WO2008151155A2 - Interférométrie spectrale sensible à la polarisation - Google Patents

Interférométrie spectrale sensible à la polarisation Download PDF

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Publication number
WO2008151155A2
WO2008151155A2 PCT/US2008/065570 US2008065570W WO2008151155A2 WO 2008151155 A2 WO2008151155 A2 WO 2008151155A2 US 2008065570 W US2008065570 W US 2008065570W WO 2008151155 A2 WO2008151155 A2 WO 2008151155A2
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Prior art keywords
sample
depth
polarization
resolved
interferometer
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PCT/US2008/065570
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English (en)
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WO2008151155A3 (fr
Inventor
Thomas E. Milner
Nathaniel J. Kemp
Eunha Kim
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Board Of Regents, The University Of Texas System
Volcano Corporation
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Publication of WO2008151155A2 publication Critical patent/WO2008151155A2/fr
Publication of WO2008151155A3 publication Critical patent/WO2008151155A3/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/4795—Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/102—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for optical coherence tomography [OCT]
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00—Measuring instruments characterised by the use of optical techniques
    • G01B9/02—Interferometers
    • G01B9/02001—Interferometers characterised by controlling or generating intrinsic radiation properties
    • G01B9/02002—Interferometers characterised by controlling or generating intrinsic radiation properties using two or more frequencies
    • G01B9/02004—Interferometers characterised by controlling or generating intrinsic radiation properties using two or more frequencies using frequency scans
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00—Measuring instruments characterised by the use of optical techniques
    • G01B9/02—Interferometers
    • G01B9/02055—Reduction or prevention of errors; Testing; Calibration
    • G01B9/02062—Active error reduction, i.e. varying with time
    • G01B9/02067—Active error reduction, i.e. varying with time by electronic control systems, i.e. using feedback acting on optics or light
    • G01B9/02069—Synchronization of light source or manipulator and detector
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00—Measuring instruments characterised by the use of optical techniques
    • G01B9/02—Interferometers
    • G01B9/0209—Low-coherence interferometers
    • G01B9/02091—Tomographic interferometers, e.g. based on optical coherence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B2290/00—Aspects of interferometers not specifically covered by any group under G01B9/02
    • G01B2290/70—Using polarization in the interferometer

Definitions

  • the field of the invention generally relates to optical imaging, and more specifically relates to Optical Coherence Tomography ("OCT”) systems and methods.
  • OCT Optical Coherence Tomography
  • Spectral modifications resulting from interference of light in can be observed with various spectral interferometric techniques, commonly consisting of a nonscanning interferometer and spectrometer in the detection path in OCT systems.
  • the superposition of two light beams that are identical except for a relative optical path-length difference L results in a new spectra with ripples that have niinima at wavelength ⁇ whenever (n + L.
  • the spacing between the adjacent minima of the resultant spectrum in the optical frequency (v) domain is a constant c/L, where c is the speed of light.
  • the interference fringes in the spectral domain can be obtained by performing Fourier transform of those recorded in the time domain, distinct differences are recognized between these two measurements.
  • L c ⁇
  • L c ⁇
  • high visibility interference fringes are not observed in the time domain.
  • high visibility fringes are formed irrespective of how long or short the optical path-length difference may be. Additionally, superior sensitivity and signal to noise ratio of spectral interferometry over time-domain approaches are recognized.
  • recorded interference fringe signals may contain an unknown time-varying random phase factor due to polarization changes induced by fiber components.
  • a method and apparatus for analyzing a sample determines depth-resolved polarization properties of the sample.
  • the method and apparatus determines depth-resolved polarization properties of the sample.
  • the interferometer comprises a light source which produces light over a multiplicity of optical frequencies.
  • the interferometer comprises an analyzer that records the intensity of light at the output of the interferometer.
  • the interferometer comprises at least one optical fiber through which the light is transmitted to the sample.
  • the interferometer comprises a receiver which receives the light reflected from the sample.
  • a computer coupled to the interferometer determines depth-resolved polarization properties of the sample.
  • Another embodiment pertains to a method for analyzing a sample with a spectral interferometer. The method comprises the steps of directing light to the sample with at least one optical fiber of the interferometer. There is the step of reflecting the light from the sample. There is the step of receiving the light with a receiver of the interferometer. There is the step of determining depth and polarization properties of the light reflected from the sample with a computer coupled to of the interferometer.
  • FIG. 1 is a schematic diagram of a polarization-sensitive spectral interferometer in accordance with one embodiment.
  • FIG. 2 a schematic diagram of a PS-OCT interferometer in accordance with one embodiment.
  • FIG. 3A depicts the typical spectral output intensity from the fiber based single channel polarization-sensitive spectral interferometer with the whole spectrum of 12.2 THz.
  • FIG. 3B depicts an enlarged small segment of 10 GHz between 190.69 THz and 190.79
  • FIG. 4A depicts the Fourier Transform magnitude of interference fringes between and from the back surfaces of the glass window.
  • FIG. 4B depicts the Fourier Transform magnitude of interference fringes between the back surface of the glass window and the birefringent sample.
  • FIG. 5 A depicts Phase retardation due to birefringence of the birefringent sample estimated from interference between the back surface of the glass window and the back surface of the birefringent sample.
  • FIG. 5B depicts Phase Retardation due to fast-axis angle of the birefringent sample estimated from interference between the back surface of the glass window and the back surface of the birefringent sample.
  • FIG. 6 is a schematic of the origin of form-birefringence (An) and form-biattenuance
  • FIG. 7 is a schematic model for form-biattenuance consisting of alternating anisotropic and isotropic layers.
  • FIG. 8 is a schematic of intervertebral disc and annulus fibrosis showing alternating fiber directions in the laboratory frame (H and V), the incident beam, and scan location (dashed red line).
  • FIG. 1OA is a graph of the ensemble averaging NA uncorrelated speckle fields increases PSNR by a factor of NA 1/2
  • FIG. 12 is a graph of the RNFL birefringence (An) in locations 1 mm inferior and 1 mm nasal to the center of the ONH on two separate days, where the error bars indicate approximate PS-OCT birefringence sensitivity.
  • FIG. 13B is a graph for the corresponding normalized Stokes parameters [Q(z), U(z), V(z)] and associated nonlinear fits.
  • FIG. 13B is a graph for the corresponding normalized Stokes parameters [Q(z), U(z), V(z)] and associated nonlinear fits. [0027] FIG.
  • FIG. 15A is a Poincare sphere showing Si(X) and associated Pi(z) and ⁇ determined by the multistate nonlinear algorithm in rat Achilles tendon; and FIG. 15B is the corresponding normalized Stokes parameters of FIG. 15A and associated nonlinear fits.
  • FIG. 17 is an intensity B-scan of annulus fibrous, the image is 0.35 mm wide, 0.5 mm deep, and intensity is plotted logarithmically using arbitrary units.
  • FIG. 18A is a Poincare sphere with the trajectory of Sm(z) for annulus fibrous; and FIG.
  • FIG. 19 a fiber orientation B-scan [6(.x,z)] of the annulus fibrous specimen shown in FIG. 17, where the fiber orientation (6) is assigned a false color representing the counterclockwise angle between the fiber axis and the horizontal as viewed along the incident beam.
  • FIG. 20 is a PS-OCT birefringence B-scan [An(x,z)] of the annulus fibrous specimen shown in FIG. 17, where the detected interfaces between lamellae are represented by black lines.
  • FIG. 21 is an intensity B-scan [/(x,z)] introduced in FIG. 17 with black lines superimposed to indicate structural features (lamellar interfaces) that were not apparent in /(x,z) but were detected in the depth-resolved polarization data [Sm(z)] 9 where the numbers on left represent mean thickness of each lamella ( ⁇ * , ⁇ m).
  • PS-OCT Polarization sensitive spectral interferometer and polarization sensitive Optical Coherence Tomography
  • OCT optical coherence tomography
  • the PS-OCT configuration includes an interferometer and a light source which produces light over a multiplicity of optical frequencies.
  • the interferometer comprises at least one optical fiber through which the light is transmitted to the sample.
  • the interferometer comprises a receiver which receives the light reflected from the sample.
  • the interferometer comprises a computer coupled to the receiver which determines depth-resolved polarimetric properties of the sample. "Depth-resolved" is may be used in the context of either measuring in the depth dimension or the local variation in a parameter versus depth [e.g., ⁇ (z)]".
  • the computer coupled to the interferometer determines simultaneously the depth-resolved polarimetric properties of the light reflected from the sample in the interferometer, hi another embodiment, the computer determines variations of the polarization of the reflected light as a function of depth of the sample. In another embodiment, the computer determines the depth resolved birefringence of the sample, depth resolved retardation of the sample, depth resolved biattenuance of the sample, and depth resolved optical axis of the sample.
  • the sample is preferably living human tissue, and the reflected light is obtained in vivo in a patient, as described in U.S. Patent Application Serial No. 11/466,683 and U.S. Patent Application Serial No.
  • the computer preferably identifies tissue type of the sample as a function of depth from the depth-resolved birefringence, retardation, biattenuance and optical axis of the sample. For instance, by maintaining a table look-up in a memory of the computer having a priori information regarding tissue types and their associated birefringence, retardation, biattenuance, and optical axis properties; when unknown tissue is tested using the techniques described herein, the birefringence, biattenuance, retardation, and optical axis properties obtained as a function of depth of the unknown tissue is compared with the known information in the table look-up, and the tissue type as a function of depth is identified.
