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`EXHIBIT 2119
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`United States Patent
`[19]
`5,596,987
`[11] Patent Number:
`
`[45] Date of Patent: Jan. 28, 1997
`
`Chance
`
`Hlllllllllllllllllllllllll||||||lll|l|||||ll||l||||lllllllllllllllllllllll
`US005596987A
`
`[54] OPTICAL COUPLER FOR IN VIVO
`EXAMINATION OF BIOLOGICAL TISSUE
`
`[75]
`
`Inventor: Britton Chance, Marathon, Fla.
`
`[73] Assignee: NonInvasive Technology, Inc.,
`Philadelphia, Pa.
`
`[21] Appl. No.: 367,939
`
`[22]
`
`Filed:
`
`Jan.3, 1995
`
`Related U.S. Application Data
`
`[63] Continuation-impart of Ser. No. 6,233, Jan. 19, 1993, Pat.
`No. 5,402,778, which is a continuation-in-part of Ser. No.
`583,006, Sep. 17, 1990, abandoned, which is a continuation
`of Ser. No. 266,116, Nov. 2, 1988, abandoned.
`
`Int. Cl.6 ........................................................ A61B 5/00
`[51]
`[52] US. Cl.
`........................... 128/633; 128/664; 128/665
`[58] Field of Search ..................................... 128/632, 633,
`128/634, 637, 664, 665, 666; 356/39, 41
`
`[56]
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`3,068,742
`3,412,729
`3,461,856
`3,638,640
`3,709,612
`3,866,599
`3,994,585
`3,998,550
`
`.......................... 88/14
`12/1962 Hicks, Jr. et a1.
`
`11/1968 Smith, Jr.
`...........
`128/2.05
`8/1969 Polanyi ............... 128/2
`
`2/1972 Shaw ............... 128/2 R
`
`1/1973 Clemens .......... 356/178
`
`2/1975 Johnson .................. 128/2 L
`
`11/1976 Frey .......................... 356/40
`12/1976 Konishi et a1.
`........................... 356/39
`
`(List continued on next page.)
`FOREIGN PATENT DOCUMENTS
`
`W092/20273
`
`11/1992 WIPO .
`
`OTHER PUBLICATIONS
`
`Chance et a1., “Photon Migration in Muscle and Brain,”
`Photon Migration in Tissues, Plenum Press, pp. 121—135,
`1989, Chance, B., ed.
`Cui et a1., “Expcrimental Study of Migration Depth for the
`Photons Measured
`at
`Surface,”
`SPIE,
`Sample
`1431:180—191, 1991.
`
`Greenfeld, “A Tissue Model For Investigating Photon
`Migration in Trans—Cranial
`Infrared Imaging,” Photon
`Migration in Tissues,Plenum Press, B. Chance, ed., pp.
`147—168, 1989.
`Sevick et a1., “Analysis of absorption, scattering, and hemo—
`globin saturation using phase modulation spectroscopy,”
`SPIE, 1431:264—275, 1991.
`Sevick et a1., “Photon migration in a model of the head
`measured using time —and frequency— domain techniques:
`potentials of spectroscopy and imaging,” SPIE, 1431:84—96,
`1991.
`
`Weng et a1., “Measurement of Biological Tissue Metabolism
`Using Phase Modulation Spectroscopy Technology,” SPIE,
`1431:161—171,1991.
`
`Primary Examiner—Angela D. Sykes
`Assistant Examiner—Eric F. Winakur
`
`Attorney, Agent, or Firm—Fish & Richardson RC.
`
`[57]
`
`ABSTRACT
`
`An optical coupler for in vivo examination of biological
`tissue includes an optical input port positionable on or near
`the examined tissue, a first light guide optically coupled to
`the optical input port and constructed to transmit optical
`radiation of a visible or infra-red wavelength from a source
`to the optical input port. The optical coupler also includes an
`optical detection port, positionable on or near the examined
`tissue, constructed and arranged to receive radiation that has
`migrated in the examined tissue from the input port. Con-
`nected to the detection port is a detector light guide, con—
`structed to transmit radiation from the detection port to an
`optical detector. Disposed at least partially around the exam-
`ined tissue and the input and detection ports is optical
`medium arranged to couple the radiation to the tissue, limit
`escape of photons, or account for photons that escaped from
`the tissue. The optical coupler also enables a precise relative
`geometry of input and detection ports. The optical coupler
`may further include a system for altering controllably
`absorptive or scattering properties of the optical medium.
