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WO2010022079A1 - Système et procédés pour diagnostiquer des lésions épithéliales - Google Patents

Système et procédés pour diagnostiquer des lésions épithéliales Download PDF

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Publication number
WO2010022079A1
WO2010022079A1 PCT/US2009/054196 US2009054196W WO2010022079A1 WO 2010022079 A1 WO2010022079 A1 WO 2010022079A1 US 2009054196 W US2009054196 W US 2009054196W WO 2010022079 A1 WO2010022079 A1 WO 2010022079A1
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WIPO (PCT)
Prior art keywords
optical fiber
tissue
spectrophotometer
light
lookup
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Ceased
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PCT/US2009/054196
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English (en)
Inventor
James W. Tunnell
Narasimhan Rajaram
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University of Texas System
University of Texas at Austin
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University of Texas System
University of Texas at Austin
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Publication of WO2010022079A1 publication Critical patent/WO2010022079A1/fr
Priority to US13/029,992 priority Critical patent/US20120057145A1/en
Anticipated expiration legal-status Critical
Priority to US14/939,044 priority patent/US20160146730A1/en
Ceased legal-status Critical Current

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Classifications

    • 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
    • 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
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/44—Detecting, measuring or recording for evaluating the integumentary system, e.g. skin, hair or nails
    • A61B5/441—Skin evaluation, e.g. for skin disorder diagnosis
    • A61B5/444—Evaluating skin marks, e.g. mole, nevi, tumour, scar
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/44—Detecting, measuring or recording for evaluating the integumentary system, e.g. skin, hair or nails
    • A61B5/441—Skin evaluation, e.g. for skin disorder diagnosis
    • A61B5/445—Evaluating skin irritation or skin trauma, e.g. rash, eczema, wound, bed sore

