Full-field optical coherence tomography imaging method

Abstract

A full-field optical coherence tomography (FFOCT) imaging method uses a system including an FFOCT device and a sample including a layer of interest (115) to be imaged, the FFOCT device including an incoherent light source (101), an imager (114), and a beam splitter (103) defining a sample arm (107) and a reference arm (108), the method including the steps of generating sample light including light of interest originating from the layer of interest and a reference light traveling from the reference arm (108), and acquiring an image from the reference light and sample light combined in the beam splitter (103), wherein at least one of the sample arm (107) and the reference arm (108) includes an optical curvature compensator that modifies the lateral variation distribution of the optical path length, so as to match the lateral variation distribution of the optical path length traveled by the reference light and the light of interest incident on the imager (114).

Description

[Technical Field]

[0001] The present invention relates to the field of optical coherence tomography (OCT) imaging technology, and more precisely to a new type of full-field OCT imaging technology. This project has received funding from the European Union's Seventh Framework Programme under HELMHOLTZ grant agreement no. 610110. [Background technology]

[0002] Full-field OCT (FFOCT) is based on broadband optical interference microscopy. Cross-sectional images are obtained by combining interference images recorded by an imager such as a CCD or CMOS camera. While conventional OCT produces B-mode (axial) images, like ultrasound imaging, full-field OCT acquires cross-sectional images in the frontal (lateral) direction. More precisely, the interference images are created by an interferometer, and path-length modulation is typically performed by an actuator (usually a piezoelectrically driven mirror in the reference arm). These images, acquired by a CCD camera, are combined in post-processing (or online) using phase-shifting interferometry, with several images (typically two or four) acquired per modulation period, depending on the algorithm used.

[0003] Thus, "en face" tomographic images are generated by wide-field illumination. This can be obtained by a Linnik arrangement of interferometers, using microscope objectives in both arms. Furthermore, while the temporal coherence of the light source must remain low, as in classical OCT (i.e., broad spectrum), the spatial coherence must also be low to avoid crosstalk that occurs when using spatially coherent light sources. Full-field OCT is an alternative method to conventional OCT for providing ultra-high-resolution images (~1 μm), e.g., using a simple halogen lamp instead of complex ultrashort-pulse laser-based light sources. Full-field OCT has several specific advantages. Because FFOCT acquires "en face" images without point-by-point or line-by-line scanning, FFOCT is not affected by lateral scanning artifacts. By using high-numerical aperture objectives, FFOCT provides higher lateral resolution (on the order of 1 μm) than conventional OCT (on the order of 10 μm). This is particularly useful for examining microscopic cellular and tissue structures in biological samples.

[0004] Full-field OCT imaging techniques are described, for example, in the article "Full-field optical coherence tomography" by A. Dubois and C. Boccara, taken from the book "Optical Coherence Tomography - Technology and Applications," edited by Wolfgang Drexler and James G. Fujimoto, published by Springer in 2009. It is also disclosed in French patent application FR2817030.

[0005] Figure 1 shows an example of a currently used full-field OCT. A spatially and temporally incoherent light source 1, such as a light-emitting diode (LED), emits a first light beam 2, which is sent to a beam splitter 3. The beam splitter splits the incoming first light beam into a second light beam 5 and a third light beam 6. The second light beam 5 is sent to a sample arm 7, and the third light beam is sent to a reference arm 8.

[0006] In a typical FFOCT experiment, the setup is usually optically symmetric, using the same objective lenses in the two arms of the interferometer. In the depicted example, both arms 7, 8 contain microscope objective lenses 9, 10 with similar optical properties.

[0007] A microscope objective 9 in the sample arm 7 focuses the second light beam 5 onto a portion of the sample 11 (here the cornea of ​​a human eye) and collects the sample light reflected from different depths within the sample 11 and transmits it to the beam splitter 3. A microscope objective 10 in the reference arm 8 focuses the third light beam 6 onto a flat reference mirror 12 and collects the reference light reflected from the flat reference mirror 12 and transmits it to the beam splitter 3.

[0008] Sample light from different layers of the sample 11 and reference light from the flat reference mirror 12 are recombined in the beam splitter 3 and focused by a tube lens 13 onto a camera 14 which captures the image. The combination of sample and reference light creates interference in the camera image plane which is captured by the camera 14 in a two-dimensional frontal image.

[0009] However, interference is conditioned by a necessary path correlation between the sample and reference light, which can only be satisfied for the portion of the sample light that follows a similar path as the reference light.

[0010] The sample light originates from different depths in the sample 11 and is therefore composed of light components with different path lengths. The different path lengths result in a change in optical path length depending on the depth at which the sample light originates. The reference light is moved a reference path length, and by interfering only with the sample light that has moved a path length equal to the reference path length within the thickness of the coherence gate, an interference sample section is defined within the sample that corresponds to the origin of the sample light interfering with the reference light. The coherence gate specifies the coincidence path length between the optical path lengths of the reference light and the sample light where interference occurs.

[0011] The reference path length defined by the reference arm 8 therefore defines the depth of the interference sample section. Therefore, full-field OCT can be defined as an optical sectioning method, since it extracts sample light originating only from the interference sample section. The thickness of the interference sample section is determined by the spectral bandwidth of the light source. The broader the spectrum of the light source, the thinner the interference sample section.

[0012] However, the camera 14 collects all sample light from the beam splitter 3, i.e., the coherent light from the coherent sample section, and the incoherent light from the rest of the sample 11 (the section in front of or behind the coherent sample section on the optical axis Z). Such an acquired image contains a superposition of the coherent sample section and other sections of the sample that are near the coherent sample section, and appears blurry. Therefore, it is necessary to eliminate the incoherent light originating from the rest of the sample.

[0013] This is typically achieved by acquiring a series of several images (typically 2-5 images) of the same sample 11 with modulated interference phase. The reference mirror 12 is translated, for example, using a piezoelectric element that generates an oscillation in the position of the reference mirror 12, thereby modulating the reference path length and, therefore, the interference phase. Each acquired image corresponds to a specific interference phase. Post-processing of the acquired series of images allows the removal of incoherent light, and the resulting full-field OCT image reveals only the interferometric sample light originating from the specific region of interest on the sample 11. A two-dimensional final en face image of the region of interest on the sample 11 is obtained.

[0014] Current two-dimensional imaging schemes for FFOCT use a planar reference mirror, which results in the reference beam having a planar path profile. As a result, the interference portion of the sample light corresponds to the interference plane in the sample beam coming from the sample and originates from a planar slice of the sample. This method of operation is useful for imaging flat sample layers of interest, such as skin or excised tissue, which are flat or can be flattened.

