Method and system for polarization sensitive optical coherence tomography

Abstract

A system for polarization sensitive optical coherence tomography (PS-OCT) of a sample comprises an interferometric arrangement comprising a reference arm and a sample arm, the sample arm being arranged to emit optical radiation towards the sample; a phase modulation system arranged at an input of the sample arm; and a detector arranged to detect a signal resulting from interference between a reference beam from the reference arm and a sample beam from the sample arm. The phase modulation system comprises an electro-optic modulator; a polarizer arranged at a rotation angle with respect to a fast axis of the electro-optic modulator; and a signal generator for delivering a drive voltage to the electro-optic modulator; wherein the rotation angle and the drive voltage are selected so that the phase modulation system produces three mutually orthogonal polarization states.

Description

Technical Field

[0001] This disclosure generally relates to methods and systems for polarization-sensitive optical coherence tomography (PS-OCT) in the field of ophthalmology, for example (but not exclusively). Background Technology

[0002] Optical coherence tomography (OCT) is the recognized imaging modality for achieving high-resolution cross-sectional and three-dimensional imaging of translucent tissues. Intensity-based OCT is the standard method for OCT imaging but does not provide tissue-specific contrast. Polarization-sensitive (PS) OCT generates contrast through the birefringence properties of the tissue. PS-OCT, therefore, provides additional information based on the additional detection of the polarization state of light.

[0003] In ophthalmology, PS-OCT has been used for imaging the anterior and posterior segments of the eye. In glaucoma, the technique has been proposed for evaluating filtering blebs after trabeculectomy and for imaging the trabecular meshwork. In corneal imaging, early detection and segmentation of keratoconus have been proposed. At the posterior pole, PS-OCT has been used to quantify the retinal nerve fiber layer for contrast with the retinal pigment epithelium and to quantify drusen volume and area. Recently, PS-OCT has also been used to study the birefringence properties of the sclera in animal models, particularly during experimental increases in intraocular pressure (IOP).

[0004] Measuring the true 3D structure of the tissue inside the eye requires explicit knowledge of the complete Mueller matrix due to bidirectional attenuation at the corneal-air interface. A complete 4×4 Mueller matrix has three distinct eigenvalues, thus requiring three measurements. However, current PS-OCT systems are limited to using two polarization states as illumination light states. While such systems can provide a comparison of tissue polarization characteristics, they cannot measure the true three-dimensional structure of the tissue.

[0005] One application of PS-OCT is in imaging the sclera, the outermost layer of the eye. The sclera protects the internal eye structures and determines the final shape and size of the sclera. The sclera is primarily composed of collagen and fibroblasts that produce its extracellular matrix (ECM). During the development and progression of myopia, the sclera thins and weakens, which is associated with the reorganization of collagen fibers. Structural and biomechanical changes in the myopic sclera are well documented in the literature, including progressive thinning, a decrease in glucosamine and collagen content, and structural disorder of the fibrillary assembly. These structural changes are associated with alterations in the biomechanical properties of the sclera, such as creep rate, which represents the elongation of the sclera over time under constant or dynamic loads.

[0006] The sclera's endoscopic microscopy (ECM) structure dominates its biomechanical properties. Over the past few decades, ex vivo tools for examining the sclera have been developed, including wide-angle X-ray scattering, small-angle light scattering, multiphoton microscopy, polarized light microscopy, magnetic resonance imaging (MRI), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM). This has greatly increased our understanding of the fine structure of the ECM at multiple scales in relation to different stages of myopia progression. However, all of these tools require the removal of the eyeball, leading to potential distortions in tissue preparation. More importantly, while ex vivo studies have demonstrated changes in biomechanical properties during myopia progression, the lack of high-resolution 3D imaging tools has hindered the clinical assessment of scleral changes in patients.

[0007] Currently, there is a lack of imaging-based biomarkers for myopia progression. While children experiencing faster axial length growth have been shown to exhibit less choroidal thickening over time, this association is too weak to be considered a true biomarker. This relates to several issues in clinical decision-making. First, it is currently unknown which children who begin to develop myopia will eventually develop pathological myopia. This is particularly important when deciding to initiate atropine treatment or other interventions to slow the progression of axial length growth.

[0008] One or more of the above difficulties need to be resolved. Summary of the Invention

[0009] This disclosure relates to a system for polarization-sensitive optical coherence tomography (PS-OCT) of a sample, comprising:

[0010] An interferometric arrangement includes a reference arm and a sample arm, the sample arm being arranged to emit light radiation toward a sample;

[0011] A phase modulation system, which is arranged at the input of the sample arm; and

[0012] A detector, which is arranged to detect the signal generated by the interference between the reference beam from the reference arm and the sample beam from the sample arm;

[0013] The phase modulation system includes:

[0014] Electro-optic modulator;

[0015] A polarizer, arranged at a rotational angle relative to the fast axis of the electro-optic modulator; and

[0016] A signal generator, which is used to deliver a drive voltage to an electro-optic modulator;

[0017] The rotation angle and driving voltage are selected so that the phase modulation system generates three mutually orthogonal polarization states.

