throbber
(19) United States
`(12) Patent Application Publication (10) Pub. No.: US 2014/0236021 A1
`Islam
`(43) Pub. Date:
`Aug. 21, 2014
`
`US 20140236021A1
`
`(54) NEAR-INFRARED SUPER-CONTINUUM
`LASERS FOR EARLY DETECTION OF
`BREAST AND OTHER CANCERS
`
`(71) Applicant: OMNI MEDSCI, INC., Ann Arbor, MI
`(US)
`(72) Inventor: Mohammed N. Islam, Ann Arbor, MI
`(US)
`
`(73) Assignee: OMNI MEDSCI, INC., Ann Arbor, MI
`(US)
`
`(21) Appl. No.: 14/109,007
`
`(22) Filed:
`
`Dec. 17, 2013
`O
`O
`Related U.S. Application Data
`(60) Provisional application No. 61/747,553, filed on Dec.
`31, 2012.
`
`Publication Classification
`
`(51) Int. Cl.
`A6 IB5/00
`
`(2006.01)
`
`(52) U.S. Cl.
`CPC ............. A61B5/0075 (2013.01); A61B5/7257
`(2013.01); A61B5/0091 (2013.01)
`USPC .......................................................... 6OO/475
`
`ABSTRACT
`(57)
`A system and method for using near-infrared or short-wave
`infrared (SWIR) light sources for early detection and moni
`toring of breast cancer, as well as other kinds of cancers may
`detect decreases in lipid content and increases in collagen
`content, possibly with a shift in the collagen peak wave
`lengths and changes in spectral features associated with
`hemoglobin and water content as well. Wavelength ranges
`between 1000-1400 nm and 1600-1800 nm may permit rela
`tively high penetration depths because they fall within local
`minima of water absorption, scattering loss decreases with
`increasing wavelength, and they have characteristic signa
`tures corresponding to overtone and combination bands from
`chemical bonds of interest, such as hydrocarbons. Broadband
`light sources and detectors permit spectroscopy in transmis
`Sion, reflection, and/or diffuse optical tomography. High sig
`nal-to-noise ratio may be achieved using a fiber-based Super
`continuum light source. Risk of pain or skin damage may be
`mitigated using Surface cooling and focused infrared light.
`
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`Aug. 21, 2014
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`NEAR-INFRARED SUPER-CONTINUUM
`LASERS FOR EARLY DETECTION OF
`BREAST AND OTHER CANCERS
`
`CROSS-REFERENCE TO RELATED
`APPLICATIONS
`0001. This application claims the benefit of U.S. provi
`sional application Ser. No. 61/747,553 filed Dec. 31, 2012,
`the disclosure of which is hereby incorporated in its entirety
`by reference herein.
`0002 This application is related to U.S. provisional appli
`cation Ser. No. 61/747,477 filed Dec. 31, 2012: Ser. No.
`61/747,481 filed Dec. 31, 2012; Ser. No. 61/747,485 filed
`Dec. 31, 2012; Ser. No. 61/747,487 filed Dec. 31, 2012; Ser.
`No. 61/747,492 filed Dec. 31, 2012; Ser. No. 61/747,472 filed
`Dec. 31, 2012; and Ser. No. 61/754,698 filed Jan. 21, 2013,
`the disclosures of which are hereby incorporated in their
`entirety by reference herein
`0003. This application is being filed concurrently with
`International Application No. PCT/US13/075700 entitled
`Near-Infrared Lasers For Non-Invasive Monitoring Of Glu
`cose, Ketones, HBA1C, And Other Blood Constituents (Attor
`ney Docket No. OMNI0101 PCT): International Application
`No. PCT/US 13/075736 entitled Short-Wave Infrared Super
`Continuum Lasers For Early Detection Of Dental Caries (At
`torney Docket No. OMNI0102PCT); U.S. application Ser.
`No. 14/108,995 entitled Focused Near-Infrared Lasers For
`Non-Invasive Vasectomy And Other Thermal Coagulation Or
`Occlusion
`Procedures
`(Attorney
`Docket
`No.
`OMNI0103PUSP): International Application No. PCT/
`US 13/075767 entitled Short-Wave Infrared Super-Con
`tinuum Lasers For Natural Gas Leak Detection, Exploration,
`And Other Active Remote Sensing Applications (Attorney
`Docket No. OMNI0104PCT); U.S. application Ser. No.