[0015] However, significant problems arise when the sample layer of interest is not flat and cannot be flattened. This is particularly true for in vivo eye imaging, where the symmetry of the interferometer is broken between the two arms, making it impossible to flatten the sample, and most of the layer of interest is not flat or appears to be flat. For example, the human cornea is a quasi-spherical structure exhibiting a large curvature (approximately 7 mm radius of curvature), and the frontal section of the FFOCT imagery displays only a small portion of the field of view for each corneal layer. Figure 2a shows a schematic cross-section of the cornea, illustrating the overlap of corneal layers between the anterior (top) and posterior (bottom) corneas. The cross-hatched layer is the imaged layer of interest 20. The thick line represents the interference plane 21 imaged by the FFOCT. Due to the curved nature of the layer of interest 20, the interference plane 21 is only partially contained within the layer of interest 20; corneal layers 22 and 23 outside the layer of interest 20 also intersect with the interference plane 21. Figure 2b shows a schematic representation of the final image acquired, which corresponds to the intersection between the interference plane 21 and the corneal layer. The layer of interest 20 appears as a disk in the center of the final image on a reduced surface area. The periphery of the final image shows other corneal layers 22, 23. Therefore, the useful field of view of the layer of interest 20 is limited by the curved nature of the layer of interest 20. As an example of this configuration, Figure 2c shows a final FFOCT image of in vivo corneal layers. Because the corneal layers are curved, some corneal layers appear as disks in good contrast in the center, while other corneal layers appear in the periphery.

[0016] Figures 3a and 3b illustrate another configuration with a similar problem. Figure 3a shows a schematic cross-section of the cornea and interference plane 31 in a manner similar to Figure 2a. This time, the periphery of the interference plane 31 intersects with the layer of interest 30, while the center of the interference plane 31 intersects with the underlying corneal layer 32. The outermost periphery of the interference plane 31 intersects with another upper corneal layer 33. Figure 3b shows a schematic final image acquired in a manner similar to Figure 2b. This time, the layer of interest 30 does not appear in the center of the final image but instead appears as a ring, while the underlying corneal layer 32 appears in the center and the upper corneal layer 33 appears at the outer edge of the image. As an example of this configuration, Figure 3c shows an example of the subbasal nerve plexus imaged in the anterior cornea, where the nerve layer appears as a bright ring-like layer in the final image. Figure 3d shows an example of the endothelial layer imaged in the posterior cornea, which also appears as a ring in the final image.

[0017] A sample can also appear non-flat if the symmetry of the FFOCT device is broken. For example, in retinal imaging, removing the microscope objective from the sample arm 7 introduces a strong asymmetry between the two arms 7, 8 of the FFOCT device. Even if we assume the retina is flat (which may be the case with a small field of view), this asymmetry causes the path profile of the light rays at the sample to be non-flat.

[0018] As a result, previous FFOCT techniques result in a frontal image with a reduced useful field of view of the sample layer of interest. Summary of the Invention

[0019] The present invention provides an FFOCT imaging method for obtaining a full-field optical coherence tomography two-dimensional frontal image of a layer of interest at a depth within a sample, the FFOCT imaging method using a system comprising an FFOCT device and a sample including the layer of interest to be imaged, the FFOCT device including a spatially incoherent light source, an imager, and a beam splitter defining a sample arm and a reference arm, the sample being positioned at the end of the sample arm, the method comprising the steps of: simultaneously illuminating the sample arm and the reference arm at an illumination moment with illumination light emitted by the incoherent light source to generate sample light traveling from the sample into the end of the sample arm along a sample optical path and reference light traveling in the reference arm along a reference optical path to the beam splitter; and obtaining a two-dimensional frontal FFOCT image of the layer of interest using the imager from the reference light and sample light combined in the beam splitter, the sample light being generated by the imager. the light of interest originating from the illumination light emitted at the moment of illumination and originating from the layer of interest of the sample, the light of interest traveling a first optical path length upon entering the sample arm, the first optical path length having a curvature profile of lateral variation distribution, and reference light incident on the imager traveling a second optical path length, wherein at least one of the sample arm and the reference arm includes an optical curvature compensator that corrects the lateral variation distribution of optical path lengths, compensating for the curvature profile of the lateral variation distribution of the first optical path length so that the lateral variation distribution of the reference optical path length traveled by the reference light incident on the imager and the lateral variation distribution of the second optical path length traveled by the light of interest incident on the imager match, so that the light of interest originating from the layer of interest interferes with the reference light, and the imager images the layer of interest over a field of view of the imager to form the two-dimensional frontal FFOCT image acquired by the imager.

[0020] Other preferred, but not limiting, aspects of the method of the present invention are as follows, either alone or in any technically possible combination:

[0021] The curvature profile of the lateral variation distribution of the first optical path length has an absolute radius of curvature comprised between 4 millimeters and 50 millimeters.

[0022] The lateral variation distribution (114) of the reference optical path length traveled by the reference light incident on the imager (114) and the lateral variation distribution (114) of the second optical path length traveled by the light of interest incident on the imager have an absolute radius of curvature difference of less than 2 millimeters.

[0023] The reference arm (108) includes an optical curvature compensator that corrects the lateral variation distribution of the reference optical path length along which the reference light incident on the imager (114) travels, the optical curvature compensator being a curved reflector (112) having a curved reflective surface, the curved reflector (112) being positioned at the end of the reference arm opposite the beam splitter (103).

[0024] The reflector has a reflectivity of less than 25%.

[0025] The curved reflective surface of the reflector is an optical lens.

[0026] The curved reflective surface of the reflector is a deformable mirror.

[0027] The optical curvature compensator is a plate of material having a refractive index and a thickness in the direction of the reference or sample path.

[0028] The optical curvature compensator includes a pair of prisms, each prism having an inclined surface that forms a non-perpendicular tilt angle with respect to an optical path, the non-perpendicular tilt angles of the pair of prisms being opposite to each other, and the prisms being movable parallel to each other.

[0029] The optical curvature compensator is a configurable optical curvature compensator, and the FFOCT device includes a control loop configured to analyze acquired images and derive commands to change a configuration of the optical curvature compensator, each configuration defining a different modification of the lateral variation distribution of optical path lengths.

[0030] The method may include the steps of: acquiring a first two-dimensional frontal FFOCT image of the layer of interest (115) from the reference light and sample light combined in the beam splitter (103) using the imager (114); determining whether the curvature profile of the lateral change distribution of the first optical path length has been compensated by the optical compensator; and, if it is determined that the curvature profile of the lateral change distribution of the first optical path length has not been compensated by the optical compensator, correcting the curvature profile of the lateral change distribution of the first optical path length so that it is; and acquiring a second two-dimensional frontal FFOCT image of the layer of interest (115) from the reference light and sample light combined in the beam splitter (103) using the imager (114).