  • Tissues may include any type of tissue including, but not limited to, arterial vessels and plaques, amyloid plaques and neurofibrillary tangles, aneurysms, urethra, tumors, cartilage, cornea, muscle, retina, nerve, skin and tendon.
  • a follow-up PS-OCT measurement may be employed, looking for changes in birefringence, biattenuance, retardation, and optical axis with the previous measurement(s).
  • the sample may be an optical fiber or general optical element transmitting device under test.
  • Another embodiment pertains to a method for analyzing a sample with a spectral interferometer.
  • the method comprises the steps of directing light to the sample with at least one optical fiber of the interferometer. There is the step of reflecting the light from the sample. There is the step of receiving the light with a receiver of the interferometer. There is a step of combining or interfering the light reflected from the sample with the light reflected from the reference surface. There is the step of determining depth and polarization properties of the light reflected from the sample with a computer of the interferometer.
  • the determining step includes the step of determining simultaneously the depth-resolved polarimetric properties of the light reflected from the sample with the computer.
  • the determining step preferably includes the step of determining variations of the polarization of the reflected light as a function of depth of the sample.
  • the determining step includes the step of determining depth resolved birefringence of the sample, depth resolved biattenuance of the sample, depth resolved retardation, and depth resolved optical axis of the sample.
  • a polarization-sensitive spectral interferometer generally comprising a broadband frequency-swept laser source, an optical spectrum analyzer ("OSA”), a fiber-based common-path spectral interferometer coupled with a fiber-optic spectral polarimetry instrument (“FOSPI”) in the detection path, and photoreceiver.
  • the fiber-based single channel polarization spectral interferometer provides depth resolved measurement of polarization transformations of light reflected from a sample.
  • the range of detectable optical path-length difference using spectral interferometry is proportional to the inverse resolution of the OSA.
  • Algebraic expressions for the Stokes parameters or alternative measure of the polarization state of light Jones vector or complex Z -parameter, at the output of the interferometer are derived for light reflected from a birefringent sample by using the cross-spectral density function.
  • the interferometer comprises a polarimeter with channeled spectra in spectral polarimetry without polarization control.
  • the polarimeter comprises of a pair of thick birefringent retarders in series with a polarizer and OSA, and a fiber optic spectral polarimetry instrument to measure polarization state of collected light with single optical frequency scan utilizing the principle of the channeled spectral polarimetry.
  • the polarimeter comprises polarization sensitivity that records four sequential single-channel measurements or simultaneous dual-channel horizontal and vertical polarization component measurements in conjunction with a well characterized reference beam. The polarimeter may be utilized to measure the polarization state of light or sample birefringence.
  • the fiber-based polarization-sensitive Michelson, Mach Zehnder or similar hybrid interferometer extracts the Stokes parameters of reflected light from a sample from the interference fringe signal recorded in two orthogonal polarization channels.
  • the recorded interference fringe signal includes the phase difference between light reflected from the reference and sample surfaces as well as amplitudes, so polarization-state control of light reflected form the reference surface may be employed.
  • the phase factor due to polarization changes induced by fiber components is common in light reflected from reference and sample surfaces and cancels in the interference fringe signals recorded in orthogonal channels.
  • the interferometer determines the depth resolved birefringence of the sample, depth resolved retardation of the sample, depth resolved biattenuance of the sample, and depth resolved optical axis of the sample.
  • PS-OCT combines polarimetric sensitivity with the high resolution tomographic capability of optical coherence tomography ("OCT") to determine phase retardation ( ⁇ ) and birefringence (An) biattenuance (A ⁇ ) and optical axis orientation ( ⁇ ).
  • OCT optical coherence tomography
  • ⁇ phase retardation
  • a ⁇ biattenuance
  • ⁇ optical axis orientation
  • Optical anisotropy properties birefringence (An), biattenuance ( ⁇ ), and axis orientation ( ⁇ ) convey information about the sub-microscopic structure of fibrous tissue (e.g., connective, muscle, nervous tissue, fibrous cap, and the like).
  • a primary obstacle to high sensitivity determination of tissue retardation and birefringence is polarimetric speckle noise.
  • Speckle noise is common to all imaging modalities that employ spatially-coherent waves (e.g. ultrasound, radar, OCT, etc.).
  • the method to determine accurately polarimetric properties addresses the degrading effects of speckle noise in polarimetric signals detected with PS-OCT configurations.
  • the method comprises the sensitivity required for accurate determination of ⁇ , An, ⁇ , and ⁇ in thin tissues with weak birefringence [e.g., primate retinal nerve fiber layer ("RNFL"), An x 10 "4 ] and/or biattenuance.
  • weak birefringence e.g., primate retinal nerve fiber layer ("RNFL"), An x 10 "4 ] and/or biattenuance.
  • the method to determine ⁇ , An, ⁇ , and ⁇ comprises multiple incident polarization states and a nonlinear fitting algorithm to determine ⁇ , An, ⁇ , and ⁇ with high sensitivity and invariance to unknown incident unitary polarization transformations that may occur in the interferometer.
  • the "multi-state nonlinear algorithm" is demonstrated in a thin turbid birefringent film.
  • Form-birefringence (An) in tissue arises from anisotropic light scattering by ordered submicroscopic cylindrical structures (e.g., microtubules, collagen fibrils, etc.) whose diameter is smaller than the wavelength of incident light but larger than the dimension of molecules.
  • form-birefringence (An) describes the effect of differential phase velocities between light polarized parallel- and perpendicular-to the fiber axis (eigenpolarizations)
  • the term form biattenuance ( ⁇ ) describes the related effect of differential attenuation on eigenpolarization amplitudes.
  • Biattenuance (A ⁇ ) is an intrinsic physical property responsible for polarization-dependent amplitude attenuation, just as birefringence (An) is the physical property responsible for polarization-dependent phase delay.
  • Diattenuation (D) gives the quantity of accumulated anisotropic attenuation over a given depth (Az) by a given optical element.
  • Optic axis orientation ( ⁇ ) provides the direction of constituent fibers relative to a fixed reference direction (i.e., horizontal in the laboratory frame).
  • the PS-OCT configurations measures depth-resolved optic axis orientation [ ⁇ (z)] deep within multiple layered tissue using.
  • the depth-resolved optic axis orientation [ ⁇ (z)] unambiguously represents the actual anatomical fiber direction in each layer or depth (z) with respect to a fixed laboratory reference and can be measured with high sensitivity and accuracy. Characterization of the anatomical fiber direction in connective tissues with respect to a fixed reference is important because functional and structural characteristics such as tensile and compressive strength are directly related to the orientation of constituent collagen fibers.
  • Depth-resolved curvature ( ⁇ (z)) of normalized Stokes vectors (S(z)) may identify boundaries in multiple-layered fibrous tissue.
  • backscattered intensity (/(z)) is not sufficient for identification of lamellar interfaces
  • the PS-OCT configurations can detect changes in depth-resolved fiber orientation and increases image contrast in multiple layered birefringent tissues. For example, interfaces in the annulus fibrous identified using depth- resolved fiber orientation or the depth-resolved curvature allowed quantification of lamellae thickness.
  • the PS-OCT configuration can detect changes in fiber orientation without intense processing needed to effectively quantify tissue retardation and diattenuation.
  • Cytoskeletal elements, cell membranes, and interstitial collagen impart form- birefringence to tissues such as arterial vessels, amyloid plaques, aneurysms, tumors, cartilage, cornea, muscle, urethra, nerve, retina, skin and tendon.
  • Noninvasive and invasive quantification of form-birefringence, retardation, and optical axis by the PS-OCT configurations 10 and 200 has implications in the clinical management and basic understanding of diseases including but not limited to osteoarthritis, myocardial heart disease, thyroid disease, aneurism, gout, Alzheimer's disease, cancers, tumors, glaucoma, and chronic myeloid leukemia.
  • changes in form-birefringence may elucidate traumatic, functional, or physiologic alterations such as the severity and depth of burns; wound healing, optical clearing by exogenous chemical agents, or the contractile state of muscle.
  • a polarization- sensitive spectral interferometer 10 generally comprising a broadband frequency-swept laser source 12, an Optical Spectrum Analyzer (“OSA") 14, a fiber-based common-path spectral interferometer 30, a Fiber-Optic Spectral Polarimetry Instrument (“FOSPI”) 50, and a photoreceiver 60.
  • the broadband frequency-swept laser source 10 operates with a mean frequency of the output spectrum that varies over time.
  • the swept laser source may be any tunable laser source that rapidly tunes a narrowband source through a broad optical bandwidth.
  • the tuning range of the swept source may have a tuning range with a center wavelength between approximately 500 nanometers and 2000 nm, a tuning width of approximately greater than 1% of the center wavelength, and an instantaneous line width of less than approximately 10% of the tuning range with an instantaneous coherence length of over 10mm.
  • the mean frequency of light emitted from the swept source may change continuously over time at a tuning speed that is greater than 100 terahertz per millisecond and repeatedly with a repetition period.
  • the OSA 14 provides real-time OSA or a clock signal 18 that is used to trigger data acquisition for real-time synchronization of output intensity with optical frequency (v) 16.
  • High spectral resolution of the laser source (or alternatively long coherence length) 12 and the OSA 14 can provide a scan range greater than 10mm and up to 3 m and allows a flexible system configuration, such as a reference-sample separation up to several centimeters. Selecting optimal optics for the frequency range of the broadband frequency-swept laser source 12 is readily known by those skilled in the art.
  • the narrowband laser source 12 is swept the over a wide optical frequency range and the optical frequency 16 is optically coupled to a processor 70.
  • the polarization-sensitive spectral interferometer 10 may be based on optical fibers for optically coupling the components thereof.
