objet et la lumière diffusée, fluorescente et/ou émise, la lumière réfléchie et la lumière transmise sont détectées et utilisées pour reconstruire le corps et/ou l'objet en utilisant une analyse itérative. En outre, le procédé et l'appareil peuvent être étendus à des applications endoscopiques pour l'obtention d'images sous-cutanées de tissus internes au-dessus, sur, dans ou au-delà des trajectoires endoscopiques tels que l'œsophage, l'estomac, le côlon, les canaux des bronches et/ou d'autres ouvertures, cavités et espaces animés ou inanimés, et dans des matériaux fabriqués par l'homme ou industriels tels que des structures en carbone/résine.
PCT/US2008/003445 2007-03-14 2008-03-14 Appareil et procédé de réduction d'espace en phase pour l'imagerie de structures fluorescentes, diffusantes et/ou absorbantes WO2008112312A1 (fr)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011121346A1 (fr) * 2010-03-29 2011-10-06 Inspection Technologies Limited Appareil et procédé d'inspection
CN103271719A (zh) * 2013-05-13 2013-09-04 执鼎医疗科技江苏有限公司 血管影像定位系统
US8942530B2 (en) 2011-09-20 2015-01-27 San Marino Capital, Inc. Endoscope connector method and apparatus
CN105342556A (zh) * 2015-09-23 2016-02-24 天津大学 一种基于集成经验模式分解的肿瘤信号提取方法

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4595008A (en) * 1979-11-27 1986-06-17 Sunset Ltd. Localized thermotherapy technique
US4711246A (en) * 1986-09-02 1987-12-08 Fiberoptic Sensor Technologies, Inc. Fiber optic coupled pressure transducer using single fiber and method of fabrication
US6216540B1 (en) * 1995-06-06 2001-04-17 Robert S. Nelson High resolution device and method for imaging concealed objects within an obscuring medium
US6240309B1 (en) * 1995-10-06 2001-05-29 Hitachi, Ltd. Optical measurement instrument for living body
US20020087047A1 (en) * 1999-09-13 2002-07-04 Visionscope, Inc. Miniature endoscope system
US6487349B2 (en) * 1995-11-20 2002-11-26 Cirrex Corp. Method and apparatus for improved fiber optic light management
US20050143662A1 (en) * 2000-05-03 2005-06-30 Rocky Mountain Biosystems, Inc. Optical imaging of subsurface anatomical structures and biomolecules
US6975898B2 (en) * 2000-06-19 2005-12-13 University Of Washington Medical imaging, diagnosis, and therapy using a scanning single optical fiber system
US7075636B2 (en) * 1999-09-17 2006-07-11 Tidal Photonics, Inc. Apparatus and methods for evaluating performance of endoscopy devices and systems

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4595008A (en) * 1979-11-27 1986-06-17 Sunset Ltd. Localized thermotherapy technique
US4711246A (en) * 1986-09-02 1987-12-08 Fiberoptic Sensor Technologies, Inc. Fiber optic coupled pressure transducer using single fiber and method of fabrication
US6216540B1 (en) * 1995-06-06 2001-04-17 Robert S. Nelson High resolution device and method for imaging concealed objects within an obscuring medium
US6240309B1 (en) * 1995-10-06 2001-05-29 Hitachi, Ltd. Optical measurement instrument for living body
US6487349B2 (en) * 1995-11-20 2002-11-26 Cirrex Corp. Method and apparatus for improved fiber optic light management
US20020087047A1 (en) * 1999-09-13 2002-07-04 Visionscope, Inc. Miniature endoscope system
US7075636B2 (en) * 1999-09-17 2006-07-11 Tidal Photonics, Inc. Apparatus and methods for evaluating performance of endoscopy devices and systems
US20050143662A1 (en) * 2000-05-03 2005-06-30 Rocky Mountain Biosystems, Inc. Optical imaging of subsurface anatomical structures and biomolecules
US6975898B2 (en) * 2000-06-19 2005-12-13 University Of Washington Medical imaging, diagnosis, and therapy using a scanning single optical fiber system

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011121346A1 (fr) * 2010-03-29 2011-10-06 Inspection Technologies Limited Appareil et procédé d'inspection
US20130015354A1 (en) * 2010-03-29 2013-01-17 Inspection Technologies Limited Inspection apparatus and method
US8933405B2 (en) * 2010-03-29 2015-01-13 Inspection Technologies Limited Inspection apparatus and method
US8942530B2 (en) 2011-09-20 2015-01-27 San Marino Capital, Inc. Endoscope connector method and apparatus
US9549662B2 (en) 2011-09-20 2017-01-24 San Marino Capital, Inc. Endoscope connector method and apparatus
CN103271719A (zh) * 2013-05-13 2013-09-04 执鼎医疗科技江苏有限公司 血管影像定位系统
CN105342556A (zh) * 2015-09-23 2016-02-24 天津大学 一种基于集成经验模式分解的肿瘤信号提取方法

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