[0031] The invention also provides a full-field optical coherence tomography (FFOCT) device, comprising: a spatially incoherent light source (101) configured to emit illumination light at an instant of illumination; an imager (114) configured to acquire a two-dimensional frontal FFOCT image of a layer of interest (115); and a beam splitter (103) defining a sample arm (107) and a reference arm (108), the sample (111) comprising the layer of interest (115) at a depth within the sample (111), the beam splitter (103) being arranged at the end of the sample arm; At least one of the sample arm (107) and the reference arm (108) includes an optical curvature compensator configured to correct the lateral variation distribution of the optical path length, thereby compensating for the curved profile of the lateral variation distribution of the first optical path length that originates from the illumination light emitted at the moment of illumination and travels through the sample arm (107) of the light of interest originating from the layer of interest of the sample, and the FFOCT device is configured to perform the method of the present invention and acquire a two-dimensional frontal FFOCT image of the layer of interest (115) at a certain depth within the sample (111). [Brief explanation of the drawings]

[0032] Other aspects, objects and advantages of the present invention will become more apparent from a reading of the following detailed description of preferred embodiments thereof, given by way of non-limiting example and with reference to the accompanying drawings, in which:

[0033] [Figure 1] As already mentioned, an example of a previously used FFOCT system is shown. [Figure 2a] It shows how the useful field of view is reduced when a curved layer of interest is imaged through an interfering plane. [Figure 2b] It shows how the useful field of view is reduced when a curved layer of interest is imaged through an interfering plane. [Figure 2c] It shows how the useful field of view is reduced when a curved layer of interest is imaged through an interfering plane. [Figure 3a] It shows how the field of view becomes ring-shaped when a curved layer of interest is imaged through an interfering plane. [Figure 3b] It shows how the field of view becomes ring-shaped when a curved layer of interest is imaged through an interfering plane. [Figure 3c] It shows how the field of view becomes ring-shaped when a curved layer of interest is imaged through an interfering plane. [Figure 4] 1 shows an example of an arrangement for performing FFOCT imaging according to a possible embodiment of the present invention, where the optical curvature compensator is a reflector in the reference arm. [Figure 5] 1 shows an example of an arrangement for performing FFOCT imaging according to a possible embodiment of the present invention, where the optical curvature compensator is a reflector in the reference arm. [Figure 6] FIG. 1 is a schematic diagram illustrating how an optical plate modifies the lateral variation distribution profile of the optical path length. [Figure 7] 10 is a graph showing an example of the relationship between the curvature of the lateral variation distribution profile of the optical path length and the thickness of the optical plate. [Figure 8] 1 shows an example of an arrangement for performing FFOCT imaging according to a possible embodiment of the present invention, where the optical curvature compensator is an optical plate placed in either the reference arm or the sample arm. [Figure 9] 1 shows an example of an arrangement for performing FFOCT imaging according to a possible embodiment of the present invention, where the optical curvature compensator is an optical plate placed in either the reference arm or the sample arm. [Figure 10a] 10 illustrates a method for determining cross-sectional images for assessing optical curvature of a coherence gate according to a possible embodiment of the present invention. [Figure 10b] 10 illustrates a method for determining cross-sectional images for assessing optical curvature of a coherence gate according to a possible embodiment of the present invention. [Figure 11a]10 is an example illustrating how different degrees of correspondence between lateral variation distributions affect the visible fringe density in a captured FFOCT image, according to a possible embodiment of the present invention. [Figure 11b] 10 is an example illustrating how different degrees of correspondence between lateral variation distributions affect the visible fringe density in a captured FFOCT image, according to a possible embodiment of the present invention. [Figure 11c] 10 is an example illustrating how different degrees of correspondence between lateral variation distributions affect the visible fringe density in a captured FFOCT image, according to a possible embodiment of the present invention. [Figure 11d] 10 is an example illustrating how different degrees of correspondence between lateral variation distributions affect the visible fringe density in a captured FFOCT image, according to a possible embodiment of the present invention. [Figure 11e] 10 is an example illustrating how different degrees of correspondence between lateral variation distributions affect the visible fringe density in a captured FFOCT image, according to a possible embodiment of the present invention. [Figure 11f] 10 is an example illustrating how different degrees of correspondence between lateral variation distributions affect the visible fringe density in a captured FFOCT image, according to a possible embodiment of the present invention. [Figure 12a] 1 illustrates a configurable optical curvature compensator constructed from a pair of prisms in a configuration that produces a lateral variation distribution of optical path length, according to a possible embodiment of the present invention. [Figure 12b] 10A-10C illustrate a configurable optical curvature compensator constructed from a pair of prisms in different configurations that produce different lateral variation distributions of optical path length, according to possible embodiments of the present invention. [Figure 13a] 10 shows the results of full-field imaging of retinal layers without optical curvature compensation, according to a possible embodiment of the present invention. [Figure 13b] 10 shows the results of full-field imaging of retinal layers with optical curvature compensation, according to a possible embodiment of the present invention. [Figure 14a] 10 shows actual final FFOCT images obtained from imaging the subbasal plexus with optical curvature compensation according to a possible embodiment of the present invention. [Figure 14b] 10 shows an actual final FFOCT image obtained from imaging the corneal endothelial layer with optical curvature compensation according to a possible embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0034] The optical path length is the product of the geometric length of the path traveled by light and the average refractive index of the medium through which the light travels. Because light rays are spatially spread in a cross-section perpendicular to the optical axis, they do not propagate only along the optical axis, and the optical path length may vary as a function of the considered position on that cross-section. This is called the lateral variation distribution of the optical path length. The lateral variation distribution of the optical path length has a profile defined by the variation of the optical path length on the cross-section.

[0035] If the optical path length is the same at all points in the cross-section, the optical path length profile will be planar. If the optical path length varies as a function of the considered position on that cross-section, the optical path length profile is not planar. For example, if the optical path length at peripheral points is longer or shorter than that at the center (i.e., on the optical axis), the optical path length profile can be defined as curved. The FFOCT system shown in Figure 1 relies on the optical path length difference between the reference arm and the sample arm. If the transverse profiles of the optical path lengths of the reference arm and the sample arm are the same, the transverse profile of the optical path difference will appear flat.

[0036] 4, 5, 8, and 9, the system includes an FFOCT device and a sample 111. Similar to the previously described devices, the FFOCT device includes an incoherent light source 101, an imager 114, a beam splitter 103 defining a sample arm 107 and a reference arm 108. The reference arm 108 extends from the beam splitter 103 to a reflector 112 disposed at the end of the reference arm 108, defining a reference optical path. A sample 111 is positioned in front of a sample end 125 of the sample arm 107, and the sample arm 107 extends from the beam splitter 103 to the sample end 125, defining a sample optical path.

[0037] The light source 101 is spatially incoherent, i.e., each point of the light source emits waves with a randomly distributed phase between these points. The light source 101 should have a broad spectrum, typically between 20 nm and 150 nm (more preferably between 30 nm and 70 nm), between 700 nm and 900 nm, and more preferably around 750 nm to 850 nm. For example, the light source 101 may be an LED or may have a filament (as in a halogen lamp).

