Apparatus and method for polarization-sensitive optical coherence tomography

Abstract

Apparatus and method are presented for performing polarization-sensitive optical coherence tomography (OCT) measurements of a sample using polarization-diversity illumination. A set of one or more measurements of the volume of a sample, such as the anterior segment or retina of a human eye, is generated by illuminating the sample volume with multi-wavelength light in different polarization states. The set of one or more measurements is processed to generate multiple tomographic volumetric images of the sample, each image being of the sample illuminated with light in a different polarization state. The multiple tomographic volumetric images may be processed, for example, to generate a three-dimensional representation of the polarization characteristics of the sample or a polarization-independent image of the sample. In certain embodiments, the polarization of the illumination is controlled using one or more rotatable waveplates, such as rotatable quarter-waveplates.

Description

[Technical Field]

[0001] The present invention relates in particular to an apparatus and method for polarization-sensitive optical coherence tomography for 3D imaging of the anterior segment or retina of the human eye. However, it should be understood that the present invention is not limited to this particular field of application.

[0002] Related applications This application claims priority from Australian Provisional Patent Application No. 2023901193, filed on 21 April 2023, the contents of which are incorporated herein by reference. [Background technology]

[0003] Nothing discussed in this specification regarding prior art should be considered in any way as an endorsement that such prior art is widely known or forms part of the common general knowledge in the art.

[0004] Optical coherence tomography (OCT) is a widely used interferometric technique to examine biological samples, including in vivo tissues such as the human eye, with lateral and depth resolution by using information contained in the amplitude and phase of light reflected or scattered by the sample. Most current OCT systems utilize the spectral domain method, in which depth information is encoded in the spectral response of the interferometric signal, which can be recorded as a time-varying function of wavelength (swept light source OCT) or by dispersing the interferometric signal and simultaneously detecting different wavelengths along the detector array (spectrometer-based OCT).

[0005] Polarization-sensitive optical coherence tomography (PS-OCT) is an extension of conventional OCT, which measures the polarization state of light interacting with a sample. Compared to conventional OCT, i.e., intensity-based OCT, it provides additional contrast channels, such as phase delay caused by birefringence in the sample. PS-OCT has been found to be valuable in several biological applications, because certain tissues, such as collagen, exhibit some degree of birefringence. Several studies of PS-OCT applications in in vivo imaging of the anterior or posterior segment of the human eye, dermatology, or tumor detection are described in De Boer et al 'Polarization sensitive optical coherence tomography—a review', Biomedical Optics Express 8(3), 1838-1873 (2017).

[0006] Furthermore, as reported, for example, by Yasuno et al. 'Visibility of trabecular meshwork by standard and polarization-sensitive optical coherence tomography', Journal of Biomedical Optics 15(6), 061705 (2010), it is known that in conventional OCT, birefringence of certain tissues can cause artifacts. This is because the OCT signal intensity can be affected by the relative difference between the polarization states of the sample beam and the reference beam.

[0007] Many reported PS-OCT devices employ a polarization diversity detection method, in which the interference signal is split into orthogonal polarization states by a polarization beam splitter, and these are detected in parallel. In some systems, the orthogonal polarization states are detected by separate detectors, as disclosed, for example, in Goetzinger et al 'High spectral domain polarization sensitive optical coherence tomography of the human retina', Optics Express 13(25), 10217-10229 (2005) and Bonesi et al 'High-speed polarization sensitive optical coherence tomography scan engine based on Fourier domain mode locked laser', Biomedical Optics Express 3(11), 2987-3000 (2012). In other systems, the orthogonal polarization states are detected by different parts of a single detector. For example, in the scanning beam apparatus disclosed in Baumann et al 'Single camera based spectral domain polarization sensitive optical coherence tomography', Optics Express 15(3), 1054-1063 (2007), spectra from orthogonal polarization channels are imaged onto adjacent portions of a line camera, and the OCT apparatus disclosed in U.S. Patent Application Publication No. 2016 / 0345820 A1, titled 'High resolution 3-D spectral domain optical imaging apparatus and method', has a multibeam spectrometer equipped with polarization walk-off elements for projecting pairs of wavelength-dispersive lines onto separate groups of pixels in a 2D detector array.

[0008] In other PS-OCT methods, orthogonal polarization channels are detected sequentially by a single detector. For example, Park et al. 'Single-camera polarization-sensitive full-field optical coherence tomography with polarization switch', Journal of Biomedical Optics 18(10), 100504 (2013) disclose a PS-OCT system equipped with a bistable polarization switching device on the detector arm.

[0009] Generally, existing PS-OCT devices are more costly and complex than conventional intensity-based OCT devices because they require additional optical components. It would be desirable to be able to add polarization-sensitive capabilities to intensity-based OCT devices without including additional optical components.