Definitions

  • the present disclosure generally relates to diagnostic systems and methods.
  • the present disclosure provides, in certain embodiments, systems and methods for diagnosis of epithelial malignancies.
  • Skin cancer including both nonmelanoma and melanoma, is the most common malignancy worldwide. There are more than a million cases and greater than 10,000 deaths in the U.S. alone each year associated with skin cancer.
  • early detection and subsequent treatment is paramount to improving prognosis.
  • Early detection of melanoma can improve mortality rates, while the early detection of nonmelanoma can improve associated morbidity and cost.
  • noninvasive detection strategies will improve mortality, morbidity, and associated costs.
  • the current early detection of skin cancers relies on a critical macroscopic visual analysis of the changes in the cutaneous lesions. Suspected malignancies are excised and analyzed using standard histopathology for diagnosis and treatment decisions. This early detection strategy has several limitations. First, diagnostic accuracy for the current clinical examination is inherently qualitative and depends largely on the experience of the physician. It has been shown that general practitioners often have a much lower diagnostic accuracy than expert dermatologist.[l] In addition, access to dermatologists can be limited by geography, financial barriers, and a shortage of supply. Second, the majority of cutaneous melanoma arise in atypical nevi which can easily go unnoticed because they appear as standard moles.
  • Figure 1 shows the spectral diagnosis system used in Examples 1 and 2.
  • L refers to plano-convex lenses; Ml - mirror; BS - beam splitter.
  • Figure 2 shows the distal end of the fiber probe used in the system shown in Figure 1.
  • Scale bar is 3 mm.
  • Figure 3 shows (a) the white light spectrum from the xenon flash lamp reflecting off of a 20% reflectance standard; and (b) excitation pulses from the nitrogen laser at 337 nm and the dye laser at 445 nm.
  • Figure 5 shows data recorded from tissue phantoms with Stilbene 3 as fluorophore under test.
  • Figure 6 shows data recorded from tissue phantoms with FAD as fluorophore.
  • Figure 6(b) shows diffuse reflectance spectra from each of the tissue phantoms.
  • Figure 6(c) shows recovery of intrinsic fluorescence spectrum of FAD from a turbid phantom containing 0.82 mg/ml of hemoglobin and comparison with the actual intrinsic fluorescence of the fluorophore.
  • Figure 6(d) shows a comparison of extracted intrinsic fluorescence spectra for different tissue phantoms.
  • Figure 7 shows fluorophore concentrations of (a) Stilbene 3 and (b) FAD extracted using least-squares regression and comparison to actual values. The solid line indicates perfect agreement.
  • Figure 9 shows a schematic diagram of the LUT inverse model. Fit parameters are ⁇ s '( ⁇ o), B, [Hb] and ⁇ .
  • the present disclosure generally relates to diagnostic systems and methods.
  • the present disclosure provides, in certain embodiments, systems and methods for diagnosis of epithelial malignancies.
  • the present disclosure provides a system comprising an optical fiber switch connected to a light source and an optical fiber probe, the optical fiber probe comprising a first optical fiber connected to the optical fiber switch and a second optical fiber connected to a spectrophotometer.
  • the present disclosure provides a system comprising an optical fiber switch connected to a light source and an optical fiber probe, the optical fiber probe comprising a first optical fiber connected to the optical fiber switch and a second optical fiber connected to a spectrophotometer; and a software interface connected to the spectrophotometer, wherein the software interface is capable of displaying a tissue parameter derived from a spectra generated by the spectrophotometer.
  • the present disclosure provides a method for assessing a tissue comprising: providing an optical fiber switch connected to a light source and an optical fiber probe, the optical fiber probe comprising a first optical fiber connected to the optical fiber switch and a second optical fiber connected to a spectrophotometer; providing a tissue disposed adjacent to the optical fiber probe; allowing light emitted from the first optical fiber into the tissue; collecting the light reemitted from the tissue with the second optical fiber.
  • the present disclosure provides a method for assessing a tissue comprising: providing an optical fiber switch connected to a light source and an optical fiber probe, the optical fiber probe comprising a first optical fiber connected to the optical fiber switch and a second optical fiber connected to a spectrophotometer; providing a software interface connected to the spectrophotometer, wherein the software interface is capable of displaying a tissue parameter derived from a spectra generated by the spectrophotometer; providing a tissue disposed adjacent to the optical fiber probe; allowing light emitted from the first optical fiber into the tissue; collecting the light reemitted from the tissue with the second optical fiber; generating a spectra of the light reemitted from the tissue with a spectrophotometer; and utilizing a look-up table based algorithm to determine one or more tissue parameters.