[0018] The rotation angle can be between approximately 17.6 degrees and approximately 38.1 degrees, and specifically, approximately 27.3678 degrees.

[0019] The driving voltage can have a sawtooth waveform, such as a 3-point step drive waveform, where the step corresponds to a modulation depth of -120 degrees, 0 degrees, and 120 degrees.

[0020] The system may include at least one processor configured to determine the Mueller matrix of a sample based on a signal detected by a detector. In one example, the at least one processor may be configured to determine the bidirectional attenuation component of the Mueller matrix via pole decomposition. In another example, the at least one processor is configured to determine the birefringence of the sample based on the Mueller matrix. The at least one processor may be configured to impose constraints on the determination of the birefringence of the sample based on prior knowledge of one or more structural parameters of the sample.

[0021] This disclosure also relates to a phase modulation system for polarization-sensitive optical coherence tomography (PS-OCT) of a sample, the phase modulation system being positionable at the input of a sample arm arranged to emit light radiation toward the sample, the phase modulation system comprising:

[0022] Electro-optic modulator;

[0023] A polarizer, arranged at a non-zero rotation angle relative to the fast axis of the electro-optic modulator; and

[0024] A signal generator, which is used to deliver a drive voltage to an electro-optic modulator;

[0025] The rotation angle and driving voltage are selected so that the phase modulation system generates three mutually orthogonal polarization states.

[0026] This disclosure further relates to a method for polarization-sensitive optical coherence tomography (PS-OCT) of a sample, comprising:

[0027] A sample beam is generated to illuminate the sample using the sample arm optics; and

[0028] Detect the interference signal generated by the interference between the sample beam and the reference beam;

[0029] The sample arm optics have a phase modulation system disposed at its input, the phase modulation system being configured such that:

[0030] The input beam is transmitted through a polarizer arranged at a rotational angle relative to the fast axis of the electro-optic modulator; and

[0031] The driving voltage is transmitted to the electro-optic modulator;

[0032] The rotation angle and driving voltage are selected so that the phase modulation system generates three mutually orthogonal polarization states.

[0033] The rotation angle can be between approximately 17.6 degrees and approximately 38.1 degrees, and specifically, approximately 27.3678 degrees.

[0034] For the above system, the driving voltage may have a sawtooth waveform, such as the 3-point step driving waveform disclosed above.

[0035] Methods may include determining the Mueller matrix of a sample based on the interference signal.

[0036] In some embodiments, the method may include determining the bidirectional decay share of the Mueller matrix through polar decomposition.

[0037] Methods may include determining the birefringence of a sample based on the Mueller matrix. Constraints may be imposed on determining the birefringence of the sample based on prior knowledge of one or more structural parameters of the sample.

[0038] In some embodiments, the sample is an eye; and the method may further include generating a fiber anisotropy image and / or fiber orientation image of the sclera of the eye. In this case, when determining the birefringence of the sample, a constraint condition of circumferential confinement of the fibrous collagen surrounding the optic nerve head on the sclera may be applied.

[0039] This disclosure further relates to a method for modulating a sample beam for polarization-sensitive optical coherence tomography (PS-OCT) of a sample, comprising:

[0040] A phase modulation system is arranged at the input of the sample arm optics of the PS-OCT system, the phase modulation system being configured as follows:

[0041] The input beam is transmitted through a polarizer arranged at a rotational angle relative to the fast axis of the electro-optic modulator; and

[0042] The driving voltage is transmitted to the electro-optic modulator;

[0043] The rotation angle and driving voltage are selected so that the phase modulation system generates three mutually orthogonal polarization states. Attached Figure Description

[0044] Some embodiments of the PS-OCT system and method taught according to the present invention will now be described with reference to the accompanying drawings and by means of only non-limiting examples, wherein:

[0045] Figure 1 (a) A block diagram of a PS-OCT system conforming to an embodiment of the present disclosure;

[0046] Figure 1 (b) is Figure 1(a) Block diagram of the modulation unit of the system;

[0047] Figure 1 (c) Demonstration of the use of Figure 1 (b) The Bonga ball of the modulation state evolution of the ramp voltage of the modulation unit;

[0048] Figure 1 (d) Display Figure 1 (b) The relationship between the driving voltage of the modulation unit and the modulation depth;