[0010] Unless the context clearly necessitates a different interpretation, words such as "comprising" and "composed" throughout this specification and the claims should be interpreted in a comprehensive sense, not in an exclusive or exhaustive sense. That is, they should be interpreted as "including, but not limited to." Similarly, unless the context clearly necessitates a different interpretation, the word "or" should be interpreted in a comprehensive sense, not in an exhaustive sense. That is, the expression "A or B" should be interpreted as "A or B or both A and B." [Overview of the Initiative] [Problems that the invention aims to solve]

[0011] An object of the present invention is to overcome or improve upon at least one limitation of the prior art, or to provide a useful alternative. In a preferred embodiment, an object of the present invention is to provide an OCT device that can be made polarization sensitive without including additional optical components. [Means for solving the problem]

[0012] According to a first aspect of the present invention, a polarization-sensitive optical coherence tomography apparatus, (i) An illumination system for illuminating the volume of a sample with light in a polarization state controllable by the adjustable polarization delay system, comprising a multi-wavelength light source and an adjustable polarization delay system, (ii) A polarizing beam splitter for splitting light from a light source into a sample beam and a reference beam, and for recombining the sample beam and the reference beam after the sample beam has interacted with the sample, (iii) A measurement system for creating a set of one or more simultaneous measurements over a wavelength range, wherein each set of one or more simultaneous measurements over a wavelength range is of a signal of light reflected or scattered by a sample illuminated with light of different polarization states, (iv) A computer for processing one or more sets of simultaneous measurements to generate multiple tomographic volume images of a sample, wherein each tomographic volume image is of a sample illuminated with light in different polarization states, A system including this is provided.

[0013] The illumination system is preferably configured to illuminate the volume of the sample with an array of beamlets, and the illumination system includes a scanning element for translating the array of beamlets across the sample between simultaneous measurements in a set of two or more simultaneous measurements in order to increase the density of the tomographic volumetric image.

[0014] In certain embodiments, the computer is configured to process multiple tomographic volumetric images to generate a three-dimensional representation of the polarization characteristics of the sample, or to generate a polarization-independent image of the sample.

[0015] In a preferred embodiment, the adjustable polarization delay system includes a rotatable quarter-wave plate. In certain embodiments, the adjustable polarization delay system includes two rotatable quarter-wave plates, or one rotatable quarter-wave plate and one rotatable half-wave plate.

[0016] The adjustable polarization delay system preferably includes one or more wave plates each composed of a birefringent material.

[0017] In certain embodiments, the adjustable polarization delay system includes a liquid crystal variable retarder.

[0018] Preferably, the apparatus is configured for in vivo polarization-sensitive optical coherence tomography of a sample including the anterior eye segment or retina of an eye.

[0019] According to a second aspect of the present invention, there is provided a method of performing measurements by polarization-sensitive optical coherence tomography of a sample, the method comprising: (a) illuminating a volume of the sample with multi-wavelength light of a polarization state controllable by an adjustable polarization delay system; (b) creating a plurality of sets of one or more simultaneous measurements over a wavelength range, wherein each set of one or more simultaneous measurements over a wavelength range is for light reflected or scattered from the sample illuminated with light of a different polarization state; (c) processing the plurality of sets of one or more simultaneous measurements to generate a plurality of tomographic volume images of the sample, wherein each of the tomographic volume images is of the sample illuminated with light of a different polarization state; and including.

[0020] The volume of the sample is preferably illuminated with an array of beamlets, and the array of beamlets is translated across the sample between simultaneous measurements in a set of two or more simultaneous measurements to increase the density of the tomographic volume image. Preferably, the number of simultaneous measurements in a set of two or more simultaneous measurements is sufficient to generate a high-density tomographic volume image.

[0021] In certain embodiments, multiple tomographic volumetric images are processed to generate a three-dimensional representation of the polarization characteristics of the sample, or to generate a polarization-independent image of the sample.

[0022] In a preferred embodiment, the adjustable polarization delay system includes a rotatable quarter-wave plate. In a particular embodiment, the adjustable polarization delay system includes two rotatable quarter-wave plates, or one rotatable quarter-wave plate and one rotatable half-wave plate.

[0023] The adjustable polarization delay system preferably includes one or more waveplates, each composed of a birefringent material.

[0024] In certain embodiments, the adjustable polarization delay system includes a liquid crystal variable retarder.

[0025] Preferably, this method is applied to a sample including the anterior segment of the eye or the retina.

[0026] A third aspect of the present invention provides a product comprising a non-temporary computer-usable medium having computer-readable program code configured to operate the apparatus according to the first aspect or to carry out the method according to the second aspect.

[0027] Here, preferred embodiments of the present invention will be described as examples only, with reference to the accompanying drawings shown below. [Brief explanation of the drawing]