  • the present disclosure provides a method for determining one or more tissue parameters comprising: emitting light from a first optical fiber into a tissue; collecting the light reemitted from the tissue with a second optical fiber; generating a spectra of the light reemitted from the tissue with a spectrophotometer; and utilizing a look-up table based algorithm to determine one or more tissue parameters, wherein the lookup-table based algorithm comprises the steps of: generating a look-up table by measuring the functional form of a reflectance measured by the spectrophotometer using one or more calibration standards with known optical properties; and implementing an iterative fitting routine based on the lookup-table.
  • the systems of the present invention comprise an optical fiber probe, a spectrophotometer, an optical fiber switch, and a software interface.
  • the optical fiber probe may comprise a plurality of optical fibers.
  • the optical fiber probe may comprise seven optical fibers. These seven optical fibers may be spatially arranged in any suitable manner. One such arrangement is the "six around one" arrangement, in which six of the seven optical fibers are disposed around the outer diameter of the seventh optical fiber.
  • one or more of the optical fibers may emit light, and the remaining fibers may collect the light emitted by one or more fibers.
  • the systems of the present invention further comprise a tissue.
  • the tissue may be any tissue suitable for being analyzed with an optical fiber probe.
  • the tissue may be an epithelial tissue, such as, but not limited to, skin, cervical, esophageal, breast, colon, or oral tissue.
  • one or more fibers in the optical fiber probe may emit light into the tissue, and the remaining fibers may collect the light reemitted from the tissue.
  • the light emitted by the optical fiber probe may be one or more a variety of light types.
  • the light may be any light type suitable for use in analyzing the optical properties of a tissue.
  • Such light types may include, but are not limited to, laser light and white light.
  • Specific examples of light that may be emitted by the optical fiber probe are laser light with a wavelength of about 337 nm, laser light with a wavelength of about 450 nm, and white light emitted from a xenon flashlamp.
  • a single type of light may be emitted from a specified optical fiber within the optical fiber probe; thus, multiple fibers may be used to emit multiple light types.
  • multiple light types may be emitted by a single optical fiber
  • the "center fiber” in the "six around one" fiber arrangement i.e. the one fiber around which the other six fibers are disposed
  • the optical fiber probe which emits the one or more light types.
  • the remaining optical fibers such as, but not limited to, the six fibers in the "six around one" fiber arrangement
  • any spectrophotometer capable of being operably connect to the optical fiber probes used in the present invention and recording light spectra for the light types used in the systems of the present invention may be used in the systems of the present invention.
  • the optical fiber switch may be any optical fiber switch suitable for use with the optical fiber probe and spectrophotometer. The choice of a suitable optical fiber switch may depend upon, among other things, the type, source and/or number of sources of light to be emitted by the one or more optical fiber probes, the spectrophotometer chosen, and the tissue type.
  • An example of an optical fiber switch which may be useful in certain embodiments of the systems and methods of the present invention is a FSM- 13 3x1 fiber optic switch, commercially available from Piezosystems Jena, Germany.
  • the software interface may display the light spectra generated by the optical fiber probe. In certain embodiments, such an interface may provide graphical plots for collected light from each light type used. In certain embodiments, the software interface may also a graphical plot of raw sample and calibration spectra taken from one or more calibration standards. In certain embodiments, the spectra generated by the spectrophotometer may be calibrated by the software interface up to or beyond a specified signal to noise ratio. In certain embodiments, such a signal to noise ratio may be about 17 dB. In certain embodiments, this calibration may be performed in a relatively short amount of time. In certain embodiments, the calibration may be performed in approximately one second or less.
  • the software interface may determine and display a number of tissue parameters, including, but not limited to, tissue redox ratio, oxygen saturation, scattering parameter, blood concentration, melanin concentration, and collagen content.
  • the systems of the present invention comprise an optical fiber probe comprising a plurality of optical fibers and a fiber tip.
  • the plurality of optical fibers may be arranged and may function as described elsewhere in the present disclosure.
  • the fiber tip in certain embodiments, may be a detachable article which does not substantially interfere with the emission or collection of light by the optical fiber probe and which provides a sterile point of contact between the optical fiber probe and a subject.
  • the fiber tip may be made of a suitable polymeric material, including, but not limited to, polystyrene.
  • the fiber tip may be secured to the optical fiber probe via a locking mechanism.
  • a locking mechanism in certain embodiments, may comprise a flexible component on the fiber probe with a male element and a rigid component on the fiber tip with a female element.
  • the male and female elements may join to secure the fiber tip to the optical fiber probe.
  • the spectra generated by the spectrophotometer may be analyzed by a look-up table (LUT) based algorithm.
