Ophthalmic imaging with K-mirror scanning, effective interferometry, and pupil alignment via spatial frequency analysis

Abstract

Various techniques for providing low-cost ophthalmic imaging systems, such as OCT or fundus imagers, are proposed. Cost reduction is achieved by using a K-lens as the scanning component. The K-lens is located at the retinal conjugate. A beam splitter is located at the pupil conjugate and can be used to provide pupil separation functionality. The shape and area of ​​the beam splitter conform to the focused light footprint of the illumination source, such that it spans only a portion of the collection window. 2D FFT is applied to capture the spectrum for selective removal of the complex conjugate component and for extracting the patient's pupil for system-collected pupil alignment. Therefore, pupil alignment is achieved using the captured OCT data without requiring an additional pupil camera.

Description

Technical Field

[0001] This invention generally relates to the field of ophthalmic imaging systems. More specifically, it relates to ophthalmic imaging systems with simplified scanning components, reduced design constraints, and ease of patient-system alignment. Background Technology

[0002] Early diagnosis is crucial for the successful treatment of various eye diseases. Optical imaging is the preferred method for non-invasive examination of the retina. Optical imaging can be used to identify the main causes of vision loss, such as age-related macular degeneration, diabetic retinopathy, and glaucoma, but a diagnosis is often not made until the damage itself has become apparent. The goal of ophthalmic medical care is to identify possible pathologies during the latent stage of disease when symptoms appear. An obstacle to this goal is the complexity and cost of advanced optical imaging systems for ophthalmic use (e.g., ophthalmic imaging systems), which limits their availability.

[0003] Various types of ophthalmic imaging systems exist, such as fundus imaging systems (e.g., fundus imagers) and optical coherence tomography (OCT) systems (see, for example, U.S. Patent Nos. 4,170,398, 4,732,466, PCT Publication No. 2012059236, U.S. Patent Application No. 2014 / 0232987, and U.S. Patent Publication No. 2015 / 0131050). Fundus imagers and OCT systems can provide in vivo imaging of the anterior and posterior regions of the human eye (e.g., the cornea, retina, etc.). Fundus imagers are typically used to capture two-dimensional (2D) surface images and can be used to image the fundus, the inner surface of the eye opposite the lens, and can include the retina, optic disc, macula, fovea, and posterior pole. OCT systems can capture three-dimensional (3D) information and generate 2D and / or 3D depth-resolved images from it.

[0004] Although fundus imagers and OCT systems differ in their fundamental implementation, they share some complexities. Both may require complex scanning components to collect imaging information (e.g., light), and both have a limited amount of optical power, thus optimizing light flux is desirable. Both also have stringent requirements regarding the positioning of the various optical components. For example, multiple optical components may need to be on the same conjugate plane, which may necessitate the creation of additional optical repeaters to define additional conjugate planes. Further complexity may arise from the need to provide alignment mechanisms to align the ophthalmic imaging system with the patient's eye (e.g., pupil alignment) and / or to provide a fixation point to guide the patient's gaze. These difficulties complicate the design and construction of fundus imagers and OCT systems, leading to higher costs.

[0005] The purpose of this invention is to provide an ophthalmic imaging system with reduced complexity and cost.

[0006] Another object of the present invention is to provide a simplified and universal scanning mechanism for use in ophthalmic imaging systems.

[0007] Another object of the present invention is to provide an architecture for mitigating optical power loss in imaging optical repeaters.

[0008] Another object of the present invention is to reduce the number of components required to provide the system to the patient's alignment and / or gaze point. Summary of the Invention

[0009] The aforementioned objectives are achieved in ophthalmic imaging systems with simplified rotational and / or linear scanning, relaxed design constraints, efficient line-field and / or full-field and / or partial-field interferometry, and simplified system-to-patient alignment. By using a K-lens as the scanning component, the complexity and cost associated with galvanometer scanners can be avoided. The use of a K-lens also avoids any aberration problems associated with prisms, such as those from Dove prisms, allowing the K-lens to be positioned in the non-collimated optical path of the ophthalmic imaging system. For example, the K-lens can be positioned such that the intermediate focal point of the scattered light leaving the eye is located within the K-lens (structure). Furthermore, this implementation removes the task of pupil separation from the scanning component, allowing it to be freely positioned in any convenient location, not limited to the pupil conjugate plane. Therefore, the K-lens of the present invention can be positioned between the scanning lens and the eyepiece lens, which is the lens closest to the eye. These reduced limitations regarding the scanning component provide reduced design constraints and ease of manufacture.

[0010] Using a K-mirror for rotational scanning allows for modulation of the available scan line length. By moving one of the three mirrors in the K-mirror structure, the output scan line is offset radially from its center of rotation. This allows for the creation of circular scan patterns and / or extension of the scan line length up to twice its original length.

[0011] Alternatively, or additionally, the K-mirror can be moved in a reciprocating motion, such as up-and-down reciprocating motion, to achieve linear scanning. This reciprocating motion causes the input scan beam (e.g., the scan line input to the K-mirror) to be reflected away from different positions on the input-facing mirror of the K-mirror structure, causing it to be reflected away from different positions on the output-facing mirror of the K-mirror structure, thereby offsetting the output position of the output scan beam. In this way, the output scan beam can be scanned across the sample at least along one translation dimension. The K-mirror of the present invention can also be combined with a second scanning component (e.g., a second K-mirror, a galvanometer scanner, etc.) to produce a two-dimensional translational scan. For example, a scan beam output from a first scanning component providing a scan along a first translational direction can be input to a K-mirror providing a scan along a second translational direction.

[0012] Furthermore, one or more mirrors of the K-lens structure can be made to be reflective on one side and transmissive on the opposite side. The reflective side can be chosen to face the interior of the K-lens structure. This can be achieved, for example, by coating or embedding a thin layer of a reflective, nearly transparent material (e.g., a dielectric coating, such as aluminum) onto a glass plate. In this way, a second input port (from the transmissive side) is created for the K-lens structure. A gaze pattern can be input into the K-lens through this second input port. Additionally, by attaching the mechanism that generates the gaze pattern to the K-lens such that the two move back and forth while their positions relative to each other remain constant, the position of the gaze pattern perceived by the patient during the scanning process can be kept constant.

[0013] By using novel beamsplitter (or beam splitter) configurations, efficient interferometry (e.g., line-field interferometry and / or flying-spot / point scanning and / or full-field interferometry and / or partial-field interferometry) can be provided, wherein the area spanned by the beamsplitter is approximately the same size (preferably not smaller than) of the beam footprint (or focal region, or optical footprint, or wavefront) of the incident beam. In this manner, the incident beam is split into a reference beam along the reference arm and a sample beam along the sample arm. For example, if the imaging system uses line scanning, the beamsplitter preferably has a slit (or linear) shape of minimal size sufficient to surround the scan line as it passes through the beamsplitter. Alternatively, if the imaging system uses a full-field imager (or point scanner), the beamsplitter preferably has a disk (or dot) shape of minimal size sufficient to surround the focal point of the illumination light as it passes through the beamsplitter. The size of the beamsplitter is minimized to maximize the amount of collected (e.g., scattered) light returning from the sample and passing through the beamsplitter (e.g., its conjugate plane) without passing through the beamsplitter (or its relative position within its conjugate plane). In other words, the beamsplitter can be designed to provide the smallest possible barrier to the scattered light returning from the imaged sample. In other words, the wavefront of the light returning (e.g., collimated) from the sample arm spans a region extending beyond the beamsplitter and preferably encloses the beamsplitter (or spans one or more hemispherical sides of the beamsplitter). As will be understood, any returning light from the sample arm passing through the beamsplitter is attenuated by the beamsplitter, but since most of the returning light from the sample arm passes through the beamsplitter without being attenuated (e.g., the area of ​​the beamsplitter can be less than 5% of the area of ​​the wavefront of the returning light from the sample arm (e.g., the size of the system collection pupil), most of the returning sample signal intensity is preserved.

[0014] Additionally, if needed, the beam splitter can be positioned to provide pupil separation functionality for the imaging system, thus relieving the scanning components of this task. It is understood that positioning a small, stationary beam splitter at the pupil conjugate plane and defining the illumination and collection areas for pupil separation is easier than placing one or more moving scanning components at the pupil conjugate plane and defining the imaging (or window) and collection (or window) areas for pupil separation.

[0015] Effective interferometry can be further provided by positioning the physical collection aperture (e.g., the system pupil aperture) at the pupil conjugate plane of the patient's eye to define the mechanical collection pupil. Optionally, the physical collection aperture can be fabricated with a modular construction. The collection aperture can be selectively varied from a coaxial construction to an off-axis construction, and vice versa. That is, the mechanical collection pupil can convert the collected light (returning from the beam splitter toward the condenser or camera) from a coaxial construction to an off-axis construction. The coaxial construction allows the maximum amount of available light to reach the condenser, but the depth information provided by this light may be reduced due to the presence of a complex conjugate image. The off-axis construction may reduce the amount of available light reaching the condenser, but avoids the creation of a complex conjugate image, thus achieving higher depth resolution (e.g., full-range A-scan or B-scan). That is, applying a 2D Fast Fourier Transform (FFT) to the collected light from the off-axis construction provides the spatial frequency distribution of the scattered light at the collection aperture (e.g., corresponding to the patient's pupil conjugate). This spatial frequency distribution separates the real signal components from their complex conjugate components, which facilitates the selection of real signal information (excluding complex conjugate components) for processing.

[0016] As those skilled in the art will understand, first-type spectral analysis (e.g., 1D FFT) is typically applied to the collected sample light (e.g., interference light) to recover depth information of the scan beam. However, as described above, by applying second-type spectral analysis (e.g., 2D FFT) to the collected sample light, the spatial characteristics of the collected light returning from the sample arm (e.g., at the collection aperture on the pupil conjugate plane) can be recovered. As described above, this information can be used to select spectral information that does not include the complex conjugate component, but it can also be used to align the imaging system with the patient. That is, these spatial characteristics can be correlated with the position of the patient's eye (e.g., the patient's pupil) relative to the ophthalmic imaging device (e.g., the device's collection aperture). It has been found that this spectral analysis can be used to determine the translational and axial positions of the eye relative to the ophthalmic imaging device. In this way, the scanning mechanism of the ophthalmic imaging device can at least partially determine the proper alignment of the patient with the ophthalmic imaging device without the need for additional, conventional alignment equipment, such as a pupil camera and its associated hardware / software. In this way, the system can provide automatic pupil alignment at least in part based on spectral analysis.

[0017] Other objects and achievements of the invention, as well as a more complete understanding of the invention, will become apparent and readily understood by referring to the following description and claims in conjunction with the accompanying drawings.

[0018] Several publications have been cited or referenced in this document to aid in understanding the invention. All publications cited or referenced herein are incorporated herein by reference in their entirety.

[0019] The embodiments disclosed herein are merely examples, and the scope of this disclosure is not limited thereto. Any feature of an embodiment mentioned in one claim class (e.g., a system) may also be claimed in another claim class (e.g., a method). Dependent claims or references in the appended claims are selected only for formal reasons. However, any subject matter arising from an intentional reference to any of the foregoing claims may also be claimed, such that any combination of the claims and their features is disclosed and can be claimed, regardless of any dependent claims selected in the appended claims. Attached Figure Description

[0020] In the accompanying drawings, the same reference numerals / labels denote the same parts:

[0021] Figure 1 A general free-space point-scan OCT system is shown, in contrast to OCT systems using fiber optic couplers.

[0022] Figure 2 A side view of a K-mirror module consisting of reflective surfaces is provided. In this paper, the K-mirror module is implemented as three mirrors M1, M2, and M3.

[0023] Figure 3 A perspective view of the rotating K-mirror module is provided.

[0024] Figure 4 An alternative K-mirror module, including a prism with a reflective surface, is provided.

[0025] Figure 5 The K-mirror of the present invention is shown in a non-collimated optical path located between the scanning lens and the eyepiece.

[0026] Figure 6 This illustrates the creation of an off-axis scan in an ophthalmic imaging system by offsetting one of the three mirrors of the K-mirror.

[0027] Figure 7 Two exemplary gaze target patterns T1 and T2 are shown, which can be viewed through... Figure 6 The rotational speed of mirror K1 and the appropriate offset of mirror M3 are used to create it.

[0028] Figure 8 The implementation of a K-mirror module with two input beams B1 and B2 is shown.

[0029] Figure 9 An alternative implementation is provided in which mirror M3 reflects the first beam B1 and transmits the second beam B2 (e.g., visible light).

[0030] Figure 10 A third alternative implementation is provided, wherein the mirror M1 reflects the first beam B1 on a first surface facing the inside of the K mirror, and transmits the second beam B2 on a second surface on the back side of the first surface (e.g., facing the outside of the K mirror).

[0031] Figure 11 and Figure 12 Two exemplary configurations of the gaze generator (second light source) are shown.

[0032] Figure 13 The K-mirror module K3 is shown, which translates along one dimension (along arrow A5) to achieve a lateral scan.

[0033] Figure 14A and Figure 14B A more detailed description of Zemax is shown. TM The simulation used a K-mirror K3 that was linearly translated along arrow A6 to perform a lateral line scan.

[0034] Figure 15 A two-piece scanning mechanism is shown, in which the first part is located at the pupil conjugate and the second part is located at the retina conjugate.

[0035] Figure 16A and Figure 16B The first K-mirror translation mechanism using a sensor actuator is shown.

[0036] Figure 17 An alternative translation mechanism is shown that uses a motor with an eccentric (e.g., an eccentric wheel / disc) to move the K-mirror, thereby deforming the parallel flexure by a given offset Δx.

[0037] Figure 18 The diagram shows a three-beam splitter (SB) configuration that can be used with a line field ophthalmic imaging system.

[0038] Figure 19 A simplified schematic diagram of the slit-BS coaxial configuration in a linear field SDOCT system is shown.

[0039] Figure 20 The first structure of the optical footprint BS suitable for line field applications is shown.

[0040] Figure 21 A second structure of the light footprint BS is shown, suitable for use with full-field or partial-field applications, wherein illumination light is focused onto a point or a small 2D area.

[0041] Figure 22 An alternative structure of the beam splitter of the present invention is shown, wherein the beam splitter does not include a small area coating on a transparent substrate, but is configured to have a coating on a total reflection substrate, wherein the illumination light LtB passes through the beam splitter to define a sample beam SB along the sample arm and reflects a reference beam RB from the beam splitter to the reference arm.

[0042] Figure 23 The spectrum 71 and the resulting representative retinal image 73 are shown. The spectrum 71 can be obtained using the optical footprint BS coaxial method of the present invention, and the representative retinal image 73 can be constructed by applying 1D FFT to the spectrum 71.