[0049] Figure 1 (e) A Poincaré sphere displaying the output state of the modulation unit;

[0050] Figure 2 This demonstrates the dependence of measurement error on the polarizer axis angle;

[0051] Figure 3 exhibit Figure 1 (a) A possible implementation of the components of the PS-OCT system;

[0052] Figure 4 Show representative cross-sectional images of models a) chicken and b) guinea pig;

[0053] Figure 5 (a) Displaying OCT images from volumetric scan slices;

[0054] Figure 5 (b) Display Figure 5 (a) Reconstructed scleral anisotropy map of the image;

[0055] Figure 5 (c) Presenting results obtained from existing ex vivo imaging techniques;

[0056] Figure 5 (d) A collagen anisotropy diagram derived using embodiments of the present disclosure is shown;

[0057] Figure 6 A representative frontal image of the living sclera structure on a de-exposed chicken model;

[0058] Figure 7 The OCT cross-sections of different stages of myopia in a myopic guinea pig model are displayed, along with 3D reconstructions with eye shape sketches inserted, frontal intensity, fiber orientation, and optical anisotropy images.

[0059] Figure 8 Comparison of images showing the retina of a live monkey: (a) an image generated by embodiments of the present disclosure; (b) an image generated by a polarization depth coding system according to the prior art; and

[0060] Figure 9Comparison of images showing the retina of a live monkey: (a) an image produced using embodiments of the present disclosure; (b) an image produced using a 2-point modulation system according to a prior art system. Detailed Implementation

[0061] Embodiments of this disclosure provide a system and method for high-resolution imaging of the 3D scleral ECM collagen structure in vivo. The embodiments utilize novel modulation devices that can be added to existing PS-OCT technology. Although the embodiments are described with reference to their use in fundus imaging, it should be understood that the techniques of this disclosure are applicable to other situations, including non-ophthalmic medical imaging and even non-medical imaging.

[0062] For example, by applying modulation equipment to ophthalmic PS-OCT, the complete Mueller properties of the sclera can be measured. Using the complete Mueller matrix, polarization modifications at the air-corneal interface can be compensated for, and depolarization, bidirectional attenuation, and retardation can be extracted as additional contrasts, allowing for the reconstruction of the sclera's three-dimensional structure at micrometer-level resolution. Metrics derived from scleral volume measurements (including collagen anisotropy at the posterior pole) can serve as novel biomarkers for myopia screening and diagnosis, as well as for other scleral diseases such as glaucoma or posterior scleritis.

[0063] In this embodiment, a modulation device is used at the optical input port of the PS-OCT. The modulation device can generate three intrinsic polarization states, enabling the PS-OCT to perform time-multiplexed measurements of the complete Mueller matrix of the sample under examination at high speed (faster than 200 kHz), thereby extracting birefringence and structural information based on computational reconstruction.

[0064] Figure 1 (a) A schematic diagram of an example PS-OCT system 100 conforming to an embodiment of the present disclosure. The PS-OCT system 100 includes a swept-frequency source laser 102, which is split by a beam-splitting optics 104 to feed a reference arm optics 110 and a sample arm optics 112. In contrast to conventional PS-OCT systems, system 100 includes a modulation unit 120 positioned to receive an input optical signal from the beam-splitting optics 104, modulate the input signal to generate an output signal comprising three orthogonal eigenstates, and output the output signal to the sample arm optics 112. Light from the sample arm 112 and the reference arm 110 is then combined and detected by an interferometry and detection unit 114, and digitized and analyzed by a digitization and post-processing unit 116. The digitization and post-processing unit may include one or more processors configured to perform various post-processing and image reconstruction operations, including determining the complete Mueller matrix of the sample, as will be described in further detail below.

[0065] like Figure 1As shown in (b), the modulation unit includes a polarizer 130 positioned in front of an electro-optic modulator (EOM) 140 driven by a driver module 142. The polarizer 130 is optimally positioned at 17.6322°, or positioned at an angle of 27.3678° relative to the fast axis of the EOM 140. At this angle, the EOM 140 generates three eigenstates representing three vectors that are mutually perpendicular or orthogonal in Bonga space on a Poincaré sphere. In the Bonga polarization representation, the EOM 140 transforms the optical state into a circle on the Bonga sphere, as... Figure 1 As shown in (c), with polarizer 130 positioned at 17.6322°, the radius of the circle is determined to be the square root of (2 / 3), which means that the three equidistant points of this particular circle primarily represent the three eigenstates.