`14,108,986 entitled Short-Wave Infrared Super-Continuum
`Lasers For Detecting Counterfeit Or Illicit Drugs And Phar
`maceutical Process Control (Attorney Docket No.
`OMNI0105PUSP); and U.S. application Ser. No. 14/108,974
`entitled Focused Near-Infrared Lasers For Non-Invasive Vari
`cose Veins And Other Thermal Coagulation Or Occlusion
`Procedures (Attorney Docket No. OMNI0106PUSP), the dis
`closures of which are hereby incorporated in their entirety by
`reference herein.
`
`TECHNICAL FIELD
`0004. This disclosure relates to lasers and light sources for
`use in near-infrared spectroscopy for early detection of Vari
`ous kinds of cancers, including breast cancer, and to systems
`and methods for using near-infrared or short-wave infrared
`light sources for early detection of breast cancer using, for
`example, a fiber-based Super-continuum source.
`
`BACKGROUND AND SUMMARY
`0005 Breast cancer is considered to be the most common
`cancer among women in industrialized countries. It is
`believed that early diagnosis and consequent therapy could
`significantly reduce mortality. Mammography is considered
`the gold standard among imaging techniques in diagnosing
`breast pathologies. However, the use of ionizing radiation in
`mammography may have adverse effects and lead to other
`complications. Moreover, Screening X-ray mammography
`may be limited by false positives and negatives, leading to
`unnecessary physical and psychological morbidity. Although
`
`breast cancer is one of the focuses of this disclosure, the same
`techniques may also be applied to other cancer types, includ
`ing, for example, skin, prostate, brain, pancreatic, and col
`orectal cancer.
`0006 Diagnostic methods for assessment and therapy fol
`low-up of breast cancer include mammography, ultrasound,
`and magnetic resonance imaging. The most effective screen
`ing technique at this time is X-ray mammography, with an
`overall sensitivity for breast cancer detection around 75%,
`which is even further reduced in women with dense breasts to
`around 62%. Moreover, X-ray mammography has a 22% false
`positive rate in women under 50, and the method cannot
`accurately distinguish between benign and malignant tumors.
`Magnetic resonance imaging and ultrasound are sometimes
`used to augment X-ray mammography, but they have limita
`tions such as high cost, low throughput, limited specificity
`and low sensitivity. Thus, there is a continued need to detect
`cancers earlier for treatment, missed by mammography, and
`to add specificity to the procedures.
`0007 Optical breast imaging may be an attractive tech
`nique for breast cancer to Screen early, augment with mam
`mography, or use in follow-on treatments. Also, optical breast
`imaging may be performed by intrinsic tissue contrast alone
`(e.g., hemoglobin, water, collagen, and lipid content), or with
`the use of exogenous fluorescent probes that target specific
`molecules. For example, near-infrared (NIR) light may be
`used to assess optical properties, where the absorption and
`scattering by the tissue components may change with carci
`noma. For most of the studies conducted to date, NIR light in
`the wavelength range of 600-1000 nm has been used for
`Sufficient tissue penetration; these wavelengths have permit
`ted imaging up to several centimeters deep in soft tissue.
`Optical breast imaging using fluorescent contrast agents may
`improve lesion contrast and may potentially permit detection
`of changes in breast tissue earlier. In one embodiment, the
`fluorescent probes may either bind specifically to certain
`targets associated with cancer or may non-specifically accu
`mulate at the tumor site.
`0008 Optical methods of imaging and spectroscopy can
`be non-invasive using non-ionizing electromagnetic radia
`tion, and these techniques could be exploited for screening of
`wide populations and for therapy monitoring. "Optical mam
`mography may be a diffuse optical imaging technique that
`aims at detecting breast cancer, characterizing its physiologi
`cal and pathological state, and possibly monitoring the effi
`cacy of the therapeutic treatment. The main constituents of
`breast tissue may be lipid, collagen, water, blood, and other
`structural proteins. These constituents may exhibit marked
`and characteristic absorption features in the NIR wavelength
`range. Thus, diffuse optical imaging and spectroscopy in the
`NIR may be helpful for diagnosing and monitoring breast
`cancer. Another advantage of Such imaging is that optical
`instruments tend to be portable and more cost effective as
`compared to other instrumentation that is conventionally used
`for medical diagnosis. This can be particularly true, if the
`mature technologies for telecommunications and fiber optics
`are exploited.