`The optical coupler may be further adapted for needle
`localization procedure, ultrasonic examination of tissue, and
`may include coils for magnetic resonance imaging of the
`tissue also examined optically.
`
`37 Claims, 10 Drawing Sheets
`
`
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`5,596,987
`
`Page 2
`
`U.S. PATENT DOCUMENTS
`
`4,086,915
`4,119,406
`4,138,727
`4,162,405
`4,167,331
`4,223,680
`4,281,645
`4,321,930
`4,380,240
`4,416,285
`
`5/1978 Kofsky el al.
`10/1978 Clemens
`2/1979 Manlz ..
`7/1979 Chance eta].
`9/1979 Nielsen
`9/1980 Jiibsis
`8/1981 Jiibsis
`3/1982 Jiibsis cl a1.
`4/1983 J6bsis el al.
`11/1983 Shaw et a1.
`
`
`
`
`.......................... 128/2 L
`422/81
`.. 364/525
`.. 250/461
`356/39
`.. 128/633
`.. 128/633
`.. 128/633
`.
`.. 128/633
`.
`
`............................. 128/634
`
`4,5 10,938
`4,612,938
`4,800,885
`4,805,623
`4,824,242
`4,846,183
`4,908,762
`4,972,331
`5,106,387
`5,119,815
`5,187,672
`
`4/ 1985
`9/ 1986
`1/ 1989
`2/ 1989
`4/ 1989
`4/ 1989
`3/ 1990
`11/1990
`4/1992
`6/1992
`2/1993
`
`............................ 128/633
`Jébsis et a1.
`Dietrich el al.
`128/665
`
`Johnson ........
`128/633
`
`Jijbsis .........
`128/633
`
`............................... 356/41
`Frick el al.
`Martin ..................................... 128/633
`Suzuki et al.
`364/413.09
`Chance .......
`364/550
`Kiltrell el al.
`128/664
`.
`Chance ..........
`128/633
`
`Chance et a1.
`.......................... 364/550
`
`
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`US. Patent
`
`Jan. 28, 1997
`
`Sheet 1 of 10
`
`5,596,987
`
` SAMPLE pa* y;
`
`FIG. 1
`
`35
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`US. Patent
`
`Jan. 28, 1997
`
`Sheet 2 of 10
`
`5,596,987
`
`
`
`FIG. 2A
`
`4°
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`US. Patent
`
`Jan. 28, 1997
`
`Sheet 3 of 10
`
`5,596,987
`
`420
`
`\a
`
`FIG.28
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`US. Patent
`
`Jan. 28, 1997
`
`Sheet 4 of 10
`
`5,596,987
`
`46
`
`NEONATE
`BRAIN
`
`
`
`PHOTON PROBABABILITY
`DISTRIBUTION
`
`
`MATCHING
`>4§\
`
`
`\\
`
`BLOCK OF
`
`‘ ’
`
`MATERIAL
`
`22
`
`INPUT FIBRE
`
`20
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`US. Patent
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`Jan. 28, 1997
`
`Sheet 5 of 10
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`5,596,987
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`US. Patent
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`Jan. 28, 1997
`
`Sheet 6 of 10
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`5,596,987
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`32
`
`11A
`
`ITEM.
`
`'lm“\5A
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`US. Patent
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`Jan. 28, 1997
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`Sheet 7 of 10
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`US. Patent
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`Jan. 28, 1997
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`Sheet 8 of 10
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`US. Patent
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`Jan. 28, 1997
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`Sheet 9 of 10
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`US. Patent
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`Jan. 28, 1997
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`Sheet 10 of 10
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`5,596,987
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`68A
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`FIG.6
`
` 65
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`

`1
`OPTICAL COUPLER FOR IN VIVO
`EXAMINATION OF BIOLOGICAL TISSUE
`
`5,596,987
`
`2
`SUMMARY OF THE INVENTION
`
`CROSS REFERENCE TO RELATED
`APPLICATIONS
`
`The present invention is a continuation—in—part application
`of a U.S. patent application Ser. No. 08/006,233 filed Jan.