[0066] Figure 1 (d) This illustrates the relationship between modulation depth and drive voltage. Light polarized along the fast axis has a lower refractive index compared to light polarized along the other slow axis. Therefore, light polarized along the fast axis passes through the EOM faster than light polarized along the slow axis. The phase shift between the fast and slow axes is the modulation depth. Three points corresponding to modulation depths of 120°, 0°, and -120° are used to form a three-point step drive waveform. These correspond to mutually perpendicular eigenstates. Figure 1 (e) Displaying the Poincargo representation of the modulation output from modulation unit 120.

[0067] Polarizer 130 can potentially be oriented at angles other than the optimal angle of 17.6322°. This is in Figure 2 The diagram illustrates the measurement error at angles different from this figure. Experiments were conducted using a phantom with known birefringence as a sample at different orientation angles. The measurement difference increases accordingly with increasing offset from the optimal angle. To maintain meaningful measurements in the case of scleral measurements, an offset within + / - 9.7 degrees is acceptable because the measurement difference is less than the common birefringence of the human sclera (1 degree / micrometer). Therefore, a specific angular description can be employed to encompass functionally equivalent angles within acceptable offsets. Thus, in the embodiment, the polarizer is optimally positioned at 17.6322° and can have rotation angles ranging from 7.9322° to 27.3322°, thereby producing a larger penetration depth with a longer wavelength. In some embodiments, the angle may be in the range of about 16.6 to 18.6 degrees; or about 15.6 to 19.6 degrees; or about 14.6 to 20.6 degrees; or about 13.6 to 21.6 degrees; or about 12.6 to 22.6 degrees; or about 11.6 to 23.6 degrees; or about 10.6 to 24.6 degrees; or about 9.6 to 25.6 degrees; or about 8.6 to 26.6 degrees.

[0068] Now refer to Figure 3 Display conforms Figure 1 This is a representative but non-limiting example of the PS-OCT system 100. In system 100, light from a swept-frequency laser source 102 is split at an fiber coupler (FC) and guided to a reference arm 110, then guided via a modulation unit 120 to a sample arm 112, and detected and digitized at a polarization diversity detection unit (PDDU) 114. The light is received at a reference arm optical circulator C1 in the reference arm 110, and transmitted from the reference arm optical circulator to a collimating lens L3 and a focusing lens L4, and focused onto a mirror mounted on a translation stage. The light reflected from the mirror then passes through lenses L4 and L3 back to the circulator C1, whereby it is transmitted to a polarization controller PC and then to a collimating lens L5, and through a linear polarizer P to the PDDU 114.

[0069] Light reaches modulation unit 120 via polarization controller (PC) and collimating lens L1, and after modulation and emission as described above, is transmitted to sample arm 112 via focusing lens L2. At sample arm 112, the modulated output light is received at sample arm optical circulator C2, thereby transmitting the modulated output light to collimating lens L7, and then to scanning galvanometer SG, which performs an xy scan of the sample (in this example, an eye). Figure 3 In this context, DM refers to a dichroic mirror, and AC refers to the camera. The light backscattered from the sample then propagates back to the circulator C2, whereby it exits the sample arm 112 via the collimating lens L6 and reaches the PDDU 114.

[0070] Determine the complete Mueller matrix

[0071] Once the polarization state of the light from the sample is detected by the PDDU 114, the light can be analyzed to determine the complete Mueller matrix, as will now be described in detail.

[0072] Without loss of generality, the input probe beams with three orthogonal inputs can be converged into a probe matrix M before passing through the system and sample optics (i.e., after leaving the modulation unit 120 and before entering the sample arm 112). 探测 :

[0073]

[0074] After passing through the system and sample represented by the Mueller matrix M, the probe light is detected by PDD unit 114, which detects the polarization state of the received light in Stokes space as [s0 s1 s2 s3]. T The raw data received by the detector can be aggregated into a detection matrix M. 检测 :

[0075] M 检测 =M·M 探测 ,

[0076] Where M is the 4×4 pure Mueller (Jones-Mueller) matrix of the all-optical loop:

[0077]

[0078] Therefore, the detection matrix can be obtained:

[0079]

[0080] Regarding D and m R As far as M is concerned, 检测 It can be expressed as

[0081]

[0082] Where D = [d1 d2 d3] T =[m 01 / m 00 m 02 / m 00 m 03 / m 00 ] T D M Defined as The superscript T indicates matrix transpose.

[0083] To solve for m 00 Construct an auxiliary matrix to remove the delay factor in the measurement:

[0084]

[0085] The detection matrix can be expressed as:

[0086]

[0087] Where a = m 00 (d1+1), b=m 00 (d2+1), c=m 00 (d3+1), a, b, c > 0.