`0009 Spectroscopy using NIR or short-wave infrared
`(SWIR) light may be beneficial, because most tissue has
`organic compounds that have overtone or combination
`absorption bands in this wavelength range (e.g., between
`approximately 0.8-2.5 microns). In one embodiment, a NIR
`or SWIR super-continuum (SC) laser that is an all-fiber inte
`grated Source may be used as the light source for diagnosing
`
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`cancerous tissue. Exemplary fiber-based Super-continuum
`sources may emit light in the NIR or SWIR between approxi
`mately 1.4-1.8 microns, 2-2.5 microns, 1.4-2.4 microns,
`1-1.8 microns, or any number of other bands. In particular
`embodiments, the detection system may be one or more
`photo-detectors, a dispersive spectrometer, a Fourier trans
`form infrared spectrometer, or a hyper-spectral imaging
`detector or camera. In addition, reflection or diffuse reflection
`light spectroscopy may be implemented using the SWIR light
`source, where the spectral reflectance can be the ratio of
`reflected energy to incident energy as a function of wave
`length.
`0010 For breast cancer, experiments have shown that with
`growing cancer the collagen content increases while the lipid
`content decreases. Therefore, early breast cancer detection
`may involve the monitoring of absorption or scattering fea
`tures from collagen and lipids. In addition, NIR spectroscopy
`may be used to determine the concentrations of hemoglobin,
`water, as well as oxygen Saturation of hemoglobin and optical
`scattering properties in normal and cancerous breast tissue.
`For optical imaging to be effective, it may also be desirable to
`select the wavelength range that leads to relatively high pen
`etration depths into the tissue. In one embodiment, it may be
`advantageous to use optical wavelengths in the range of about
`1000-1400 nm. In another embodiment, it may be advanta
`geous to use optical wavelengths in the range of about 1600
`1800 nm. Higher optical power densities may be used to
`increase the signal-to-noise ratio of the detected light through
`the diffuse scattering tissue, and surface cooling or focused
`light may be beneficial for preventing pain or damage to the
`skin and outer layer Surrounding the breast tissue. Since opti
`cal energy may be non-ionizing, different exposure times may
`be used without danger or harmful radiation.
`0011. In one embodiment, a diagnostic system includes a
`light source configured to generate an output optical beam
`comprising one or more semiconductor Sources configured to
`generate an input beam, one or more optical amplifiers con
`figured to receive at least a portion of the input beam and to
`deliver an intermediate beam to an output end of the one or
`more optical amplifiers, and one or more optical fibers con
`figured to receive at least a portion of the intermediate beam
`and to deliver at least the portion of the intermediate beam to
`a distal end of the one or more optical fibers to form a first
`optical beam. A nonlinear element is configured to receive at
`least a portion of the first optical beam and to broaden a
`spectrum associated with the at least a portion of the first
`optical beam to at least 10 nanometers through a nonlinear
`effect in the nonlinear element to form the output optical
`beam with an output beam broadened spectrum, and wherein
`at least a portion of the output beam broadened spectrum
`comprises a short-wave infrared wavelength between
`approximately 1000 nanometers and approximately 1400
`nanometers or between approximately 1600 nanometers and
`approximately 1800 nanometers, and wherein at least a por
`tion of the one of more fibers is a fused silica fiber with a core
`diameter less than approximately 400 microns. An interface
`device is configured to receive a received portion of the output
`optical beam and to deliver a delivered portion of the output
`optical beam to a tissue sample, wherein the delivered portion
`of the output optical beam is configured to generate a spec
`troscopy output beam from the tissue sample, and wherein at
`least a part of the delivered portion of the output optical beam
`penetrates into the tissue sample a depth of two millimeters or
`more. A receiver is configured to receive at least a portion of
`
`the spectroscopy output beam having a bandwidth of at least
`10 nanometers and to process the portion of the spectroscopy
`output beam to generate an output signal representing at least
`in part a composition of collagen and lipids in the tissue
`sample.