  • the LUT based algorithm is a LUT-based inverse model that is valid for fiber-based probe geometries with close source- detector separations and tissues with low albedos.
  • the LUT inverse model may comprise (1) generating a LUT by measuring the functional form of the reflectance using calibration standards with known optical properties and (2) implementing an iterative fitting routine based on the LUT.
  • a nonlinear optimization fitting routine may be used to fit the reflectance spectra.
  • a chromophore e g., melanin, beta-carotene, a dye (e.g , indocyanine green)
  • the absorption in the visible range may be due to oxy- and deoxy-hemoglobin.
  • the expression for ⁇ a( ⁇ ) can be modified to include the absorption cross-sections of other absorbing chromophores.
  • the look-up algorithm may be used to determine the tissue parameters displayed by the software interface of the systems of the present invention.
  • laser excitation at 337 ran generates fluorescence from the metabolic coenzyme NADH and collagen, while laser excitation at 400 nm generates fluorescence from FAD
  • white light such as light from xenon flashlamps, may be used to collect elastic scatte ⁇ ng spectra. Both NADH and FAD are associated with tissue metabolism and can be used to determine the tissue redox ratio
  • elastic scatte ⁇ ng spectra can be fit to a diffusion theory model to extract the blood oxygen saturation, blood concentration, melanin concentration, and tissue scatte ⁇ ng parameters.
  • fluorescence spectroscopy may be used to extract biochemical properties Fluorescence photons are scattered and absorbed du ⁇ ng their path to the tissue surface where they are collected via the optical fiber probe Therefore, the spectral features of the collected fluorescence can be significantly distorted, making the extraction of biochemical composition of the tissue from the measured signal difficult.
  • tissue absorbers such as hemoglobin Int ⁇ nsic fluorescence spectroscopy (IFS) is a technique that extracts the fluorescence of the molecules unaffected by the absorption and scatte ⁇ ng events from the bulk fluorescence
  • IFS hemoglobin Int ⁇ nsic fluorescence spectroscopy
  • a LUT-based inverse model may be used to measure the tissue optical properties and correct the acquired fluorescence
  • FIG. 1 A representation of the spectral diagnosis system used in this example is shown in Figure 1.
  • Three light sources were used: 1) a pulsed xenon flashlamp (L7684, Hamamatsu Photonics, Bridgewater, NJ) to collect white light reflectance; 2) a pulsed nitrogen laser (NL-100, Stanford Research Systems, Mountain View, CA) at 337 nm and 3) a nitrogen-pumped dye laser at 450 nm.
  • Coumarin 450 Example Inc., Dayton, OH
  • a long pass filter (340 nm; Asahi Spectra, Torrance, CA) was placed in the optical path of the xenon flash lamp to minimize exposure to UV light.
  • the specifications for each light source are listed in Table 1. The energy/pulse noted for each light source was the energy measured at the distal end of the output fiber.
  • the white light and laser pulses are coupled into optical fibers and guided into a 3x1 fiber optic switch (FSM-13, Piezosystems Jena, Germany).
  • the switch controls the excitation sequence and is triggered by TTL signals.
  • the switch's output fiber is mated with the input fiber of the fiber optic probe.
  • the distal end of the 2 m long bifurcated fiber optic probe (FiberTech Optica, Ontario, Canada) consists of 7 optical fibers arranged in a 6-around-l configuration ( Figure 2b).
  • a source-detector separation of 300 ⁇ m was chosen. This distance allowed sampling the skin superficially.
  • the six collection fibers were arranged in a linear configuration and aligned parallel to the entrance slit of the spectrograph (SP-150, Princeton Instruments, Trenton, NJ).
  • the spectrograph contained a 150g/mm grating blazed at 500 nm which disperses the collected light onto a cooled CCD (Photometries, Arlington, AZ).
  • the CCD was cooled to a temperature of -30 0 C to minimize dark current.
  • the CCD was gated (50 ⁇ s), to acquire data only during an excitation pulse.
  • the wavelength scale of the CCD is calibrated with a standard mercury-argon (HgAr) lamp.
  • HgAr mercury-argon
  • a background spectrum was recorded with the light sources turned off and subtracted from every reflectance spectrum. This eliminated the effects of CCD dark current and ambient light.
  • white light reflectance from a 20% reflectance standard (Labsphere, North Sutton, NH) was recorded before the start of any measurement cycle. The background- corrected reflectance spectrum was then divided by the standard reflectance to obtain a relative diffuse reflectance measurement.
  • the reflectance from a standard solution of polystyrene microspheres in water (0.12%; Polysciences, Warrington, PA) was measured.
  • Diffuse reflectance spectra measured from phantoms are normalized with respect to standard solution of microspheres.
  • the fluorescence spectra are corrected for the spectral response of the system using a NIST traceable tungsten calibration standard (LS-I-CAL, Ocean Optics, Dunedin, FL).
  • the fluorescence from a Rhodamine B solution in water (0.01 g/1) was measured to calibrate both the nitrogen and the dye laser for variations in intensity.
  • Mie theory was used to calculate the reduced scattering coefficients ( ⁇ s ') of the tissue phantoms, and we measured the absorption coefficient ( ⁇ a ) of the stock Hb solution using a spectrophotometer (DU 720, Beckman Coulter, Fullerton, CA).