[0038] At the moment of illumination, the light source 101 emits illumination light. The illumination light forms a first beam 102 that is sent to the beam splitter 103. The beam splitter 103 splits the incident first beam 102 of illumination light into a second beam 105 and a third beam 106. The second beam 105 is sent to the sample arm 107, and the third beam 106 is sent to the reference arm 108. Thus, the sample arm 107 and the reference arm 108 are simultaneously illuminated with the same illumination light.

[0039] In the reference arm 108, light travels along the reference path from beam splitter 103 to reflector 112, and from reflector 112 to beam splitter 103. A second beam 105 travels along the sample path from beam splitter 103 to the sample tip of sample arm 107. The light exits sample arm 107 and enters sample 111. The sample light from second beam 105 incident on sample 111 is reflected from different depths within sample 111 to the sample end of sample arm 107. The sample light includes light resulting from illumination light emitted at the moment of illumination, originating from different depths in sample 111 and therefore from different layers of sample 111.

[0040] The imaging method aims to acquire an image of a particular layer of interest 115. The layer of interest 115 is defined by its depth and shape within the sample 111. Typically, the layer of interest 115 is not flat, but rather has a curved surface relative to the optical axis of the FFOCT device. For example, if the sample 111 is an eye, the layer of interest 115 may have a convex shape as viewed from the sample arm 107, such as for the cornea or lens, or a concave shape as viewed from the sample arm 107, such as for the retina.

[0041] When light of interest originating from the layer of interest 115 of the sample 111 enters the sample arm 107, the light of interest has traveled a first optical path length. The first optical path length is the product of the geometric length of the path the light took to enter the sample arm 107 and the average refractive index of the medium through which the light traveled. If the layer of interest 115 is curved rather than flat, the transverse profile of the geometric length is altered. In addition to the change in the geometric length traveled by the light of interest, a change in the lateral profile may also result from the refractive index of the medium through which the light of interest travels. The layer of interest 115 is at a specific depth in the sample 111, which means the light of interest must travel back and forth through upper layers of the sample 111. If the sample 111 is non-uniform, those upper layers may have different refractive indices, which may be non-uniformly distributed. For example, if the layer of interest 115 is a retinal layer, the light of interest must pass through the vitreous, lens, pupil, and cornea.

[0042] In any case, upon entering the sample arm 107, the light of interest travels down a first optical path length that has a curved lateral variation distribution. For example, the curved lateral variation distribution of the first optical path length has an absolute radius of curvature between 4 millimeters and 50 millimeters. If not compensated for, this curved lateral variation distribution is submitted to optical division by the reference light, resulting in a reduced useful field of view of the sample layer of interest, as previously described with reference to Figures 2a-c and 3a-d.

[0043] To avoid this problem, the FFOCT device is provided with an optical curvature compensator that corrects the lateral variation distribution of the optical path length. The optical curvature compensator can be located in the sample arm 107 or the reference arm 108. The optical curvature compensator is a curvature compensator configured to compensate for the relative curvature of the reference light and the light of interest profiles. When the optical curvature compensator is located in the reference arm 108, the optical curvature compensator changes the reference optical length across the imaging field of view. When the optical curvature compensator is located in the sample arm 107, the optical curvature compensator changes the sample optical length across the imaging field of view. The optical curvature compensator is configured so that the reference optical path length traveled by the reference light incident on the imager 114 or the second optical path length traveled by the light of interest incident on the imager 114 has the same lateral variation distribution, i.e., so that the lateral variation distribution of the reference optical path length traveled by the reference light incident on the imager 114 and the lateral variation distribution of the second optical path length traveled by the light of interest incident on the imager 114 match within the range of the temporal coherence length.

[0044] The difference in absolute radius of curvature between the two respective lateral variation distribution profiles is preferably less than 2 mm, more preferably less than 1 mm. When the light reaches the imager 114, the light waves of the light of interest and the reference light interfere with each other, resulting in interference. Interference occurs at each point in the field of view of the imager 114 when the optical path length difference between the waves is superimposed within the temporal coherence length defined by the illumination light. Therefore, the proposed optical curvature compensation results in the light of interest emanating from the layer of interest 115 interfering with the reference light on the image plane of the imager 114, causing the imager 114 to image the layer of interest in the field of view of the imager 114.

[0045] The optical curvature compensator can be a reflector with a curved reflective surface disposed within the reference arm 108. Therefore, the optical curvature compensator can be a reflector 112 disposed at the end of the reference arm 108 facing the beam splitter 103, provided that the reflector 112 is curved. Figures 4 and 5 show an example using a curved reflector as the optical curvature compensator. In Figure 4, the layer of interest 115 is the anterior surface of the ocular lens, which is convex as viewed from the FFOCT device. The reflector 112 is also convexly curved as viewed from the reference optical path. The curvature of the reflector 112 corresponds to that of the anterior lens, and the radius of curvature is approximately between 9 mm and 15 mm, more preferably between 11 mm and 13 mm. When the layer of interest 115 is the anterior cornea, the radius of curvature of the reflector 112 is between 7 mm and 8 mm. When the layer of interest 115 is the posterior cornea, the radius of curvature of the reflector 112 is between 6 mm and 7 mm. In Figure 5, the layer of interest 115 is a retinal layer, which is concave as viewed from the FFOCT device. The reflector 112 is also concavely curved as viewed from the reference optical path. The curvature of the reflector 112 corresponds to the curvature of the retinal layer, with a radius of curvature between approximately -11 mm and -13 mm. Furthermore, the retinal imaging configuration in Figure 5 removes the microscope objective lens 109 in the sample arm 7, which was present in the previous embodiment. Removing the microscope objective lens 109 from the sample arm 7 creates a strong asymmetry between the two arms 7 and 8 of the FFOCT device. This asymmetry, combined with the asymmetry caused by the eye medium in front of the retinal layer of interest 115, leads to a laterally varying distribution with a curved profile in the second optical path length traveled by the light of interest entering the imager 114. Therefore, the curvature of the reflector 112 can be selected to be higher than the curvature of the retinal layer of interest to compensate for the asymmetry.

[0046] It should be noted that the values ​​shown here are merely examples, and other values ​​can typically be used if the sample 111 is not an eye. Even in the case of a human eye, other values ​​can be used to match the curvature of the layer of interest 112. For example, for a layer of interest 115 constituted by the anterior corneal layer of a patient with keratoconus, the radius of curvature of the reflector 112 will be less than 6 mm.

[0047] The curved shape of curved reflector 112 causes the reflected light to travel a varying optical path length across the cross section of the reference optical path, thereby causing a lateral variation distribution of the reference optical path length. By selecting the curvature of curved reflector 112 to correspond to the curvature of layer of interest 115, the reference optical path length traveled by the reference light incident on imager 114 and the second optical path length traveled by the light of interest incident on imager 114 have the same lateral variation distribution. As a result, the optical division performed by the reference light on the sample light selects only the light of interest.