[0028] [Figure 1] A schematic plan view shows an OCT device configured to take in vivo snapshots of the anterior segment of the human eye. [Figure 2A] A schematic plan view shows a polarization-sensitive OCT apparatus according to one embodiment of the present invention, which includes an adjustable polarization delay system within the sample arm. [Figure 2B-2E]A schematic plan view shows an adjustable polarization delay system according to various embodiments of the present invention. [Figure 3A-3B] Figure 2A shows en-face images and horizontal volumetric slices of the anterior segment of the sample eye, extracted from tomographic volumetric images acquired using a standard configuration of the apparatus. [Figure 3C-3G] The signal intensity on the posterior corneal surface of the sample eye is shown, extracted from tomographic volumetric images acquired using the apparatus in Figure 2A when the rotatable quarter-wave plates were at -22.5°, 22.5°, 45°, 67.5°, and 112.5°, respectively. [Figure 4A-4B] The polarization-independent signal from the posterior corneal surface of the sample eye and the polarization-independent volume slice of the anterior segment are shown, respectively. [Figure 5A-5B] Images of cumulative phase delay and birefringence axis variation across the posterior surface of the cornea of ​​the sample eye are shown, respectively. [Figure 5C] This shows volume slices of cumulative phase delay in the anterior segment of the sample eye. [Figure 6A-6B] Figures 3B and 4B show enlarged views of the anterior chamber angle region from volume slices, respectively. [Figures 7A-7B] The volume slices of a sample eye and the degree of polarization uniformity (DOPU) of a portion of the retina, obtained when the rotatable quarter-wave plate was at 45°, are shown, respectively. [Figure 8] A schematic plan view shows a polarization-sensitive OCT apparatus according to one embodiment of the present invention, which includes an adjustable polarization delay system within the sample arm. [Modes for carrying out the invention]

[0029] Figure 1 shows a schematic plan view of a spectral domain optical coherence tomography (OCT) apparatus 100, similar to the apparatus described in U.S. Patent Application Publication No. 2019 / 0365220A1, entitled 'Optical Coherence Metrology and Tomography with Improved registration', the contents of which are incorporated herein by reference. The apparatus 100 shown in Figure 1 is configured to take in vivo snapshots of the anterior segment 102 of a human eye 104 at multiple points, and the snapshot nature of the images mitigates the effects of patient movement. The anterior segment 102 is generally understood to include all anterior parts of the eye, including the cornea 108, iris 110, and lens 112, in the vitreous fluid 106. First, the operation of this OCT apparatus 100 will be described, and then how it can be improved in a surprisingly simple way to provide polarization-sensitive functionality.

[0030] Light 114 from a multi-wavelength light source 116, in the form of a broadband light source such as a superluminescent diode with a central wavelength of 840 nm and a bandwidth of 40 nm, is collimated by a collimating element 118 such as a lens or parabolic mirror, linearly polarized by a polarizer 120, and then split into a reference beam and sample beams 124, 126 by a polarizing beam splitter (PBS) 122. If the light source 116 emits appropriately polarized light, the polarizer 120 may be omitted. The reference arm 128 includes a mirror 130 and a quarter-wave plate 132 for polarization conversion of the reference beam 124, thereby the light reflected by the reference mirror 130 is incident on the detection arm 134 through the PBS 122. The reference arm 128 may also include relay elements and dispersion matching components to compensate for dispersion in the optical system of the sample arm 136 or of the sample 104. The mirror 130 can be moved axially to adjust the path length of the reference arm 128 relative to the sample arm 136, for example, to match different eye positions or to acquire information from structures at different depths within the eye 104, such as the retina 138. Alternatively or additionally, the entire apparatus 100 can be moved axially relative to the eye 104 to adjust the distance between the eye and the apparatus, and therefore the path length of the sample arm 136. In other embodiments described in U.S. Patent Application Publication No. 2019 / 0365220A1, the reference mirror 130 is replaced or interchangeable with a composite reflector having two axially separated reflective surfaces. This modification extends the imaging depth range of the apparatus 100, facilitating simultaneous depth-resolved imaging of, for example, the anterior segment 102 and the retina 138.

[0031] The sample arm 136 includes a quarter-wave plate 140 and a spatial sampling element 144 in the form of a two-dimensional (2D) lenslet array, which generates a 2D array of sample beamlets 146 from the sample beam 126, which is relayed to the anterior eye portion 102 via a 4F lens system 148, thereby illuminating the volume of the anterior eye portion in a grid of points. For simplicity of explanation, the lenses in the relay lens system 148 are shown as simple single-element lenses, but in preferred embodiments, they have multiple elements to reduce distortion of the relay beamlets over the wavelength range of light 114. Generally, the number of beamlets 146 depends on the design of the 2D lenslet array 144. In certain embodiments, at a nominal focal plane 150, i.e., the waist of the beamlets 146, which can be located within the anterior eye portion 102 as shown in the figure, there may be beamlets of the order of 100 or 1000 in a square or rectangular pattern with a density of, for example, 4 to 100 beamlets per square millimeter. In one particular embodiment, the 2D lenslet array 144 is designed to generate 1008 beamlets 146 on a 24 × 42 grid, in which case the beam waist is approximately 30 μm. Generally, the lateral range of the illuminated volume is determined by the size of the area above the eye encompassed by the array of beamlets 146, which could be, for example, 4 mm × 8 mm, while the lateral resolution is determined by the diameter of the beamlet waist.