  • the swept laser source 12 is optically coupled to an input polarization state preparation optics 20, comprising a lens 22 and a polarizing element 24.
  • the input polarization optics preparation optics 20 allows the preparation of a variety of fixed user-specified states.
  • the light then collected by a lens 26 and transmitted to the fiber circulator 28.
  • the sample and reference beams share a common path 38 in the spectral interferometer 10. This configuration provides automatic compensation for dispersion and polarization difference in the sample and reference paths up to the sample and nearly ideal spatial overlap of reflected sample and reference beams, giving high fringe visibility.
  • the common-path spectral interferometer 30 including, the fiber optic circulator 28, a lens 32, a glass window 34 as a reference, and a sample 36 in a common path 38.
  • Emitted light from the source 12 is transmitted to the fiber optic circulator 28, which prevents any unnecessary light loss returning to the source 12 so a fiber based system can be implemented.
  • Emitted light inserted into one port of the circulator 28 is transmitted to a center tap, while the reflected light from the glass window 16 reference and sample 18 is transmitted to the third port of the circulator 22 to a detection path 40.
  • the back surface of the glass window 34 serves as a reference surface.
  • the thickness of the glass window 34 is large enough, so that reflection from the front surface of the glass window does not contribute to the spectral interferogram between light reflected from the reference and that reflected from the sample.
  • a borosilicate glass window of 6.3 mm thickness is used.
  • an end facet of the sample path illuminating fiber instead of the glass window 34 can be used in the sample path.
  • the sample path can be coupled to a probe or catheter via a fiber optic rotary junction. Examples of a rotating catheter tip for the sample path include, a Catheter for In Vivo Imaging as described in 60/949,511, filed July 12, 2007, or an OCT catheter as described in Provisional Application Serial No.
  • the catheter 242 can be located within a subject to allow light reflection off of subject tissues to obtain optical measurements, medical diagnosis, treatment, and the like.
  • the reference 16 can be coupled to a reflective surface of a ferrule coupled to a lens and rotating prism to provide the common path 38.
  • Data acquisition is synchronized with calibrated optical clock transitions generated by the OSA 14, so each measured and digitized light intensity corresponds to uniformly spaced or a known optical frequency or spectral component of the spectral interferogram in equation (1).
  • Equation (1) includes autocorrelation terms that arise from interference between surfaces within the sample are not shown. Autocorrelations terms can appear as artifacts and coherent noise; they can be separated from the interference term between the reference and the sample containing useful depth information by shifting the reference and sample containing useful depth information by shifting the reference surface by a distance larger than the sample optical thickness.
  • Equation (2) interference fringes can be analyzed by a Fourier transform of the recorded spectrum.
  • Equation (2) is the inverse Fourier transform of Equation (1) with respect to optical frequency v.
  • the detection path 40 includes a first Polarization-Mamtaining ("PM") fiber segment 42, a second PM fiber segment 44, and a polarization controller 46 coupled to the FOSPI 50.
  • the first and second PM fibers 42 and 44 are spliced at 45 degrees with respect to each other.
  • the PM fibers are a birefringent optical waveguide that has two orthogonal axes with different refractive indices due to internal stress structures.
  • the first and second PM fiber segments 42 and 44 are used as sequential linear retarders in a retarder system. In one embodiment, the first PM fiber 42 is 2.5 m and the second PM fiber 44 is 5 m.
  • the use of longer PM fiber segments would allow wider channel separation and provide better estimates of sample phase retardation and fast-axis orientation.
  • the PM fibers are thermally isolated in mechanical enclosures to improve the stability of PM fiber phase retardations.
  • Orthogonal oscillating field components of collected light experience different phase delays due to internal birefringence while passing through the first PM fiber segment 42.
  • both oscillating field components are projected equally on fast and slow axes of the second PM fiber segment 44 and experience different phase delays.
  • Light exiting the second PM fiber 44 segment has four field components with different phase delays depending on the propagation path and passes through an analyzer 36 aligned with the fast axis of the first PM fiber segment 42.
  • All four field components of light are projected onto the transmission axis of the analyzer 36 and produce interference fringes with characteristic time delay ( ⁇ ) given by the PM fiber segments 42 and 44.
  • ⁇ characteristic time delay
  • the use of thermally isolated mechanical enclosure improves the stability of PM fiber phase retardations.
  • the use of longer PM fiber segments allows wider channel separation and provides better estimates of sample phase retardation and fast-axis orientation.
  • the FOSPI is but one implementation of an apparatus to accomplish interference between the different polarization states. Bulk optical elements may accomplish more or less the same objective of the FOSPI. Bulk components may include better stability but the size ranges of optical delays that can be realized are limited, as described in K. Oka and T. Kato, "Spectroscopic polarimetry with a channeled spectrum," Opt.
  • the FOSPI 50 includes an analyzer 52 coupled to a photoreceiver 60.
  • the analyzer 52 includes a collimating lens 54, a polarizer 56, and a lens 58.
  • output intensity from the common-path spectral interferometer 30 is collected by the FOSPI 50, which is then coupled into the photoreceiver 60 and then input into an analog-to- digital converter 62 that acquires output intensity data by a processor 70 under a Lab ViewTM software interface.
  • the full set of Stokes parameters of light backscattered from specific sample depths can be obtained without either polarization-control components in the reference, sample, or detection paths of the interferometer or prior knowledge of the polarization state of light incident on the sample.
  • the OSA 14 provides real-time OSA or clock signal 18 that is used to trigger data acquisition for real-time synchronization of output intensity with optical frequency
  • S 01n (v) , S 1 m (v) , and S 23 1n OO S 21n (v) -iS 3 m (v) representing Stokes spectra of collected light (i.e., incident on the first PM fiber segment 32).
  • ⁇ x (v) and ⁇ 2 (v) are the phase retardations due to the first and second segments of the PM Fiber 42 and 44 and dependent on optical frequency v,
  • Simple Fourier transformation of I out (y) isolates each Stokes spectral component in the time- delay domain ( ⁇ ) or optical path length difference (c ⁇ ) domain.
  • Equation (5) A Fourier transform of Equation (5) gives seven components for each backreflection of light in the positive optical path-length difference domain (c ⁇ > 0), which are centered at respectively, with
  • Equations (6-9) By computing an inverse Fourier transform of each isolated component in the optical path-length difference domain (c ⁇ ), Equations (6-9) are obtained:
  • ⁇ (v) can be obtained from the location of the S t (O
  • Equation (13) is obtained:
  • sample phase retardation ( ⁇ (z)) and fast-axis angle ( ⁇ or ⁇ ) can be estimated with the interference fringes and without knowledge of the polarization state of the incident light.
  • the segment can be considered a known portion of the birefringent sample with a specified polarization transformation, and the analysis may be modified to determine the depth- resolved birefringence (An) and fast axis ( ⁇ or ⁇ ) of a sample, as explained in the Optical Axis and Birefringence sections below.
  • Exemplary PS-OCT Configuration As shown in FIG.
  • another embodiment of the PS-OCT system can comprise, a Mach- Zehnder interferometer in a PS-OCT configuration 200, which measures the complex mutual coherence function (magnitude and phase) between two non-reciprocal optical paths, one path encompassing an object under test (i.e. "the sample") and the other a reference path.
  • a Michelson interferometer configuration which measures the same coherence function in a reciprocal configuration (i.e. the same splitter/coupler is used for both input splitting and output recombination).
  • the PS-OCT interferometer can comprise a Michelson interferometer configuration which measures the same coherence function in a reciprocal configuration, i.e.
  • the PS-OCT system and calculations for the OCT interferometer is generally described and explained by the inventors in U.S. Patent Application Serial No. 11/446,683, and Provisional Application Serial No. 60/932,546, herein incorporated by reference.
  • the PS-OCT system has a light source 210 with cascaded fiber optic couplers to subdivide the source light into three primary modules (1) the primary OCT interferometer, (2) an auxiliary wavemeter interferometer 260, and (3) an optical trigger generator 262.
  • the light source 210 is a High Speed Scanning Laser HSL- 2000 (Santec) with an instantaneous coherence length of over 10mm.
  • the swept laser source 210 includes emitted light with a mean frequency of the output spectrum that varies over time.
  • the mean frequency of light emitted from the swept source may change continuously over time at a tuning speed that is greater than 100 terahertz per millisecond and repeatedly with a repetition period.
  • the swept laser source may be any tunable laser source that rapidly tunes a narrowband source through a broad optical bandwidth.
  • the tuning range of the swept source may have a tuning range with a center wavelength between approximately 500 nanometers and 2000 nm, a tuning width of approximately greater than 1% of the center wavelength, and an instantaneous line width of less than approximately 10% of the tuning range.
  • the swept laser source 210 is coupled to an electro-optic polarization modulator to modulate the polarization state of the source light periodically in time between two semi orthogonal polarization states.
  • the auxiliary wavemeter 260 and the optical trigger generator 262 are for clocking the swept light source in order for providing an external clock signal to a high speed digitizer 270, as disclosed in commonly assigned application serial no. 60/949,467, filed July 12, 2007, herein incorporated by reference.
  • the Uniform Frequency Sample Clock signal is repeatedly outputted for each subsequent optical trigger that occurs as the laser is sweeping and the optical trigger is generated.
  • the optical trigger is generated from the optical trigger generator 262.
  • the high-speed digitizer card 270 is coupled to the output of the OCT interferometer, output of the auxiliary interferometer 260, the trigger signal from the trigger generator 262, and the arbitrary waveform generator.
  • the high-speed PCI digitizer card 270 can be a dual-channel high resolution 16 bit, 125 MS/s waveform for a PCI bus.