[0088] Further simplify M aux :

[0089]

[0090] Note cos 2 κ=|D| 2 D = [(a-1) / m 00 (b-1) / m 00 (c-1) / m00 ] T And therefore, it can be seen from M aux The entries in D are used to obtain an equation, for example:

[0091]

[0092] Although more than one equation can be obtained, they are redundant with each other. 00 The solution is as follows:

[0093]

[0094] Where ε=(ab+bc+ac-M) aux (1,2)-M aux (1,3)-M aux (2, 3)) / 3.

[0095] It should be noted that m 00 Solve from a second-order polynomial equation with two roots. Only one of the above-listed solutions is valid.

[0096] Once m is solved 00 D and m can then be reconstructed sequentially. D m R Furthermore, the organization's 4×4 Mueller matrix M can be subsequently reconstructed, as shown below.

[0097]

[0098]

[0099]

[0100]

[0101] The original fringe data is recorded using the described system. Dispersion calibration is applied by optimizing a third-order polynomial phase correction term that maximizes the contrast of the magnitudes of the Fourier transform of the original data. The phase change from the laser is extracted from the calibration signal and compensated for in the fringes. The complete Mueller matrix of the sample is obtained from the sequentially measured Stokes vectors.

[0102] In ophthalmic PS-OCT, the bidirectional attenuation term primarily induced by the cornea can be obtained through polar decomposition and removed from the sample Mueller matrix. Depth-resolved birefringence can be analyzed by solving the differential equation of the cumulative Mueller matrix M:

[0103]

[0104]

[0105] Where LB represents linear birefringence, LD represents linear bidirectional attenuation, CB represents circular birefringence, and CD represents circular bidirectional attenuation.

[0106] The solution is expressed as a matrix exponent exp(βx). The 3D vector β describes the fiber structure of the underlying sample. Specifically, the Euclidean length of β represents the fiber anisotropy, and the direction of β represents the fiber orientation. However, β may not be solvable unless another constraint is added based on prior knowledge of the sample. Therefore, to recover the absolute fiber orientation, β can be rotated by a factor. This is based on the prior condition that the fibrous collagen surrounds the optic nerve head on the sclera in a circular pattern. In some embodiments, it should be understood that the absolute orientation may be unimportant, making it unnecessary to impose constraints based on prior knowledge. In this case, the overall measurement will be randomly offset by the phase factor. However, it can still produce a graph that shows information indicating the relative orientation of objects within the image.

[0107] Experimental results

[0108] An example system was constructed according to the present invention. Chicken and guinea pig models were studied. A group of 10 chickens and 4 guinea pigs was studied. Myopia was induced by covering the experimental eye with an astigmatic lens, while the other eye was left open for control. On the day of imaging (day 14 for chickens and day 80 for guinea pigs), in vivo imaging of the eyes was performed and subsequently collected for axial length measurement and histological verification. Preliminary results confirmed that potential biomarkers could be extracted from the measured scleral fibrous structure information.

[0109] Figure 4 Representative cross-sectional images from a) chickens and b) guinea pigs are presented. Histological verification was performed to validate the scleral layer of interest. In the chicken model, the sclera has two layers: a cartilage layer and a collagen fiber layer. These two layers are identifiable from OCT images and exhibit unique characteristics of high anisotropy and high tissue orientation. In the guinea pig model, the scleral layer is clearly visible beneath the choroid and passes histological examination. Fiber anisotropy and orientation further confirm the collagen-rich scleral structure. The cross-sectional images can be stacked to reconstruct a 3D image of the scleral fibrous structure.

[0110] Figure 5 The results are shown from live monkeys. Figure 5 (a) Intensity imaging showing the central fossa. Figure 5 (b) Demonstration of the anisotropy of reconstructed scleral fibers. The scleral fiber architecture can be reconstructed through volumetric scanning. Circumferential, radial, and tangential fiber structures are visible in the images. The observations are consistent with previous reports based on ex vivo imaging techniques. Figure 5 (c) Measured values ​​can be derived from the results of this 3D measurement, including but not limited to collagen geometry and high-resolution anisotropy maps. Figure 5 (d)).

[0111] Figure 6 Representative frontal images of the scleral structure in a living chicken model are shown. In the refractive eye, the sclera (left image) shows remodeling, and the fibrous structure is deorganized compared to the control image (right image). The deorganization of collagen structure can be seen from the fiber anisotropy map, evidenced by the non-uniformly distributed anisotropy values. The deorganization is more evident in the fiber orientation image, where the star-shaped orientation pattern not seen in the refractive eye is not present in the control eye.