`19, 1993, now U.S. Pat. No. 5,402,778, which is a continu-
`ation-in-part application of U.S. patent application Ser. No.
`07/583,006 filed Sep. 17, 1990, abandoned, which is a
`continuation of U.S. patent application Ser. No. 07/266,116,
`filed Nov. 2, 1988, now abandoned, all of which are incor-
`porated by reference as if set forth in their entities herein.
`
`BACKGROUND OF THE INVENTION
`
`Continuous wave (CW) spectrophotometers have been
`widely used to determine in vivo concentration of an opti-
`cally absorbing pigment (e.g., hemoglobin, oxyhemoglobin)
`in biological
`tissue. The CW spectrophotometers,
`for
`example, in pulse oximetry introduce light into a finger or
`the ear lobe to measure the light attenuation and then
`evaluate the concentration based on the Beer Lambert equa—
`tion or modified Beer Lambert absorbance equation. The
`Beer Lambert equation (1) describes
`the relationship
`between the concentration of an absorbent constituent (C),
`the extinction coefficient (6),
`the photon migration path—
`length <L>, and the attenuated light intensity (Illa).
`
`logU/Iu]
`<L>
`
`= 2 etc;
`
`(1)
`
`However, direct application of the Beer Lambert equation
`poses several problems. Since the tissue structure and physi-
`ology vary significantly, the optical pathlength of migrating
`photons also varies significantly and can not be simply
`determined from geometrical position of a source and detec—
`tor. In addition, the photon migration pathlength itself is a
`function of the relative concentration of absorbing constitu-
`ents. As a result, the pathlength through an organ with high
`blood hemoglobin concentration, for example, will be dif-
`ferent from the same with a low blood hemoglobin concen-
`tration. Furthermore, the pathlength is frequently dependent
`upon the wavelength of the light since the absorption
`coefficient of many tissue constituents is wavelength depen-
`dent. One solution to this problem is to determine 6., C, and
`<L> at the same time, but this is not possible with the pulse
`oximeters known previously.
`Furthermore, for quantitative measurement of tissue of a
`small volume (e.g., a finger) photon escape introduces a
`significant error since the photons escaped from the tissue
`are counted as absorbed. Other errors may occur due to
`irregular coupling of light to the examined tissue or varying
`relative geometry of the input and detection ports.
`The time resolved (TRS-pulse) and phase modulation
`(PMS) spectrophotometers can measure the average path—
`length of migrating photons directly, but the proper quanti-
`tation of the time resolved or frequency resolved spectra can
`be performed only when the spectra are collected at a
`relatively large source-detector separation. This separation
`is difficult to achieve for a small volume of tissue such as the
`earlobe, a finger or a biopsy tissue.
`Therefore, there is a need for an optical coupler used with
`a spectrophotometric system and method that quantitatively
`examines a relatively small volume of biological tissue.
`
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`The invention features a spectrophotometric system for
`examination of a relatively small volume of biological tissue
`of interest using visible or infra-red radiation.
`According to one aspect of the invention, a spectropho-
`tometn'c system for examination of a relatively small object
`of interest
`(e.g., biological
`tissue, organic or inorganic
`substance in a solid, liquid or gaseous state) using visible or
`infra-red radiation introduced to a path passing through the
`object. The system includes a spectrophotometer with an
`optical input port adapted to introduce radiation into the
`object and an optical detection port adapted to detect radia—
`tion that has migrated through a path in the object, photon
`escape preventing means arranged around the relatively
`small object of interest and adapted to limit escape of the
`introduced photons outside the object, and processing means
`adapted to determine an optical property of the object based
`on the changes between the introduced and the detected
`radiation.