  • the external sample clock signal is derived from an auxiliary optical wavemeter photoreceiver during a start-up calibration step, and then repeatedly outputted by the arbitrary waveform generator for each subsequent optical trigger signal that occurs as the laser is sweeping.
  • the external clocking system allows for the wavemeter-generated clock signal to be filtered and processed in software before being outputted on the arbitrary waveform generator.
  • the external clock derived from the auxiliary wavemeter is regenerated by the arbitrary waveform generator (Gage CompuGen) to allow acquisition of interferometer output data directly in wavenumber (k) space.
  • Coupler 212 splits 90% of the light source power is split into the primary OCT interferometer and 10% into the coupler 216 for the auxiliary wavemeter 260 and trigger generator 262.
  • a polarization modulator may be placed in the source path to modulate the polarization state of the light source periodically in time between two "semi-orthogonal" polarization states.
  • the modulation cycle may be synchronized to the wavelength scan or during each A-line scan. Coupler 214 then splits the light 90% directed to port 1 of a 3 -port polarization sensitive optical circulator 220 for the sample path and 10% of the light is directed to port 1 of a 3-port polarization sensitive optical circulator 222 for the reference path. Port 2 of circulator 220 for the sample path is coupled to a polarization controller 230 and to a sample 240.
  • the polarization controller 230 may include, but is not limited to, a fiber-optic polarization controller based on bending-induced birefringence or squeezing. The polarization controller 230 can be used to match the polarization state of the reference arm to that of the sample arm.
  • the polarization controller 230 may be a polarization control circuit.
  • the sample path can be coupled to a probe or catheter 242 via a fiber optic rotary junction. Examples of a rotating catheter tip for the sample path include, a turbine-type catheter as described in Patent
  • the catheter 242 can be located within a subject to allow light reflection off of subject tissues to obtain optical measurements, medical diagnosis, treatment, and the like.
  • the coupler 216 also receives from port 3 of optical circulator 222, where port 2 of optical circulator 222 includes a polarization controller 232 and a Variable Delay Line ("VDL") 246.
  • VDL 246 comprises of an input fiber, a retro-reflecting mirror on a translation stage, and an output fiber.
  • a dial controls the variable length, or delay, inserted into the optical path.
  • the typical length variance is about 6 cm, while the typical time delay is about 300 picoseconds.
  • an adjustable phase delay system can be included to modulate phase, which includes a piezo-operated stage, to provide much finer phase control, e.g., in the sub-wavelength range.
  • the VDL provides for larger path-length adjustments with micron- size adjustment being the smallest increments.
  • the VDL may be coupled to an OCT implementation 252 that allows for a single detection path or receiver, which is generally described in U.S. Patent Application Serial No. 12/018,706, incorporated by reference herein.
  • the photoreceiver 250 comprise a detection element, such as an InGaAs photodiode and a transimpedance amplifier, which converts the electrical current signal generated by photons absorbed by the photodetector element into a voltage signal that can be read by the digitizer.
  • a polarizing beam splitter divides horizontal and vertical polarization components returning from the sample and reference paths.
  • Dual photoreceivers measure horizontal and vertical interference fringe intensities versus depth, F / ,(z) and r v (z), respectively.
  • spectral interferometric techniques with polarization sensitivity may be implemented by recording four sequential single-channel measurements or simultaneous dual-channel horizontal and vertical polarization component measurements in conjunction with the well characterized reference path.
  • some gain amplification is given at this stage or in a following stage, as well as some filtering for removing noise that is outside of the relevant electrical bandwidth.
  • the gained and filtered voltage signal is digitized.
  • the OCT interferogram [S(k)] is digitized at 16-bit resolution using a high-speed PCI digitizer board 270 (AlazarTech ATS660, Toronto, Canada) coupled to photoreceiver 250 and the primary OCT signal and auxiliary wavemeter 260 signal.
  • the external clock derived from the wavemeter and regenerated by the arbitrary waveform generator (Gage CompuGen) allows acquisition of data directly in wavenumber (k) space.
  • S(k) is converted using the Fast Fourier Transform (FFT) into the pathlength (z) domain.
  • ] represents the backscattered magnitude at depth z in the sample.
  • the digitizer 270 is coupled to a computer processor, which is a state-of-the-art workstation with a fast multi-core processor, RAID striped disk array, and large RAM space.
  • a computer processor which is a state-of-the-art workstation with a fast multi-core processor, RAID striped disk array, and large RAM space.
  • the sample path of the OCT system can propagate through a calibration system 248 including a plurality of retardation plates on the distal end of the sample path fiber to have its polarization state transformed, as shown in FIG. 2.
  • the detected transformation will be different than the expected and actual transformation due to the ambiguity caused by the fiber optic.
  • Polarization ambiguity in a fiber-based PS-OCT can change dramatically upon movement and bending of the fiber cable during catheterization procedures.
  • the comparison of the detected transformation with the expected transformation of polarization in the system of retardation plates will provide calibration coefficients, such as the Jones matrix of the catheter fiber, to overcome the ambiguity and compensate or correct polarization data from back- scattering events happening distal to the calibration retardation plate system.
  • An exemplary catheter for OCT systems is disclosed in common assigned provisional application serial no. 60/949,511 , filed July 12, 2007, herein incorporated by reference.
  • the calibration system 248 includes a system of retardation plates with at least a first birefringent material and a second birefringent material. If a PS-OCT approach is used to calibrate, each retardation plate must have sufficient thickness and reflectivity to be visualized in an OCT image. In one embodiment, each retardation plate can be visualized concurrently with specimen imaging.
  • the calibration retardation plate system can be imaged in the same A-scan if scan depth is sufficiently long, or with a separate interferometer (separate reference arm of different path length and separate readout) sharing only the sample path (catheter) fiber.
  • Light must be focused/collimated and reflectivity chosen such that signal-to-noise ratio from surfaces of retardation plates is sufficiently high to avoid noise in calibration coefficients but not have detrimental self-interference patterns in the specimen imaging interferometer.
  • One of the references would have to be looking at a non-focused image.
  • Calibration may be used to detect absolute axis orientations using single mode fiber base PS-OCT. Calibration requires that some signal be collected from a known element distal to the entire fiber.
  • a calibration system in the distal, post- fiber portion of a catheter probe.
  • separate retardation plates are placed between collimating/focusing elements and a rotating/deflecting prism.
  • the collimating/focusing elements can be GRIN lenses.
  • dual-layered birefringent material is used as the capsule material of the catheter.
  • the sample beam is split with a partially reflective prism, which allows the transmitted portion to propagate to the calibrating retardation plates.
  • the sample beam is split with a dichroic wavelength-dependent prism and a separate light source is used to calibrate the fiber independently of the imaging beam.
  • a separate light source is used to calibrate the fiber independently of the imaging beam.
  • the calibration will be for a different wavelength than the imaging signal wavelength and Polarization Mode Dispersion
  • a separate interferometer is coupled to the sample path with the retardation plates, in order to separately image the retardation plate system.
  • the separate interferometer includes a separate reference arm of different optical path length and separate readout.
  • Birefringence and Retardation [0082] Form-birefringence is an optical property exhibited by media containing ordered arrays of anisotropic light scatterers which are smaller than the wavelength of incident light. Form- birefringence arises in biological structures when cylindrical fibers with diameters on this size scale are regularly oriented in a surrounding medium with different refractive index.
  • the electric field of incident light oscillating perpendicular to the fibers (Ei) induces surface charges that create an induced field (Eo) within the fiber, as shown in FIG. 6.
  • the induced field (Eo) anisotropically modifies forward scattered light so that phase and amplitude of Ei is altered relative to the electric field component polarized parallel to the fibers (Ey).
  • the electric field of incident light which is polarized perpendicular to the fiber axis (Ei) produces a surface charge density with an induced field (Eo). This changes the dielectric susceptibility and gives higher refractive index (ris) relative to that experienced by light polarized parallel to the fiber axis (En).
  • Form-biattenuance causes anisotropic attenuation of amplitude between Ei and E ⁇ .
  • Many fibrillar tissue structures are optically anisotropic; however, values of An vary considerably among species and tissue type.
  • the incremental phase retardation ( ⁇ i) incurred by the perpendicular component (Ei) results in slower light transmission and larger refractive index (ris) than that experienced by light polarized parallel to the fiber axis (En) with refractive index n/.
  • Incremental phase retardations ( ⁇ ;) accumulate through fibrous structures and the composite retardation ( ⁇ ) between components polarized parallel (En) and perpendicular (Ei) to the fibers after propagating a distance ⁇ z is: where ⁇ is given in degrees.
  • Polarimetric speckle noise is one noise source impeding accurate determination of polarimetric properties of the sample under test.
  • intensity speckle noise which is common to both polarization channels and only degrades /(z)
  • polarimetric speckle noise is different for horizontal and vertical polarization channels and degrades depth resolved polarization data ("S(z)").
  • intensity speckle noise is removed in part from polarization data by normalization of Stokes vectors.
  • First order statistics of the Stokes vector of scattered light for the case when horizontal and vertical fields are uncorrelated show that the probability density for the intensity is a sum of two orthogonal speckle fields (i.e. horizontal and vertical) and the Stokes parameters are Laplace variants.
  • speckle statistics of the Stokes vector for partially polarized light can be derived assuming Gaussian correlated field amplitudes.
  • the statistics of polarimetric speckle noise likely depend on the tissue under investigation and possibly configuration of the sample path optics (e.g., numerical aperture of focusing lens, distal optics, and the like).