[0043] Figure 24 It shows the relationship with Figure 23 The same spectrum 71, but with a collecting pupil, is used to construct a spatial frequency analysis image 75 by applying 2D FFT.

[0044] Figure 25 2D FFT analysis of the spectra captured by the conventional coaxial, off-axis, and optically footprinted BS coaxial structures is shown.

[0045] Figure 26 Three sample OCT images are shown, taken using both coaxial and off-axis optical footprint BS constructions / modes.

[0046] Figure 27 An exemplary beam splitting scenario and an illumination / detection pupil for full-field or partial-field interferometry are shown.

[0047] Figure 28 It shows that for Figure 27 Exemplary detection signals in the 2D spatial frequency domain for each of the three scenarios (e.g., obtained by applying 2D FFT).

[0048] Figure 29 Spatial frequency analysis of pupil alignment for use in the LF-SDOCT system is shown.

[0049] Figure 30 An exemplary workflow for determining pupil alignment in an OCT system is provided.

[0050] Figure 31 , Figure 32 , Figure 33 and Figure 34 Empirical data from spatial frequency analysis are shown for use in pupil alignment in LF-SDOCT.

[0051] Figure 35 , Figure 36 , Figure 37 , Figure 38 and Figure 39 Multiple pupil alignment scenarios applied to volumetric scans (e.g., volumetric scans, cubic structure scans, or C-scans) and their corresponding 2D FFT analyses are shown.

[0052] Figure 40 An exemplary workflow of the present invention can be applied to volumetric OCT data.

[0053] Figure 41A and Figure 41B Instructions are provided for using 2D FFT analysis to identify experimental data that are misaligned in the Y direction.

[0054] Figure 42A , Figure 42B and Figure 42C Experimental data related to the use of 2D FFT analysis in LF-SDOCT to detect Z misalignment are shown.

[0055] Figure 43A Three selected B-scan OCT images (and their corresponding 2DFFT data) are shown, which are derived from cubic structure scans of the eye being tested while aligned with the imaging system throughout the XYZ.

[0056] Figure 43B Three selected OCT images (and their corresponding 2D FFT data) from three B-scans are shown, which are derived from cubic structure scans of the eye being tested with the imaging system misaligned in the X-direction.

[0057] Figure 44 Exemplary processing steps that can be performed to determine pupil alignment from spatial frequency content are shown.

[0058] Figure 45 , Figure 46 and Figure 47 Several implementations for presenting alignment information to a user, for example, via a graphical user interface (GUI) on a screen / electronic display, are shown.

[0059] Figure 48 Another example of the present invention applied to a full-field (FF) TDOCT system is shown.

[0060] Figure 49 An exemplary workflow for using spatial frequency analysis to perform alignment and obtain feedback is shown.

[0061] Figure 50 An example of a slit-scan ophthalmic system for imaging the fundus is shown.

[0062] Figure 51A generalized frequency-domain optical coherence tomography system is shown for collecting 3D image data of the eye suitable for use with some embodiments of the present invention.

[0063] Figure 52 An example of a frontal vascular tissue image is shown.

[0064] Figure 53 An exemplary computer system (or computing device or computer) is shown. Detailed Implementation

[0065] As discussed more fully below, fundus imagers can provide high-resolution grayscale or color images of the fundus, while optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) enable non-invasive depth-resolved (e.g., A-scan), volumetric (e.g., C-scan), and two-dimensional (e.g., frontal (frontal plane) or B-scan (cross-section)) visualization of retinal vascular tissue. Typically, OCT provides structural images of tissue (e.g., vascular structures), while OCTA provides functional images of vascular tissue (e.g., blood flow). For example, OCTA can image vascular flow by using the motion of blood flow as an intrinsic contrast. A brief overview of such a device is given for ease of discussion, as this device relates to the present improvement. A more detailed discussion of various types of ophthalmic imaging systems is provided below in the "Fundus Imaging Systems" and "Optical Coherence Tomography (OCT) Imaging Systems" sections. Aspects of the present invention can be applied to any or all such ophthalmic imaging systems. For example, various implementations are described herein as being applied to OCT systems, but unless otherwise stated, it should be understood that these improvements can be implemented within OCTA systems and / or fundus imagers.

[0066] Figure 1A generalized, free-space point-scan OCT system 11 is shown in contrast to the OCT system of Figure 42 (which uses optical fibers and fiber couplers). In this example, the OCT system includes a light source 13 (e.g., a swept-frequency laser source or a broadband light source with a short time coherence length) that emits a beam LtB (e.g., a spatially coherent point illumination beam), which passes through an optional shaping aperture 15 and a collimating lens 17 to a beam splitter 19. As is known in the art, a beam splitter is an optical device that splits / divides a beam into two beams. In this example, a first portion of the illumination (light) beam LtB is a reference beam RB split on (e.g., through transmission) a reference arm (reference optical path), and a second portion of the beam LtB is a sample beam SB split on (e.g., through reflection or folding) a sample arm (sample optical path). The reference arm may include a back reflector 21 with adjustable optical delay. It should be noted that, typically, the beam attenuates (e.g., loses power) each time it passes through the beam splitter. For example, the beam may attenuate by 50% each time it passes through (transmits through) beam splitter 19.

[0067] The sample arm may include a scanning component 23, which in this example includes two galvanometers 25 and 27 (e.g., servo-controlled rotating (or oscillating) mirrors). The first galvanometer 25 can provide a vertical scan (e.g., a V-scan) of the sample beam SB (e.g., providing a scan in the Y-axis direction, which defines a column of sample points on the sample to be imaged), and the second galvanometer 27 can provide a horizontal scan (e.g., an H-scan) of the sample beam (e.g., providing a scan in the X-axis direction, which defines a row of sample points on the sample). For example, the H-scan galvanometer 27 can rotate to horizontally scan the sample beam in discrete steps (or in continuous and definable steps) to define a row of sample points. After completing a row of sample points, the V-scan galvanometer 25 can rotate its mirror vertically to move the sample beam to a new vertical offset position, thus preparing for scanning a new row. The optical path between the scanning component 23 and the eye 29 typically includes a scanning lens 31 and an eyepiece (or ophthalmic lens) 33. The eyepiece is typically the lens closest to the eye and focuses the sample beam SB onto the retina 35 of the eye 29. The scattered light to be collected (e.g., the collecting beam CB) exits the eye 29 through the pupil and forms an intermediate focal point Intr-FP between lenses 33 and 31 before passing through scanning element 23 and reaching beam splitter 19. Because the return path of the collecting beam CB from eye 29 is similar to the path of the sample beam SB to the eye, galvanometers 27 and 25 have the effect of "de-scanning" (or not scanning) the returning light CB, so that the returning light is a relatively stationary or stable beam (not scanned) when it reaches beam splitter 19.

[0068] At beam splitter 19, the return light from the sample arm (e.g., the collected beam CB) and the return light from the reference arm (e.g., the reference beam RB) are recombined and guided through focusing lens 37 and aperture 39 (which can block out-of-focus light) onto collector 41 (e.g., a photodetector / photosensor 42 in the case of time-domain (e.g., Fourier domain) OCT, or a spectrometer consisting of grating 40 and photosensor 42 in the case of spectral domain (SD) OCT). It should be understood that this structure constitutes an interferometer that superimposes beams to generate an interference pattern captured by collector 41, which can be used to calculate the path difference traveled by the multiple interfering beams.

[0069] Each scan point constitutes an A-scan and is individually captured (or detected) by the light collector 41. A series of A-scans are collected as the sample beam SB from the scanning unit 23 is scanned on the sample in a raster pattern to construct a composite B-scan or C-scan of the retina 35. Each A-scan detected by the light collector 41 can be processed by a computer or CPU 43 to form a B-scan, a C-scan, and / or a frontal image. In this example, a frontal image 45 is constructed. The resulting images (A-scan, B-scan, C-scan, and / or frontal image) can be displayed on a video display 47 or stored for further processing.

[0070] If the system is a linear scanner, light source 13 will produce a narrow beam, thus forming a line beam instead of a point beam. If the line beam spans the desired scanning area in the first dimension, the area can be imaged by scanning the line beam in a second dimension (e.g., perpendicular to the first dimension). In this case, only one of galvanometers 25 and 27 will be needed.

[0071] A challenge in using beamsplitter 19 in a free-space OCT system is that the power of the light decreases each time it passes through beamsplitter 19. It should be understood that reducing the amount of light power lost by beamsplitter 19 before sampling the eye 29 and / or before reaching the collector 41 would be advantageous. Another challenge is the complexity introduced by using "pupil separation," a technique to reduce the amount of light interference between the sample beam SB entering the eye and the scattered light CB leaving the eye, which is captured by collector 41.

[0072] When scanning the fundus, it is generally desirable to avoid collecting (e.g., capturing or imaging) incoming light, as well as reflected light from the cornea and scattered light from the lens (e.g., as due to cataracts). Pupil separation blocks reflected light from the cornea and scattered light from the lens by providing different paths for the scanning beam entering the eye and the returning (scattered) light leaving the eye at optimally selected areas of the pupil. For example, these areas can be selected to avoid pupil clipping (e.g., a portion of the beam being blocked by the iris, which centrally defines the pupil), scattered light from cataracts (e.g., opaque areas of the lens), and specular reflection of light (e.g., reflection) (e.g., such as that which may be produced by the scanning beam striking the cornea as it enters the eye). Essentially, pupil separation divides the eye pupil into a pupil sampling region (or window) and a pupil collecting region (or window), through which the illumination beam SB enters the eye (e.g., to scan a specific location on the fundus), and the pupil collecting region determines which portion of the scattered light CB leaving the eye will be captured by the condenser 41.

[0073] Typically, scanning component 23 provides pupil separation. Since the pupil sample region and pupil collection region are imaged at the pupil, scanning component 23 needs to be located at (or near) the conjugate plane of the pupil. However, in this case, this would mean that both galvanometers 25 and 27 need to be located at the pupil conjugate plane. Therefore, they need to be very close together, so that they are close to the pupil conjugate plane, which complicates the structure and component selection. Alternatively, it might be necessary to construct additional optical repeaters so that each galvanometer can be located at a separate, corresponding pupil conjugate plane, which again complicates the structure and increases component costs. Relaxing the positioning requirements of the scanning component would be advantageous.

[0074] The following provides various solutions to these problems. Each solution is described separately.

[0075] Scanning components

[0076] The first solution proposes a method to simplify the scanning components. Although the aforementioned OCT is a point scanning system, other more efficient scanning systems include translational and rotating line scanning systems. One way to construct a rotating line scanning system is to use a prism, such as a Dove prism. A scanning system based on a rotating Dove prism can transform a line imaging mechanism into a disk imaging mechanism by rotating the prism. Cedric Blatter et al. provided an example of a Dove prism for providing rotating scanning in “Dove Prism Based Rotating Dual BeamBidirectional Doppler OCT” (2013 OSA, July 1, 2013, Vol. 4, No. 7, BiomedicalOpticals Express 1188), the entirety of which is incorporated herein by reference. In this method, the Dove prism is positioned in the sample path before a pair of galvanometers, which ensures that the Dove prism is within the collimated optical path and highlights the limitations of the prism. Prisms are typically limited to the collimated optical path. That is, image rotation optics using prisms can only be placed in collimated optical paths, because if the prism is placed in a non-collimated optical path, a large number of aberrations will be introduced.

[0077] In ophthalmic imaging applications (e.g., fundus imagers or OCT / OCTA systems), it may be desirable to have an intermediate focal point (e.g., Figure 1 The intermediate focal point (Intr-FP) is used to adjust the eyepiece (e.g., lens 33) along the optical axis to correct refractive errors in the eye. In this case, the space near the intermediate focal point would be a convenient location for placing scanning components (e.g., image rotating optics). However, this is typically not a collimated optical path, thus ruling out the use of prisms. Therefore, for ophthalmic imaging, aberration-free rotating optics are desirable.

[0078] This paper proposes using a K-mirror (3-mirror structure) as the scanning component, which overcomes the collimation path limitations of the Dove prism. The K-mirror structure resembles the letter "K," with two reflectors joined at an angle and facing an opposing third reflector. The K-mirror uses three reflections to define its beam-inverting property, and as described below, the K-mirror is suitable for rotational and lateral scanning.

[0079] Figure 2A side view of a K-mirror module K1 consisting of reflective surfaces is provided, implemented herein as three mirrors M1, M2, and M3. Rays L1, L2, and L3 are shown entering and exiting the K-mirror module K1. For ease of discussion, depending on the indicated directions of rays L1, L2, and L3, reflective surface M1 may be referred to as the input mirror (or reflecting surface), M2 may be referred to as the intermediate mirror, and M3 may be referred to as the output mirror. In this implementation, rays L1, L2, and L3 enter the K-mirror, are reflected by the tilted input mirror M1 towards the non-tilted (flat) intermediate mirror M2, and then from the intermediate mirror M2 towards the counter-tilted output mirror M3, exiting the K-mirror module K1 in the same direction as the incident rays (e.g., along the same optical axis).

[0080] Figure 3 A perspective view of the rotating K-mirror module K1 is provided. As the entire K-mirror module rotates by an angle θ around its optical axis, as indicated by arrow A1 at mirror M1, the input image will rotate by an angle 2θ at the output of the K-mirror module, as indicated by arrow A2 at mirror M3. For example, an input scan line that enters the K-mirror module at M1 and is oriented along angle θ will exit the K-mirror module along a second angle 2θ. Therefore, for each individual rotation of the input scan line at mirror M1, the output scan line at mirror M3 will undergo two rotations. For the return path (e.g., a beam that enters the K-mirror at mirror M3 and is present at mirror M1), the beam will be reflected from M3 to M2, reflected back to M1, and rotated back to its original orientation (e.g., descanned).

[0081] Figure 4 An alternative K-mirror module K2 is provided. In this configuration, the input mirrors M1 and M3 of the K-mirror module K1 are replaced by a triangular prism structure P1, wherein the outer surfaces M1' and M3' are made reflective, preventing light from passing through the prism P1 and introducing aberrations. In this implementation, the mirrors M1 and M3 of the K-mirror module K1 are replaced by two reflective surfaces M1' and M3' on a single prism P1, which simplifies its fabrication. The reflective surfaces M1' and M3' can be constructed by applying a reflective coating to the top surface of the triangular prism P1.