[0112] Figure 7 Imaging results from guinea pigs are presented. A group of guinea pigs (suffering from Dunkin' Hadley albino and Elm Hill coloration) were housed in the field. Refractive development of each animal was measured weekly using retinoscopy. At 70 days of rearing, four guinea pigs representing different stages of myopia (corresponding to...) were selected. Figure 7 (Four columns in the image). Animals were anesthetized by intramuscular injection of a mixture of ketamine hydrochloride and imaged using a PS-OCT system 100. The sclera was manually segmented and frontal images were generated by calculating the average value of the scleral tissue along the depth. Figure 7 This study presents OCT cross-sections of different stages of myopia, 3D reconstructions with inserted eye shape sketches, frontal intensity, fiber orientation, and optical anisotropy images. Structural changes were observed, including thinning and increased curvature of the posterior sclera. It was also observed that changes in scleral collagen anisotropy patterns could be used to screen for myopia progression. Increased scleral fiber anisotropy was found during myopia progression, likely due to stretching of the posterior sclera during the elongation phase of the eyeball. Of particular interest is the reduction in scleral fiber anisotropy to lower values ​​in staphyloma cases, thus differentiating pathological scleral myopia from non-pathological myopia.

[0113] Figure 8 (a) A comparison between PS-OCT systems demonstrating embodiments of this disclosure, and Figure 8 (b) Demonstrates a prior art system for polarization depth encoding as described in PCT Publication WO2010 / 054097. Compared to this prior art system, the present invention offers advantages in imaging depth, sensitivity, and penetration. Using the same system parameters, the imaging depth of the present invention is doubled and the sensitivity is improved by 2-5 dB (penetration is improved by 200-500 micrometers). Mechanically, the present invention is also more compact and robust.

[0114] In contrast to the three-step modulation of this disclosure, other prior art systems use two-step modulation. Due to complete corneal compensation, the technique disclosed in this invention is superior to such prior art systems in terms of reliable measurement. In the case of two-step modulation, interference from the cornea cannot be compensated, resulting in biased or even misleading structural results. Figure 9 An example is shown. It can be seen that the PS-OCT system 100 accurately reconstructs the 3D structure of the eye, such as... Figure 9 As shown in (a), the deviation from the actual structure can be seen in Figure 9 (b) in.

[0115] The embodiments may have one or more of the following features and / or advantages:

[0116] - A modulation device capable of generating three intrinsic polarization states at high speeds. This device uses an electro-optic modulator positioned at an angle of 27.3678° relative to the fast axis of the modulator. This specific rotation angle of the polarizer enables the generation of all three intrinsic polarization states. A three-point step drive waveform is applied to the electro-optic modulator to generate the three intrinsic polarization states.

[0117] - A polarization-sensitive optical coherence tomography system based on a swept-frequency light source with enhanced ranging depth and sensitivity, capable of imaging deep retinal sclera.

[0118] - A method for computationally reconstructing a complete Mueller matrix of scleral collagen structure information using measured data and prior knowledge of scleral architecture.

[0119] - A method of segmenting the sclera based on the depolarization properties of the choroid and noise signals generated by deep orbital structures.

[0120] - A method for quantifying the measured data and deriving a measure indicating the underlying physiological state of the sclera of the subject (i.e., collagen anisotropy) through white matter beam imaging processing.

[0121] Measurements derived from scleral volume measurements (including collagen anisotropy in the posterior pole) can serve as novel biomarkers for myopia screening, diagnosis, risk stratification, and treatment monitoring, and as surrogate results for clinical trials and other diseases involving the sclera, such as glaucoma or posterior scleritis.

[0122] Many modifications will be apparent to those skilled in the art without departing from the scope of the invention.

[0123] Throughout this specification, unless the context otherwise requires, the word “comprise” and its variations (such as “comprises” or “comprising”) shall be construed as implying inclusion of the stated integer or step or group of integers or steps, but not excluding any other integer or step or group of integers or steps.

[0124] Any prior publications (or information derived therefrom) or any known matters referenced in this specification are not, and should not be construed as, an endorsement or acknowledgment or any implication that prior publications (or information derived therefrom) or known matters constitute part of general common knowledge in the field of work to which this specification pertains. One or more embodiments of the invention are disclosed in the following numbered statements.

[0125] 1. A system for polarization-sensitive optical coherence tomography (PS-OCT) of a sample, comprising:

[0126] An interferometric arrangement includes a reference arm and a sample arm, the sample arm being arranged to emit light radiation toward the sample;

[0127] A phase modulation system, which is arranged at the input of the sample arm; and

[0128] A detector arranged to detect the signal generated by the interference between a reference beam from the reference arm and a sample beam from the sample arm;

[0129] The phase modulation system includes:

[0130] Electro-optic modulator;

[0131] A polarizer, arranged at a rotational angle relative to the fast axis of the electro-optic modulator; and

[0132] A signal generator for transmitting a drive voltage to the electro-optic modulator;

[0133] The rotation angle and the driving voltage are selected such that the phase modulation system generates three mutually orthogonal polarization states.