  • PSNR signal-to-noise ratio
  • Iwc arc length of the noise-free model polarization arc [P(z)] associated with measured S(z).
  • Standard deviation of polarimetric speckle noise (“ ⁇ speckie”) is a statistical measure of the point-by-point angular variation on the Poincare sphere between detected S(z) and model P(z): where J is the total number of depth-resolved sample points within the specimen.
  • the analysis for determining retardation from S(z) recorded by the PS-OCT configurations is for a region of sample depths with homogeneous polarimetric properties. If the sample is heterogeneous in depth, then retardation by the PS-OCT configurations for each range of depths where the sample polarimetric properties are homogenous is completed.
  • determining retardation from S(z) recorded with the PS-OCT configurations comprises estimating the three model parameters which mathematically specify the noise-free model polarization arc [P(z)]: (1) angle of arc rotation, which is equal to the double-pass retardation (2(5); (2) rotation axis (A)and (3) the arc's initial point, which represents the polarization at the specimen's front surface [P(O)].
  • a nonlinear fitting algorithm that takes S(z) as input and estimates model parameters has been developed.
  • Implementation of the nonlinear fitting algorithm to estimate 25, A, and P(O) comprises formulation of a residual function (Ro) which specifies goodness of fit between S(z) and P(z):
  • preceding layers e.g. single-mode optical fiber, anterior segment of the eye
  • a multi-state residual function (RM) that is the algebraic sum of R 0 (Eq.
  • RM gives the composite squared deviation between M sets of depth-resolved polarization data [Sm(X)] and corresponding M noise-free model polarization arcs [Pm(Z)] .
  • Model parameters [2 ⁇ , A, and Pm(O)] are estimated by minimizing R M using a Levenberg-Marquardt algorithm and represent the best estimates of Pm(z) arcs.
  • the ability of the multi-state nonlinear algorithm to determine model parameters is verified on simulated noisy depth-resolved polarization data.
  • the multi-state approach comprises all M noise-free model polarization arcs [P»;(z)] that rotate around the same rotation axis A by the same angle (2 ⁇ ) regardless of Pm(O), larc.m, or Jm.
  • the uncertainty in any single Pm(z) arc is offset through constraints placed upon the other M- I arcs by the multi-state residual function.
  • the multi-state nonlinear algorithm comprises a single estimate of unknown parameters using all depth-resolved data points in the scan, allowing the consideration of more than two points at a time [S(O) and S( ⁇ z)] and the incorporation of S(z) arc curvature.
  • Birefringence in tissue is predominantly the form type and results from an anisotropic distribution of refractive index from ordered fibrillar structures.
  • a nonlinear fitting of normalized Stokes vectors from multiple incident polarization states provides accurate determination of retardation in thin, weakly birefringent tissue specimens such as a turbid birefringent film.
  • the highly sensitive PS-OCT configuration detects changes in birefringence, monitors the pathological conditions which alter fibrillar tissue structure, fibrillar structures corresponding to pathological conditions such as fibrous caps (fibrillar structures can correspond to pathological conditions such as fibrous caps), and diagnoses other clinical conditions.
  • RNFL Retinal Nerve Fiber Layer
  • birefringence may provide a measure of fibril density ( ⁇ t ) within the volume sampled by the PS-OCT sample beam.
  • the PS-OCT configuration can quantify the number of RNFL neurotubules during the progression of glaucoma, localize collagen denaturation in the skin of burn victims, and aid in the diagnosis of other pathologies or traumas that affect the fibrous structure of form birefringent tissue.
  • each fibril e.g. microtubule, collagen filament, actin-myosin complex
  • the sampled specimen volume V may be approximated by a cylinder of light defined by the beam waist radius (w 0 ) and specimen thickness ( ⁇ z): (21) where A 0 is the cross-sectional area of one fibril.
  • W 0 the beam waist radius
  • ⁇ z specimen thickness
  • the determination of specimen thickness and retardation provides a measure of the number (Ni) and density (p,) of fibrils in the sampled specimen volume:
  • ⁇ i and fy are the complex eigenvalues representing changes in amplitude and phase for orthogonal eigenpolarization states with free-space wavelength ⁇ 0 propagating a distance Az through the medium. Attenuation common to both eigenpolarizations does not affect the light polarization state and is neglected here.
  • phase retardation ( ⁇ , expressed in radians) between eigenpolarization states after propagation through the medium is the difference between the arguments of the eigenvalues, ⁇ - arg( ⁇ ,) - arg( ⁇ 2 ), which allows simplification of the Jones matrix to
  • T 1 and T 2 are the intensity transmittances for the two orthogonal eigenpolarizations and the attenuation can be a consequence of either anisotropic absorption or anisotropic scattering of light out of the detected field.
  • Birefringence is the phenomenon responsible for phase retardation ( ⁇ ) of light propagating a distance ⁇ z in an anisotropic element and is given by: where n s and n f are the real- valued refractive indices experienced by the slow and fast eigenpolarizations, respectively.
  • Form-birefringence (An) is proportional to and given experimentally by the phase retardation-per-unit-depth ( ⁇ IAz).
  • Dichroism describes the phenomenon of diattenuation in an anisotropically absorbing element (such as that exhibited by a sheet polarizer), and the term is also used to describe differential transmission or reflection between spectral components (such as that exhibited by a dichroic beam splitter), leading to confusion if taken in the incorrect context.
  • spectral components such as that exhibited by a dichroic beam splitter
  • Neither dichroism nor diattenuation nor polarization dependent loss (“PDL”) can be expressed on a per-unit-depth basis and are thus unsuitable quantities for depth-resolved polarimetry in scattering media.
  • Attenuance has come to describe the loss of transmittance by either absorption or scattering; biattenuance is the differential loss of transmittance between two eigenpolarization states by either absorption (dichroism) or scattering.
  • Form-biattenuance is an experimentally and theoretically relevant term that can be expressed on a per-unit-depth basis.
  • biattenuance (“4£") is given by Equation (28): where ⁇ and ⁇ /-are attenuation coefficients of the slow and fast eigenpolarizations. For absorbing (dichroic) media, ⁇ and ⁇ / -are simply imaginary- valued refractive indices.
  • phase retardation ( ⁇ ) and thickness (Az) of an element are linearly related by its birefringence (An).
  • the relationship between an element's diattenuation [D, Eq. (26)] and thickness (Az) is nonlinear. This nonlinear relationship complicates expression of an element's form-biattenuance: one cannot generally and without approximation refer to a diattenuation-per-unit-depth as one can refer to form-birefringence as a phase retardation-per- unit-depth.
  • Diattenuation (D) is related to relative-attenuation ( ⁇ ) by:
  • detected photocurrents representing horizontal and vertical polarimetric fringe signals (T 1 (Z) and F,(z)) are pre-amplified, bandpass filtered, and digitized. Coherent demodulation of F,,(z) and F,(z) yields signals proportional to the horizontal and vertical electric field amplitudes [E/r(z) and Ev(z)] and relative phase [ ⁇ (z)] of light backscattered from the specimen at each depth z within the A-scan.
  • An ensemble (N A ) of A-scans representing uncorrelated or weakly correlated speckle fields are acquired on a grid within a small square region (50 ⁇ m x 50 ⁇ m) at each location of interest on the specimen.
  • phase shifts ( ⁇ LCVR,m) of a polarization control element (e.g., Liquid Crystal Variable Retarder, LCVR).
  • a polarization control element e.g., Liquid Crystal Variable Retarder, LCVR.
  • the calibrated LCVR phase shift ( ⁇ LCVR,m) is subtracted from the demodulated relative phase [ ⁇ > ⁇ (z)] to compensate for the light's return propagation through the LCVR.
  • Non-normalized Stokes vectors are calculated from E ⁇ , ⁇ ;(Z), Ev,m(z), and ⁇ c,m(z) for each of NA A-scans in the ensemble and for each M.
  • Ensemble averaging over NA at each depth z reduces ⁇ speckie by a factor of approximately NA 112 and then
  • a normalization yields M sets of depth-resolved polarization data [Sm(z)] for each location,
  • Wm(z) is used as a scalar weighting factor in the multistate nonlinear algorithm to estimate phase retardation ( ⁇ ) and relative-attenuation ( ⁇ ).
  • Exemplary Multistate nonlinear algorithm to determine form-biattenuance is accomplished using a nonlinear fitting algorithm based on the approach for determining form- birefringence (An) with the PS-OCT configurations.
  • a modified multistate residual function may be implemented which gives the composite squared deviation between M sets of depth- resolved polarization data [Sm(z)] and corresponding M noise-free model polarization arcs [Pm(z)] weighted by Wm(z), where Ro is the weighted single-state residual function, and the subscript "f is used to denote the discrete nature of sampled data versus depth (z).
  • Model parameters [2 ⁇ , 2 ⁇ , ⁇ , and Pm(O)] are estimated by minimizing i?Musing a Levenberg-Marquardt algorithm and represent the best estimate of Pm(z). At increased penetration depths (lower electrical signal-to-noise ratio) or large initial separation-angles [Jm(O)], Wm(z) decreases and Sm(z) are given less weight.
  • FIG. 7 The phenomenon of form-biattenuance and a model predicting the relative contribution of An and ⁇ to transformations in polarization state of light propagating in anisotropic media is shown in FIG. 7.
  • the model may be used as examples of tissues with alternating anisotropic media and isotropic layers. Other models are possible that would generally be considered to explain polarimetric properties of tissues.
  • Optic axis orientation ( ⁇ ) provides the direction of constituent fibers relative to a fixed reference direction (i.e., horizontal in the laboratory frame).