`0012. In another embodiment, a measurement system
`includes a light source configured to generate an output opti
`cal beam comprising a plurality of semiconductor sources
`configured to generate an input optical beam, a multiplexer
`configured to receive at least a portion of the input optical
`beam and to form an intermediate optical beam, and one or
`more fibers configured to receive at least a portion of the
`intermediate optical beam and to form the output optical
`beam, wherein the output optical beam comprises one or
`more optical wavelengths. An interface device is configured
`to receive a received portion of the output optical beam and to
`deliver a delivered portion of the output optical beam to a
`tissue sample, wherein the delivered portion of the output
`optical beam is configured to generate a spectroscopy output
`beam from the sample based on diffuse light spectroscopy,
`and wherein at least a part of the delivered portion of the
`output optical beam penetrates into the tissue sample a depth
`of two millimeters or more. A receiver is configured to receive
`at least a portion of the spectroscopy output beam and to
`process the portion of the spectroscopy output beam to gen
`erate an output signal, wherein the output signal is based on a
`chemical composition of the tissue sample.
`0013. In yet another embodiment, a method of measuring
`includes generating an output optical beam comprising gen
`erating an input optical beam from a plurality of semiconduc
`tor sources, multiplexing at least a portion of the input optical
`beam and forming an intermediate optical beam, and guiding
`at least a portion of the intermediate optical beam and forming
`the output optical beam, wherein the output optical beam
`comprises one or more optical wavelengths, wherein at least
`a portion of the optical wavelengths is between approxi
`mately 1000 nanometers and 1400 nanometers or between
`approximately 1600 nanometers and 1800 nanometers. The
`method may also include receiving a received portion of the
`output optical beam and delivering a delivered portion of the
`output optical beam to a tissue sample and generating a spec
`troscopy output beam having a bandwidth of at least 10
`nanometers from the tissue sample. The method may further
`include receiving at least a portion of the spectroscopy output
`beam, and processing the portion of the spectroscopy output
`beam and generating an output signal based on a wavelength
`dependence of the spectroscopy output beam over the band
`width of at least 10 nanometers, and wherein the output signal
`is based on a chemical composition of the tissue sample.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`0014 For a more complete understanding of the present
`disclosure, and for further features and advantages thereof,
`reference is now made to the following description taken in
`conjunction with the accompanying drawings, in which:
`0015 FIG. 1 illustrates the optical absorption of pure
`water, hemoglobin without oxygen, and hemoglobin Satu
`rated with oxygen.
`0016 FIG. 2 shows examples of various absorption bands
`of chemical species in the wavelength range between about
`1200-2200 nm.
`(0017 FIG.3 depicts the structure of a female breast.
`0018 FIG. 4 illustrates particular embodiments of imag
`ing systems for optically scanning a breast.
`
`Page 27 of 39
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`
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`

`US 2014/0236021 A1
`
`Aug. 21, 2014
`
`0019 FIG. 5 shows the normalized absorption spectra of
`main tissue absorbers in the NIR for breast cancer, between
`about 600-1100 nm.
`0020 FIG. 6 illustrates the normalized absorption coeffi
`cient in the wavelength range between about 500-1600 nm for
`many of the components of breast tissue.
`0021
`FIG. 7 shows the typical spectra of the cancerous
`site of a treated rat and the corresponding site of a normal rat.
`(A) Logarithm of the inverse of reflection spectra; and (B)
`second derivative spectra.
`0022 FIG. 8 shows the second derivative of spectral
`changes over several weeks between about 1600-1800 nm in
`rats with breast cancer.
`0023 FIG. 9 illustrates the second derivative spectra for
`cholesterol, collagen and elastin.
`0024 FIG. 10 shows the absorption coefficient as a func
`tion of wavelength between about 1000 nm and 2600 nm for
`water, adipose and collagen.
`0025 FIG. 11 illustrates the absorbance for four types of
`collagen: collagen I, collagen II, collagen III, and collagen IV.
`0026 FIG. 12 shows an experimental set-up for testing
`chicken breast samples using collimated light. In this experi
`ment, the collimated light has a beam diameter of about 3mm.
`0027 FIG. 13 plots the measured depth of damage (in
`millimeters) versus the time-averaged incident power (in
`Watts). Data is presented for laser wavelengths near 980 nm,
`1210 nm and 1700 nm, and lines are drawn corresponding to
`penetration depths of approximately 2 mm, 3 mm, and 4 mm.
`0028 FIG. 14 illustrates the optical absorption or density
`as a function of wavelength between approximately 700 nm
`and 1300 nm for water, hemoglobin and oxygenated hemo
`globin.
`0029 FIG. 15 shows a set-up used for in vitro damage
`experiments using focused infrared light. After a lens system,
`the tissue is placed between two microscope slides.