[0032] Light 152 from the grid of the beamlet 146, scattered or reflected by one or more structures of the anterior segment 102, such as the anterior or posterior surface of the cornea 108, returns through the relay lens system 148, is then refocused by the lenslet array 144, undergoes polarization conversion in the quarter-wave plate 140, and is directed by the PBS 122 away from the light source 116 into the detection arm 134. The reference beam 124 is coupled with the scattered or reflected light 152 in the PBS 122, and the resulting coupled beamlet 154 is analyzed by the polarizer 156 to interfere with the light from the sample arm 136 and the reference arm 128. The resulting interference pattern is relayed by the lens system 158 and an optional aperture 160 for removing stray light and spectrally analyzed in a measurement system including a spectrometer 162 at a grid of spatial positions identified by a spatial sampling element 164 in the form of a two-dimensional lenslet array, and the corresponding two-dimensional aperture array 166. Generally, the lenslet arrays 144 and 164 are aligned so that the combined beamlet 154 is directed towards the spectrometer 162.

[0033] The spectrometer 162 can analyze multiple grid points, beams, or beamlets simultaneously, or at least within one frame of the two-dimensional sensor array 168, for snapshot acquisition. Each snapshot acquisition is a simultaneous measurement over a wavelength range of light reflected or scattered from the volume of the eye 104 illuminated by the array of beamlets 146, the wavelength range roughly corresponding to the bandwidth of the broadband light source 116. After the interference beamlet enters the spectrometer 162, it is redirected to the lens 172 by the PBS 170, which collimates the beamlet so that it can be dispersed by a wavelength-dispersive element 174 in the form of a transmission diffraction grating, and then passes twice through a quarter-wave plate 176 via reflection at the mirror 178, rotating the polarization state by 90°. The dispersed spectral components, after passing through the PBS 170, are imaged onto the two-dimensional sensor array 168, such as a CMOS camera, by the lens 172. The interferogram detected by the two-dimensional sensor array 168 is read out in one frame for later analysis by a computer 180 equipped with appropriate computer-readable program code. In a preferred embodiment, the diffraction grating 174 is oriented such that each of the coupled beamlets 154 entering the spectrometer 162 is distributed on separate pixel groups of the two-dimensional sensor array 168 with respect to a grid of spatial positions identified by the two-dimensional lenslet array 164 and the corresponding two-dimensional aperture array 166, as described in U.S. Patent Application Publication No. 2016 / 0345820A1. The computer 180 may, for example, apply a well-known Fourier transform technique to obtain a sparse tomographic image of the illuminated volume of the anterior segment 102 of the eye 104, which includes depth-resolved information from points within the eye illuminated by the beamlets 146.

[0034] To obtain a more complete, i.e., a higher-density tomographic image of the illuminated volume, one or more additional snapshot acquisitions, i.e., simultaneous measurements over a certain wavelength range, may be performed using an array of beamlets 146 that are progressively translated across the eye 104 in one or two lateral dimensions to "fill" the gaps between the beamlets over the eye. The set of snapshot acquisition results can then be processed by a computer 180 to generate a higher-density tomographic image of the illuminated volume. In a preferred embodiment, the number of snapshot acquisitions in one set is sufficient to ensure that every point within the target volume of the eye 104 is illuminated at least once in order to provide a complete, or higher-density, tomographic volumetric image. The snapshot acquisitions in one set can be recorded by substantially overlapping regions encompassed by the array of beamlets 146. In the illustrated embodiment, the array of beamlets 146 can be progressively translated across the eye 104 using a scanning element 182 in the form of a MEMS mirror located in the sample arm relay system 148. The scanning element 182 may also be used for a wider range of movement of the beamlet array 146, for example, to acquire another set of snapshots in adjacent volumes of the eye 104. For simplicity of explanation, the scanning element 182 is shown as a transmissive type rather than a reflective type.

[0035] The combination of one PBS 122 and two quarter-wave plates 132 and 140 offers the advantage of efficient light utilization in the apparatus 100. Specifically, the PBS 122 splits the appropriately deflected light source 114 into orthogonal linearly polarized states. When the quarter-wave plate 132 of the reference arm is oriented so that its birefringence axis is 45° with respect to the linearly polarized state directed towards the reference arm 128 by the PBS 122, the reference beam 124 becomes circularly polarized. After the rotation direction of the circular polarization is reversed by reflection at the mirror 130, the quarter-wave plate 132 converts the reference arm light into orthogonal linearly polarized light that passes through the PBS 122 and enters the detection arm 134 with minimal loss. Similarly, when the quarter-wave plate 140 of the sample arm is oriented such that its birefringence axis is at a 45° angle with respect to the linearly polarized state reaching the sample arm 136 through the PBS 122, and in the case of polarization-preserving reflection or scattering from the sample 104, the reflected or scattered light 152 is redirected by the PBS 122 to the detection arm 134 with minimal loss. However, as mentioned in the background section, birefringence or depolarization in the sample 104 can significantly alter the polarization state of the reflected light 152, which may contain important information but may also be interpreted as artifacts in the OCT image acquired by the instrument 100.

[0036] The inventors found that by making the quarter-wave plate 140 of the sample arm adjustable, the apparatus 100 could be modified to provide polarization-sensitive imaging, and as a result, different polarization states of the sample arm light 126 could be used to obtain measurements of the eye 104. In this embodiment, no additional or different optical components are required, and the polarization-sensitive function can be achieved in a simple and cost-effective manner.