[0048] The curved reflector 112 can be a mirror, particularly a curved metal mirror, for example with an aluminum coating as the reflective surface. However, most mirrors have a high reflectivity, typically greater than 90%. Such a high reflectivity is detrimental to FFOCT, since image quality is best when the reflectivity of the curved reflector 112 matches that of the sample 111. Because the sample 111 and layer of interest 115 typically have low reflectivities, the curved reflector 112 is selected to have a reflectivity of less than 25%, preferably less than 10%.

[0049] The curved reflector 112 does not necessarily have to be a mirror but can be, for example, an optical lens. Such an optical lens can be made of glass (e.g., RoHS-compliant borosilicate crown glass), fused silica, or other suitable materials. Optical glass lenses naturally have low reflectivity, typically less than 5%, comparable to the reflectivity of many organic samples 111. Optical lenses are inexpensive and can be found with any curvature. For example, an optical lens with a 6.2 mm radius of curvature can be used to match the natural curvature of the human posterior cornea, which is 6.4 mm. A drawback of optical lenses is that reflections (secondary reflections) can occur not only from the surface of the optical lens but also from the back surface of the optical lens. This can be avoided by placing an absorptive filter (e.g., a glass absorptive filter) behind the optical lens, placing an immersion liquid between the back surface of the optical lens and the absorptive filter, and selecting the absorptive filter and immersion liquid to have refractive indices close to the refractive index of the optical lens (e.g., 1.518). This allows light transmitted through the optical lens to be absorbed by the absorptive filter without secondary reflections. In addition, by selecting a material for the optical lens that absorbs light within the wavelength range of the illumination light (for example, optical filter glass that selectively absorbs light within a specific wavelength range), unwanted reflection from the back surface can be avoided.

[0050] The optical curvature compensator may be a plate of material with a compensating refractive index and a compensating length along the reference or sample path. Such an optical curvature compensator may therefore be placed in the reference arm 108 or the sample arm 107. The plate, or optical window, is an optically flat piece of transparent optical material. Figure 6 is a schematic diagram illustrating the effect of an optical window on the optical path length profile of a light ray. This simplified example deals with the propagation of light between a proximal arm point A and a distal arm point B, here defined by an optical lens. The proximal arm point A and the distal arm point B are separated by a distance e along the optical axis. air The medium between the proximal arm point A and the distal arm point B is assumed to be air (refractive index 1) except for the optical window 120. The optical window 120 is made of a material with a refractive index n'. The optical window 120 has a thickness e' between two planes 121 and 122 perpendicular to the optical axis.

[0051] The center point C of the field of view on the optical axis is located at the upper boundary U c and the linear lower boundary D c The central optical path length OPL is the straight line path defined between arm points A and B. c is OPL c =e air A non-center point P of the field of view is offset from the optical axis, and light from that non-center point P propagates between arm point B and optical window 120 at an angle θ, then propagates within the optical window at an angle θ′, and then propagates again between optical window 120 and arm point A at an angle θ. According to the Snell-Descartes law, the relationship between θ′ and θ is

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[0052] Figure 7 is a graph showing an example of how various degrees of curvature (in arbitrary units) of the lateral variation distribution profile of the optical path length can be obtained for optical windows of different thicknesses. The degree of curvature here is expressed as a parabolic function f(x) = ax that models the lateral variation distribution profile of the optical path length. 2 This corresponds to the first coefficient of +bx+c. It is required to compensate for the curved lateral variation distribution profile of light coming from the curved corneal layer of a healthy human eye. The optical window is made of borosilicate crown glass, more precisely, N-BK7 glass. Without the optical window (thickness 0), the degree of curvature is approximately -73. To obtain a (second-order) planar lateral variation distribution profile and compensate for the average curvature of the retinal layer of a healthy human eye, an optical window with a thickness of 22.3 mm is required. Note that light travels twice along the reference arm 108 or the sample arm 107. As a result, the traveling light crosses the optical plate 120 twice, and the curvature of the lateral variation distribution profile of the optical path length is affected twice by the optical plate 120.

[0053] FIG. 8 illustrates an example arrangement for implementing FFOCT imaging, in which the optical curvature compensator is an optical plate 120 located in the reference arm 108. The optical plate 120 is located in the reference optical path between the beam splitter 103 and the reflector 112. The optical plate 120 can be located on either side of the sample microscope objective 110, but is preferably located between the beam splitter 103 and the sample microscope objective 110. As previously described, the optical plate 120 curves the lateral variation distribution profile of the reference light so that the reference optical path length traveled by the reference light incident on the imager 114 and the second optical path length traveled by the light of interest incident on the imager 114 have the same lateral variation distribution profile.

[0054] The reflector 112 at the end of the reference arm 108 does not need to be curved, but can be flat. However, it is possible to combine embodiments, and it is also possible to equip the curved reflector 112 with the optical plate 120. In this case, the curvature of the profile of the lateral variation distribution of the reference optical path length introduced by the curved reflector 112 is added to the curvature of the profile of the lateral variation distribution of the reference optical path length introduced by the optical plate 120. Thus, the characteristics of the curved reflector 112 and the optical plate 120 are selected such that the reference optical path length traveled by the reference light incident on the imager 114 and the second optical path length traveled by the light of interest incident on the imager 114 have the same lateral variation distribution profile.

[0055] FIG. 9 shows an example arrangement for implementing FFOCT imaging, in which the optical curvature compensator is an optical plate 120 positioned in the sample arm 107. As shown, the sample arm preferably does not have a microscope objective 109. The optical plate 120 is positioned in the sample light path between the beam splitter 103 and the sample end 125 of the sample arm 107. As previously described, the optical plate 120 curves the lateral variation distribution profile of the sample light, so that the sample path length traveled by the reference light incident on the imager 114 and the second path length traveled by the light of interest incident on the imager 114 have the same lateral variation distribution profile.

[0056] The characteristics of the optical curvature compensators 112, 120 related to the change in optical path length are selected to compensate for the optical curvature of the layer of interest 115, i.e., the curvature of the profile of the lateral change distribution of the optical path length traveled by the light of interest emanating from the layer of interest 115. If the geometry or optical characteristics of the layer of interest 115 are known, for example, a layer of the anterior cornea with a radius of curvature of around 7.8 mm, the optical curvature of the layer of interest 115 can be known. However, it may happen that the optical curvature of the layer of interest 115 is not known, or at least not accurately enough. It may be necessary to estimate the optical curvature of the layer of interest 115.