[0082] The K-mirror-based scanning / rotating component of this invention is not hindered by the aberration characteristics of the Dove prism, and therefore can be positioned in either a collimated or non-collimated optical path. For example, as Figure 5 As shown, in ophthalmic imaging applications (e.g., fundus imagers or OCT / OCTA systems), the K-lens K1 of the present invention can be positioned in a non-collimated path between the scanning lens 31 and the eyepiece 33. More specifically, the K-lens-based scanning component of the present invention can be positioned such that the intermediate focal point (e.g., Figure 1The Intr-FP is located within the K-mirror K1, for example, within the open space along the optical path between mirrors M1, M2, and M3, or on the surface of the mirror. As shown in the front plan view F1 defining the scanning field of view (FOV) of the iris, a rotating scan A4 can be created from a single static beam A3 by rotating the K-mirror K1.

[0083] The rotating device of the present invention also provides a mechanism for changing the scanning beam therethrough. For example, such as... Figure 6 As shown, an off-axis scan can be created in an ophthalmic imaging system by offsetting one of the three mirrors of mirror K1 (e.g., the output mirror, or the exit optics M3). That is, offsetting the output mirror M3 (e.g., radially) results in a (e.g., radial) displacement of the position of the output image. In this way, the diameter of the scanned FOV F1' can be extended to twice the length of the original (e.g., input) scan line A3. In this case, the effective FOV of the scan is doubled. If mirror M3 is offset further, a circular (e.g., annular) scan pattern can be created.

[0084] Optionally, the scanning component based on the K-lens can be used to provide a gaze target to the patient. For example, in the case of visible light applications, a visible light beam can be input into the K-lens K1 to create a gaze target for the patient prior to actuated imaging scanning. Figure 7 Two exemplary gaze target patterns, T1 and T2, are shown, which can be created by adjusting the appropriate offset of mirror M3 and the rotation speed of mirror K1. This may require controlling the rotation speed of mirror K based on human visual perception.

[0085] As a second example, the K-lens can be used to provide a fixation target in a field of vision tester. In this case, a series of fixation points of different intensities and / or sizes are presented to the patient at predetermined locations within the field of vision, and the patient is asked to identify the presence or absence of the fixation points.

[0086] Alternatively, a K-lens can be configured with multiple inputs to provide multiple beam outputs, one of which can be used to define the gaze target. Figure 8 An implementation of a K-mirror module with two input beams B1 and B2 is shown. In this case, mirrors M1 and M2 are configured to reflect beam B1 and transmit beam B2 (e.g., transparent). In this way, mirror M1 defines two separate input paths to the K-mirror. For example, mirrors M1 and M2 may have dichroic surfaces and transmit light of a predetermined frequency. In exemplary operation, beam B1 may be rotated or otherwise shifted by the K-mirror, but beam B2 may pass through the K-mirror without attenuation. In this example, beams B1 and B2 may be visible (e.g., each selectively defining a corresponding gaze target), or one may be a scanning beam while the other defines the gaze target.

[0087] Figure 9An alternative implementation is provided in which mirror M3 is configured to reflect the first beam B1 and transmit the second beam B2 (e.g., visible light). In this way, mirror M3 defines a second input path to mirror K. In this example, fourth mirror M4 deflects beam B2 from gaze generator FG (e.g., a second light source) to output through mirror M3 and define a gaze pattern for the patient.

[0088] Figure 10 A third alternative implementation is provided, wherein mirror M1 is made reflective (e.g., reflector B1) on a first surface facing the interior of mirror K, thus as referenced above. Figures 2 to 7 The ground works as described above, and the transmitted beam B2 is formed on the second surface behind the first surface. This second surface constitutes the second input of the K-mirror module and can be used to provide gaze input. For example, the gaze light source FG can input the gaze beam B2 (e.g., a wire) to the K-mirror through the second input surface of mirror M1, and reflect it from mirrors M2 and M3 to produce an output gaze pattern to the patient (e.g., as shown in the image). Figure 7 (The rotation pattern shown). This gaze pattern can be provided simultaneously with the application of an imaging scan (e.g., beam B1).

[0089] In all the above embodiments, the gaze light source FG can optionally be mechanically fixed to the K-lens, allowing the two to move / rotate one after the other. In this way, the gaze pattern can appear relatively static to the patient during the imaging scan.

[0090] Figure 11 and Figure 12 Two exemplary configurations of the gaze generator (second light source) are shown. Figure 11 In the diagram, the gaze generator FG is shown as a linear strip comprising light-emitting diodes (LEDs) (exemplarily shown as comprising seven diodes D1 to D7), any combination of which can be selectively switched on. In the example shown, diodes D1, D3, D5, and D7 are switched on. If this pattern is submitted to a K-mirror for rotation, the resulting gaze pattern will be a series of concentric circles C1. Alternatively, as... Figure 12 As shown, the gaze generator FG may include a plurality of diodes arranged in a circular pattern. In this configuration, the scan beam can be transmitted within the center of the circular arrangement of the diodes. In this case, the gaze beam does not need to be rotated to create a circular pattern. Alternatively, the gaze generator may include a two-dimensional array of diodes (not shown), thereby defining multiple different patterns. This configuration can be achieved by arranging multiple diode strips (e.g., Figure 11 (As shown) are arranged adjacent to each other to form the structure.

[0091] The K-mirror configuration of the present invention can be further extended to provide linear (or lateral) scanning instead of or supplement rotational scanning. For example, the imaging system can selectively rotate and / or translate the K-mirror to switch between rotational and / or translational scanning operations.

[0092] Horizontal line scanning using a K-lens

[0093] In retinal imaging, line scanning is typically performed using a galvanometer placed near the pupil conjugate. When space is limited or inaccessible near the pupil conjugate, a scanning mechanism implemented near the retinal conjugate is preferred. This avoids the need for an additional optical repeater to create another pupil conjugate.

[0094] The use of prisms to create rotating beams is known, as described, for example, by Donald L. Sullivan in "Alignment of Rotational Prisms" (Applied Optics, Vol. 11, No. 9, September 1972) and by Liu et al. in "Field Rotation and Polarization Properties of the Porro Prism" (J. Opt. Soc. Am. A, Vol. 26, No. 5, May 2009). However, its ability as a scanning mechanism has not been fully explored. U.S. Patent 7,463,394 describes the use of roof prisms for scanning purposes, but appears to be limited to prisms with two mutually perpendicular reflective surfaces. More importantly, as mentioned above, prisms can produce undesirable aberrations if the light passing through them is not collimated. Therefore, prisms are unsuitable as scanning components placed at or near the retinal conjugate, where the beam in ophthalmic imaging systems is focused (uncollimated). An example of point rotation scanning using mirrors is described in Steelman’s “A Scanning System for Angle-Resolved Low-Coherence Interferometry” (Opt Lett, November 15, 2017, 42(22): 4581-4584). However, as discussed by Sullivan, aligning rotation scanning mechanisms can be challenging. Lateral (or translational or one-dimensional) scanning mechanisms would avoid some of these challenges and are easier to align. Therefore, lateral scanning mechanisms may be the preferred choice in some applications, if possible. This paper provides a scanning mechanism that uses K-mirrors to achieve a simplified lateral scanning mechanism.

[0095] Figure 13A K-mirror module K3 is shown that translates along one dimension (along arrow A5) to achieve lateral scanning. In this embodiment, the K-mirror K3 is positioned at or near the retinal conjugate between the scanning lens 31 and the eyepiece 33. For illustrative purposes, the light source 13 is shown to provide an illumination beam LB that passes through the scanning lens 31 (or optionally, the objective lens), through the scanning component (e.g., the K-mirror K3), and through the eyepiece 33 to scan the retina of the eye 29, as indicated by the displaced scanning beams SB1 and SB2. For illustrative purposes, mirrors M1, M2, and M3 are shown in a first position, and mirrors M1b, M2b, and M3b are shown in a second linear displacement position along arrow A5. When the K-mirror K3 is in the first position indicated by mirrors M1, M2, and M3, the beam LB is reflected from mirror M1 to mirror M2 and back to mirror M3 to define the outgoing scanning beam SB1. Similarly, when mirror K is in the second position indicated by mirrors M1b, M2b, and M3b, the beam LB is reflected from the second offset position on mirror M1b to mirror M2b and back to mirror M3b to define the outgoing scanning beam SB2. By applying reciprocating motion to mirror K3, the beam SB can be scanned along one dimension on the retina of eye 29 to achieve 1D lateral scanning. This lateral scanning mechanism solves the need for a scanner at the conjugate of the retina and mitigates the undesirable aberrations and dispersion characteristics of the prism by using a mirror reflector. Furthermore, the lateral scanning mechanism of the present invention can be aligned more easily than a rotational scanning mechanism.

[0096] Figure 14A and Figure 14B A more detailed Zemax diagram is shown, demonstrating lateral line scanning using K-mirror K3 (linear translation along arrow A6). TM simulation. Figure 14A An example using a line field system (e.g., a line beam) is shown. The K-mirror K3 is moved + / - mm at the conjugate plane of the retina to illuminate the retina horizontally across an 8 mm band, as shown by scan beams SB1 to SB5. The frontal plane view of the scanned retina is shown. Figure 30 Five line scan beams SB1 to SB5 at different scan positions are shown, as generated by the (linear) translational motion of the K-mirror. For ease of illustration, Figure 14B Five separate lateral / displacement positions of the K-lens are shown, which define five scanning beams SB1, SB2, SB3, SB4 and SB5 at five different scanning positions on the retina.

[0097] Using a mirror reflector or reflective surface, as in K-mirror K3, eliminates unwanted aberrations introduced by the prism into the non-collimated beam. The absence of aberrations makes this method preferably suitable as a scanning mechanism at the retinal conjugate, where the beam is typically not collimated. Scanners near the retinal conjugate can be useful when access to the pupil conjugate plane is limited or unavailable. This embodiment also shows that a roof structure, for example, described in U.S. Patent 7,463,394, is not necessary for generating beam displacement for lateral scanning, as the K-mirror proposed herein does not have a roof structure. Another advantage of this embodiment is that lateral scanning is generally simpler in terms of alignment compared to rotational scanning.

[0098] Other mirror assemblies with multiple reflective surfaces for lateral scanning are possible. Typically, odd-numbered reflections through the mirror system cause the beam to move in the same direction, while even-numbered reflections cause the beam to move in the opposite direction. A first amount of lateral movement of the mirror module can result in a second amount of lateral displacement / movement / scanning of the output scanning beam, multiplied by a factor of two or more.

[0099] When translating a K-mirror results in a lateral scan in one corresponding dimension, multiple K-mirrors can be combined to scan in more than one dimension. For example, combining two K-mirrors with a vertical scan axis enables two-dimensional scanning. However, the scanning speed of this structure may be limited by the speed constraints associated with the translation mirror assembly.

[0100] K-mirror lateral scanning can also be combined with other scanning methods. For example, Figure 15 A two-piece scanning mechanism is shown, wherein the first part is located at the pupil conjugate and the second part is located at the retinal conjugate. In this embodiment, the K-mirror K4 is placed at or near the retinal conjugate for slow-axis scanning. The galvanometer scanner G1 is placed near the pupil conjugate for fast-axis scanning. For example, in the case of two-dimensional point scanning, where scanning points are scanned horizontally to define a row of scanning points, and then moved vertically to a new row position, the horizontal scan would be a fast-axis scan, and the vertical scan would be a slow-axis scan. In this embodiment, the two scanners are spatially separated (K4 and G1) to facilitate system integration. This embodiment also allows the scanning pivot point (or galvanometer G1) to be substantially at the pupil conjugate, which would be difficult to achieve if both galvanometer scanners needed to be at one pupil conjugate, for example, as Figure 1 As shown.

[0101] Various translation mechanisms for K-mirrors are suitable for this invention. Figure 16A and Figure 16B A first K-mirror translation mechanism using a sensor actuator 61 is shown.

[0102] In this method, the inductive actuator 61 is combined with a parallel flexure (e.g., an isotropic spring) 63, each providing opposing forces as indicated by arrows A7 and A8. Figure 16B As shown, when the inductive actuator 61 is actuated / activated, for example by applying an appropriate current i, a force is generated that causes the support rod 62 (and the attached K-mirror K5) to move and produce a proportional translational offset Δx. Conversely, when the inductive actuator 61 is not actuated, or when the applied current i decreases, the spring force of the parallel flexure 63 moves the K-mirror K5 in the opposite direction to eliminate or reduce the offset Δx. The inductive actuator 61 provides quieter operation compared to a mechanical actuator. The parallel flexure 63 allows for a compact inline arrangement. Moreover, the displacement is a function of the current, Δx = f(i), and therefore the need for an encoder is eliminated. This is because the inductive actuator 61 applies a force F i The force is a function of the current i, F i (i) works in conjunction with a spring, which applies a force F proportional to the displacement Δx. k For example, F k (Δx) = kΔx, where k is the spring constant. In equilibrium, F i (i)=F k (Δx)=kΔx, therefore the displacement (Δx=F) i (i) / k) is thus a function of the current i.

[0103] Figure 17 An alternative translation mechanism is shown, which uses a motor 65 with an eccentric (e.g., an eccentric wheel / disc 67) to move the K-mirror K5, thereby deforming the parallel flexure 63 by a given offset Δx. The object rotated by the motor 65 (e.g., the wheel or disc 67) is asymmetrical relative to the center of rotation, so its rotation can, for example, cause translation of the adjacent parallel flexure 63 by pushing the K-mirror K5. The object 67 rotated by the motor 65 does not need to be a disc. Any shape (e.g., a teardrop shape) can be designed to provide the desired scanning speed and / or pattern.

[0104] As described above, because the present invention allows scanning components (e.g., K-lens) to be positioned at the retinal conjugate, it cannot be used for pupil separation. Therefore, the present invention proposes positioning a fixed beam splitter of a specific size and shape at the pupil conjugate to provide pupil separation. Since the beam splitter is fixed, it is easy to position it at the pupil conjugate to achieve pupil separation, which further simplifies the assembly of ophthalmic imaging systems. As will be discussed more fully below, this configuration provides additional benefits for interferometric applications, such as OCT / OCTA.

[0105] Beam splitter design for efficient interferometry

[0106] For ease of discussion, this embodiment is described as being applied to an OCT system; however, it should be understood that similar pupil separation functionality can be applied to fundus imagers or OCTA systems. Again, for ease of discussion, this embodiment focuses on the relevant components, as referenced above. Figure 1 The invention is discussed in the context of OCT examples, but configured for specific field configurations such as line-field or full-field imaging. An implementation for line-field imaging is first presented, followed by a discussion of the benefits of applying the invention to full-field imaging. However, it should be understood that the invention can be applied to other optical field configurations.