[0037] Figure 2A is a schematic plan view of a polarization-sensitive spectral-domain optical coherence tomography (OCT) apparatus 200 according to one embodiment of the present invention. Generally, the elements of apparatus 200 labeled 2xx in Figure 2A correspond to the elements of apparatus 100 labeled 1xx in Figure 1, except that apparatus 200 has an adjustable polarization delay system 284 for controlling the polarization state of the light 226 that illuminates the eye 104. In certain embodiments, the adjustable polarization delay system 284 is located close to the PBS 222 as shown in the figure, but may be located at other locations within the sample arm 236. In certain embodiments, the adjustable polarization delay system 284 is an optical element located at the end of the sample arm 236, i.e., an optical element located between the relay lens system 248 and the eye 104 when apparatus 200 is in use. This has the advantage of suppressing reflections at the lenses of the relay system 248, ensuring that the residual background from these surfaces remains constant when the polarization of the illumination to the eye is adjusted.

[0038] In a preferred embodiment shown in Figure 2B, the adjustable polarization delay system 284 is in the form of a quarter-wave plate 140 similar to the quarter-wave plate 240 of the apparatus 100 in Figure 1, but is configured to rotate 286 its high-speed axis around an axis 288 corresponding to the direction of light propagation to the sample. In the particular embodiment shown in Figure 2B, the quarter-wave plate 240, for example made of crystalline quartz, is housed in a rotatable mount 290 actuated by a motor 292 controlled by a computer 280 (not shown). In other embodiments, the rotation 286 may be performed manually.

[0039] The operation of the PS-OCT apparatus 200 differs from that of a conventional OCT apparatus 100 in that it acquires multiple sets of snapshots of a sample eye 104 by illuminating the eye with light 226 in different polarization states identified by an adjustable polarization delay system 284. In the selected illumination polarization state, light 252 from the grid of the beamlet 246, reflected or scattered by one or more structures of the anterior segment 102, returns through the adjustable polarization delay system 284 and is then coupled with the reference beam 224 in the PBS 222. The polarization state of the reference beam 224 is not affected by the adjustable polarization delay system 284. Each set of snapshots is a set of simultaneous measurements across wavelength ranges of light 252 reflected or scattered by the volume of the eye 104 illuminated with light 226 in different polarization states. The computer 280 is configured to read out multiple sets of simultaneous measurements and process them to generate multiple tomographic volumetric images of the eye, each of which is of the eye 104 illuminated with light 226 in different polarization states. As described below, multiple tomographic volumetric images can be processed to generate a 3D representation of the polarization characteristics of the eye 104 or a polarization-independent image of the eye.

[0040] Within a set of simultaneous measurements, the position of the beamlet array 246 on the eyeball is gradually moved using the scanning element 282, and the number of simultaneous measurements in a given set is selected according to the required density of the resulting tomographic volumetric image. In a preferred embodiment, the number of simultaneous measurements in a given set is sufficient to provide a complete or high-density tomographic volumetric image. Using the scanning element 282 in the form of a high-speed settling MEMS mirror and the 2D sensor array 268 in the form of a CMOS camera with a frame rate of 300 Hz, simultaneous measurements on the order of 100 over a certain wavelength range can be acquired in 0.3 seconds.

[0041] First, the operation of the PS-OCT apparatus 200 will be described in terms of an embodiment in which the adjustable polarization delay system 284 takes the form of a rotatable quarter-wave plate 240 as shown in Figure 2B. This embodiment has the advantage of simplicity, as it does not require additional optical components compared to the conventional apparatus 100 shown in Figure 1. In the following examples, the rotatable quarter-wave plate 240 is often referred to as being at a specific angle, for example, 45°. This simply states that the rotatable quarter-wave plate 240 is oriented at that angle with respect to the polarization axis, i.e., with respect to the linearly polarized state that passes through the PBS 222 and enters the sample arm 236. A “horizontal volume slice” of the sample is a volume slice oriented in the horizontal plane of the sample.

[0042] Figures 3A and 3B show en-face and horizontal volumetric slices of a sample eye extracted from high-density tomographic volumetric images acquired using apparatus 200 with a rotatable quarter-wave plate 240 at 45°, respectively, which is a standard configuration for intensity-based OCT using apparatus 100 shown in Figure 1. Among the features of the anterior segment visible in Figure 3B are the anterior and posterior surfaces 301 and 303 of the cornea, the iris 310, and the anterior surface 305 of the lens. Figures 3C, 3D, 3E, 3F, and 3G show signal intensity across the curved posterior corneal surface 303 extracted from high-density tomographic volumetric images acquired when the rotatable quarter-wave plate 240 was at -22.5°, 22.5°, 45°, 67.5°, and 112.5°, respectively. Figures 3C-3G show that the spatial variation of the intensity pattern across the posterior corneal surface 303 is determined by the orientation of the rotatable quarter-wave plate 240, and therefore differs depending on the polarization state of the light illuminating the eye. These variations in intensity within and between images indicate that the sample eye has some degree of birefringence.