  • a method for measuring depth- resolved optic axis orientation [ ⁇ (z)] deep within multiple layered tissues uses the PS-OCT, as described previously.
  • Collagen organization in cartilage and intervertebral disc cartilage may be used as a model tissue on which to demonstrate the depth-resolved polarimetric imaging ability of PS- OCT.
  • intervertebral discs are located between spinal vertebrae and consist of the annulus fibrous ("AF"), enclosing an inner gel-like nucleus pulposis ('TSTP").
  • AF annulus fibrous
  • 'TSTP inner gel-like nucleus pulposis
  • Annulus fibrous is composed of axially concentric rings (i.e. lamellae) of dense type I collagen fibers
  • fibrocartilage the orientation of which is consistent within a single lamella but approximately perpendicular to fibers in neighboring lamellae, forming a lattice-like pattern.
  • Regular orientation of collagen fibers within a single lamella is responsible for form-birefringence [ ⁇ r ⁇ (z)], and alternating fiber directions between successive lamellae correspond to alternation of optic axis orientation [ ⁇ (z)] within the annulus fibrous.
  • Multiple layered fibrous tissue such as the annulus fibrous is modeled as a stack of K linearly anisotropic, homogeneous elements, each with arbitrary phase retardation ( ⁇ /c), relative- attenuation ( ⁇ /c), optic axis orientation ( ⁇ k), and corresponding Mi Jones matrix [Js(i ⁇ ( ⁇ k, ⁇ k, ⁇ k)].
  • Incident polarized light (Em) propagating to the rear of the Mi intermediate element and back out in double-pass (Edp_outr ⁇ ) is represented by:
  • Edp_out(2) Js(iyrJs(2) T Js(2)Js(i)Ein.
  • Matrix algebra and knowledge of Js(i) allows recovery of Js(2)( ⁇ %,6"2, ⁇ %).
  • ⁇ i, S 2 , and & ⁇ can be found using a nonlinear fit to the trajectory between Sdp_out(i) and Sdp_out(2) after compensation of anisotropy in the superficial layer (reverse rotation by — ⁇ i and reverse collapse by -S 1 with respect to P 1 ). This process is repeated for successively deeper layers in the stack to determine ⁇ k , ⁇ k , and ⁇ k for all k layers.
  • the calibration system 248 may allow fiber-based PS-OCT configurations to overcome distortion in the optical fiber.
  • the PS-OCT instrument has stable Jc with linear eigenvectors in the laboratory frame; therefore Jc reduces to simple phase retardation ( ⁇ c, due to the beamsplitter and retroreflector) between horizontal and vertical interference fringes.
  • the PS-OCT configuration incorporates a liquid crystal variable retarder ("LCVR") to modulate the launched polarization state incident on the specimen by applying a voltage-controlled phase retardation ( ⁇ 5LCVR).
  • LCVR liquid crystal variable retarder
  • the optic axis of the LCVR is horizontal, thus the total systematic phase retardation ( ⁇ 5LCVR + Sc) can be compensated by subtraction of ⁇ SLCVR+ & from the relative phase of the detected horizontal and vertical interference fringe signals, allowing unambiguous and undistorted measurement of the anatomical fiber direction ( ⁇ k) absolutely referenced to the laboratory frame.
  • Transformations in the depth-resolved polarization state of light backscattered from linearly anisotropic media such as fibrous tissue can be represented as depth-resolved normalized Stokes vector (S(z)) arcs on the Poincare sphere.
  • S(z) depth-resolved normalized Stokes vector
  • the trajectory of S(z) arcs in the presence of An and A ⁇ is governed by a vector differential equation, as by a vector differential equation.
  • S(z) arcs rotate in a circular trajectory around an eigenaxis ( ⁇ ) by an angle equal to the double- pass phase retardation (2 ⁇ ) of the specimen.
  • ⁇ tissue biattenuance
  • ⁇ is constant and biattenuance is negligible (A ⁇ « An)
  • the unit tangent vector [T (z)] of S(z) is given by: where Lrc is the arc length of S(z) on the Poincare sphere.
  • Lrc is the arc length of S(z) on the Poincare sphere.
  • abrupt changes in fiber orientation [ ⁇ (z)] versus specimen depth produce corresponding changes in both ⁇ and in the trajectory of S(z).
  • Discontinuities in the unit tangent vector [T ⁇ (z)] give rise to instances of infinite or very large curvature [ ⁇ (z)] for continuous z.
  • the unit tangent vector is:
  • and curvature is:
  • Aneurism vulnerability may be assessed with the PS-OCT configurations described above.
  • the likelihood of an aneurism rupturing is related to the mechanical properties of collagen in the arterial walls. If collagen fibers are oriented regularly with the artery longitude, then there is reduced mechanical strength in the perpendicular (circumferential) direction. If aneurisms that contain a more random orientation of fibers (and thus distribute strength in both longitudinal and circumferential directions) are less likely to rupture, then the PS-OCT configurations may assess the risk or vulnerability of aneurysms' to rupture.
  • fiber-based PS-OCT configuration is capable of estimating absolute collagen orientation when a known polarization reference is fixed to the distal scanning end. This could be accomplished by using a capsule made out of a known birefringent material as the reference, which is indicated above with a birefringent material in the capsule material of the catheter.
  • AD Alzheimer's disease
  • Cerebral amyloid pathologies exhibit linear birefringence and dichroism, which may be detected by the PS-OCT configurations.
  • Collagen XVIII In amyloid angiopathy, deposition of collagen fibrils in the walls of capillaries and veins results in narrowed lumina and even occlusion has been observed in patients with AD.
  • Collagen XVIII accumulates in all types of cerebral blood vessels including arteries, arterioles, capillaries, venules, and veins in patients with AD.
  • Collagen XVIII is associated with amyloid deposition in blood vessel walls and may be involved in the pathogenesis of AD.
  • the mechanisms leading to the reduced blood flow may be found in the retina and are related to those that produce the cerebral blood flow abnormalities in AD. Narrowing of the retinal venous diameter may be related to an increased venous wall thickness due to collagen deposition, as found in cerebral veins.
  • the PS-OCT configurations may assess such characteristics in the characterization of AD.
  • RNFL thickness measurements using the PS-OCT configurations are useful in identifying the early changes associated with glaucomatous optic neuropathy ("GON").
  • GON glaucomatous optic neuropathy
  • Inferior RNFL loss corresponding to superior visual field loss is a typical pattern found in early GON.
  • the predominant inferior visual field loss seen in patients with GON and AD would correspond structurally to superior RNFL losses.
  • a specific pattern of superior RNFL loss could be detected by using the PS-OCT configurations in patients with early AD.
  • the PS-OCT configurations may be applied to aid alignment of collagen fiber axes.
  • Coronary artery bypass grafting (“CABG”) is the most commonly performed major surgery and a critical determinant of its outcome has been postulated to be injury to the conduit vessel incurred during the harvesting procedure or any pathology preexistent in the harvested vessel.
  • Intravascular PS-OCT imaging from the radial arteries (“RA") and/or saphenous veins may reliably detect atherosclerotic lesions in the RAs and discerns plaque morphology as fibrous, fibrocalcific, or fibroatheromatous.
  • the PS-OCT configurations can also be used to identify patent or healthy regions in longitudinal sections of radial arteries or saphenous veins for grafting [00132]
  • the PS-OCT configurations may be used for margin detection in bronchial tumors.
  • the PS-OCT configurations may also perform early diagnosis of tumors and cancerous tissue.
  • the PS-OCT configuration images may identify bronchial tumor presence as destructive growth by ignoring and effacing normal tissue boundaries.
  • Featureless PS-OCT configuration images or regions with reduced form-birefringence may lack the ordered multilayered appearance of the healthy airway wall.
  • the PS-OCT configurations may also differentiate between areas of chronic inflammation and invasive malignancy; where the clear demarcations of epithelium and lamina basement may be observed at inflamed sites and may be lost in presence of invasive neoplasia.
  • the PS-OCT configurations may individually define the epithelium, subepithelial components, and cartilage.
  • the PS-OCT configurations may identify morphologic changes associated with inflammatory infiltrates, squamous metaplasia, and tumor presence.
  • the PS-OCT configurations may assess the coronary plaque collagen content. Arterial plaques include intimal collagen, which degrades and leads to plaque destabilization.
  • Collagens are major structural components of the arterial wall extracellular matrix, comprising 20% - 50% of the dry weight, with the predominant types being Type I and III, where type IV is in the basement membrane.
  • the tensile strength of plaque is determined by fibrillar collagen (type I) and extracellular lipid. Inflammation leads to release of collagenases and collagen breakdown increasing the risk of plaque rupture.
  • Collagen birefringence is a function of highly organized alignment and also the nature of the chemical groups of the collagen encountered and layer thickness. Form-birefringence is almost exclusively a function of the fibrous nature of the structure and two refractive indices of the fiber and surrounding material. The intimal region over the necrotic core exhibits high polarization sensitivity with organized collagen.
  • the PS- OCT configurations may assess plaque collagen content.
  • the fibrous cap is a layer of fibrous connective tissue is thicker and less cellular than the normal intima.
  • the fibrous cap contains macrophages and smooth muscle cells.
  • the fibrous cap of an atheroma is composed of smooth muscle cells, macrophages, foam cells, lymphocytes, collagen and elastin.).
  • the PS- OCT configurations may assess plaque collagen content and generate high resolution structural assessments to identify the thin caps associate with high risk plaques.
  • EXAMPLE 1 Phase retardation and fast-axis angle of a birefringent sample
  • a mica retarder (Meadowlark Optics) is positioned in the common-path spectral interferometer 10, as shown in FIG. 1, orthogonal to the direction of incident light propagation and used as a birefringent sample.