[0107] Figure 18 Three beamsplitter configurations that can be used with a linear field ophthalmic imaging system are shown. It should be understood that similar configurations can be used with a full field ophthalmic imaging system. The first beamsplitter configuration may be referred to as a “conventional coaxial” configuration, with the beamsplitter BS centered on the illumination / collection optical axis to the sample (e.g., the eye) and spanning the entire optical path from the illumination (light) signal / beam LtB (shown herein as the scan line SL) to the eye and the entire collected signal / beam CB from the sample. The sample beam SB points to the sample being imaged (e.g., the sample arm of the system), for example, the eye being tested. The FOV of the collected beam (e.g., from the condenser angle) is shown here as a circular collection window CW. Since in the conventional coaxial configuration of the present invention, the entire collected signal CB passes through the beamsplitter BS on its way to the condenser, the collection window CW is shown as completely darkened to show that the entire collected beam CB is attenuated by the beamsplitter BS on its way to the condenser. For completeness, the system pupil aperture PS, such as the physical aperture aperture, is also shown. The pupil aperture (PS) can be placed at the pupil conjugate of the imaged eye. In this case, the pupil aperture (PS) helps to define the capture window (CW).

[0108] The second configuration can be referred to as an "off-axis" configuration, and it offsets the beam splitter BS from the illumination / collection optical axis such that it only spans a portion (e.g., approximately half) of the optical path returning to the collection beam CB. In this configuration, a portion of the collection window CW is shown as darkened corresponding to the portion of the collection beam CB that passes through the beam splitter SB, and the remaining portion of the collection window CW is shown as white to highlight the portion of the collection beam CB that passes through the plane of the beam splitter BS but does not cross the beam splitter and is therefore not attenuated by the beam splitter BS. In this case, the focus of the line scan LS (e.g., the illumination beam LtB) is shown within the dark portion of the collection window.

[0109] The third configuration, referred to herein as "optical footprint BS coaxial," uses a beam splitter BS whose shape conforms to the optical footprint of the illumination beam LtB. In a line-field example of this aspect, the beam splitter BS of the optical footprint BS coaxial configuration can be shaped as an elongated slit (or rectangle) whose area (or size) conforms to the optical footprint of the incident illumination beam LtB, and can be slightly larger than the optical footprint. In this case, since most of the collected beam passes undiminished above and below the beam splitter BS, the collection window CW is mostly shown as white. Only the central region of the collection window CW is shown as dark, which corresponds to the location at the focal point of the line scan LS (e.g., the illumination beam LtB) of the beam splitter BS.

[0110] In line-field OCT using conventional coaxial construction, the beam splitter (BS) in the interferometer is typically a plate or cube beam splitter with a uniform beam splitting ratio across the entire optical surface, as referenced above. Figure 1 This is under discussion. In this typical implementation, the beamsplitter directs a limited amount of sample light SB toward the sample (e.g., the fundus) and attenuates the backscattered light signal CB from the sample, thus limiting detection sensitivity. For example, in a conventional coaxial configuration, the illumination beam LtB passes through the beamsplitter BS twice (once when it splits into the reference beam RB and the sample beam SB, and again when the collection beam CB returns from the sample). For a 50 / 50 beamsplitter, this means a 75% loss of illumination light LtB (50% for each pass). This power inefficiency is undesirable, especially when power supply and the amount of light allowed to reach the eye are limited. A method is needed to efficiently direct the probe light (e.g., the sample light SB) toward the sample and efficiently collect the backscattered light CB returning from the sample.

[0111] Previous efficiency improvements have been proposed. Polarization-based methods are described in U.S. Patents 7,145,661 and 9,778,020, assigned to the same assignee as this application. This method uses a polarization beam splitter (BS) and a polarization rotator as a non-reciprocal beamsplitter in the probe path, allowing the polarization of the backscattered light to be rotated and efficiently passed through the polarization beamsplitter. However, the birefringence of the sample may alter the polarization state of the backscattered light, thus reducing efficiency. Furthermore, polarization optics are generally more expensive and unsuitable for low-cost devices. An off-axis detection method is described in common U.S. Patent Application 2018 / 0259316, in which the beamsplitter is positioned to partially cover the collecting pupil, allowing for more efficient guidance of the probe light and higher signal light throughput. However, this method still blocks most of the collecting pupil and signal light. Additionally, because the beamsplitter is conjugate to the collecting pupil of the optical sensor or camera, it cannot provide pupil separation functionality (of the eye). For example, another method described in U.S. Patents 7,648,242 and 6,758,564 uses an aperture beamsplitter in a scanning laser ophthalmoscopy (SLO) system; however, to date, none of the advantages of aperture beamsplitters for interferometry have been fully realized. Another approach is to replace the aforementioned free-space beamsplitter construction with a dedicated fiber optic coupler. For example, fiber-based optical circulator implementations have been described in conjunction with point scanning (e.g., point field) OCT, as described, for example, in U.S. Patent 7,362,444B2; however, this method is not suitable for line field OCT and increases cost.

[0112] In this method, the off-axis configuration allows a portion of the backscattered collected light CB to pass through the same plane as the beam splitter (e.g., the same pupil conjugate plane), but avoids passing through the beam splitter itself. Additionally, the physical aperture diaphragm (or pupil diaphragm) PS can be positioned at another pupil conjugate plane and configured to help define the pupil separation region. The physical aperture diaphragm, used in conjunction with the beam splitter, can provide pupil separation functionality. Furthermore, as described below, the shape of the pupil diaphragm can be selected according to specific imaging needs, such as for higher axial depth resolution and / or for light intensity and lateral resolution. In this example, the pupil diaphragm PS is shaped to block most of the beam splitter area.

[0113] In a linear field OCT system, the illumination beam LtB is focused (uncollimated) in one dimension / orientation of the beamsplitter (e.g., along the width dimension of the line scan LS) and remains uncollimated in an orthogonal dimension (e.g., along the length dimension of the line scan LS). This illumination forms mutually perpendicular lines at the pupil and object plane in the system, respectively. In a coaxial configuration of the optical footprint BS, the beamsplitter BS can be a slit beamsplitter (slit BS) with a narrower optical surface in the dimension where the illumination beam LtB is focused, and can be several times (e.g., 10 times) the beam width, as determined by the system's mechanical / operational tolerances. The slit beamsplitter can also have a wider optical surface in the dimension along the scan line. Similarly, the beamsplitter can be placed at or near the (eye's) pupil conjugate plane. This slit beamsplitter can also have a high reflectance-transmittance ratio (e.g., 10 / 90) to guide most of the source light LtB toward the sample, and a high throughput for the collected signal light CB without (or with minimal) obstruction or attenuation by the slit beamsplitter. A 10 / 90 reflectance-transmittance ratio means that the light signal beam attenuates by 90% each time it passes through the beamsplitter, and is therefore generally unsuitable for conventional coaxial methods, as this would significantly reduce the collected signal CB returning from the sample. However, in the optical footprint BS coaxial construction of the present invention, a high reflectance-transmittance ratio is possible because most of the returning collected signal light CB does not pass through the slit BS and therefore does not undergo its 90% attenuation. Compared to a conventional coaxial design with a 50 / 50 beam splitting ratio, the slit beamsplitter of the present invention provides approximately 6 dB of sensitivity improvement. Moreover, compared to other designs, the slit beamsplitter (of the optical footprint BS coaxial construction) is a reciprocal component in line-field interferometry that effectively guides the necessary light only in each aspect (illumination, collection, reference).

[0114] Advantageously, the ophthalmic imaging system of the present invention can be configured to switch between an off-axis configuration and a coaxial configuration with a light footprint (BS). That is, by changing the pupil aperture (PS), the instrument can switch between coaxial and off-axis operation without changing the optics. Because both modes have their own advantages, this flexibility enables the device to be used in a wide range of applications. The slit beamsplitter blocks low spatial frequency signal light and allows for clear separation of background and illumination signals.

[0115] This feature is useful in systems with fluctuating light source spectra, such as pulsed tuned diode lasers. The low spatial frequency block also rejects corneal reflections. Coaxial designs are easier to implement than off-axis methods, and slit beam splitters are less expensive than polarization-based methods. Furthermore, slit beam splitters allow for line-scan scanning laser ophthalmoscopy (SLO) with identical settings, which cannot be achieved through an aperture in the lens.

[0116] Figure 19A simplified schematic diagram of the coaxial configuration of the optical footprint BS in a line-field SDOCT system is shown. The slit beam splitter (slit BS) is positioned at or near the pupil conjugate plane. It should be noted that the coaxial design of the optical footprint BS allows for efficient guidance of the illumination (sample) beam SB and minimizes attenuation or obstruction of the collection beam CB. As described above, the collection beam CB and the return reference beam RB pass through aperture 39 to the collector 41, which can be constructed from a spectrometer. A diffraction grating 40 splits the incident light into components of different frequencies, and a light sensor 42 captures the resulting spectrum.

[0117] Figure 20 A first structure for a light footprint beam splitter suitable for line field applications is shown. For fabrication, the slit BS can be a slit-like coating 62 on a larger substrate 64. For example, the slit BS can consist of a slit-like coating on a thin glass substrate 66. Alternatively, the slit BS can be a thin strip 66 of a uniformly coated substrate. The substrate can be a plate or a prism, and the coated surface can be sandwiched between the two substrates.

[0118] Figure 21 A second structure of the optical footprint BS suitable for use with full-field or partial-field applications is shown, wherein the illumination light is focused onto a point, dot, or small 2D region. In this case, a dotted (e.g., circular) beam splitter 68, the size of which is determined by the illumination light footprint, can be used. The dotted beam splitter 68 can be coated on a larger substrate 64, or it can be a uniformly coated circular substrate 70. The dotted beam splitter 68 will be a small two-dimensional region at the pupil conjugate plane.

[0119] Figure 22 An alternative structure of the beam splitter of the present invention is shown, wherein the beam splitter is not comprised of a small-area coating on a transparent substrate (e.g., a thin glass substrate 64), but is configured as a coating on a total reflection substrate, wherein the illumination light LtB passes through the beam splitter to define a sample beam SB on the sample arm and is deflected by the beam splitter to define a reference beam RB on the reference arm.

[0120] Similar benefits of efficient illumination and collection, as well as spatial frequency analysis, will apply to all these beam splitter constructions.

[0121] Typically, a 1D FFT is applied to the spectrum (e.g., captured by the light sensor 42) to reconstruct depth information at the retina of the eye. However, by first applying a 2D FFT to the captured spectrum, the spatial spectral distribution at the pupil conjugate can be reconstructed. For example, Figure 23 The spectrum 71, which can be obtained using the optical footprint BS coaxial method, is shown, along with the resulting representative retina 73, which can be constructed by applying 1D FFT to the spectrum 71. Figure 24 The same spectrum 71 is shown, but the 2D FFT result is applied to the spatial frequency image 75.

[0122] Figure 25 2D FFT analyses of the spectra captured for conventional coaxial, off-axis, and optically footprinted BS coaxial constructs are shown. Each analysis shows the restored reference signal and two interference signals, one above and one below the zero z-axis reference. One of these interference signals (e.g., the one above the zero z-axis) can be the true interference signal, while the other (e.g., the interference signal below the zero z-axis) can correspond to the complex conjugate of the true interference signal. In the case of a conventional coaxial design, the reference signal and the interference signal overlap each other, making them difficult to separate. By comparison, the 2D FFTs of the signals obtained from off-axis and optically footprinted BS coaxial constructs show that at low spatial frequencies (e.g., close to zero U... x The reference signal at the lower spatial frequency (U0) is clearly separated from the interference signal at higher spatial frequencies. This allows for direct retrieval of the reference spectrum from the interferogram, and is of particular interest for sources with fluctuating spectra (e.g., pulsed tuned diode lasers). Compared to conventional coaxial methods, off-axis methods not only collect more light with higher lateral resolution but also acquire full spatial frequency content that allows for full phase analysis / correction along one dimension. For example, maskable zero U0... x The spectrum below the value, and along zero U x Analyzing the Z dimension in the spectral portion above yields the full range (e.g., higher depth resolution) without obstruction from complex conjugate components. However, the full range capability and sensitivity advantages for near-zero delay imaging may be reduced or lost. A coaxial design with a light footprint (BS) can provide higher imaging sensitivity (including near-zero delay) and can be easily converted to off-axis operation by implementing different aperture diaphragms (PS) at the pupil conjugate plane. This flexibility allows the system to operate in different modes for different applications. For high-sensitivity and lateral resolution applications where depth range is not critical, such as retinal and skin imaging, the instrument can operate in light footprint (BS) coaxial mode. For long depth range applications where sensitivity and lateral resolution may be compromised, such as anterior segment (eye) imaging, the instrument can operate in off-axis mode. For example, in the off-axis spectrum shown, as along the z-axis, the full depth range can be obtained from the interference signal on the reference signal side without overlap between the real interference signal and its complex conjugate, allowing for greater axial resolution. This opens up possibilities for various applications with a versatile OCT device.

[0123] By introducing a variable (system) aperture at the pupil conjugate, ophthalmic imaging systems can easily switch between coaxial mode for higher sensitivity and off-axis mode for greater resolution. For example, Figure 26Three sample OCT images are shown, taken using both coaxial and off-axis modes of the light footprint BS. Image 77 shows a slit BS with coaxial mode on skin, and image 78 shows a slit BS with off-axis mode on skin. As shown, image 78 achieves higher depth resolution but with reduced light and lower lateral resolution. For highly scattering samples like skin, the coaxial mode of the light footprint BS (image 77) can be superior to the off-axis mode for higher sensitivity because tissue allows for limited penetration depth. However, for more transparent samples, such as the anterior segment of the eye or tape, the off-axis mode provides a longer depth range, as shown in image 79.

[0124] Figure 27 An exemplary beam-splitting scenario and an illumination / detection pupil for full-field or partial-field interferometry are illustrated. In this case, the optical footprint BS is implemented as a point beam splitter, the size of which is determined by the full-field (FF) focal region (e.g., the optical footprint) of the illumination signal LtB. Figure 18 All components similar to those described above have similar reference numerals.

[0125] Figure 28 Showing the target Figure 27 Exemplary detection signals in the 2D spatial frequency domain for each of the three scenarios (e.g., obtained by applying 2D FFT). As previously described, the reference signal 81 and the interference signal 83 in the conventional coaxial mode overlap each other, but they are separate in the coaxial mode and in the optical footprint BS coaxial mode.