[0043] The volume images obtained when the rotatable quarter-wave plate 240 is at -22.5°, 22.5°, 45°, 67.5°, and 112.5° form a data set from which, as described below, generally individual tomographic volume images are recorded by the computer 280, that is, after being aligned to remove eye movement, an image independent of polarization and a phase delay can be extracted. In this regard, the adjustment of the polarization delay system 284 can be relatively slow, for example, 0.5 seconds for one rotation 286 of the quarter-wave plate 240, so it is recognized that significant eye movement can occur between sets of snapshot acquisitions.

[0044] Assuming that z represents the axial direction, that is, the depth within the sample 104, the OCT signal amplitude S(z), and thus the intensity, I(z) = |S(z)| 2 can be expressed in terms of the elements of the Jones matrix as follows:

Equation

[0045] From Equation (1), it can be proven that the single-pass phase delay is given by the following equation:

Equation

[0046] Here, I45° This utilizes the fact that signal intensity does not depend on the birefringence axis θ. φ This shows the signal intensity measured when the rotatable quarter-wave plate is at angle φ. total This can be calculated at one or more selected points, or for a set of tomographic volumetric images, in order to generate polarization-independent images.

[0047] When additional tomographic volumetric images are acquired with the rotatable quarter-wave plate 240 at 0°, I on the birefringence axis 0° By utilizing the signal intensity dependence, the following expression for θ can be obtained: 112.5° +I -22.5° -I 22.5° -I 67.5° If >0,

number

number

[0048] Figure 4A shows polarization-independent images from the posterior corneal surface, i.e., polarization-independent versions of the images shown in Figures 3C-3G, and Figure 4B shows polarization-independent horizontal volume slices of the anterior segment. There is a slight difference in the intensity patterns between the polarization-independent volume slices in Figure 4B and the volume slices in Figure 3B obtained with a standard configuration, i.e., when the rotatable quarter-wave plate 240 is at 45°, which can provide useful information as will be explained later.

[0049] Figures 5A and 5B show images of cumulative phase delay and birefringence axis (θ) variation over a radius of 5 mm on the posterior surface of the cornea, respectively, and Figure 5C shows a horizontal volume slice of cumulative phase delay. In Figures 5A and 5C, the phase delay is -10log(cos 2 (δ) is expressed as cos 2(δ) is calculated using equation (2). The brighter-looking region in the volume slice of Figure 5C, including the iris and the outer portion of the posterior corneal surface, indicates tissue with higher birefringence. A rhomboid contour indicating π / 2 single-pass phase delay is seen in Figure 5A, and a similar shape is evident in the intensity image of Figure 3E, acquired when our apparatus is in a standard configuration, i.e., when the rotatable quarter-wave plate 240 is at 45°. This deviation from the normal shape has been shown to indicate early onset of keratoconus, as reported by Fukuda et al 'The corneal phase retardation measured by a prototype of anterior segment polarization-sensitive OCT', Investigative Ophthalmology & Visual Science 61, 4312 (2020).

[0050] Figure 6A shows a magnified view of the anterior chamber angle region from the volume slice of Figure 3B acquired with a standard configuration, and Figure 6B shows the corresponding magnified view from the polarization-independent volume slice of Figure 4B. The birefringent anterior chamber angle structure adjacent to the trabecular meshwork is evident in the standard configuration image of Figure 6A and the phase-delayed volume slice of Figure 5C. The improvement in Schlemm's canal contrast due to birefringence artifact reduction can be seen in the polarization-independent image of Figure 6B and is highlighted with a white arrow.

[0051] Embodiments using an adjustable polarization delay system 284 in the form of a rotatable quarter-wave plate 240, as shown in Figure 2B, have the advantage of being simple and inexpensive in terms of optical components, but may require a relatively large number of separate sets of acquisitions to obtain specific polarization parameters. The number of separate measurements required can be reduced by not adhering to embodiments in which one quarter-wave plate is used to identify the incident change state.

[0052] For example, in an embodiment in which the adjustable polarization delay system 284 is in the form of an active waveplate element, such as a liquid crystal variable delay with adjustable phase delay Φ and axis angle φ, Φ,φ =I90,45 , I 180,22.5 and I 180,67.5 Three scans (i.e., one scan with a 45° quarter-wave plate function and two scans with a 22.5° to 67.5° half-wave plate function) were used to calculate the polarization-independent signal I using the following equation. total This is sufficient to make that decision.

number

[0053] Figure 2C schematically shows an adjustable polarization delay system 284 in the form of a liquid crystal variable retarder 294, which includes a voltage-controlled liquid crystal cell 296 located in a rotatable mount 290 actuated by a motor 292. The phase delay Φ and the axial angle φ can be controlled independently by adjusting the applied voltage 298 and the mechanical rotation 286, respectively.

[0054] Similar functionality can be obtained if the adjustable polarization delay system 284 is in the form of a series of two independently rotatable quarter-wave plates 240A, 240B as shown in Figure 2D, or in the form of a rotatable quarter-wave plate 240 and a rotatable quarter-wave plate 241 as shown in Figure 2E.