  • FIG. 3A depicts the typical spectral output intensity of a mica retarder positioned in the common path fiber based single channel polarization-sensitive spectral interferometer orthogonal to the direction of incident light propagation and used as a birefringent sample.
  • the output spectral width of the whole spectrum was 12.2 THz, as shown in FIG. 3 A.
  • FIG 3B depicts a small segment of 10 Ghz between 190.69 and 190.79 THz of the whole spectrum (12.2 THz) to view fringes in more detail.
  • the output spectrum in FIG. 3A and 3B is modulated with several distinct high frequencies, and a swept source and OSA with high resolution are required to avoid undersampling.
  • FIGS. 4A and 4B shows the Fourier transform magnitude of interference fringes between the front and back surfaces of the glass window, as shown in FIG. 4A, and between the back surface of the glass window and the birefringent sample, as shown in FIG. 4B.
  • the ISA provides the corresponding optical frequency for each recorded spectral component of output intensity, successive spectral samples of output intensity are not equally spaced in optical frequency.
  • a Nonuniform Fourier Transform (“NUFT") algorithm was used rather than a simple fast Fourier transform, which assumes uniform sampling.
  • NUFT Nonuniform Fourier Transform
  • FIG. 4 A four Stokes spectral components of interfering light are separated into seven peaks in the optical path-length difference domain. The position of the fourth peak and spacing between peaks are determined by the optical path length difference between interfering beams generated in the common-path spectral domain interferometer and phase retardations due to the two PM fiber segments in the FOSPI, respectively.
  • the first seven peaks are formed from interference between the back surface of the glass window and the font surface of the birefringent sample and are similar to those from interference between the front and the back surfaces of the glass window in FIG. 4 A, indicating the polarization state between the window and the sample is unchanged.
  • the rightmost seven peaks in FIG. 4B resulting from interference between the back surface of the birefringent sample show the polarization-state change of double-pass light propagation through the birefringent sample.
  • Spectral modulations introduced by the common-path spectral interferometer and by the FOSPI combine sequentially so that the polarization and depth information are encoded into separate channels in the time-delay domain.
  • multiple scans are required to average out polarimetric speckle noise, as described above.
  • Multiple scans may be implemented to average out polarimetric speckle noise — as described above.
  • Output from the fiber based single channel polarization sensitive spectral interferometer is a convolution of the FOSPI output and that from the common path spectral interferometer.
  • the full set of Stokes parameters of interfering light at a specific optical path-length difference consists of seven channels in the time-delay domain, and channel separation is dependent on two factors: spectral resolution ( ⁇ v) of the instrument and choice of PM fiber lengths in the FOSPI.
  • ⁇ v spectral resolution
  • a general bulk optical element does not require PM fibers as mentioned above.
  • Such large channel separations in the time delay domain require optically stable kilometer-length PM fiber segments in the FOSPI.
  • the sample used here is optically transparent, and its optical thickness is large enough so that the two sets of seven channels due to refraction from the front and back surfaces are sufficiently separated.
  • the bandwidth of each peak in the time delay domain is determined by the optical thickness of the sample, and wide channel separation in the time delay domain is required to isolate each channel.
  • Difference in Stokes parameters determined from the reference and interference fringe signals are optical path-length difference [ ⁇ (v)] and the phase retardation [ ⁇ (v)] of a birefringent sample. If a sample is non birefringent, Stokes parameters of an interfering fringe signal are
  • phase retardation and fast-axis angle of a birefringent sample are difficult to measure when the direction of an incident light oscillation is primarily parallel to the fast axis of the sample retarder.
  • the polarization state of light entering the interferometer should be modified.
  • Such modification can be implemented by the input polarization state preparation optics 20 inserted between the reference and the sample surfaces, the segment can be considered a known portion of the birefringent sample with a specified polarization transformation, and the analysis presented may be modified to determine the birefringence and fast axis of a sample.
  • Such an analysis is presented in the paper by Kemp, NJ et. al. Opt. Express 2005: 13:4507, herein incorporated by reference.
  • the FOSPI 50 is a PM fiber based instrument to measure the polarization state of collected light and incorporation of the FOSPI 50 into a common-path spectral interferometer 30 allows measurement of the full set of Stokes parameters of interfering light with a single optical frequency scan where multiple A-scans are required to average polarimetric speckle noise unless multiple A-scans are required to average polarimetric speckle noise as indicated above.
  • the high spectral resolution of the broadband frequency swept laser source enables encoding and decoding both the polarization and depth information into separate channels in the time delay domain.
  • Performance of the fiber based single channel polarization sensitive spectral interferometer has been demonstrated by measuring phase retardation ⁇ and fast axis angle ⁇ of a mica retarder while rotated in 5° increments from 0° to 90°. A single optical frequency scan is sufficient to estimate both phase retardation and fast axis angle of a mica plate without knowledge of the polarization state of incident light.
  • the fiber based single channel polarization sensitive spectral interferometer presented allows measurement of both phase retardation and fast axis angle of a birefringent sample.
  • Performance of the fiber based single channel polarization sensitive spectral interferometer is sensitive to phase retardations due to two PM fiber segments in a FOSPI (( ⁇ 1 (v) and ( ⁇ 2 (v) in Equation 4).
  • the PS-OCT configurations may minimize variations in phase retardations induced by environmental, mechanical and thermal fluctuations.
  • the coupling of a thermally isolated mechanical enclosure to the polarization sensitive spectral interferometer improves the stability of PM fiber phase retardations ⁇ ⁇ (v)and( ⁇ , (v) ). Also, by selecting optimal optics for the frequency range of the broadband laser source the signal-to-noise ratio of the system is improved.
  • the experimental results i.e., estimated phase retardation and fast axis angle of a birefringent sample
  • Fourier transformation followed by processing in the optical pathlength domain and simple arithmetic are used in the present analysis to determine phase retardation and fast axis angle.
  • a model-based approach may provide estimates of position of reflecting surfaces and birefringence properties. The proposed methodology may be applied to measure in real time the depth resolved polarization state of back-reflected light from a variety of samples.
  • EXAMPLE 2 High-sensitivity determination of birefringence in turbid media
  • FIG. 1OA and 1OB averaging NA uncorrelated speckle fields reduces polarimetric speckle noise ⁇ a speckle
  • ⁇ of the birefringent film is determined for a range of mica waveplate slow-axis orientations ranging from 0° to 180° in increments of 10°.
  • Retardation ( ⁇ ) of the birefringent film was determined for a range of mica waveplate slow-axis orientations ranging from 0° to 180° in increments of 10°.
  • a coaxial visible aiming beam was placed directly onto the optic nervehead for registration at the start of each scan.
  • Sample arm optics were configured for pupil-centric scanning. Prior to recording high resolution maps, a low-resolution fast scan was performed to insure the selected lateral area included all desired peripapillary features.
  • the data acquisition time to record a single peripapillary map may vary according to the optical configuration; however, the time to record the data may not be that important inasmuch as longer acquisition times are desired.
  • Laser power incident on the cornea was 2.8 mW during lateral scanning and 1.7 mW while stationary.
  • Approximate laser spot size at the retinal surface was 30 ⁇ m.
  • Axial resolution was determined by the 5 ⁇ m coherence length of the laser source in air.
  • Lateral scanning in the x and y dimensions allowed acquisition of TI 7 (Z J ) and r v (z y ) at two user-specified locations: 1 mm inferior to the center of the ONH and 1 mm nasal to the center of the ONH.
  • the anterior surface of the RNFL ⁇ z ⁇ 0) was determined automatically by thresholding, and the posterior RNFL surface was identified manually from the depth-resolved interference fringe intensity [/(z))].
  • the multistate nonlinear algorithm was applied to extract V(z j ) from S(zJ) and determine in vivo primate RNFL retardation (C>RNFL) and birefringence ( ⁇ RNFL)-
  • Noise-free model polarization arcs [Pm(X), black] and rotation axis (A) were extracted by the multi-state nonlinear algorithm.
  • Table 1 summarizes the detected RNFL ⁇ Z RNFL5 ⁇ 5 R NFL , and ⁇ «RHFL given in units of degrees per 100 micrometers.
  • the NA 112 behavior of averaged polarimetric speckle noise allows trial-and-error discovery of the optimum spacing between speckle fields without a priori knowledge of the scatterer microstructure.
  • the optimum spacing between speckle fields for imaging the birefringent film with our system was determined empirically (8 ⁇ m). Larger spacing results in reduced lateral resolution and smaller spacing leaves speckle fields partially correlated thereby diminishing the NA 1/2 noise reduction achieved through ensemble averaging.
  • the likelihood of combining polarization data from adjacent anatomical features is decreased with marginal additional instrumentation complexity by averaging over a small two-dimensional square grid region rather than a pattern of traditional rastered B-scan.
  • results of the birefringent film experiments indicate the multi-state nonlinear algorithm may be applied to determine retardation in turbid birefringent media. Moreover, determination of ⁇ by the multi-state nonlinear algorithm is invariant to unknown unitary polarization transformations from preceding birefringent layers as demonstrated by the mica waveplate rotation.
  • EXAMPLE 3 Form-biattenuance in fibrous tissues
  • each tail was cut from the body and a longitudinal incision the length of the tail was made in the skin on the dorsal side. Skin was peeled back and tertiary fascicle groups were extracted with tweezers and placed in phosphate buffered saline solution to prevent dehydration before imaging. Anatomical terminology used is consistent with the structure of the rat tail tendon. Tertiary fascicle groups were teased apart into individual fascicles with tweezers and placed in a modified cuvette in the sample path of the PS-OCT configuration.