`0030 FIG.16 presents histology of renal arteries compris
`ing endothelium, media and adventitia layers and some renal
`nerves in or below the adventitia. (A) No laser exposure. (B)
`After focused laser exposure, with the laser light near 1708
`.
`0031 FIG. 17 illustrates the experimental set-up for ex
`Vivo skin laser treatment with Surface cooling to protect the
`epidermis and top layer of the dermis.
`0032 FIG. 18 shows MTT histo-chemistry of ex vivo
`human skin treated with ~1708 nm laser and cold window (5
`seconds precool; 2 mm diameter spot exposure for 3 seconds)
`at 725 mW (A and B) corresponding to ~70J/cm average
`fluence and 830 mW (C and D) corresponding to ~80 J/cm
`average fluence.
`0033 FIG. 19 illustrates a block diagram or building
`blocks for constructing high power laser diode assemblies.
`0034 FIG. 20 shows a platform architecture for different
`wavelength ranges for an all-fiber-integrated, high powered,
`Super-continuum light source.
`0035 FIG.21 illustrates one embodiment for a short-wave
`infrared Super-continuum light source.
`0036 FIG.22 shows the output spectrum from the SWIR
`SC laser of FIG. 21 when about 10 m length of fiber for SC
`generation is used. This fiber is a single-mode, non-disper
`sion shifted fiber that is optimized for operation near 1550
`.
`0037 FIG. 23A illustrates high power SWIR-SC lasers
`that may generate light between approximately 1.4-1.8
`microns.
`
`0038 FIG. 23B illustrates high power SWIR-SC lasers
`that may generate light between approximately 2-2.5
`microns.
`
`DETAILED DESCRIPTION
`0039. As required, detailed embodiments of the present
`disclosure are described herein; however, it is to be under
`stood that the disclosed embodiments are merely exemplary
`of the disclosure and may be embodied in various and alter
`native forms. The figures are not necessarily to Scale; some
`features may be exaggerated or minimized to show details of
`particular components. Therefore, specific structural and
`functional details disclosed herein are not to be interpreted as
`limiting, but merely as a representative basis for teaching one
`skilled in the art to variously employ the present disclosure.
`0040. To perform non-invasive optical mammography,
`one desired attribute is that the light may penetrate as far as
`possible into the breast tissue. In diffuse reflection spectros
`copy, a broadband light spectrum may be emitted into the
`tissue, and the spectrum of the reflected or transmitted light
`may depend on the absorption and scattering interactions
`within the target tissue. Since breast tissue has significant
`water and hemoglobin content, it is valuable to examine the
`wavelength range over which deep penetration of light is
`possible. FIG. 1 illustrates the optical absorption 100 of pure
`water (dotted line) 101, hemoglobin without oxygen (thinner
`solid line) 102, and hemoglobin saturated with oxygen
`(thicker solid line) 103. It can be noted that above about 1100
`nm, the absorption of hemoglobin is almost the same as water
`absorption. The penetration depth may be proportional to the
`inverse of the optical absorption. Therefore, the highest pen
`etration depth will be at the absorption valley, approximately
`in the wavelength range between about 900 nm and about
`1300 nm. Although not as low in absorption compared to the
`first window, another absorption valley lies between about
`1600 nm and 1800 nm. Thus, non-invasive imaging prefer
`ably should use wavelengths that fall in one of these two
`absorption valleys.
`0041
`FIG. 2 shows examples of various absorption bands
`of chemical species 200 in the wavelength range between
`about 1200 nm and 2200 nm. Although the fundamental
`absorptions usually lie in the mid-infrared (e.g., wavelengths
`longer than about 3 microns), there are many absorption lines
`in the NIR corresponding to the second overtone region 201
`between about 1000 nm and 1700 nm, the first overtone
`region 202 between about 1500 nm and 2050 nm, and the
`combination band region 203 between about 1900 nm and
`2300 nm. As an example, hydrocarbon bonds common in
`many biological Substances have their fundamental absorp
`tion in the mid-IR near 3300-3600 nm, but they also have
`many combination band lines between 2000-2500 nm, and
`other lines at shorter wavelengths corresponding to the first
`and second overtones. Fortunately, there are spectral features
`of FIG. 2 that overlap with the absorption valleys in FIG. 1.