[0134] 2. The system according to claim 1, wherein the rotation angle is between about 17.6 degrees and about 38.1 degrees.

[0135] 3. The system according to claim 2, wherein the rotation angle is 27.3678 degrees.

[0136] 4. The system according to any one of 1 to 3, wherein the driving voltage has a sawtooth waveform.

[0137] 5. The system according to 4, wherein the sawtooth waveform is a 3-point step drive waveform, the steps corresponding to modulation depths of -120 degrees, 0 degrees and 120 degrees.

[0138] 6. The system according to any one of 1 to 5, wherein the detector includes a polarization diversity detection unit (PDDU).

[0139] 7. The system according to any one of 1 to 6, comprising at least one processor configured to determine the Mueller matrix of the sample based on the signal detected by the detector.

[0140] 8. The system according to claim 7, wherein the at least one processor is configured to determine the bidirectional decay fraction of the Mueller matrix by polar decomposition.

[0141] 9. The system according to 7 or 8, wherein the at least one processor is configured to determine the birefringence of the sample based on the Mueller matrix.

[0142] 10. The system according to claim 9, wherein the at least one processor is configured to impose constraints on the determination of the birefringence of the sample based on prior knowledge of one or more structural parameters of the sample.

[0143] 11. A phase modulation system for polarization-sensitive optical coherence tomography (PS-OCT) of a sample, the phase modulation system being positionable at an input of a sample arm arranged to emit light radiation toward the sample, the phase modulation system comprising:

[0144] Electro-optic modulator;

[0145] A polarizer, arranged at a non-zero rotation angle relative to the fast axis of the electro-optic modulator; and

[0146] A signal generator for transmitting a drive voltage to the electro-optic modulator;

[0147] The rotation angle and the driving voltage are selected such that the phase modulation system generates three mutually orthogonal polarization states.

[0148] 12. The phase modulation system according to 11, wherein the rotation angle is between about 17.6 degrees and about 38.1 degrees.

[0149] 13. The phase modulation system according to 12, wherein the rotation angle is 27.3678 degrees.

[0150] 14. The phase modulation system according to any one of 11 to 13, wherein the driving voltage has a sawtooth waveform.

[0151] 15. The phase modulation system according to 14, wherein the sawtooth waveform is a 3-point step drive waveform, the steps corresponding to modulation depths of -120 degrees, 0 degrees and 120 degrees.

[0152] 16. A method for polarization-sensitive optical coherence tomography (PS-OCT) of a sample, comprising:

[0153] A sample beam is generated by the sample arm optics to illuminate the sample; and

[0154] Detect the interference signal generated by the interference between the sample beam and the reference beam;

[0155] The sample arm optics have a phase modulation system disposed at its input, the phase modulation system being configured to:

[0156] The input beam is transmitted through a polarizer arranged at a rotational angle relative to the fast axis of the electro-optic modulator.

[0157] Instruments; and

[0158] The driving voltage is transmitted to the electro-optic modulator;

[0159] The rotation angle and the driving voltage are selected such that the phase modulation system generates three mutually orthogonal polarization states.

[0160] 17. The method according to 16, wherein the rotation angle is between about 17.6 degrees and about 38.1 degrees.

[0161] 18. The method according to 17, wherein the rotation angle is 27.3678 degrees.

[0162] 19. The method according to any one of 16 to 18, wherein the driving voltage has a sawtooth waveform.

[0163] 20. The method according to 19, wherein the sawtooth waveform is a 3-point step drive waveform, the steps corresponding to modulation depths of -120 degrees, 0 degrees and 120 degrees.

[0164] 21. The method according to any one of 16 to 20, wherein the interference signal is detected by a polarization diversity detection unit (PDDU).

[0165] 22. The method according to any one of 16 to 21, comprising determining the Mueller matrix of the sample from the interference signal.

[0166] 23. The method according to 22, comprising determining the bidirectional decay fraction of the Mueller matrix by polar decomposition.

[0167] 24. The method according to 22 or 23, comprising determining the birefringence of the sample based on the Mueller matrix.

[0168] 25. The method of 24, comprising imposing constraints on the determination of the birefringence of the sample based on prior knowledge of one or more structural parameters of the sample.

[0169] 26. The method according to any one of 16 to 25, wherein the sample is an eye.

[0170] 27. The method of 26, further comprising generating a fiber anisotropy image and / or fiber orientation image of the sclera of the eye.