[0126] In summary, in the above embodiments, the beam splitter BS is placed at the pupil conjugate of the line-field OCT system for efficient illumination and signal collection. A variable or switchable system pupil aperture can be placed (e.g., another) at the pupil conjugate for switching between coaxial and off-axis modes, or for selecting the size / shape of the collection pupil. As described above, this structure can use a beam splitter to perform pupil separation of the sample beam and the collection beam. This embodiment also allows the separation of the low spatial frequency components of the reference signal read from the light sensor / camera from the interferometric measurement signal. The reference signal can then be used as a background signal for OCT processing. The use of 2D FFT provides the spatial spectral distribution at the pupil conjugate and allows selection of the interferometric signal excluding any complex conjugate components. Moreover, the slit BS design of the present invention allows for the integration of line-field OCT and line-scan SLO using the same setup.

[0127] It should also be noted that performing a 2D FFT on the captured spectrum provides a 2D spatial frequency distribution at the pupil conjugate (e.g., at the pupil of the patient's eye). This allows for the use of spatial frequency analysis to align the ophthalmic imaging system with the patient's eye before capturing the image.

[0128] Spatial frequency analysis of pupil alignment in OCT

[0129] Proper alignment of an ophthalmic imaging system / device with the patient's eye is a critical step in image acquisition, which can affect image quality and the information derived from the captured image. Unfortunately, achieving proper alignment can be a complex process requiring additional imaging components and interaction with numerous technicians. In ophthalmic OCT instruments, an iris camera (or other alignment aids / mechanisms) is typically required to image the posterior aspect of the patient's eye as part of the process of aligning the patient's pupil with the instrument. This requirement complicates the system and increases its cost. Therefore, a simple and cost-effective method for pupil alignment is desired, especially when the objectives are compact and low-cost OCT devices.

[0130] The spatial frequency in OCT interferometry arises from the offset of the backscattered light and the reference light at the pupil conjugate. By analyzing the spatial frequency content (e.g., a two-dimensional FFT of the interferometry in a line-field SD-OCT system), the spatial distribution of the backscattered signal within the system's collecting pupil can be inferred. This information is built into the OCT data (integrated into the OCT data) and can be extracted for patient alignment of the OCT device, thereby simplifying OCT device setup and reducing its cost.

[0131] The study of spatial frequency analysis in OCT has opened up possibilities for eye imaging in recent years. The spatial frequency content of full-field (FF) frontal OCT images has been used for digital aberration correction, see, for example, Kumar et al., “Numerical focusing methods for full-field OCT: a comparison based on a common signal,” Opt. Express, Vol. 22, No. 13, 16061-16078, 2014. However, the use of spatial frequency analysis (e.g., 2D or 3D FFT) in OCT for patient pupil alignment has not been fully investigated. This paper presents a method that provides a direct solution to the problem of patient pupil alignment.

[0132] In this method, the spatial frequency in the OCT interferometric signal (e.g., the 2DFFT of the interferometer in a volumetric LF-SDOCT system) serves as a cue for patient pupil alignment. It can be used as part of, for example, a fully or semi-automatic pupil alignment subsystem, or as a system providing alignment instructions, suggestions, or identifying potential sources of alignment error to the system operator. The spatial frequency content can be generated from the backscattered signal and the offset of the reference light at the pupil conjugate. The spatial frequency content can be visualized and analyzed in FFT space, and the alignment of the patient's pupil relative to the instrument's pupil can be inferred within FFT space. For example, in an online scanning OCT system, alignment information in a dimension can be inferred from the spatial frequency content along the dimension of linear illumination parallel to the retina.

[0133] For illustrative purposes, an example of the optical footprint BS coaxial method implemented in the above-described online field (LF)-SDOCT system is provided. It should be understood that the present invention can be implemented using other types of OCT systems, such as full-field, partial-field, and helical scanning OCT systems. Figure 29 Spatial frequency analysis for pupil alignment is illustrated in an exemplary LF-SDOCT system of the present invention. In this embodiment, the illumination beam / signal forms a beam 91 at the pupillary plane (note that a corresponding [e.g., substantially orthogonal] beam is also formed at the retinal plane, e.g., forming line illumination on the retina, not shown), and the instrument's collecting pupil 92 may be a circular region (or other shaped region) centered on the illumination beam 91. Figure 29 As further illustrated, from the perspective of the light sensor, the reference signal can be located within the region of the illumination beam 91 at the collecting pupil 92. When the collecting pupil 92 is aligned with the patient's pupil 93, as shown in Example Ex1, the full spatial frequency content 94 within the collecting pupil 92 is detected. However, as shown in Example Ex2, when the collecting pupil 92 is offset at the patient's pupil 93 along a first direction perpendicular to the beam 91, a portion of the spatial frequency 95 is missing compared to the spatial frequency 94 of Example Ex1. The missing portion corresponds to the degree of misalignment between the collecting pupil 92 and the patient's pupil 93 along this first direction. It should be noted that, as shown in Example Ex3, the offset of the collecting pupil 92 along a second direction parallel to the beam 91 (e.g., perpendicular to the linear illumination on the retina, not shown) cannot be readily determined from the obtained spatial frequency 96 (e.g., using a single scan (e.g., a B scan) along a single scan dimension at a single scan position on the retina). In this case, the beam 92 can be rotated to be orthogonal to the second direction, thereby noting any offset in this second direction. That is, in some implementations, the collecting pupil offset in 2D space can be identified, for example, by using two mutually perpendicular scans through a rotating scanning mechanism. Therefore, pupil alignment along two dimensions can be inferred from these two measurements.

[0134] Alternatively, since misalignment information can be easily determined along one direction of the line field OCT, misalignment information / hints can optionally be obtained by determining an FFT along that direction. For example, displacement can be determined by calculating an FFT along a dimension parallel to the line bundle 91. In this case, a one-dimensional (1D) FFT can be used to determine the misalignment information, and it is not necessary to calculate a 2D FFT.

[0135] Therefore, spatial frequency analysis in OCT provides a direct cue for patient pupil alignment. This method reduces or eliminates the need for additional setups / devices (e.g., iris cameras) for providing alignment cues within the OCT apparatus.

[0136] Figure 30 An exemplary workflow for determining pupil alignment in an OCT system according to an embodiment of the present invention is provided. In step S1, at least one OCT interferometric dataset (e.g., a single retinal scan) is collected. This dataset can be, for example, a linear field or full-field SDOCT / TDOCT dataset. In step S2, an FFT along the at least one dimension of the dataset reveals the spatial frequency content along that direction. An optional second FFT along an orthogonal direction can reveal the spatial frequency content along that second direction. For example, in the case of linear field OCT, the FFT can be selectively determined along a direction parallel to the line beam. In step S3, the spatial frequency distribution is determined. This specific spatial frequency data is then processed, and in step S4, the pupil alignment of the patient relative to the system's collecting pupil is determined. In step S5, the alignment information can be used by the system for automatic alignment or presented to a human system operator in a user-friendly format to guide alignment.

[0137] Figure 31 , Figure 32 , Figure 33 and Figure 34 Empirical data for spatial frequency analysis of pupil alignment in LF-SDOCT according to this embodiment are shown. Each figure shows a corresponding OCT image 101, its corresponding interferometric image 103 in 2D FFT (showing the spatial frequency signal), and corresponding images 105 and 107 of the patient's pupil (e.g., the test eye) taken with an iris camera using OCT, for reference. Figure 31 The first dataset is shown when the patient's pupil is aligned with the system's collecting pupil in the X, Y, and Z directions. As shown, the entire spatial frequency signal is visible in the interferometric image 103.

[0138] Figure 32The second dataset is shown when the patient's pupil is offset in the Y direction. In this case, a quarter of the spatial frequency components are missing from its interferogram 103 due to the offset. Furthermore, it was observed that the greater the offset, the more spatial frequency information is missing. One advantage of this method is that it is directly related to OCT illumination and acquisition; therefore, both the patient's perception of illumination and the obtained OCT images are related to the alignment. Figure 32 In this example, it is evident that the loss of spatial frequency content is also observed as a corresponding loss of lateral resolution in OCT image 101. The offset along the Y-axis results in the tilt of the retinal structures in OCT image 101.

[0139] Figure 33 An example is shown when the eye is too close to the instrument, and Figure 34 An example is shown when the eye is too far from the instrument. Given a Y offset, Figure 33 and Figure 34 The halos in the OCT image 101 convey information about the offset along the Z-axis. More specifically, in its 2D FFT space 103, the Z-off is represented by an inverse slope at the edges of the spatial frequencies. Additionally, the patient will perceive portions of the halos illuminated due to misalignment. This information can be used, alone or in combination, as a cue to guide pupil alignment, through an automated subsystem, a semi-automatic subsystem, or a manual process.

[0140] In an alternative embodiment, the invention can be applied to multiple B-scans spanning a 2D region (e.g., the retina), which may be found or extracted from volumetric / cubic (or cubic) scans (e.g., C-scans). For example, a 2D FFT of the interference in a volumetric LF-SDOCT system (or other scan-type OCT system) can be used as a cue for the alignment of the patient's pupil with the OCT system. Additional alignment information can be obtained by using multiple B-scans along the displacement location on the retina. Alignment information in this dimension can be inferred from the spatial frequency content along the illumination parallel to the retina. The spatial frequency content can be visualized and analyzed in FFT space, where the alignment of the patient's pupil relative to the instrument's pupil can be inferred. Pupil alignment in other dimensions can be inferred from the position of the retina within one or more reconstructed B-scans, which can be determined by the difference in optical path length between light backscattered from the sample and light backscattered from the reference mirror. Conveniently, information about misalignment in all three dimensions (X, Y, Z) can be inferred using a 2D FFT analysis of a set of interferograms (e.g., B-scans), which may include volumetric scans or be selected from B-scans that include volumetric scans.

[0141] In a preferred embodiment, the method is implemented using a volumetric LF-SDOCT system. (See above reference.) Figure 29As explained, the illumination beam from the light source forms a beam 91 at the pupillary plane (and also at the retinal plane), and the collecting pupil 92 of the instrument can be a region (e.g., a circular region) centered around the beam 91.

[0142] Figures 35 to 39 Different pupil alignment scenarios are shown, and their corresponding 2DFFT analyses are applied, for example, to volumetric scans. Figures 35 to 39 Zhongyu Figure 29 All elements in the drawing have similar reference numerals, as described above. Because... Figures 35 to 39 The implementation illustrates volumetric scanning (or multiple B-scans spanning a predetermined 2D region), so more than one B-scan can be acquired / analyzed. The number of acquired B-scans can vary depending on the scanning frequency of the OCT system. For example, a cubic structure scan (C-scan) in a typical OCT system / device may include (e.g., capture or acquire) more than one hundred B-scans in a single acquisition mode operation. However, it should be understood that not all B-scans that include volumetric scanning require 2D FFT analysis. Selected B-scans spanning a 2D region can be extracted from the C-scan. For example, 2D FFT analysis can be applied to a portion of the B-scans in the C-scan (e.g., 10%, 25%, 50%, etc.). For example, every other B-scan in the C-scan can be selected for 2D FFT analysis (or every fourth B-scan, etc.). The B-scans selected for 2D FFT analysis can span a large portion (e.g., more than half) of the entire scan area of ​​the C-scan, or can be selected from a predetermined portion / small portion (e.g., less than half) of the scan area of ​​the C-scan.

[0143] like Figure 35 As shown (and) Figure 29 As shown in Example Ex1), within a single B-scan, the full spatial frequency content 94 within the pupil is detected and collected when the patient's pupil 93 is aligned in the X, Y, and Z dimensions. Figure 19 In the case of instance Ex2, as shown in Figure 36 Within the single B-scan shown, when the pupil is offset from the linear illumination at the pupil (or parallel to the dimension of the linear illumination on the retina), for example along the Y-axis, a portion of the spatial frequency 95 is missing. This missing portion may correspond to the degree of misalignment of the patient's pupil 93 along this direction.

[0144] like Figure 37 and Figure 38 As shown, by positioning / positioning their spatial interferences 97 and 99 respectively with the spatial interference 94 of the alignment state (e.g., Figure 35 By comparing (as shown), incorrect working distances (e.g., in the Z direction) can also be detected within a single B-scan. When the patient's pupil 93 is not located at the correct working distance in the Z direction (e.g., ... Figure 37 The image is too far from the imaging device or as shown Figure 38 When the image is too close to the device (as shown), the vertical positions of the corresponding spatial interferences 97 and 99 will differ from those in the aligned case 94. The offset of the spatial interference relative to the aligned state can provide information about the misalignment and misalignment direction along the working distance (Z).

[0145] Figures 35 to 38 This illustrates that misalignment information in the Y and Z directions can be extracted from a single B-scan. However, it should be understood that, if necessary, additional Y and Z misalignment information can be extracted from supplementary B-scans (e.g., from different locations on the retina), as this will provide additional information, such as for confirming the amount of misalignment calculated or for averaging misalignment measurements from multiple B-scans. As described above, misalignment in the X direction can be determined by rotating the beam 91 to an orthogonal position and determining its resulting spatial frequency. However, detection of misalignment in the X direction can also be determined without rotating the beam 91 by comparing (and / or contrasting) the 2D FFT space of multiple B-scans from different locations on the patient's retina (e.g., by determining how the B-scans change with changing locations in 2D FFT space).

[0146] refer to Figure 39In volumetric OCT scans (or alternatively, acquiring / capturing / accessing any number of B scans, such as 8 B scans spanning a 2D region), lateral misalignment of the patient's pupil in the X direction (e.g., no rotation of the beam 91) can manifest as a progressive shift of the retinal position across multiple B scans (or volumes), and as different vertical interference positions in 2D FFT space. Optionally, a volumetric scan can be part of the overall C-scan capture mode operation of the OCT system, or any (e.g., predetermined) number of B scans (e.g., 8 B scans) can be part of a specific alignment scan mode operation of the OCT system. As shown, when the 2D FFT of different B scans along a given 2D region of the retina is determined, the position of the interference pattern (e.g., vertically along the Z-axis) varies. For example, it may move closer to each other (e.g., near each other) or further away from each other (it may itself be some distance from each other) depending on the amount of misalignment in the X direction. In this example, the 2D FFT of the Nth B-scan shows spatial interference patterns far from each other and from the properly aligned position 86 / 88. However, when the 2D FFTs of the (N+1)th and (N+2)th B-scans are determined, the spatial interference patterns are closer to each other. By determining how the 2D FFT interference changes with the B-scan position (e.g., relative to the properly aligned position 86 / 88), misalignment information in the X direction (e.g., the amount and / or direction of misalignment) can be inferred. The misalignment in the X direction (e.g., the amount and / or direction ±X) can be correlated with the amount and / or direction of the change in the 2D FFT interference over a given 2D region on the retina from B-scan to B-scan. Additional information can be collected by combining this X-direction information with Y and Z information extracted from one or more B-scans within a given 2D region.