  • Intrinsic fluorescence phantoms Commercially available fluorophores were used to prepare tissue phantoms for measuring fluorescence. FAD (Sigma, St. Louis, MO) was available commercially and hence was used as the fluorophore under test with the dye laser (445 nm excitation). Stilbene 3 (Exciton, Dayton, OH) was chosen to simulate NADH fluorescence due to the similar position of its peak emission wavelength. The tissue phantoms were fabricated in three stages. Non- scattering solutions of the two fluorophores were first prepared to measure the intrinsic fluorescence. The fluorophore concentrations were selected so that the solutions were optically dilute. 0.64 ⁇ M of Stilbene 3 and 42.1 ⁇ M of FAD were used in the experiments.
  • tissue phantoms were used to validate the accuracy of the LUT inverse model and consequently the system.
  • a subset of tissue phantoms was used to create the LUT.
  • No test samples used to validate the system had the same optical properties of the phantoms used to create the LUT.
  • a nonlinear optimization fitting routine was implemented to fit the reflectance spectra.
  • the absorption in the visible range was assumed to be due to oxy- and deoxy- hemoglobin.
  • ⁇ a can be modified to include the absorption cross-sections of other absorbing chromophores.
  • System Performance Signal to noise ratio
  • a typical white light spectrum reflecting off of a 20% reflectance standard is shown in Figure 3.
  • the signal to noise ratio of a typical reflectance spectrum ( Figure 4a) is ⁇ 34 dB.
  • the fluorescence spectra from both lasers also show excellent signal to noise (-40 dB).
  • Figure 4 illustrates the results of fitting the measured spectra for the same phantom to the model. Each panel represents a particular optical property recovered.
  • Figure 4 illustrates extracted physical parameters for each test tissue phantom, demonstrating good agreement between the expected and the measured values of ⁇ s '( ⁇ o) and [Hb]. In all phantoms, the oxygen saturation was held a constant and did not vary by more than 2%.
  • FIG. 5 shows the results of fluorescence measurements on tissue-simulating phantoms with both scattering and absorption (hereafter referred to as turbid phantom). Fluorescence spectra from tissue phantoms with varying concentrations of hemoglobin were plotted and compared to the intrinsic fluorescence spectrum of Stilbene 3 ( Figure 5a). The addition of hemoglobin introduces a distortion in the fluorescence spectrum around 420 nm. This can be attributed to absorption by hemoglobin in the Soret band.
  • Figure 6 demonstrates the results of fluorescence measurements on turbid phantoms with FAD as the fluorophore.
  • the fluorescence spectrum of FAD is distorted by hemoglobin absorption, the effect is not as prominent as that for 337 nm excitation (Figure 5a). This is probably because FAD emits in the Q-bands of hemoglobin where the absorption is not as high as in the Soret band ( Figure 5b). This is seen in the corresponding diffuse reflectance spectra of these phantoms ( Figure 5b) which show a relatively small depression in the Q-bands due to hemoglobin absorption.
  • there was still a significant correction introduced in the measured fluorescence spectrum of FAD Figure 5c.
  • Stilbene 3 there was good agreement between the measured and extracted intrinsic fluorescence (RMS error less than 10%) ( Figure 4d).
  • ⁇ refers to intrinsic fluorescence from a turbid phantom
  • ⁇ d ii the intrinsic fluorescence from an optically dilute solution of the fluorophore.
  • concentration of the phantom C was the free parameter that was extracted.
  • Figure 7 shows a comparison of the actual and recovered values of the fluorophore concentrations. The average errors in estimating the concentrations of Stilbene 3 and FAD were 5.87% and 11.1 %, respectively.
  • a pulsed xenon flash lamp L7684, Hamamatsu Photonics, Bridgewater, NJ
  • the light collected by the fiber optic probe was focused on the entrance slit of a spectrograph (SP-150, Princeton Instruments, Trenton, NJ) that dispersed the light onto a 12-bit CCD (CoolSnap, Photometries, Arlington, AZ).
  • SP-150 Princeton Instruments, Trenton, NJ
  • CCD CoolSnap, Photometries, Arlington, AZ
  • India ink solution was measured using a spectrophotometer (DU 720, Beckman Coulter,
  • tissue phantoms were used with different chromophores to create the LUT and validate the accuracy of the inverse model.
  • Tissue phantoms for the validation set were fabricated using polystyrene microspheres and hemoglobin (Sigma, St. Louis, MO) as the absorber.
  • a matrix (3x6) of 18 different tissue phantoms was then created for the validation set by varying the values of ⁇ s '( ⁇ o) and [Hb].
  • the absorption in the visible range was assumed to be due to oxy- and deoxy-hemoglobin.
  • the expression for ⁇ a ( ⁇ ) can be modified to include the absorption cross-sections of other absorbing chromophores.
  • the performance of the LUT-based model was compared to a diffusion approximation (DA)-based model described by Farrell et al. (Table 1).
  • DA diffusion approximation
  • the LUT model represents a significant improvement in the recovery of the physical parameters over the DA model.
  • the LUT model improved the accuracy in recovering scattering at 630 nm ( ⁇ s '( ⁇ o) and hemoglobin concentration ([Hb]) by factors of 2.5 and 5.5, respectively.
  • a fundamental limitation of analytical solutions such as the diffusion approximation is that scattering should dominate absorption by at least a factor of 10 ( ⁇ s ' > 10 ⁇ a ).