`
`According to another aspect of the invention, a system for
`examination of a relatively small volume of biological tissue
`of interest using visible or infra-red radiation includes a
`spectrophotometer with a light source adapted to introduce
`radiation at an optical input port, a detector adapted to detect
`radiation that has migrated through a path from the input
`port to an optical detection port, and a processor adapted to
`evaluate changes between the introduced and the detected
`radiation. The system also includes an optical medium of a
`relatively large volume, forming photon escape preventing
`means, having selectable scattering and absorptive proper-
`ties, positioning means adapted to locate the biological
`tissue of interest into the migration path to create a tissue-
`medium optical path, the optical medium substantially lim-
`iting escape of photons from the tissue-medium optical path,
`and processing means adapted to determine a physiological
`property of the tissue based on the detected optical property
`of the tissue-medium optical path and the scattering or
`absorptive properties of the optical medium.
`Preferred embodiments of these aspects of the invention
`include one or more of the following features.
`The photon escape preventing means include an optical
`medium of a selectable optical property surrounding the
`object. The selectable optical property is an absorption or
`scattering coefficient.
`The photon escape preventing means include an optical
`medium surrounding the object; the medium has at least one
`optical property substantially matched to the optical prop-
`erty of the object.
`The spectrophotometer is a continuous wave spectropho-
`tometer as described in a PCT application WO 92/20273, a
`phase modulation spectroscopic unit as described in U.S.
`Pat. Nos. 4,972,331 or 5,187,672, time resolved spectro-
`scopic (TRS) unit as described in U.S. Pat. No. 5,119,815 or
`WO 94/22361, or a phased array system as described in WO
`93/25145 all of which are incorporated by reference as if set
`forth in their entities herein.
`
`The determined physiological property is the hemoglobin
`saturation, the concentration of an enzyme or the concen-
`tration of a tissue substance such as glucose.
`The system performs a single measurement or a continu-
`ous, time-dependent monitoring of the selected physiologi-
`cal property.
`The above-described system operates by introducing into
`the object, surrounded by the photon escape preventing
`means, electromagnetic radiation of a selected wavelength
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`3
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`5,596,987
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`and detecting radiation that has migrated in the object from
`the input port to the optical detection port. The system
`determines an optical property of the object based on the
`changes between the introduced and the detected radiation.
`In addition, different photon escape preventing means hav-
`ing a surrounding optical medium with the optical property
`comparable to the optical property of the object may be
`selected. Then, the system measures again the optical prop-
`erty of the object. The measurements may be repeated
`iteratively until
`the optical property of the surrounding
`medium is substantially matched to the optical property of
`the object.
`According to another important aspect, the invention is an
`optical coupling system for non-invasively monitoring a
`region of living tissue. The coupling system includes an
`excitation (input) port positionable at the tissue and adapted
`to introduce optical radiation into the monitored tissue, a
`first light guide defining an excitation channel for conveying
`the radiation from a source to the excitation port, and a
`detection port, positionable at the tissue, adapted to receive
`radiation that has migrated in the monitored tissue from the
`excitation port to the detection port. The detection port has
`a detection area larger than a input area of the excitation
`port. Connected to the detection port is a detecting light
`guide, for conveying the radiation from the detection port to
`an optical detector. The coupling system also includes
`optical matching fluid contained within a flexible optically
`transparent bag and disposed partially around the monitored
`tissue and the excitation and detection ports.
`Preferred embodiments of this aspect of the invention
`includes one or more of the following features.
`The optical coupling system may include multiple exci—
`tation (input) ports positionable at the tissue and adapted to
`introduce radiation of the source into the monitored tissue,
`and multiple light guides, each defining an excitation chan-
`nel for conveying the radiation from the source to the
`corresponding excitation port.
`The optical coupling system may also include multiple
`detection ports positionable at the tissue and adapted to
`receive radiation that has migrated in the monitored tissue,
`and multiple detecting light guides each connected to the
`corresponding detection port for conveying the radiation
`from the detection port to at least one optical detector.
`The optical matching fluid may be positioned partially
`between the ports and the monitored tissue. The optical
`matching fluid may have known scattering or absorptive
`properties.
`The optical coupling system may further include means
`for changing scattering or absorptive properties of the opti—
`cal matching fluid and means for calibrating the coupling
`system by controllably changing scattering or absorptive
`properties of the optical matching fluid.
`According to another important aspect, the invention is an
`optical coupler for in vivo examination of biological tissue.