  • the cuvette maintained saline solution around the fascicle, prevented mechanical deformation in the radial direction, and allowed 20 g weights to be attached at each end of the fascicle. Weights provided minimal longitudinal loading in order to flatten the collagen fibril crimp structure present in rat tail tendon.
  • a total of 111 different fascicle locations were imaged from the four rats, each at the location of maximum diameter across its transverse cross-section (as determined by an OCT B- scan image). Achilles tendon specimens from the same rats were harvested in a straightforward manner and imaged while positioned in the modified cuvette with the same loading conditions. Four different Achilles tendons were imaged in 45 different randomly chosen locations.
  • PSNR Polarimetric signal-to-noise ratio
  • PSNR ranged from 76 to 175 and ⁇ speckie ⁇ 0.20 rad for the 45 rat Achilles tendon locations measured.
  • 16A shows typical Sm(z) and Pm(z) plotted on the Poincare sphere for the region 1 mm inferior to the ONH center in the primate RNFL.
  • PSNR ranged from 3 to 16 and ⁇ S p eck i e ⁇ 0.06 rad for the six inferior locations measured.
  • RNFL thickness averaged 50 ⁇ m and PSNR was too low for reliable estimates of ⁇ in the nasal region of the primate RNFL.
  • the RNFL exhibits only a fraction of a wave of phase retardation compared to multiple waves exhibited by tendon specimens in FIGS. 13 A and 14 A.
  • the range of systematic variation in measurements of ⁇ and ⁇ due to placement of the beam focus was negligible. Variation in measured ⁇ (6.2%) due to different initial separation- angles [y>n(0)] was higher than variation in ⁇ (0.35%).
  • ⁇ speckie has a roughly exponential dependence on Jm(O).
  • Difference in values may be due to wide inherent anatomical variation in form-biattenuance, nonstandard tissue extraction and preparation, or large uncertainty in the methodologies. Details such as tissue freshness, anatomical origin of the harvested specimens, and detailed description of the expected uncertainty are not available. Additionally, crimp structure present in non-loaded tendon specimens could cause spatial variations in collagen fiber orientation over the sample beam diameter, resulting in poor agreement with a homogeneous linear retarder/diattenuator model [Eq. (30)] and artifacts in measurements of ⁇ .
  • M incident polarization states
  • Sm(O) states
  • M 2 incident polarization states which are positioned orthogonally to each other in their representation on the Poincare sphere and are suited for detecting ⁇ and An.
  • M 2 polarization states which are oriented parallel and perpendicular to the optic axis in physical space (and opposite to each other in their representation on the Poincare sphere) may provide the best estimates of ⁇ and ⁇ .
  • the small-angle approximation introduces minimal error for diattenuation-per-unit- depth (D/ Az ⁇ ⁇ / ⁇ z) observed in thin tissue specimens (Az ⁇ 1 mm).
  • D diattenuation
  • DIAz diattenuation-per-unit-depth
  • Biattenuance ( ⁇ ) requires no approximation and is analogous and complementary to a well-understood term, birefringence (An).
  • Biattenuance overcomes the need to specify when a diattenuation-per-unit-depth approximation is valid.
  • Consistency in definitions between birefringence (An) and biattenuance ( ⁇ ) or between phase retardation ( ⁇ ) and relative- attenuation ( ⁇ ) allow a meaningful and intuitive comparison of the relative values (i.e. A ⁇ /An, ⁇ / ⁇ ) of amplitude and phase anisotropy hi any optical medium or specimen.
  • the availability of narrow line-width swept-source lasers allows construction of Fourier-domain PS-OCT instruments having scan depths far longer than current PS-OCT mstruments.
  • the PS-OCT configuration probes significantly deeper into tissue specimens than 1-2 mm, likely making the small-angle approximation invalid even in tissues with low biattenuance.
  • a narrow line width laser source will allow longer scan distances as described in the common path spectral domain PS-OCT configuration.
  • the ability to determine the biattenuance with a spectral domain approach is dependent on the multi-state fitting algorithm or similar approach as described above.
  • the spectral domain approach as described in the PS-OCT configuration 10 and 200, allows faster acquisition of the data and provide improved estimates (relative to time domain systems) of birefringence and biattenuance.
  • PS-OCT characterizes non-biological samples which may have higher D and not satisfy the small-angle approximation.
  • Biattenuance is useful in employing other polarimetric optical characterization techniques, which can detect anisotropically scattered light and for which dichroism is therefore inappropriate.
  • depth- resolved is frequently used in the context of either "measured in the depth dimension” or "local variation in a parameter versus depth [e.g., ⁇ (z)]
  • biattenuance is independent of the particular interpretation. The first interpretation may be applied to biattenuance, but the multistate nonlinear algorithm can be extended in a straightforward manner to provide local variation in biattenuance versus depth [ ⁇ (z)].
  • Biattenuance is an intrinsic physical property responsible for polarization-dependent amplitude attenuation, just as birefringence (An) is the physical property responsible for polarization-dependent phase delay.
  • Diattenuation (D) gives the quantity of accumulated anisotropic attenuation over a given depth ( ⁇ z) by a given optical element.
  • ⁇ relative-attenuation
  • ⁇ phase retardation
  • the PS-OCT configurations includes: (1) theoretical and experimental validation for a new term in optical polarimetry, biattenuance ( ⁇ ), which describes the phenomenon of anisotropic or polarization-dependent attenuation of light amplitudes due to absorption (dichroism) or scattering; (2) detailed mathematical formulation of ⁇ and relative-attenuation ( ⁇ ) in a manner consistent with established polarimetry (i.e., birefringence and phase retardation), and mathematical relationships to related polarimetric terms diattenuation and dual attenuation coefficients; (3) analytic expression for trajectory of normalized Stokes vectors on the Poincare sphere in the presence of both birefringence and biattenuance; (4) expression for arc length (law) and PSNR of normalized Stokes vector arcs on the Poincare sphere in the presence of both birefringence and biattenuance; (5) modification of a multistate nonlinear algorithmto provide sensitive and accurate
  • Form-biattenuance and form-birefringence are closely related but physically distinct phenomena which may convey different information about tissue microstructure.
  • the form- biattenuance diagnostic capabilities remain with how accurate the determination of form- biattenuance and form-birefringence are concurrently used in biomedical research or clinical diagnostics.
  • Form-biattenuance may quantify the effect of tendon crimp on An and ⁇ and to establish the acceptable uncertainty in biattenuance for diagnosis of various pathological tissue states.
  • Other fibrous tissues at multiple imaging wavelengths may refine the physical model and establish a comprehensive anatomical range for biattenuance.
  • EXAMPLE 4 Fiber Orientation Contrast for Depth-Resolved Identification of Structural Interfaces in Birefringent tissue.
  • Fiber orientation ( ⁇ k ) and birefringence (Ari k ) for each lamella k and for all 20 lateral clusters were calculated from Az ⁇ , ⁇ k and ⁇ k as discussed above and assembled into B-scan images of depth-resolved fiber orientation ( ⁇ (x, z), FIG. 19) and birefringence (An(x, z), FIG. 20).
  • FIG. 19 shows the lamellar structure is clearly visible due to high contrast between fiber orientations in successive layers.
  • Relative attenuation ( ⁇ k ) was at or below the sensitivity limit for the deeper lamellae in this cartilage specimen and therefore a B-scan image of biattenuance is not shown.
  • black lines indicate lamellar interfaces determined by identifying segments in trajectories of S,,,(z) with high curvature ( ⁇ (z)).
  • FIG. 21 shows these interfaces superimposed on the original backscattered intensity OCT B-scan image (I(x, z)). A sliding averaging window (15% of image width) was applied across each interface to smooth black lines in FIG. 21. Quantitative estimates for mean lamellae thickness ( ⁇ z k ) are also indicated in FIG. 21. [00209] The determination of boundaries and lamellar thickness ( ⁇ z k ) using the trajectory of S m (z) provides vastly improved contrast over I(x, z) in the annulus fibrous specimen, as shown in FIG.
  • a fiber-optic rather than bulk-optic PS-OCT configuration has stability and portability advantages in a clinical environment.
  • the method using depth-resolved curvature ( ⁇ (z)) of normalized Stokes vectors (S(z)) to identify boundaries in multiple-layered fibrous tissue can be applied to all phase-sensitive PS-OCT configurations that detect depth-resolved Stokes vectors, whether fiber-based or bulk-optic, single-incident-state or multi-incident-state, time-domain or frequency-domain.
  • a PS-OCT cross section provides the orientation of fibers into and out of the B-scan plane, whereas a histological analysis cannot reveal this three-dimensional structure without a complex process of registering multiple sections taken parallel to the lamellae at successively deeper locations.
  • the PS-OCT configuration collects ultrastructural information similar to that acquired using histology.
  • Polarization-related properties such as fiber orientation ( ⁇ (x, z)) can be used to identify and quantify structural properties (e.g., thickness) in OCT images, regardless of poor contrast in the backscattered intensity B-scan image.
  • Structure properties e.g., thickness
  • Comprehensive PS-OCT imaging of cartilage structures may elucidate injury mechanisms, stress distribution and age variables as well as provide feedback on novel treatment approaches or engineered cartilage-replacement constructs.

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L'invention concerne un appareil d'interféromètre spectral sensible à la polarisation et un procédé pour analyser un échantillon. L'appareil d'interféromètre spectral sensible à la polarisation et le procédé déterminent des propriétés de polarisation de l'échantillon.
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