[0171] 28. According to the method of 27, when attached to 25, the constraint condition is that the fibrous collagen surrounds the optic nerve head on the sclera in a circular shape.

[0172] 29. A method for modulating a sample beam for polarization-sensitive optical coherence tomography (PS-OCT), comprising:

[0173] A phase modulation system is arranged at the input of the sample arm optics of the PS-OCT system, the phase modulation system being configured as follows:

[0174] The input beam is transmitted through a polarizer arranged at a rotational angle relative to the fast axis of the electro-optic modulator; and

[0175] The driving voltage is transmitted to the electro-optic modulator;

[0176] The rotation angle and the driving voltage are selected such that the phase modulation system generates three mutually orthogonal polarization states.

[0177] 30. The method according to 29, wherein the rotation angle is between about 17.6 degrees and about 38.1 degrees.

[0178] 31. The method according to 30, wherein the rotation angle is 27.3678 degrees.

[0179] 32. The method according to any one of 29 to 31, wherein the driving voltage has a sawtooth waveform.

[0180] 33. According to the method of 32, the sawtooth waveform is a 3-point step drive waveform, and the step corresponds to a modulation depth of -120 degrees, 0 degrees and 120 degrees.

Claims

1. A system for polarization-sensitive optical coherence tomography (PS-OCT) of a sample, comprising: An interferometric arrangement includes a reference arm and a sample arm, the sample arm being arranged to emit light radiation toward a sample; A phase modulation system is arranged at the input of the sample arm; as well as A detector arranged to detect the signal generated by the interference between a reference beam from the reference arm and a sample beam from the sample arm; The phase modulation system includes: Electro-optic modulator; A polarizer, arranged at a rotational angle relative to the fast axis of the electro-optic modulator; and A signal generator for transmitting a drive voltage to the electro-optic modulator; The rotation angle is 27.3678 degrees, and the driving voltage is a 3-point step driving waveform. The steps correspond to modulation depths of -120 degrees, 0 degrees, and 120 degrees, so that the phase modulation system generates three mutually orthogonal polarization states in the bond space.

2. The system according to claim 1, wherein the driving voltage has a sawtooth waveform.

3. The system of claim 1, further comprising at least one processor configured to determine the Mueller matrix of the sample based on the signal detected by the detector.

4. The system of claim 3, wherein the at least one processor is configured to determine the birefringence of the sample based on the Mueller matrix.

5. The system of claim 4, wherein the at least one processor is configured to impose constraints on the determination of the birefringence of the sample based on prior knowledge of one or more structural parameters of the sample.

6. A phase modulation system for polarization-sensitive optical coherence tomography (PS-OCT) of a sample, the phase modulation system being positionable at an input of a sample arm arranged to emit light radiation toward the sample, the phase modulation system comprising: Electro-optic modulator; A polarizer arranged at a non-zero rotation angle relative to the fast axis of the electro-optic modulator; as well as A signal generator for transmitting a drive voltage to the electro-optic modulator; The rotation angle is 27.3678 degrees, and the driving voltage is a 3-point step driving waveform. The steps correspond to modulation depths of -120 degrees, 0 degrees, and 120 degrees, so that the phase modulation system generates three mutually orthogonal polarization states in the bond space.

7. A method for polarization-sensitive optical coherence tomography (PS-OCT) of a sample, comprising: A sample beam is generated by the sample arm optics to illuminate the sample; as well as Detect the interference signal generated by the interference between the sample beam and the reference beam; The sample arm optics have a phase modulation system disposed at its input, the phase modulation system being configured to: The input beam is transmitted through a polarizer arranged at a rotational angle relative to the fast axis of the electro-optic modulator; as well as The driving voltage is transmitted to the electro-optic modulator; The rotation angle is 27.3678 degrees, and the driving voltage is a 3-point step driving waveform. The steps correspond to modulation depths of -120 degrees, 0 degrees, and 120 degrees, so that the phase modulation system generates three mutually orthogonal polarization states in the bond space.

8. The method of claim 7, wherein the driving voltage has a sawtooth waveform.

9. The method of claim 7, further comprising determining the Mueller matrix of the sample based on the interference signal.

10. The method of claim 9, further comprising determining the birefringence of the sample based on the Mueller matrix.

11. The method of claim 10, further comprising imposing constraints on the determination of the birefringence of the sample based on prior knowledge of one or more structural parameters of the sample.

12. The method of claim 11, wherein the sample is an eye, and wherein the method further comprises generating a fiber anisotropy image and / or fiber orientation image of the sclera of the eye.

13. The method of claim 12, wherein the constraint condition is that the fibrous collagen surrounds the optic nerve head on the sclera in a circular shape.

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