[0147] Therefore, analysis of two-dimensional interferograms in volumetric OCT (e.g., LF-SDOCT) can provide direct cues for the alignment of the patient's pupil in all directions (relative to the OCT device). This method can reduce or even eliminate the need for additional setups (e.g., iris cameras) to provide alignment cues within such devices. It can also provide real-time alignment feedback to the OCT operator during scan acquisition, and / or facilitate automatic alignment and / or automatic acquisition for the scan.

[0148] Figure 40An exemplary workflow of the present invention is provided, which can be applied to volumetric OCT data. In step St1, at least one volumetric LF-SDOCT of an interferometric dataset (e.g., comprising multiple B scans) is collected. In step St2, a 2D FFT analysis is applied to the (interferogram) dataset, or B scans are selected from the dataset spanning a 2D region. In step St3, the spatial frequency distribution and depth profile are determined. That is, the 2D FFT analysis reveals the spatial frequency-depth profile (information along the Z direction and spatial frequency along the Y direction). In step St4, this data is processed over the entire cube, or processed in a selected number of B scans within the cube or a selected portion of the cube, to determine the alignment of the patient's pupil relative to the system's collected pupils (e.g., in three dimensions). In step St5, the OCT system can use the alignment information to automatically align the system with the patient, and / or can present the alignment information to the system operator and / or the patient in a user-friendly format to guide system alignment. That is, the system can use the determined pupil alignment to provide suggestions to the system operator or patient on adjusting the system or patient to improve alignment, or to suggest possible sources (or incorrect system use) that may cause incorrect alignment. Patients can use the information provided in the patient self-alignment application.

[0149] One advantage of this implementation is that it is directly related to the illumination and acquisition of OCT, so the patient's perception of the illumination and the obtained OCT images are both related to the alignment. Figure 41A and Figure 41B Experimental data are provided, demonstrating the use of 2DFFT analysis to determine misalignment in the Y direction. Figure 41A and Figure 41B OCT images 100a / 100b from B-scans, corresponding 2D FFT analyses of B-scans 102a / 102b, and images 104a / 104b (photographs) of the tested eye (e.g., the eye under test) as seen (captured) by the system's iris camera are shown, for example, images commonly used to determine proper patient-system alignment in conventional OCT systems. For comparative purposes, Figure 41A The state of proper XYZ alignment is shown. Figure 41B This illustrates a misaligned state in the Y direction / dimension (where the XZ dimensions remain properly aligned). As mentioned above, misalignment information in the Y direction can be extracted from a single B-scan. Therefore, Figure 41B An OCT 100b image of a single B-scan and interference in 2D FFT space 102b are shown, along with the corresponding iris camera image 104b. However, as mentioned above, Y misalignment can optionally be determined from more than one B-scan of the volumetric OCT scan.

[0150] When the patient's pupil is aligned with the system's collecting pupil in the X, Y, and Z directions, the following information is obtained: Figure 41A The dataset was obtained when the patient's pupil was deflected in the Y direction (e.g., approximately 2.5 mm towards the top of the optical axis). Figure 41B The dataset. In this example, approximately one-quarter of the spatial frequency component 102b is missing due to offset (compared to the spatial frequency component 102a in the aligned case). Furthermore, the interference pattern fringes of frequency component 102b are different from those in the aligned case. Figure 41A The interference pattern fringes are thicker or wider in the aligned state compared to the misaligned state. Furthermore, it has been observed that the greater the misalignment offset, the greater the amount of missing spatial frequency patterns (e.g., these can be proportional and / or correlated with each other). Loss of spatial frequency content has also been observed as a loss of lateral resolution in OCT image 100b. That is, a Y-shift may lead to tilting of retinal structures, as shown in OCT image 100b.

[0151] Figure 42A , Figure 42B and Figure 42C Experimental data related to the detection of Z misalignment using 2D FFT analysis in LF-SDOCT are presented. Specifically, the impact of Z misalignment (misalignment along the optical axis of the OCT system) on OCT images and 2D FFT is shown. Figure 42A , Figure 42B and Figure 42C The OCT images 106a / 106b / 106c of the B scan, the corresponding 2D FFT analysis 108a / 108b / 108c of the B scan, and the corresponding images 110a / 110b / 110c of the tested eye during the acquisition of the B scan are shown respectively. Figure 42A The state of proper XYZ alignment is shown. Figure 42B The diagram shows a misalignment (e.g., Z-offset) in the Z direction toward the OCT device (where XY is properly aligned), and Figure 42C The misalignment in the Z direction, away from the OCT device (where XY is properly aligned), is shown.

[0152] The vertical axis in 2D FFT and OCT images represents the depth profile (information along the Z-direction). As a result, any discrepancy between the distance between the patient's pupil and the imaging device and the designed / desired working distance can be represented along this axis. Misalignment can also be derived. For example, if the patient's eye is positioned closer to the imaging device than the designed working distance, interference fringes in the 2D FFT data will be closer along the vertical axis (108b vs. 108a), and the retinal layer will be positioned / displayed more towards the top of the OCT image (106b vs. 106a). Figure 42B This illustrates an exemplary case with a 0.4mm Z-offset that is closer to (e.g., towards) the imaging device. Furthermore, if the patient's eye is positioned further away from the designed working distance (e.g.... Figure 42C As shown), interference fringes 108C tend to separate from each other / move further away in 2D FFT data along the vertical axis (108c compared to 108a), and the retinal layer in OCT image 106C is shown / placed more towards the bottom of the OCT image (106c compared to 106a). Figure 42C The last dataset shows a case with a Z offset of 0.4 mm, which is far from the imaging device (e.g., an OCT system).

[0153] As described above, accessing multiple B-scans from different portions of a 2D region (e.g., on the retina or other target to be imaged / scanned) allows for the determination of X-misalignment information without rotating the current scan orientation (e.g., without rotating the scan beam). For example, X-misalignment can be detected (e.g., X-misalignment information can be determined) by acquiring a volumetric OCT scan (or acquiring multiple B-scans across a 2D region) and comparing the vertical position and / or intensity of interference fringes in the 2D FFT data. For this purpose, existing full cubic structure scans (e.g., 128 B-scans from a typical C-scan acquisition mode) or a portion of a full cubic structure scan (e.g., 8 B-scans, which may be part of a separate alignment mode, e.g., a scan acquisition mode implemented separately for alignment purposes) can be used. For comparison purposes, Figure 43A OCT images 112a to 112c of three selected B-scans from a cubic structure scan of a test eye 116 perfectly XYZ aligned with the imaging system (and their corresponding 2D FFT data 114a to 114c) are shown. Figure 43B Three selected OCT images 118a to 118c (and their corresponding 2D FFT data 119a to 119c) from three B-scans of a test eye 116 that is misaligned in the X-direction (while aligned in the YZ-direction) relative to the imaging system are shown. That is, Figure 43A and Figure 43B Provides a fully aligned case ( Figure 43A ) and cases with 1mm misalignment ( Figure 43B A comparison between the three exemplary OCT images from the B scan (e.g., ...). In both cases, the comparison between the three exemplary OCT images from the B scan (e.g., ...) Figure 43A 112a to 112c and Figure 43B The data (118a to 118c) and their corresponding 2DFFT data represent the first, middle, and final B-scans of the entire cubic structure scan. As shown in the figure, the misalignment in the X direction indicates that the interval between frequency components in the spatial frequency analysis (2D FFT 119a to 119c) gradually increases as the scan progresses from the first B-scan to the 64th B-scan and then to the last (128th) B-scan in the volumetric LF-SDOCT scan.

[0154] Therefore, the 2D FFT of the line field interferogram can be directly used as a cue for pupil alignment. For example, it can be used to detect XYZ misalignment by comparing the 2D FFT of the current scan with the 2D FFT data of a perfectly aligned case as a reference, and / or to detect / determine / measure some misalignment, such as misalignment in the Y and X directions, without a reference scan. Alternatively, or additionally, the 2D FFT data can be processed (e.g., by filtering, binarylization, centroid finding, and / or input into machine learning algorithms) to obtain more information about pupil alignment or positioning.

[0155] Figure 44 Exemplary processing steps that can be performed to determine pupil alignment from spatial frequency content are illustrated. First, in step St10, the upper half 120 of the signal 121 (e.g., the true interference signal) in 2D FFT space 121 is clipped to remove complex conjugate artifacts. In steps St12 and image 122, the clipped signal is summed at each spatial frequency (e.g., column). This defines a 1D profile representing the intensity of the backscattered signal relative to the spatial frequency. A linear ramp 123 can be used as a variable threshold to binarize the pupil alignment of step St12 at positive and negative spatial frequencies, as shown in step St13 and binary mask 125, respectively. Values ​​above the threshold defined by ramp 123 are determined to indicate the portion of the patient's pupil aligned with the instrument's collecting pupil. Thus, binary mask 125 is defined by showing the aligned portion in color (e.g., gray) and the misaligned portion in white. In step St14, the centroid of the binary mask 125 is calculated to determine the centroid 126 of the patient's pupil. This provides alignment information (e.g., alignment measurement) by indicating its relative position along an axis (e.g., the Y-axis). This alignment measure can then be used in the automatic alignment subsystem or component of the imaging system, or provided to the user to assist in the manual alignment process.

[0156] Alignment information can be represented in a variety of ways that are easy for users to interpret. Figure 45 , Figure 46 and Figure 47 Several implementations for displaying alignment information to a user, for example, via a screen, are shown. Figure 45 One implementation shows an area displaying the position of an indicating instrument (e.g., a collector) pupil relative to a patient's pupil, which can be shown as a colored or shaded area. Figure 46 An alternative implementation is shown in which the shaded area is used to indicate the portion of the patient's pupil that aligns with the instrument's collecting pupil (e.g., located within the area of ​​the instrument's collecting pupil). This information can also be graphically presented to the user if the pupil position and size can be further inferred from the processed data. Figure 47 An alternative implementation is shown, in which, for simplicity, only the centroid of the patient's pupil is shown to the user.

[0157] Figure 48 Another example of the invention applied to a full-field (FF) TDOCT system is shown. As previously described, the patient's pupil 93 is shown as a shaded area, and the collecting pupil is shown as a dashed circle 92. In this case, the illumination forms a small circular area 91' at the focal point of the pupillary plane, and the collecting pupil 92 is a circular area centered on the illumination focal point 91'. Example Ex4 shows the case where the collecting pupil 92 is aligned with the patient's pupil 93. In this case, the full-space frequency content 131 within the collecting pupil is detected.

[0158] When the pupil is misaligned, as shown in Examples Ex5 and Ex6, corresponding portions of spatial frequencies 132 and 133 are missing, respectively. In each of Examples Ex5 and Ex6, the missing portions of the corresponding spatial frequencies 132 and 133 are shown as being contained within the dashed circle 135. Similarly, the missing portions correspond to the degree of pupil misalignment. However, it should be noted that in the full-field case of the present invention, 2D misalignment can be directly visualized in any direction in FFT space (e.g., from 2D FFT).

[0159] The results of the above pupil detection method can be fed back to the user for alignment and / or back to the instrument for automatic alignment and / or triggering scanning or automatic image acquisition.

[0160] Figure 49 This illustrates an exemplary workflow for using spatial frequency analysis for alignment and feedback acquisition. This example is built upon... Figure 44 To provide additional feedback functionality within the workflow. Figure 44All components similar to those in the figure have similar reference numerals and are as described above. This workflow can begin system-pupil alignment in step S100 by notifying the system operator (or a system automation routine or mechanism). This is followed by the steps described above for pupil alignment. These steps may include step S101, which collects data (e.g., a scan), calculates its 2D FFT (or 1D FFT along a direction parallel to the line scan beam SB), and shears the desired signal (e.g., the real interference signal) from the 2D FFT space. This is followed by step S102, which sums the sheared signal at spatial frequencies, and step S103, which binarizes the summed signal. At this point, a first decision step D1 may check whether the aligned portion of the pupil is above a predetermined percentage threshold (e.g., 50%), which can be empirically determined as sufficient overlap between the patient's pupil and the instrument's collecting pupil to capture a good image. If not (D1 = No), the system can determine that the pupil position is unknown (step S105) and can feed this information back to the user or system (step S106) to continue the search until this alignment condition is met. However, if decision step D1 determines that the pupil alignment portion is above a predetermined threshold (D1 = Yes), the process can proceed to step S104 and calculate the centroid. Then, the second decision step D2 checks whether the determined centroid indicates good alignment within a predetermined tolerance range (e.g., within 5 pixels) or in which direction the patient / instrument should move to achieve better alignment. If decision step D2 determines that the pupil is not sufficiently aligned (D2 = No) and position adjustment is required, this information is fed back to the user or system in steps S107 and S106. For example, in Figure 44 In step S108, the centroid 126 is determined to be above the alignment position 127. This information can be fed back to the system, the patient, or the system operator to lower the patient's pupil and improve alignment with the instrument. If decision step D2 determines that the pupil is adequately aligned within a predetermined tolerance (D2 = Yes), a scan or image can be automatically captured in step S108. Then, a third decision step D3 can check that enough data (e.g., a scan) has been collected. If additional data is needed (D3 = No), the process can notify the system or user (step S106) before collecting new data in step S101. That is, this process can be repeated until enough data is collected and D3 = Yes. At this point, in step S109, the OCT imaging operation can be stopped, and the user can be notified that the session has ended.

[0161] The above implementation for using spectral analysis to determine the alignment of a patient's pupil with the system's collecting pupil is an exemplary implementation. Other implementations will be apparent to those skilled in the art. For example, this method can be implemented using an LF-TDOCT or FF-SDOCT system. Moreover, the method can be implemented in a point-scanning system that detects off-axis backscattered light. As yet another example, if interference is detected at the pupil conjugate plane, such as using holography, the spatial distribution of backscattered light within the system's collecting pupil can be directly inferred from the holographic spatial distribution signal. In this case, the step of determining the (2D)FFT for the spatial frequency distribution can be bypassed.

[0162] Therefore, the spatial frequency distribution in the FFT space can be directly used as a cue for pupil alignment.

[0163] Descriptions of various hardware and architectures applicable to this invention are provided below.