`The optical coupler includes an optical
`input port of a
`selected input area positionable on or near the examined
`tissue, a first light guide optically coupled to the optical
`input port and constructed to transmit optical radiation of a
`visible or infra-red wavelength from a source to the optical
`input port, wherein the optical input port is constructed and
`arranged to introduce the optical radiation to the examined
`tissue, and an optical detection port of a selected detection
`area positionable on or near the examined tissue. The
`detection port is constructed and arranged to receive radia-
`tion that has migrated in the examined tissue from the input
`port to the detection port. Optically coupled to the detection
`
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`port is a detector light guide constructed to transmit the
`radiation from the detection port to an optical detector. The
`optical coupler also includes optical medium disposed at
`least partially around the examined tissue and the input are
`detection ports and constructed to limit escape of, or account
`for photons escaped from the examined tissue.
`According to another important aspect, the invention is an
`optical coupler for in vivo examination of biological tissue.
`The optical coupler includes an optical
`input port of a
`selected input area directed toward the examined tissue, an
`optical detection port of a selected detection area directed
`toward the examined tissue, and optical medium disposed at
`least partially around the examined tissue and the input and
`detection ports. The optical medium is also placed between
`the tissue and the input area of the input port and between
`the tissue and the detection area of the detection port, and the
`optical medium exhibits known scattering or absorptive
`properties. Optically coupled to the optical input port is a
`first light guide constructed to transmit optical radiation of
`a visible or infra-red wavelength from a source to the optical
`input port that is constructed and arranged to introduce the
`radiation to the optical medium. The optical detection port is
`constructed and arranged to receive radiation that has
`migrated in the examined tissue and the optical medium
`from the input port to the detection port. Optically coupled
`to the detection port is a detector light guide constructed to
`transmit the radiation from the detection port to an optical
`detector.
`
`Preferred embodiments of this aspect of the invention
`includes one or more of the following features.
`The optical medium may have absorptive or scattering
`properties substantially matched to the absorptive or scat-
`tering properties of the examined tissue.
`The optical coupler may further include an optical system
`constructed and arranged to alter controllably absorptive or
`scattering properties of the optical medium. The system may
`be adapted to substantially match the absorptive or scatter-
`ing properties of the optical medium to the absorptive or
`scattering properties of the examined tissue.
`The optical coupler may further include a second input
`port of a selected input area, and a light guide optically
`coupled to the second input port. The detection port may be
`pieced symmetrically relative to the first input port and the
`second input port. The detection port may be arranged in a
`transmission geometry or in a backseattering geometry
`relative to the input ports.
`The optical coupler may accommodate movable optical
`ports relative to the examined tissue.
`The optical coupler may further include multiple input
`ports, and multiple light guides optically coupled to the
`corresponding input ports. The multiple input ports may be
`arranged to introduce simultaneously radiation of known
`time varying pattern to form resulting introduced radiation
`possessing a substantial gradient of photon density in at least
`one direction. The multiple input ports may form a one
`dimensional or two dimensional array. The optical detection
`port may be movable to another location relative to the
`examined tissue.
`
`The optical coupler may also include multiple detection
`ports, and multiple detector light guides optically coupled to
`the corresponding detection ports.
`The optical medium may include solid particles of
`smooth,
`spherical
`surface, or
`styrofoam. The optical
`medium may include a liquid of selectable scattering or
`absorptive properties such as an intralipid solution. The
`optical medium may include a pliable solid of selectable
`scattering or absorptive properties.
`
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`The optical coupler may have the detection area of the
`optical detection port is larger than the input area of said
`optical input port.
`The optical coupler may further include a port for the
`needle localization procedure or may be arranged for ultra-
`sonic examination of the tissue performed simultaneously
`with, or subsequently to the optical examination of the
`tissue. The optical coupler may further include a set of MRI
`coils arranged to perform an MRI examination of the tissue.
`According to another important aspect, the invention is an
`optical coupler for in vivo examination of biological tissue.