[0057] Here, we describe a simple method for estimating the optical curvature of the layer of interest 115, enabling the selection of an appropriate optical curvature compensator. Several FFOCT frontal images (x, y) of the sample 111 are acquired while the reflector 112 of the reference arm 108 is moved at a constant speed along the optical axis (z-axis). In this way, various depths of the sample 111 are imaged, resulting in a three-dimensional data volume (in the x, y, and z directions), as shown in Figure 10a, where three acquired images 35, 36, and 37 (extending in x and y) are organized. Cross-sectional images (x, z) of the sample 111 can be generated by selecting the same pixel lines 35a, 36a, and 37a in each image of the acquired image sequence and concatenating the selections. Such cross-sectional images are depicted in Figure 10b.

[0058] During the translation of the interference arm 108, the coherence gate maintained its curved shape and translated in the z direction. The resulting cross-sectional image shows various imaged interference sample sections (defined by the coherence gate) corresponding to the origin of the interfering sample light with the reference light. Thus, the lower and upper limits 38 and 39 of the imaged area correspond to the profile of the coherence gate. The difference Δ in depth (z) between the center point of the limits 38, 39 and the end points of the limits 38, 39 can be measured. From the difference Δ and the distance (y) between the center point and the end points, the optical curvature of the coherence gate can be derived. Other criteria can also be used.

[0059] The same approach can be used to evaluate whether the optical curvature of the layer of interest 115 is properly compensated by the optical curvature compensator. When properly compensated, the coherence gate appears fairly flat on the cross-sectional image, as shown in Figure 10b. The coherence gate is considered flat if, for example, the difference Δ in depth (z) between the center point of the limits 38, 39 and the end points of those limits 38, 39 is less than half the coherence gate thickness, which depends on the bandwidth of the light source 1. For example, if the coherence gate thickness is 8 μm and the difference Δ is less than 4 μm, the curvature of the coherence gate can be considered compensated.

[0060] It is also possible to verify the optical curvature compensation performed by the FFOCT device using the interference fringes of the acquired images. A test reflector is placed as a sample in front of the sample arm 107. The test reflector is centered relative to the optical axis, i.e., the curvature of the test reflector is centered. The test reflector has a known curvature corresponding to the curvature to be compensated. For example, to verify the optical curvature compensation of a curved layer with a radius of 7.8 mm, the test reflector is selected to have a radius of curvature close to, and preferably equal to, 7.8 mm. The test reflector can be a flat or curved reflector, a mirror, or possibly a dispersive medium associated with the curved reflector that introduces a known curvature into the lateral variation distribution of the optical path length of light propagating through the dispersive medium.

[0061] The test reflector is then illuminated and an image acquired, similar to the sample 111. The acquired image can then be processed to determine the curvature compensation performed by the optical curvature compensator of the FFOCT device based on the visible interference fringe density. Fringe density is defined as the maximum number of alternating fringes per mm (perpendicular to the fringes) and is directly related to the match between the radius of curvature of the test reflector and the radius of curvature of the lateral variation distribution of the optical path length.

[0062] For example, FIG. 11a shows an image corresponding to a first test reflector 60 having a radius of curvature of 7.8 mm, imaged with an optical curvature compensator configured to compensate for the 7.8 mm radius of curvature, resulting in a coherence gate defining an interference section (corresponding to the origin of the sample light interfering with the reference light) with the same curvature as the first test reflector 60, as shown in FIG. 11b. In the image of FIG. 11a, the fringes are spaced farther apart and less dense. FIG. 11c shows an image corresponding to a second test reflector 62 having a radius of curvature of 6.2 mm, imaged with an optical curvature compensator configured to compensate for the 7.8 mm radius of curvature, resulting in a coherence gate defining an interference section 63 (corresponding to the origin of the sample light interfering with the reference light) that is closer to but not quite the same as the second test reflector 62, as shown in FIG. 11d. In the image of FIG. 11c, the fringes are closer together and more dense than in FIG. 11a. Figure 11e shows the corresponding image for a third test reflector 65 that was flat (infinite radius of curvature) and imaged with an optical curvature compensator configured to compensate for a 7.8 mm radius of curvature, resulting in a curved coherence gate defining a curved interference section 64, as shown in Figure 11f. In the image in Figure 11e, the fringes are very close together and much more numerous than in Figures 11a and 11c, resulting in a very high fringe density.

[0063] This is because the fringe density is related to the optical path difference between the surface of the test reflector and the interference section defined by the coherence gate of the FFOCT device. Interference fringes appear whenever the optical path difference reaches the wavelength of the illumination light (850 nm in our example). This is why the fringe density can be used to evaluate whether the lateral variation distribution of the reference optical path length traveled by the reference light matches the lateral variation distribution of the second optical path length traveled by the light of interest. As can be seen in Figures 11b, 11d, and 11f, due to the curved nature of the coherence gate, the optical path difference is larger at the edge of the field of view (FOV) (where the optical path difference is larger) than in the center of the FOV (where the optical path difference is smaller). This explains the concentric aspect of the interference fringes. Therefore, the maximum density is usually found at the edge of the image, which corresponds to the edge of the FOV.

[0064] A simple criterion for fringe density can be established to assess whether the profiles of two respective lateral variation profiles have a difference in absolute radius of curvature of less than 2 mm. For an 850 nm illumination light and a 1.3 mm FOV, the optical curvature of the test reflector is considered compensated when the maximum fringe density is less than 60 fringes / mm, preferably less than 50 fringes / mm. Note that the density is expressed according to the field of view of the imaged object, i.e., taking into account the magnification. In the example shown, the maximum fringe density of the image in Figure 11a is less than 15 fringes / mm, indicating good agreement between the lateral variation profiles, i.e., between the test reflector profile and the coherence gate. The maximum fringe density of the image in Figure 11c is less than 50 fringes / mm, indicating acceptable agreement between the lateral variation profiles. However, the maximum fringe density of the image in Figure 11e is greater than 100 fringes / mm, indicating no agreement between the lateral variation profiles.

[0065] As a result, a simple measurement involving a test reflector with known curvature can determine whether the optical curvature compensation matches the known curvature.

[0066] The optical curvature compensator can be invariant, meaning that the change in the lateral variation distribution profile of the optical path length caused by the optical curvature compensator is always the same. For example, the deformation caused by the curved reflector 112 depends on the curvature of the curved reflector 112, and the deformation caused by the optical plate 120 depends on the thickness and refractive index of the optical plate 120. As a result, such an invariant optical curvature compensator can only compensate for the curvature of the lateral variation distribution profile within a limited range. This can be problematic because the curvature of the layer of interest 115 may be known inaccurately. For example, in clinical applications, patients may exhibit a significant variation in eye length, which will affect the selection of an appropriate optical window or curved mirror. As mentioned above, the radius of curvature of the reflector 112 is less than 6 mm in the anterior corneal layer of a patient with keratoconus, while it is approximately 7.8 mm in the healthy anterior corneal layer.