[0164] Fundus imaging system

[0165] Two types of imaging systems used for fundus imaging are flood illumination imaging systems (or flood illumination imagers) and scanning illumination imaging systems (or scanning imagers). A flood illumination imager, for example, uses a flash lamp to simultaneously flood the entire field of view (FOV) of interest of a sample, and captures a full-frame image of the sample (e.g., the fundus) with a full-frame camera (e.g., a camera with a sufficiently large two-dimensional (2D) light sensor array to capture the desired FOV overall). For example, a flood illumination fundus imager would flood the fundus of the eye and capture a full-frame image of the fundus in a single image capture sequence from the camera. A scanning imager provides a scan beam that scans across an object (e.g., the eye), and as it scans across the object, the scan beam images at different scan locations, creating a series of image fragments that can be reconstructed (e.g., combined) to create a synthetic image of the desired FOV. The scan beam can be a point, a line, or a two-dimensional region, such as a slit or a wide line.

[0166] Figure 50An example of a slit-scanning ophthalmic system SLO-1 for imaging the fundus F is shown. The fundus F is the inner surface of the eye E opposite to the lens (or crystalline lens) CL and may include the retina, optic disc, macula, fovea, and posterior pole. In this example, the imaging system is in a so-called “scan-to-de-scan” configuration, wherein the scan beam SB passes through the optical components of the eye E (including the cornea Crn, iris Irs, pupil Ppl, and lens CL) to scan the fundus F. In the case of a floodlight fundus imager, a scanner is not required, and light is applied immediately across the entire desired field of view (FOV). Other scanning configurations are known in the art, and a specific scanning configuration is not critical to the invention. As depicted, the imaging system includes one or more light sources LtSrc, preferably a multicolor LED system or a laser system, wherein the light collection rate has been appropriately adjusted. An optional slit Slt (adjustable or static) is located in front of the light source LtSrc and can be used to adjust the width of the scan beam SB. Additionally, the slit Slt can remain stationary during imaging or can be adjusted to different widths to allow for different confocalities and applications, either for a specific scan or to suppress reflections during scanning. An optional objective lens ObjL can be placed in front of the slit Slt. The objective lens ObjL can be any lens in the prior art, including but not limited to refractive, diffractive, reflective, or hybrid lenses / systems. Light from the slit Slt passes through the pupil separator SM and is directed toward the scanner LnScn. It is desirable to bring the scanning plane and the pupil plane as close together as possible to reduce vignetting in the system. Optional optics DL can be included to manipulate the optical distance between the images of the two components. The pupil separator SM allows the illumination beam from the light source LtSrc to pass through to the scanner LnScn and reflects the detection beam from the scanner LnScn (e.g., reflected light returning from the eye E) toward the camera Cmr. The task of the pupil separator SM is to separate the illumination beam and the detection beam and to help suppress system reflections. The scanner LnScn can be a rotating galvanometer scanner or other types of scanners (e.g., piezoelectric or voice coil, microelectromechanical system (MEMS) scanner, electro-optic deflector, and / or rotating polygon scanner). Depending on whether pupil separation is performed before or after the scanner LnScn, the scanning can be divided into two steps, where one scanner is in the illumination path and a separate scanner is in the detection path. A specific pupil separation arrangement is described in detail in U.S. Patent 9,456,746, which is incorporated herein by reference in its entirety.

[0167] An illumination beam passes from a scanner LnScn through one or more optics, in this case a scanning lens SL and an ophthalmic lens or eyepiece OL, which allows the pupil of the eye E to image the system's image pupil. Typically, the scanning lens SL receives the scanning illumination beam from the scanner LnScn at any of a plurality of scanning angles (incident angles) and produces a scanning line beam SB with a substantially flat focal plane (e.g., a collimated optical path). The ophthalmic lens OL can focus the scanning line beam SB onto the fundus F (or retina) of the eye E and image the fundus. In this way, the scanning line beam SB creates a scanning line through the fundus F. One possible configuration of these optics is a Keplerian telescope, in which the distance between two lenses is chosen to create an approximately telecentric intermediate fundus image (4-f configuration). The ophthalmic lens OL can be a single lens, an achromatic lens, or an arrangement of different lenses. All lenses can be refractive, diffractive, reflective, or hybrid lenses known to those skilled in the art. Depending on the desired field of view (FOV), the focal length(s) of the ophthalmic lens (OL), the scanning lens (SL), and the size and / or form of the pupillary separator (SM) and scanner (LnScn), an arrangement can be envisioned where, depending on the field of view, multiple components can be switched into and out of the beam path, for example, by using optical flipping, motorized wheels, or detachable optical elements. Since changes in the field of view result in different beam sizes at the pupil, pupillary separation can also vary along with the FOV. For example, a field of view of 45° to 60° is typical or standard for fundus cameras. Higher fields of view, such as 60° to 120° or larger, wide field of view FOVs are also feasible. A wide field of view FOV may be desired for combinations of wide-line fundus imaging (BLFI) with another imaging modality such as optical coherence tomography (OCT). The upper limit of the field of view can be determined by the achievable working distance combined with the physiological conditions around the human eye. Because the typical human retina has a field of view (FOV) of 140° horizontally and 80° to 100° vertically, it may be desirable to have an asymmetric field of view for the highest possible FOV on the system.

[0168] The scanning beam SB passes through the pupil Ppl of the eye E and is directed towards the retina or fundus surface F. The scanner LnScn1 adjusts the position of the light on the retina or fundus F so that a range of lateral positions on the eye E is illuminated. The reflected or scattered light (or emitted light in the case of fluorescence imaging) is guided back along a similar path to the illumination to define the collection beam CB on the detection path to the camera Cmr.

[0169] In the "scan-de-scan" configuration of the exemplary slit-scan ophthalmic system SLO-1 of the present invention, the light returning from the eye E is "de-scanned" by the scanner LnScn on its path to the pupillary separator SM. That is, the scanner LnScn scans the illumination beam from the pupillary separator SM to define a scanning illumination beam SB spanning the eye E, but since the scanner LnScn also receives the returning light from the eye E at the same scanning position, the scanner LnScn has the effect of de-scanning the returning light (e.g., canceling the scanning action) to define a non-scanning (e.g., stable or stationary) collection beam from the scanner LnScn to the pupillary separator SM, which deflects the collection beam toward the camera Cmr. At the pupillary separator SM, the reflected light (or emitted light in the case of fluorescence imaging) is separated from the illumination light onto a detection path pointing toward the camera CMr, which may be a digital camera with a light sensor for capturing an image. An imaging lens (e.g., an objective lens) ImgL may be located in the detection path to image the fundus onto the camera Cmr. As with the objective lens ObjL, the imaging lens ImgL can be any type of lens known in the art (e.g., a refractive lens, a diffractive lens, a reflective lens, or a hybrid lens). Additional operational details, particularly methods for reducing artifacts in images, are described in PCT Publication WO2016 / 124644, the contents of which are incorporated herein by reference in their entirety. The camera Cmr captures received images, and for example, creates image files that can be processed by one or more (electronic) processors or computing devices (e.g., ...). Figure 44 The computer system shown further processes the data. Therefore, the collection beam (returning from all scan positions of the scan beam SB) is collected by the camera Cmr, and the full-frame image Img can be constructed from a combination of individually captured collection beams, for example, by stitching. However, other scanning configurations are also conceivable, including those in which the illumination beam scans on the eye E and the collection beam scans on the camera's light sensor array. Several embodiments of the slit scanning ophthalmoscope, including various designs in which the return light sweeps across the camera's light sensor array and the return light does not sweep across the camera's light sensor array, are described by reference to PCT Publication WO 2012 / 059236 and U.S. Patent Publication 2015 / 0131050, which are incorporated herein by reference.

[0170] In this example, the camera Cmr is connected to a processor (e.g., a processing module) Proc and a display (e.g., a display module, computer screen, electronic screen, etc.) Dspl. Both can be part of the imaging system itself, or they can be part of a separate, dedicated processing and / or display unit, such as a computer system, where data is transmitted from the camera Cmr to the computer system via cable or a computer network including wireless networks. The display and processor can be an integrated unit. The display can be a conventional electronic display / screen or touchscreen type and can include a user interface for displaying and receiving information from the instrument operator or user. The user can interact with the display using any type of user input device known in the art, including but not limited to a mouse, knob, button, pointer, and touchscreen.

[0171] It may be desirable for the patient's gaze to remain fixed during imaging. One way to achieve this is to provide a fixation target that the patient can be guided to fixate on. Depending on which area of ​​the eye is to be imaged, this fixation target can be inside or outside the instrument. Figure 50 An implementation of an internal gaze target is illustrated. In addition to the main light source LtSrc used for imaging, a second optional light source FxLtSrc, such as one or more LEDs, can be positioned such that a light pattern is imaged onto the retina using a lens FxL, a scanning element FxScn, and a reflector / mirror FxM. The gaze scanner FxScn can move the position of the light pattern, and the reflector FxM directs the light pattern from the gaze scanner FxScn to the fundus F of the eye E. Preferably, the gaze scanner FxScn is positioned such that it is located at the pupillary plane of the system, allowing the light pattern on the retina / fundus to move according to the desired gaze position.

[0172] Slit-lamp ophthalmoscope systems can operate in different imaging modes by selecting filter elements based on the light source and wavelength used. True-color reflectance imaging (similar to the imaging observed by clinicians when examining the eye using a handheld or slit-lamp ophthalmoscope) is achieved when the eye is imaged using a series of colored LEDs (red, blue, and green). The image for each color can be progressively built up with each LED turned on at each scanning position, or the entire image for each color can be captured individually. These three color images can be combined to display a true-color image, or they can be displayed individually to highlight different features of the retina. The red channel best highlights the choroid, the green channel highlights the retina, and the blue channel highlights the anterior retinal layer. Additionally, light of specific frequencies (e.g., individual colored LEDs or lasers) can be used to excite different fluorophores in the eye (e.g., autofluorescence), and the resulting fluorescence can be detected by filtering out the excitation wavelength.

[0173] Fundus imaging systems can also provide infrared reflection images, for example, by using an infrared laser (or other infrared light source). The advantage of infrared (IR) mode is that the eye is insensitive to IR wavelengths. This allows the user to continuously capture images without interfering with the eye (e.g., in preview / alignment mode) to assist the user during instrument alignment. Furthermore, IR wavelengths have increased penetration through tissues and can provide improved visualization of choroidal structures. Additionally, fluorescein angiography (FA) and indocyanine green (ICG) angiography imaging can be performed by collecting images after the fluorescent dye has been injected into the subject's bloodstream.

[0174] Optical coherence tomography system

[0175] Besides fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FA), and ophthalmic images can also be created using other imaging modalities, such as optical coherence tomography (OCT), OCT angiography (OCTA), and / or ocular ultrasound. The present invention can be applied to these other ophthalmic imaging modalities, or at least several portions of the invention with minor modifications, as understood in the art, can be applied to these other ophthalmic imaging modalities. More specifically, the present invention can also be applied to ophthalmic images generated by OCT / OCTA systems that produce OCT and OCTA images. For example, the present invention can be applied to frontal OCT / OCTA images. Examples of fundus imagers are provided in U.S. Patents 8,967,806 and 8,998,411, examples of OCT systems are provided in U.S. Patents 6,741,359 and 9,706,915, and examples of OCTA imaging systems can be found in U.S. Patents 9,700,206 and 9,759,544, all of which are incorporated herein by reference in their entirety. For completeness, this article provides an exemplary OCT / OCTA system.

[0176] Figure 51A generalized frequency-domain optical coherence tomography (FD-OCT) system suitable for collecting 3D image data of the eye is illustrated. The FD-OCT system OCT_1 includes a light source LtSrc1. Typical light sources include, but are not limited to, broadband light sources with short time coherence lengths or swept-frequency laser sources. The beam from the light source LtSrc1 is typically guided by an optical fiber Fbr1 to illuminate a sample, such as the eye E; a typical sample is tissue in the human eye. The light source LrSrc1 can be a broadband light source with a short time coherence length in the case of spectral-domain OCT (SD-OCT), or a wavelength-tunable laser source in the case of swept-frequency OCT (SS-OCT). The light can typically be scanned using a scanner Scnr1 between the output of the optical fiber Fbr1 and the sample E, such that the beam (dashed line Bm) scans laterally (in x and y) over the region of the sample to be imaged. In the case of full-field OCT, no scanner is required, and light is applied immediately over the entire desired field of view (FOV). The light scattered from the sample is typically collected into the same fiber Fbr1 used to guide the light for illumination. The reference light from the same light source LtSrc1 travels a separate path, in this case involving fiber Fbr2 and a back reflector RR1 with adjustable optical delay. Those skilled in the art will recognize that a transmission reference path can also be used, and this adjustable delay can be placed in either the sample or reference arm of the interferometer. The collected sample light is typically combined with the reference light in a fiber coupler Cplr1 to form optical interference in an OCT photodetector Dtctr1 (e.g., a photodetector array, digital camera, etc.). Although a single fiber port is shown leading to detector Dtctr1, those skilled in the art will recognize that various designs of the interferometer can be used for balanced or unbalanced detection of the interference signal. The output from detector Dtctr1 is provided to a processor Cmp1 (e.g., a computing device) that converts the observed interference into depth information of the sample. The depth information can be stored in memory associated with processor Cmp1 and / or displayed on a display (e.g., a computer / electronic display / screen) Scn1. The processing and storage functions can be located within the OCT instrument, or they can be located in an external processing unit where the collected data is transmitted (e.g., Figure 53 This unit executes on the computer system shown. It can be dedicated to data processing or perform other, fairly general-purpose tasks not specific to the OCT device. The processor Cmp1 may include, for example, a field-programmable gate array (FPGA), a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a graphics processing unit (GPU), a system-on-a-chip (SoC), a central processing unit (CPU), a general-purpose graphics processing unit (GPGPU), or a combination thereof, which performs some or all of the data processing steps before being passed to the host processor or in parallel.

[0177] The sample and reference arms in the interferometer can consist of bulk optics, fiber optics, or hybrid bulk optics systems, and can have different architectures, such as Michelson, Mach-Zehnder, or common-path-based designs known to those skilled in the art. The beams used herein should be interpreted as any carefully guided optical path. Instead of a mechanical scanning beam, an optical field can illuminate a one-dimensional or two-dimensional region of the retina to generate OCT data (see, for example, U.S. Patent 9332902; D. Hillmann et al., “Holoscopy–holographic optical coherence tomography” Optics Letters 36(13): 2390 2011; Y. Nakamura et al., “High-Speed ​​three-dimensional human retinal imaging by line field spectral domain optical coherence tomography” Optics Express 15(12): 7103 2007; Blazkiewicz et al., “Signal-to-noise ratio study of full-field Fourier-domain optical coherence tomography” Applied Optics 44(36): 7722 (2005)). In time-domain systems, the reference arm needs to have an adjustable optical delay to generate interference. Balanced detection systems are commonly used in TD-OCT and SS-OCT systems, while spectrometers are used for the detection port of SD-OCT systems. The invention described herein can be applied to any type of OCT system. Aspects of the invention can be applied to any type of OCT system or other types of ophthalmic diagnostic systems and / or multiple ophthalmic diagnostic systems, including but not limited to fundus imaging systems, field-of-view testing devices, and scanning laser polarimeters.