`The optical coupler includes an optical input port of a first
`selected area directed toward the examined tissue and a
`second selected area oppositely oriented to the first area, and
`an optical detection port of a selected detection area directed
`toward the examined tissue. The input port is constructed to
`accept a light beam scanned over the second area and
`introduce the beam to the tissue at the first area. The optical
`coupler also includes optical medium disposed at
`least
`partially around the examined tissue and the input and
`detection ports. The optical medium is also placed between
`the tissue and the input area of the input port and between
`the tissue and the detection area of the detection port. The
`optical medium exhibits known scattering or absorptive
`properties. The optical detection port
`is constructed and
`arranged to receive radiation that has migrated in the exam~
`ined tissue and the optical medium from the input port to the
`detection port. Optically coupled to the detection port is a
`detector light guide constructed to transmit the radiation
`from the detection port to an optical detector.
`Preferred embodiments of this aspect of the invention
`includes one or more of the following features.
`The detection area of the optical detection port may
`include a multiplicity of detection subareas located at a
`known position of the detection area. Each detection subarea
`is constructed and arranged to receive radiation that has
`migrated in the examined tissue and convey the received
`radiation to a detector.
`
`The optical detector may include an array of semicon—
`ducting detectors each receiving light from a corresponding
`detection subarea via the detector light guide. Thus a time
`profile of the detected radiation can be measured at the
`individual locations.
`
`The light beam may be scanned over the input port using
`a selected pattern relative to a detection sequence accumu-
`lated over the detection subareas. Then, by knowing the
`input and detection locations of the migrating photons,
`average photon migration paths may be calculated.
`In general, the optical coupling system provides an excel-
`lent coupling of light to the examined tissue, substantime
`prevents escape of photons from the tissue surface and
`achieves semi-infinite boundary conditions for the intro-
`duced radiation. A larger volume of optical medium is
`usually used for a small tissue size. The optical coupling
`system also achieves precisely a selected geometry of the
`input (excitation) ports and the detection ports regardless of
`the tissue shape or property. The precise geometry is fre-
`quently important for proper evaluation of the photon migra-
`tion patterns measured by the continuous wave unit, the
`phase modulation unit, the TRS unit, or the phased array
`unit.
`
`BRIEF DESCRIPTION OF THE DRAWING
`
`FIG. 1 is a diagrammatic view of a spectrophotometric
`system for examination of tissue of a relatively small
`dimension.
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`60
`
`65
`
`FIGS. 2 and 2A show different views of a cylinder for
`preventing escape of photons during spectrophotometric
`measurements of a finger.
`FIG. 2B shows a set of cylinders of preselected optical
`properties for a finger oximetry.
`FIG. 3 is a diagrammatic view of an optical fiber holder
`for a spectrophotometric study of the head.
`FIG. 4 a plan view of an optical coupling system for
`monitoring the oxygenation-deoxygenation state of the
`hemoglobin within the brain tissue of a subject.
`FIG. 4A depicts an optical coupling system for examina-
`tion of the brain tissue utilizing several input and detection
`ports.
`FIGS. 5 and 5A through 5C depict several optical cou—
`pling systems for optical examination of the breast tissue.
`FIG. 5D depicts an optical coupling system with a two
`dimensional input array also adapted for the needle local—
`ization procedure.
`FIGS. 5E and SF depict optical coupling systems adapted
`for optical examination together with ultrasound and mag-
`netic resonance imaging, respectively.
`FIG. 6 depicts an optical coupling system with optical
`windows adapted for a scanning system with an array
`detector.
`
`DESCRIPTION OF THE PREFERRED
`EMBODIMENTS
`
`Referring to FIG. 1, a system 10 for examination of
`biological tissue of a relatively small volume, includes an
`optical medium 12 of selectable optical properties, a spec-
`trophotometer 18, a titrimetn'c circulation system 30, and
`computer control 35. Biological
`tissue of interest 14,
`attached to a locator 15, is inunersed in optical medium 12.
`Spectrophotometer 18 examines optical properties of
`medium 12 by employing visible or infra-red light con—
`ducted via light guides 20 and 22. Light guides 20 and 22,
`which in a preferred embodiment are optical fibers, are
`connected to a light source 17 and a light detector 23,
`respectively. Photons introduced at an optical input port 19
`migrate in medium 12 through a scattering and absorptive
`path and are detected at a detection port 21. The selectable
`fixed geometry of input port 19 and detection port 21
`controls the migration path, i.e., optical field 25.