[0067] One solution is to use a variable optical curvature compensator to fit the curvature of the various possible layers of interest. However, this can be a lengthy process based on trial and error, requiring many different optical curvature compensators. However, it is possible to make the optical curvature compensator easier to change; for example, an optical wheel can be motorized with a stepper motor.

[0068] Another solution is to provide a configurable optical curvature compensator. The configurable optical curvature compensator can be a deformable mirror whose reflective surface can be deformed. The deformable mirror can be shaped to fit various types of surfaces, not just curved surfaces. For example, the deformable mirror can be based on a continuous reflective surface that is moved by a magnetic actuator.

[0069] As shown in Figures 12a and 12b, the configurable optical curvature compensator can also be a pair of prisms. The pair of prisms constitutes an assembly that can be viewed as an optical plate for moving light. In fact, the pair of prisms is essentially an optical plate divided into two parts. The two prisms are preferably made of the same material and have the same shape. There is a first prism 131 and a second prism 132. Each prism 131, 132 has a flat surface 131a, 132a perpendicular to the optical axis. The two flat surfaces 131a, 132a form the outer surface of the optical curvature compensator. Each prism 131, 132 has an inclined surface 131b, 132b that forms a non-perpendicular inclination angle with respect to the optical axis. The two inclined surfaces 131b, 132b are opposite each other and therefore face each other. The two inclined surfaces 131b, 132b have complementary inclinations. Light passing through the optical curvature compensator, for example, passes through flat surface 131a of first prism 131, inclined surface 131b of first prism 131, flat surface 132a of second prism 132, and inclined surface 132b of second prism 132. In the configuration of Figure 12a, such light would have passed through a first thickness e1 of material of first prism 131 and a second thickness e2 of material of second prism 132. Thus, the pair of prisms corresponds to an optical plate with a thickness of e1 + e2.

[0070] However, the prisms 131 and 132 are translatable relative to each other. More precisely, at least one, and preferably both, of the prisms 131 and 132 are translatable perpendicular to the optical axis. The translation can be achieved by a motor. Such lateral translation results in a change in the thickness of the material traversed by the traveling light. Figure 12b shows the result of translating both prisms 131 and 132 in opposite directions lateral to the optical axis. Due to the inclined surfaces 131b and 132b of the two prisms, the translation results in a change in the pass thickness, or more precisely, a decrease in the pass thickness for the example shown in Figure 12b. The apparent thickness e'1 of the first prism 131 and the apparent thickness e'2 of the second prism 132 are reduced relative to the apparent thicknesses e1 and e2 of the first configuration in Figure 12a. In the second configuration, the pair of prisms corresponds to a thinner optical plate with a thickness e'1 + e'2. This allows for a configurable optical curvature compensator, equivalent to an optical plate with a configurable thickness. These examples refer to the optical axis. Such optical axis is the optical axis of the arm in which the optical curvature compensator is located. Since the optical paths in the arm are parallel to the optical axis, any designation given for the optical axis can be understood as a designation given for the optical paths in that arm.

[0071] To adapt the optical curvature compensator to the desired lateral variation distribution profile of the optical path length, the FFOCT can include a control loop for finding an appropriate optical path length correction profile. The control loop aims to maximize the useful field of view. The control loop is based on an analysis of the two-dimensional image acquired by the imager 114, from which actuator commands for directing the optical curvature compensator are derived. Therefore, the control loop includes a suitable component, such as a processor. For example, the analysis aims to identify areas where a signal is present and areas where a signal is not present. For example, the acquired image can be divided into multiple zones (e.g., 5 to 20 zones) distributed across the surface of the acquired image. The zones can be simply square or rectangular. In each zone, the pixel values ​​(e.g., grayscale values) of all pixels in that zone are summed. By comparing the resulting sum with a preset threshold, each zone can be classified into "good" areas where a signal is present because the coherence gates match, and "bad" areas where a signal is not present because the coherence gates do not match. The configurable optical curvature compensator is then changed to turn the bad region into a good region. A control loop can also be used to select from among a set of invariant optical curvature compensators.

[0072] Thus, this method may include acquiring a first two-dimensional frontal FFOCT image of the layer of interest 115, and then acquiring a second two-dimensional frontal FFOCT image of the layer of interest 115 using improved compensation for the curvature profile of the lateral variation distribution of the first optical path length. From the first two-dimensional frontal FFOCT image, it is determined whether the curvature profile of the lateral variation distribution of the first optical path length has been compensated for by the optical compensator. As described above, such determination may depend, for example, on the density of visible interference fringes, the shape (ring shape) of the imaging field, and / or the signal level. If it is determined that the curvature profile of the lateral variation distribution of the first optical path length has not been compensated for by the optical compensator, for example, because the fringe density is too high, the optical compensator is modified to better compensate for the curvature profile of the lateral variation distribution of the first optical path length. Next, a second two-dimensional frontal FFOCT image of the layer of interest 115 is acquired using the imager 114 from the reference light and the sample light combined by the beam splitter 103. Because the modification of the optical compensator is intended to improve compensation, the criteria used to evaluate the compensation should also show an improvement over the first image. For example, the fringe density should be reduced. If satisfactory results are still not obtained, the modified optical compensator can be changed again to better compensate for the curvature profile of the lateral variation distribution of the first optical path length, and another image can be acquired, until the compensation for the curvature profile of the lateral variation distribution of the first optical path length meets expectations.

[0073] In the example of FIG. 2c, the defective region corresponds to a peripheral zone of the acquired image, which means that the coherence gates only match at the center, as shown schematically in FIG. 2a. In the example of FIG. 3c, the defective region corresponds to a central zone of the acquired image, which means that the coherence gates only match at the periphery, as shown schematically in FIG. 3a. A command is generated to curve the lateral variation distribution profile of the optical path length of the arm in which the optical curvature compensator is located so that a reference optical path length traveled by the reference light incident on the imager 114 and a second optical path length traveled by the light of interest incident on the imager 114 have the same lateral variation distribution profile. For example, if the optical curvature compensator is a deformable curved mirror 112 in the reference arm 108, the command is applied to an actuator that controls the curvature of the deformable curved mirror 112 to increase the curvature. If the optical curvature compensator is a pair of prisms, the command is applied to an actuator that controls the lateral translation of the prisms. When a pair of prisms is placed in the reference arm 108, the prisms are translated to increase the apparent thickness of the material in order to further curve the lateral variation distribution profile of the reference optical path length. When a pair of prisms is placed in the sample arm 108, the prisms are translated to decrease the apparent thickness of the material in order to decrease the curvature of the lateral variation distribution profile of the sample optical path length.