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Abstract

L'invention concerne des systèmes qui comportent un commutateur de fibres optiques relié à une source de lumière et une sonde à fibres optiques, la sonde à fibres optiques comportant une première fibre optique reliée au commutateur de fibres optiques et une seconde fibre optique reliée à un spectrophotomètre. Des procédés pour déterminer un ou plusieurs paramètres de tissu comportent : l'émission d'une lumière à partir de la première fibre optique dans un tissu; la récupération de la lumière réémise par le tissu à l'aide de la seconde fibre optique; la création d'un spectre de la lumière réémise par le tissu à l'aide d'un spectrophotomètre, et l'utilisation d'un algorithme selon une table de conversion pour déterminer un ou plusieurs paramètres de tissu, l'algorithme selon la table de conversion comportant les étapes consistant : à produire une table de conversion par la mesure de la forme fonctionnelle d'un facteur de réflexion mesurée par le spectrophotomètre en utilisant un ou plusieurs standards de calibrage ayant des propriétés optiques connues, et la mise en œuvre d'un programme d'ajustement itératif selon la table de conversion.
PCT/US2009/054196 2008-08-18 2009-08-18 Système et procédés pour diagnostiquer des lésions épithéliales Ceased WO2010022079A1 (fr)

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US14/939,044 US20160146730A1 (en) 2008-08-18 2015-11-12 Systems and methods for diagnosis of epithelial lesions

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US61/089,736 2008-08-18

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Citations (4)

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Publication number Priority date Publication date Assignee Title
US6167297A (en) * 1999-05-05 2000-12-26 Benaron; David A. Detecting, localizing, and targeting internal sites in vivo using optical contrast agents
US6301004B1 (en) * 2000-05-31 2001-10-09 Lj Laboratories, L.L.C. Apparatus and method for measuring optical characteristics of an object
US20080037024A1 (en) * 2006-05-12 2008-02-14 Vadim Backman Systems, methods, and apparatuses of low-coherence enhanced backscattering spectroscopy
US20080049214A1 (en) * 2006-08-28 2008-02-28 Alexei Maznev Measuring Diffractive Structures By Parameterizing Spectral Features

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6167297A (en) * 1999-05-05 2000-12-26 Benaron; David A. Detecting, localizing, and targeting internal sites in vivo using optical contrast agents
US6301004B1 (en) * 2000-05-31 2001-10-09 Lj Laboratories, L.L.C. Apparatus and method for measuring optical characteristics of an object
US20080037024A1 (en) * 2006-05-12 2008-02-14 Vadim Backman Systems, methods, and apparatuses of low-coherence enhanced backscattering spectroscopy
US20080049214A1 (en) * 2006-08-28 2008-02-28 Alexei Maznev Measuring Diffractive Structures By Parameterizing Spectral Features

Non-Patent Citations (1)

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Title
ZONIOS ET AL.: "Diffuse Reflectance Spectroscopy of Human Adenomatous Colon Polyps In Vivo.", APPLIED OPTICS, vol. 38, no. 1, 1 November 1999 (1999-11-01), pages 6628 - 6637 *

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