`System 30 is adapted to change precisely the scattering
`and absorptive properties of medium 12. Medium 12
`includes intralipid solution (made by Kabi Vitrum, Inc.,
`Clapton, N.C.) that exhibits scattering properties depending
`on its concentration and carbon black india ink that exhibits
`absorptive properties. The scattering or absorptive proper-
`ties of medium 12 can be either maintained constant and
`
`uniform by properly mixing the solution or can be changed
`almost continuously by changing the concentration of the
`constituents in titration system 30. Tubes 32 and 34 are
`adapted for continuous circulation of the solution.
`In system operation, tissue 14 is first located away from
`optical field 25. Spectrophotometer 18 examines medium 12
`in field region 25, and control 35 compares the detected data
`to the preselected values of the absorption coeflicient (pa)
`and the scattering coeflicient (p5). Next, locator 15 positions
`tissue 14 into field 25 and spectrophotometer 18 measures
`the optical properties of tissue 14 and medium 12. From the
`spectral data collected with and without tissue 14, computer
`control 35 detemrines the optical properties of tissue 14.
`
`IPR2017—003 15
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`CONDITIONAL MOTION TO AMEND
`
`VALENCELL, INC.
`EXHIBIT 2119 — PAGE 16
`
`IPR2017-00315
`CONDITIONAL MOTION TO AMEND
`
`VALENCELL, INC.
`EXHIBIT 2119 - PAGE 16
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`7
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`8
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`5,596,987
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`In another preferred method of operation, after measuring
`the optical properties of medium 12,
`the scattering and
`absorptive properties of medium 12 are matched by titration
`to the properties of tissue 14 so that, when inserted into field
`25, tissue 14 does not cause perturbation of field 25. After
`matching the scattering and absorption coefficients of
`medium 12 to the coefficients of tissue 14, spectrophotom-
`eter 18 detects the same data with or without tissue 14. The
`known titrated values of pa* and u} are equal to the pa and
`u, values of tissue 14. The matching process is performed by
`first matching pa and then fix or vice versa.
`The described method is applicable to both in vivo and in
`vitro tissue examination. Tissue 14 may be a biopsy speci-
`men enelosed in an optically transparent material or a
`portion of a human finger inserted into medium 12. The
`wavelength of light used by spectrophotometer 18 is
`selected depending on the tissue component of interest (e.g.,
`hemoglobin, oxyhemoglobin, glucose, enzymes); it is within
`the scope of this invention to use multiple wavelengths.
`The present invention envisions the use of different pre—
`ferred embodiments of optical medium 12. Referring to FIG.
`2, a hollow cylinder 42 filled with medium 12 surrounds, for
`example, a finger 40 and prevents escape of introduced
`photons. The optical properties, pressure and volume of
`medium 12 are controlled by system 30 connected to cyl—
`inder 42 by tubes 32 and 34. The inside walls of cylinder 42
`are made of a pliable, optically transparent banier 44. After
`insertion into cylinder 42, barrier 44 fits snugly around the
`finger. The dimension of inside barrier 44 is such that after
`finger 40 is withdrawn, medium 12 fills the volume of
`cylinder 42 completely. This enables both a background
`measurement of medium 12 and a measurement of finger 40
`in medium 12 in the same way as described in connection
`with FIG. 1. Optical field 25, controlled by the position of
`input port 19 and detection port 21, is either in transmission
`or reflection geometry.
`Refening to FIG. 2B, in another embodiment, cylinder 42
`is replaced by a set of cylinders 42A, 42B, 42C .
`.
`.
`, each
`containing medium 12 in a fluid or solid state with a constant
`preselected absorption and scattering coefficient. The solid
`optical medium is titanium oxide, or other scatterer, imbed—
`(led in an absorbing, pliable medium such as a gel.
`A human finger is inserted into the individual cylinders,
`and the optical properties of the inserted finger are measured
`by spectrophotometer 18. Using the known optical proper-
`ties of the cylinders and the input port—detection port geom—
`etry, the optical properties (i.e., pa and pi) of the finger can
`be matched to the properties of one of the cylinders.
`The preferred embodiments of spectrophotometer 18 are
`a continuous wave spectrometer, a phase modulation spec—
`trometer and a time—resolved spectrometer, all of them
`described in the above-cited documents.
`
`System 10 operating with a du