[0074] FIG. 13a shows an actual FFOCT image obtained from imaging the retinal layer of an artificial eye without optical curvature compensation as disclosed above. The result is a ring shape 50 of the imaged retinal layer, with a central portion 51 corresponding to the overlay layer. The lateral distributions of the optical path lengths traveled by the reference light and the light of interest incident on the imager 114 do not match. This corresponds to the situation shown in FIGS. 3a-3d. FIG. 13b shows an actual FFOCT image obtained as a result of imaging the retinal layer of an artificial eye such as that shown in FIG. 13a by implementing the method disclosed above, in which an optical curvature compensator modifies the lateral distributions of the optical path lengths traveled by the reference light and the light of interest incident on the imager so that the lateral distributions of the optical path lengths traveled by the reference light and the light of interest incident on the imager match. In this image, it can be seen that the imager 114 imaged the layer of interest over the entire field of view 52 of the imager 114. This means that the light of interest originating from the layer of interest interfered with the reference light over the entire field of view 52 of the imager 114. This method therefore allows imaging of a layer of interest over a complete and continuous field of view.

[0075] FIG. 14a shows an actual final FFOCT image obtained from imaging the subbasal plexus as in FIG. 3c, by implementing the method disclosed above, this time with optical curvature correction. Compared to FIG. 3c, where the imaged anterior corneal endothelial layer appeared as a ring in the final image, the anterior corneal endothelial layer is no longer ring-shaped and occupies the entire field of view. FIG. 14b shows an actual FFOCT image obtained from imaging the corneal endothelial layer as in FIG. 3d, by implementing the method disclosed above, this time with optical curvature correction. Compared to FIG. 3d, where the imaged posterior corneal endothelial layer appeared as a ring in the final image, the posterior corneal endothelial layer is no longer ring-shaped and occupies the entire field of view. It can thus be seen that the disclosed method enables imaging of each layer throughout the field of view of the imager 114.

[0076] While the present invention has been described with respect to certain preferred embodiments, it is clear that it is not limited thereto, but includes all technical equivalents of the described means and combinations thereof. It will be apparent to those skilled in the art that various changes and modifications can be made thereto without departing from the scope of the invention, in particular as defined in the appended claims.

Claims

1. 1. A full-field optical coherence tomography (FFOCT) imaging method for acquiring a two-dimensional en face FFOCT image of a layer of interest at a depth within a sample, comprising: The FFOCT imaging method uses a system comprising an FFOCT device and a sample including a layer of interest to be imaged; the FFOCT device includes a spatially incoherent light source, an imager, and a beam splitter defining a sample arm and a reference arm, the sample being disposed at the end of the sample arm; The method comprises: simultaneously illuminating a sample arm and a reference arm at an instant of illumination with illumination light emitted by the incoherent light source to generate sample light traveling from the sample along a sample optical path into the end of the sample arm and reference light traveling along a reference optical path in the reference arm to a beam splitter; acquiring a two-dimensional frontal FFOCT image of a layer of interest using the imager from reference light and sample light combined in the beam splitter, wherein the sample light originates from the illumination light emitted at the moment of illumination and includes light of interest originating from the layer of interest of the sample, the light of interest having traveled a first optical path length upon entering the sample arm, the first optical path length having a curved profile with a laterally varying distribution, and wherein the reference light incident on the imager has traveled a reference optical path length and the light of interest incident on the imager has traveled a second optical path length; At least one of the sample arm and the reference arm includes an optical curvature compensator that modifies the lateral change distribution of the optical path length, compensating for the curvature profile of the lateral change distribution of the first optical path length so that the lateral change distribution of the reference optical path length traveled by the reference light incident on the imager matches the lateral change distribution of the second optical path length traveled by the light of interest incident on the imager, such that the light of interest emanating from the layer of interest interferes with the reference light, and the imager images the layer of interest over a field of view of the imager to form the two-dimensional frontal FFOCT image acquired by the imager.

2. The method of claim 1 , wherein the curvature profile of the lateral variation distribution of the first optical path length has an absolute radius of curvature comprised between 4 millimeters and 50 millimeters.

3. 3. The method of claim 1, wherein the lateral variation distribution of the reference optical path length traveled by the reference light incident on the imager and the lateral variation distribution of the second optical path length traveled by the light of interest incident on the imager have a difference in absolute radius of curvature of less than 2 millimeters.

4. 4. The method of claim 1, wherein the reference arm includes an optical curvature compensator that modifies the lateral variation distribution of the reference optical path length traveled by the reference light incident on the imager, the optical curvature compensator being a curved reflector having a curved reflective surface, the curved reflector being disposed at an end of the reference arm facing a beam splitter.

5. The method of claim 4 , wherein the curved reflector has a reflectivity of less than 25%.

6. The method of claim 4 or 5, wherein the curved reflective surface of the curved reflector is an optical lens.

7. The method of claim 4 or 5, wherein the curved reflective surface of the curved reflector is a deformable mirror.

8. The method according to any one of claims 1 to 3, wherein the optical curvature compensator is a plate of a material having a refractive index and a thickness in the direction of the reference or sample path.

9. 4. The method of claim 1, wherein the optical curvature compensator includes a pair of prisms, each prism having an inclined surface that forms a non-perpendicular tilt angle with respect to the optical path, the non-perpendicular tilt angles of the pair of prisms being opposite to each other, and the prisms are translatable relative to each other.

10. 10. The method of claim 1, wherein the optical curvature compensator is a configurable optical curvature compensator, and the FFOCT device includes a control loop configured to analyze acquired images and derive commands for changing a configuration of the optical curvature compensator, each configuration defining a different modification of the lateral variation distribution of optical path length.

11. acquiring a first two-dimensional frontal FFOCT image of the layer of interest from reference light and sample light combined in the beam splitter using the imager; determining whether the curvature profile of the lateral variation distribution of the first optical path length is compensated by the optical curvature compensator; if it is determined that the curvature profile of the lateral variation distribution of the first optical path length has not been compensated by the optical curvature compensator, modifying the curvature profile of the lateral variation distribution of the first optical path length to be so compensated; and acquiring a second two-dimensional frontal FFOCT image of the layer of interest from the reference light and sample light combined in the beam splitter using the imager.

12. 1. A full-field optical coherence tomography (FFOCT) device, comprising: a spatially incoherent light source configured to emit illumination light at an illumination instant; an imager configured to acquire a two-dimensional frontal FFOCT image of the layer of interest; a beam splitter defining a sample arm and a reference arm, the sample including the layer of interest at a depth within the sample, the beam splitter being disposed at an end of the sample arm; At least one of the sample arm and the reference arm includes an optical curvature compensator configured to correct the lateral variation distribution of the optical path length, thereby compensating for the curved profile of the lateral variation distribution of the first optical path length that originates from the illumination light emitted at the moment of illumination and that light of interest originating from the layer of interest of the sample has traveled after entering the sample arm, and the FFOCT device is configured to perform the method of any one of claims 1 to 11, and to acquire a two-dimensional frontal FFOCT image of the layer of interest at a certain depth within the sample.

Images