[0055] In addition to measuring the birefringence of samples such as in vivo tissues, PS-OCT can be used to characterize the depolarization characteristics of samples. As described in the aforementioned PS-OCT review by De Boer et al., a metric applicable to OCT systems, known as polarization uniformity (DOPU), can be evaluated using a Stokes vector representation of the polarization state averaged over a small area of ​​the sample. In areas with significant depolarization, the local polarization state changes rapidly across speckle points, and the DOPU value is less than 1.

[0056] The Stokes vector describing the single-pass polarization state output from a sample, and thus the representation of the DOPU, can be obtained, for the nominal input polarization state, as a basis set of measurements obtained with a sample illuminated with light of different polarization states. For example, if the adjustable polarization delay system 284 is in the form of a rotatable quarter-wave plate 240 as shown in Figure 2B, the DOPU describing the single-pass polarization state output from the illuminated volume of eye 104 can be calculated from a dataset of six volume images acquired when the rotatable quarter-wave plate 240 is -22.5°, 0°, 22.5°, 45°, 67.5°, and 112.5°. The polarization-independent signal I is calculated using equation (3). total Therefore, the Stokes vector components Q, U, and V can be calculated by the following equation:

number

number

[0057] Multiple sets of tomographic volume images at different illumination polarizations were acquired and processed by a device 200 consisting of different lens relays 248 for imaging the illuminated volume of the retina 128 rather than the anterior segment 102 of eye 104. Figures 7A and 7B show horizontal volume slices and the DOPU of the retina, respectively, acquired when a rotatable quarter polarizer was at 45°. Noting that the darker regions in Figure 7B indicate higher DOPU, the retinal pigment epithelium (RPE) appears as a relatively bright layer 702, which is consistent with the known depolarization effect of the RPE.

[0058] Figure 8 shows a schematic plan view of a polarization-sensitive spectral-domain OCT apparatus 800 according to another embodiment of the present invention. The difference between this apparatus 800 and the apparatus 200 shown in Figure 2A is that the sample arm 236 lacks a spatial sampling element 244, and as a result, a selected volume 850 of the eye 104 is illuminated with an unstructured beam 886. An objective lens 888 is included to control the lateral range of the illuminated volume 850, which may be located in the anterior segment 102 as shown in the figure, or in the retina 128, depending on the details of the optical system 248, 888. Similar to the apparatus 200 shown in Figure 2A, an adjustable polarization delay system 284 may be located close to the PBS 222 as shown in the figure, or may be located at other positions within the sample arm 236. Light 252 reflected or scattered from the illuminated volume 850 collected by the objective lens 888 passes through the adjustable polarization delay system 284 and is then coupled with the reference beam 224 in the PBS 222. The coupled beam 854 is spatially sampled by the 2D lenslet array 264, and the resulting beamlets are directed to the spectrometer 262 for spectral analysis, as described above, and snapshots over a certain wavelength range are taken, i.e., simultaneous measurements, by the 2D sensor array 268, after which the tomographic volumetric image is calculated in the computer 280.

[0059] In this embodiment, the cross-sectional area of ​​the illuminated volume 850 generally needs to be relatively small, on the order of 100 μm × 100 μm, in order to reduce the effects of multiple scattering and because the number of sampling points provided by commercially available 2D lenslet arrays is limited. This is significantly smaller than the cross-sectional area accessible by the beamlet method of the apparatus 200 shown in Figure 2A, which may be, for example, 4 mm × 8 mm as mentioned above. If data from only one illuminated volume 850 is required, it is sufficient to take only one snapshot for each setting of the adjustable polarization delay system 284 for polarization-sensitive analysis. On the other hand, if a larger volume of the sample is to be measured, for each setting of the adjustable polarization delay system 284, the illuminated volume 850 can be moved laterally using the scanning element 282 to generate a set of two or more snapshots, preferably overlapping to some extent for registration of the snapshot acquisition.

[0060] We described a surprisingly simple way to modify a spectral domain OCT instrument, configured to acquire snapshots of volumetric data from a sample, to perform polarization-sensitive imaging by illuminating the sample with light in different polarization states and capturing multiple volumetric images. The instrument's ability to rapidly acquire and record multiple volumetric images is a significant advantage for this application.

[0061] Polarization sensitivity is provided by including an adjustable polarization delay system 284 in the illumination optical system. In many of the embodiments described, the adjustable polarization delay system 284 is in the form of one or more rotatable waveplates, which may be made of crystalline silica, for example. In alternative embodiments, the adjustable polarization delay system 284 may be in the form of one or more voltage-controlled liquid crystal retarders or other electro-optic devices such as Pockel cells. Combinations of rotatable waveplates and electro-optic devices can also be used.

[0062] In each of the embodiments shown in the figure, focusing of light is performed using an optical power element in the form of a lens. However, other forms of optical power elements, such as parabolic mirrors or ellipsoidal mirrors, can also be used. In the apparatus 200 shown in Figure 2A, sample 104 is illuminated with a 2D array of beamlets 246 generated using a spatial sampling element 244 in the form of a 2D lenslet array, enabling spatially resolved snapshots of the illuminated volume of the sample. Alternatively, sample 104 can also be illuminated with a 1D grid of beamlets using a 1D lenslet array. In yet another embodiment, the 1D or 2D array of beamlets 246 can be generated using a spatial sampling element 244 in the form of a appropriately designed aperture array, diffractive optical element, or micromirror array. In another variant, the transmission diffraction grating 274 of the spectrometer 262 can be replaced with other forms of wavelength-dispersive elements, such as a reflection diffraction grating, prism, wedge pair, or diffraction grating / prism pair.