[0178] In Fourier domain optical coherence tomography (FD-OCT), each measurement is a real-valued spectral interferogram (Sj(k)). The real-valued spectral data typically undergoes several post-processing steps, including background subtraction and dispersion correction. The Fourier transform of the processed interferogram produces a complex-valued OCT signal output. The absolute value |Aj| of this complex-valued OCT signal reveals the profile of the scattering intensity at different path lengths, and thus reveals scattering as a function of depth (z-direction) in the sample. Similarly, the phase... It can also be extracted from complex-valued OCT signals. The scattering profile as a function of depth is called an axial scan (A-scan). A set of A-scans measured at adjacent locations in a sample produces a cross-sectional image (computed tomography or B-scan) of the sample. The collection of B-scans collected at different lateral locations on the sample constitutes a data volume or cubic unit. For a given amount of data, the term fast axis refers to the scanning direction along a single B-scan, while slow axis refers to the axis along which multiple B-scans are collected. The term "cluster scan" can refer to a single data cell or block generated by repeatedly acquiring data at the same (or substantially the same) location (or region) for the purpose of analyzing motion contrast, which can be used to identify blood flow. A cluster scan can consist of multiple A-scans or B-scans collected at approximately the same location on the sample at relatively short time intervals. Because the scans in a cluster scan are of the same region, the static structure remains relatively unchanged between scans within the cluster scan, and the motion contrast between scans that meet predefined criteria can be identified as blood flow. Various methods for creating B-scans are known in the art, including but not limited to: along the horizontal or x-direction, along the vertical or y-direction, along the diagonals of x and y, or in a circular or spiral pattern. A B-scan can be in the xz dimension, but can be any cross-sectional image including the z dimension.

[0179] In OCT angiography or functional OCT, analytical algorithms can be applied to OCT data collected at the same or substantially the same sample location on the sample at different times (e.g., cluster scans) to analyze motion or flow (see, for example, U.S. Patent Publications 2005 / 0171438, 2012 / 0307014, 2010 / 0027857, 2012 / 0277579 and U.S. Patent 6,549,801, all of which are incorporated herein by reference in their entirety). OCT systems can use any of a variety of OCT angiography processing algorithms (e.g., motion contrast algorithms) to identify blood flow. For example, motion contrast algorithms can be applied to intensity information derived from image data (intensity-based algorithms), phase information from image data (phase-based algorithms), or complex image data (complex image-based algorithms). A frontal image is a 2D projection of 3D OCT data (e.g., by averaging the intensity of each individual A-scan, such that each A-scan defines pixels in the 2D projection). Similarly, a frontal vascular tissue image is an image that displays motion contrast signals, where the data dimension corresponding to depth (e.g., along the z-direction of the A-scan) is typically displayed as a single representative value (e.g., a pixel in a 2D projected image) by summing or integrating all or isolated portions of the data (see, for example, U.S. Patent 7,301,644, which is incorporated herein by reference in its entirety). An OCT system providing angiographic imaging capabilities may be referred to as an OCT angiography (OCTA) system.

[0180] Figure 52 An example of a frontal vascular tissue image is shown. After processing the data using any motion contrast technique known in the art to enhance motion contrast, a range of pixels corresponding to a given tissue depth from the surface of the internal limiting membrane (ILM) in the retina can be summed to generate a frontal (e.g., frontal view) image of the vascular tissue.

[0181] Computing device / system

[0182] Figure 53 An example computer system (or computing device or computer apparatus) is illustrated. In some embodiments, one or more computer systems may provide the functionality described or illustrated herein and / or perform one or more steps of one or more methods described or illustrated herein. The computer system may take any suitable physical form. For example, the computer system may be an embedded computer system, a system-on-a-chip (SOC), a single-board computer system (SBC) (e.g., a computer-on-module (COM) or system-on-module (SOM)), a desktop computer system, a laptop or notebook computer system, a computer system grid, a mobile phone, a personal digital assistant (PDA), a server, a tablet computer system, an augmented / virtual reality device, or a combination of two or more of these. Where appropriate, the computer system may reside in a cloud, which may include one or more cloud components within one or more networks.

[0183] In some implementations, the computer system may include a processor Cpnt1, a memory Cpnt2, a storage device Cpnt3, an input / output (I / O) interface Cpnt4, a communication interface Cpnt5, and a bus Cpnt6. The computer system may also optionally include a display Cpnt7, such as a computer monitor or screen.

[0184] Processor Cpnt1 includes hardware for executing instructions, such as those that make up a computer program. For example, processor Cpnt1 may be a central processing unit (CPU) or general-purpose computing on a graphics processing unit (GPGPU). Processor Cpnt1 may fetch (or retrieve) instructions from internal registers, internal caches, memory Cpnt2, or storage device Cpnt3, decode and execute the instructions, and write one or more results to internal registers, internal caches, memory Cpnt2, or storage device Cpnt3. In certain embodiments, processor Cpnt1 may include one or more internal caches for data, instructions, or addresses. Processor Cpnt1 may include one or more instruction caches and one or more data caches, for example, to hold data tables. Instructions in the instruction cache may be copies of instructions in memory Cpnt2 or storage device Cpnt3, and the instruction cache may accelerate the retrieval of these instructions by processor Cpnt1. Processor Cpnt1 may include any suitable number of internal registers and may include one or more arithmetic logic units (ALUs). Processor Cpnt1 may be a multi-core processor; or may include one or more processors Cpnt1. Although this disclosure describes and illustrates a particular processor, this disclosure considers any suitable processor.

[0185] Memory Cpnt2 may include main memory for storing instructions so that processor Cpnt1 can execute or maintain intermediate data during processing. For example, a computer system may load instructions or data (e.g., data tables) from storage device Cpnt3 or from another source (e.g., another computer system) into memory Cpnt2. Processor Cpnt1 may load instructions and data from memory Cpnt2 into one or more internal registers or internal caches. To execute instructions, processor Cpnt1 may retrieve and decode instructions from internal registers or internal caches. During or after instruction execution, processor Cpnt1 may write one or more results (which may be intermediate or final results) to internal registers, internal caches, memory Cpnt2, or storage device Cpnt3. Bus Cpnt6 may include one or more memory buses (each bus may include an address bus and a data bus) and may connect processor Cpnt1 to memory Cpnt2 and / or storage device Cpnt3. Optionally, one or more memory management units (MMUs) facilitate data transfer between processor Cpnt1 and memory Cpnt2. Memory Cpnt2 (which may be fast volatile memory) may include random access memory (RAM), such as dynamic RAM (DRAM) or static RAM (SRAM). Storage device Cpnt3 may include long-term or high-capacity storage for data or instructions. Storage device Cpnt3 may be internal or external to a computer system and includes one or more of the following: disk drives (e.g., hard disk drives, HDDs, or solid-state drives SSDs), flash memory, ROM, EPROM, optical disks, magneto-optical disks, magnetic tape, Universal Serial Bus (USB) accessible drives, and other types of non-volatile memory.

[0186] The I / O interface Cpnt4 can be software, hardware, or a combination of both, and includes one or more interfaces (e.g., serial or parallel communication ports) for communicating with I / O devices, enabling communication with a person (e.g., a user). For example, I / O devices may include a keyboard, keypad, microphone, monitor, mouse, printer, scanner, speaker, still camera, pen, writing tablet, touchscreen, trackball, camera, another suitable I / O device, or a combination of two or more of these.

[0187] The communication interface Cpnt5 can provide a network interface for communicating with other systems or networks. The communication interface Cpnt5 may include a Bluetooth interface or other types of packet-based communication. For example, the communication interface Cpnt5 may include a network interface controller (NIC) and / or a wireless NIC or a wireless adapter for communicating with a wireless network. The communication interface Cpnt5 can provide communication with Wi-Fi networks, ad hoc networks, personal area networks (PANs), wireless PANs (e.g., Bluetooth WPANs), local area networks (LANs), wide area networks (WANs), metropolitan area networks (MANs), cellular telephone networks (e.g., Global System for Mobile Communications (GSM) networks), the Internet, or a combination of two or more of these.

[0188] The Cpnt6 bus can provide communication connections between the aforementioned components of a computing system. For example, the Cpnt6 bus may include an Accelerated Graphics Port (AGP) or other graphics bus, an Enhanced Industry Standard Architecture (EISA) bus, a Front Side Bus (FSB), HyperTransport (HT) interconnect, an Industry Standard Architecture (ISA) bus, an InfiniBand bus, a Low Pin Count (LPC) bus, a memory bus, a Micro Channel Architecture (MCA) bus, a Peripheral Component Interconnect (PCI) bus, a PCI-Express (PCIe) bus, a Serial Advanced Technology Accessory (SATA) bus, a Video Electronics Standards Association Local (VLB) bus, or other suitable buses, or a combination of two or more of these.

[0189] Although this disclosure describes and illustrates a particular computer system having a particular number of particular components in a particular arrangement, this disclosure contemplates any suitable computer system having any suitable number of any suitable components in any suitable arrangement.

[0190] In this document, one or more computer-readable non-transitory storage media may include one or more semiconductor-based or other integrated circuits (ICs) (e.g., field-programmable gate arrays (FPGAs) or application-specific integrated circuits (ASICs)), hard disk drives (HDDs), hybrid hard disk drives (HHDs), optical disk drives (ODDs), magneto-optical disks, magneto-optical disk drives, floppy disks, floppy disk drives (FDDs), magnetic tape, solid-state drives (SSDs), RAM drives, secure digital cards or drives, any other suitable computer-readable non-transitory storage media, or, where appropriate, any suitable combination of two or more of these. Where appropriate, computer-readable non-transitory storage media may be volatile, non-volatile, or a combination of volatile and non-volatile.

[0191] Although the invention has been described in conjunction with several specific embodiments, many further substitutions, modifications, and variations will be apparent to those skilled in the art from the foregoing description. Therefore, the invention described herein is intended to cover all such substitutions, modifications, applications, and variations that fall within the spirit and scope of the appended claims.

Claims

1. An ophthalmic imaging system for imaging a target region of the eye, comprising: The light source produces a beam of light; A first optical element receives the illumination beam and focuses the illumination beam along a non-collimated optical path; A beam scanning mechanism, located in the non-collimated optical path and at the conjugate plane of the target region, has an inlet for receiving the illumination beam from the first optical element and an outlet for outputting the scanning beam, the scanning position of which depends on the movement of the scanning mechanism, wherein the beam scanning mechanism includes a K-mirror; and A second optical element receives the scanning beam from the beam scanning mechanism and focuses the scanning beam onto the target region of the eye.

2. The system according to claim 1, wherein, The target area is the retina of the eye, and the beam scanning mechanism is positioned at the conjugate of the retina of the eye.

3. The system according to claim 1 or 2, wherein, The beam scanning mechanism receives the illumination beam along the direction of the optical axis, and the beam scanning mechanism outputs the scanning beam along the same direction of the optical axis.

4. The system according to claim 1 or 2, wherein: The first optical element is a scanning lens, the second optical element is an eyepiece, and the scanning lens focuses the illumination beam to a focal point within the beam scanning mechanism.

5. The system according to claim 1 or 2, wherein, The illumination beam is a beam of wires that passes through the axial output direction of the light source.

6. The system according to claim 1 or 2, wherein, The beam scanning mechanism is rotatable to define a two-dimensional illumination pattern, the two-dimensional illumination pattern comprising the scanning beam rotated by the rotation of the beam scanning mechanism. The beam scanning mechanism includes a plurality of reflective surfaces, including an output-facing reflective surface at the exit where the scanning beam is output. This output-facing reflective surface can be configured to radially shift and impart a corresponding radial shift to the scanning beam. Wherein, the output-facing reflective surface forms a predetermined angle with the exit axis of the scanning mechanism, the output-facing reflective surface is radially displaced along the predetermined angle, the illumination beam is a wire bundle of a first length, and the scanning beam is radially displaced by at least the length of the wire bundle. The lighting pattern has a ring shape.

7. The system according to claim 1 or 2, wherein, The beam scanning mechanism rotates about the axis of the output scanning beam, and the output scanning beam rotates twice for each rotation of the beam scanning mechanism.

8. The system according to claim 1 or 2, wherein, The ophthalmic imaging system is an optical coherence tomography (OCT) system, an optical coherence tomography angiography (OCTA) system, or a fundus imaging system.

9. The system according to claim 1 or 2, wherein, The light source is a series of linear light-emitting diodes (LEDs), each of which can be selectively actuated.

10. The system according to claim 1 or 2, wherein, The light source is a circular arrangement of light-emitting diodes (LEDs) that can be actuated in a predetermined pattern.

11. The system according to claim 1 or 2, wherein, The beam scanning mechanism includes at least one frequency-selective optics that reflects a first beam frequency and transmits a second beam frequency, and the beam scanning mechanism defines a second optical path that guides light of the second beam frequency to the exit.

12. The system according to claim 11, wherein, The illumination beam at the entrance of the beam scanning mechanism includes a first light component at the first beam frequency and a second light component at the second beam frequency, the output scanning beam is defined by the first light component, and the second light component defines a gaze image along the second optical path to the exit.

13. The system according to claim 1 or 2, wherein, The beam scanning mechanism includes at least one mirror having a first surface that reflects the illumination beam received at the inlet and a second surface that transmits a second illumination beam, the second surface being opposite to the first surface and forming into a second inlet of the beam scanning mechanism.

14. The system according to claim 1 or 2 further includes a motion translation mechanism, the motion translation mechanism being coupled to the beam scanning mechanism and imparting a one-dimensional translational motion to the beam scanning mechanism.

15. The system according to claim 14, wherein, The motion translation mechanism includes a parallel flexural section.

16. The system according to claim 15, wherein, The motion translation mechanism includes an inductive actuator or motor with an eccentricity.

17. The system of claim 1 or 2 further includes a scanning system, the scanning system including a first scanning component that generates a first scanning signal input to a second scanning component including the beam scanning mechanism; in, The first scanning component is located at the pupil conjugate of the eye, and the second scanning component is located at the retina conjugate of the eye.

18. The system according to claim 17, wherein, The first scanning component includes a galvanometer located at the pupil conjugate, and the beam scanning mechanism is located at the retina conjugate.

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