`These are likely to be the wavelengths of interest for spectro
`scopic analysis of cancerous regions.
`0042. In women, the breasts (FIG.3)300 overlay the pec
`toralis major muscles 302 and cover much of the chest area
`and the chest walls 301. The breast is an apocrine gland that
`produces milk to feed an infant child; the nipple 304 of the
`breast is surrounded by an areola 305, which has many seba
`ceous glands. The basic units of the breast are the terminal
`duct lobules 303, which produce the fatty breast milk. They
`give the breast its function as a mammary gland. The lobules
`
`Page 28 of 39
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`OMNI 2121 - IPR21-00453
`
`

`

`US 2014/0236021 A1
`
`Aug. 21, 2014
`
`303 feed through the milk ducts 306, and in turn these ducts
`drain to the nipple 304. The Superficial tissue layer (superfi
`cial fascia) may be separated from the skin 308 by about
`0.5-2.5 cm of adipose of fatty tissue 307.
`0043. Breast cancer is a type of cancer originating from
`breast tissue, most commonly from the inner lining of milk
`ducts 306, the lobules 303 that supply the ducts with milk,
`and/or the connective tissue between the lobules. Cancers
`originating from ducts 306 are known as ductal carcinomas,
`while those originating from lobules 303 or their connective
`tissue are known as lobular carcinomas. While the over
`whelming majority of human cases occur in women, male
`breast cancer may also occur.
`0044 Several particular embodiments of imaging systems
`400, 450 for optically scanning a breast are illustrated in FIG.
`4. In these particular embodiments, the patient 401, 451 may
`lie in a prone position with her breasts inside a box 402,452
`with probably a transparent window on the detector side. A
`compression plate 403, 453 may hold the breast in place
`against the viewing window by mildly compressing the breast
`to a thickness between about 5.5 and 7.5 cm. The box 402,452
`may then be filled with a matching fluid with optical proper
`ties similar to human breast. In one instance, the matching
`fluid may comprise water, india ink for absorption, and a fat
`emulsion for scattering. The embodiments in FIG.4 may also
`have one or more detectors 404, 455, one or more light
`Sources 404, 454, various electronics, and even an imaging
`system based on charge coupled devices 405. As illustrated in
`FIG.4, the light sources 404, 454 and detectors 404, 455 may
`be coupled to the box 402, 452 through one or more fibers
`406,456. Also, the imaging may be in reflection mode (top of
`FIG. 4), transmission mode (bottom of FIG. 4), or some
`combination.
`0045 Beyond the geometry and apparatus of FIG. 4, the
`optical imaging system may use one or more of three different
`illumination methods: continuous wave, time-domain photon
`migration, and frequency-domain photon migration. In one
`embodiment, continuous-wave systems emit light at approxi
`mately constant intensity or modulated at low frequencies,
`such as 0.1-100 kHz. In another embodiment, the time-do
`main photon migration technique uses relatively short, Such
`as 50-400 psec, light pulses to assess the temporal distribution
`of photons. Since scattering may increase the times of flight
`spent by photons migrating in tissues, the photons that arrive
`earliest at the detector probably encountered the fewest scat
`tering events. In yet another embodiment, the frequency
`domain photon migration devices modulate the amplitude of
`the light that may be continuously transmitted at relatively
`high frequencies, such as 10 MHz to 1 GHz. For example, by
`measuring the phase shift and amplitude decay of photons as
`compared to a reference signal, information may be acquired
`on the optical properties of tissue, and scattering and absorp
`tion may be distinguished. Beyond these three methods, other
`techniques or combinations of these methods may be used,
`and these other methods are also intended to fall within the
`Scope of this disclosure.
`0046 Although particular embodiments of imaging archi
`tectures are illustrated in FIG. 4, other system architectures
`may also be used and are also intended to be covered by this
`disclosure. For example, in one embodiment several couples
`of optical fibers for light delivery and collection may be
`arranged along one or more rings placed at different distances
`from the nipple 304. In an alternate embodiment a 'cap' with
`fiber leads for light sources and detectors may be used that fits
`
`over the breast. In yet another embodiment, imaging optics
`and light sources and detectors may surround the nipple 304
`and areola 305 regions of the breast. As yet another alterna
`tive, a minimally invasive procedure may involve inserting
`needles with fiber enclosure (to light sources and detectors or
`receivers) into the breast, so as to probe regions such as the
`lobules 3

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