[0063] Although the present invention has been described in relation to specific embodiments, those skilled in the art will see that it can be embodied in a variety of other forms.

Claims

1. A polarization-sensitive optical coherence tomography system, (i) An illumination system for illuminating a sample volume with light in a polarization state controllable by the adjustable polarization delay system, comprising a multi-wavelength light source and an adjustable polarization delay system, (ii) A polarizing beam splitter for splitting light from the light source into a sample beam and a reference beam, and for recombining the sample beam and the reference beam after the sample beam has interacted with the sample, (iii) A measurement system for creating a set of one or more simultaneous measurements over a wavelength range, wherein each set of one or more simultaneous measurements over a wavelength range is a signal of light reflected or scattered by the sample illuminated with light in different polarization states, (iv) A computer for processing one or more sets of simultaneous measurements to generate multiple tomographic volume images of the sample, wherein each of the tomographic volume images is of the sample illuminated with light in different polarization states, A polarization-sensitive optical coherence tomography (OCT) system, including a polarization-sensitive optical coherence tomography (OCT) system.

2. The apparatus according to claim 1, wherein the illumination system is configured to illuminate the volume of the sample with an array of beamlets, and the illumination system includes a scanning element for translating the array of beamlets across the sample between simultaneous measurements in a set of two or more simultaneous measurements in order to increase the density of the tomographic volumetric image.

3. The apparatus according to claim 1 or 2, wherein the computer is configured to process the plurality of tomographic volumetric images to generate a three-dimensional representation of the polarization characteristics of the sample.

4. The apparatus according to claim 1 or 2, wherein the computer is configured to process the plurality of tomographic volumetric images to generate a polarization-independent image of the sample.

5. The apparatus according to any one of claims 1 to 4, wherein the adjustable polarization delay system includes a rotatable quarter-wave plate.

6. The apparatus according to claim 5, wherein the adjustable polarization delay system includes two rotatable quarter-wave plates.

7. The apparatus according to claim 5, wherein the adjustable polarization delay system includes one rotatable quarter-wave plate and one rotatable half-wave plate.

8. The apparatus according to any one of claims 5 to 7, wherein the adjustable polarization delay system includes one or more waveplates, each made of a birefringent material.

9. The apparatus according to any one of claims 1 to 4, wherein the adjustable polarization delay system includes a liquid crystal variable retarder.

10. The apparatus according to any one of claims 1 to 9, configured for in vivo polarization-sensitive optical coherence tomography of a sample including the anterior segment of the eye or the retina.

11. A method for performing measurements of a sample using polarization-sensitive optical coherence tomography, (a) The step of illuminating the volume of the sample with multi-wavelength light with a polarization state controllable by an adjustable polarization delay system, (b) A step of creating a set of one or more simultaneous measurements over a wavelength range, each set of one or more simultaneous measurements over a wavelength range being for light reflected or scattered by the sample illuminated with light in different polarization states, (c) A step of processing the plurality of sets of one or more simultaneous measurements to generate a plurality of tomographic volume images of the sample, wherein each of the tomographic volume images is of the sample illuminated with light in a different polarization state, A method that includes this.

12. The method according to claim 11, wherein the volume of the sample is illuminated by an array of beamlets, and the array of beamlets is translated across the sample between simultaneous measurements in a set of two or more simultaneous measurements in order to increase the density of the tomographic volume image.

13. The method according to claim 12, wherein the number of simultaneous measurements in a set of two or more simultaneous measurements is sufficient to generate a high-density tomographic volumetric image.

14. The method according to any one of claims 11 to 13, wherein the plurality of tomographic volumetric images are processed to generate a three-dimensional representation of the polarization characteristics of the sample.

15. The method according to any one of claims 11 to 13, wherein the plurality of tomographic volume images are processed to generate a polarization-independent image of the sample.

16. The method according to any one of claims 11 to 15, wherein the adjustable polarization delay system includes a rotatable quarter-wave plate.

17. The method according to claim 16, wherein the adjustable polarization delay system includes two rotatable quarter-wave plates.

18. The method according to claim 16, wherein the adjustable polarization delay system includes one rotatable quarter-wave plate and one rotatable half-wave plate.

19. The method according to any one of claims 16 to 18, wherein the adjustable polarization delay system includes one or more waveplates, each made of a birefringent material.

20. The method according to any one of claims 11 to 15, wherein the adjustable polarization delay system includes a liquid crystal variable retarder.

21. The method according to any one of claims 11 to 20, applicable to a sample including the anterior segment of the eye or the retina.

22. A product comprising a non-temporary computer-usable medium having computer-readable program code configured to operate the apparatus described in any one of claims 1 to 10, or to perform the method described in any one of claims 11 to 21.

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