Patent Application
20220257114
The present disclosure relates to an ophthalmoscope and method for imaging a retina, e.g. its structure and optical properties.
For the assessment of a several diseases with an impact on optical properties of cells in the human retina, the in-vivo analysis of multiple scattering in the tissue is an important tool. These diseases can be directly related to the vision system, but can also include diseases of the neuronal system like Alzheimer or Parkinson. To obtain additional information, various types of measurements can be performed, e.g. confocal or multi-scatter. However it can be difficult to align the different measurements, e.g. due to artefacts from eye movements. It can also be challenging to collect sufficient scattering light.
There is yet a need for an improved ophthalmoscope which can quickly and accurately obtain desired information from retinal measurements.
Aspects of the present disclosure relate to imaging of the retina, e.g. using an ophthalmoscope. According to a preferred aspect, a ring-shaped light pattern of source light is projected onto a retinal focal plane coinciding with the retina. In at least one detection channel, scattered light can be collected and measured originating (exclusively) from a central spot at a center of the ring-shaped light pattern on the retinal focal plane. In this way the scattered light results from the source light of the ring-shaped light pattern scattering via the retina (excluding the direct illuminated surrounding area of the ring). As will be appreciated, using a ring shaped illumination pattern can provide a relative high intensity of scattered light at a central measurement spot compared to the reversed situation of illuminating at a central spot and measuring in a ring around the central spot. For example, the light intensity per unit area of the projected ring shape can be relatively low compared to the same amount of light focused in a spot, while the light from all around the ring can scatter over the same distance to a center of the ring.
In some embodiments an ophthalmoscope for imaging a retina comprises an illumination system with at least one light source and a first set of projection optics configured to project a respective light pattern of source light from the respective light source onto a retinal focal plane coinciding with the retina; and a measurement system with at least one light detector and a second set of projection optics configured to measure light from the retinal focal plane resulting from the source light of the respective light pattern interacting with the retina. Preferably, the illumination system is configured to project at least one ring shaped pattern of respective source light onto the retinal focal plane, and the measurement system is configured to measure scattered light from the retinal focal plane resulting from scattering of the at least one ring shaped pattern of respective source light via the retina. Most preferably, the scattered light is measured from a spot at a center of the ring shaped pattern on the retinal focal plane.
In some embodiments, a first spatial filter is disposed in a conjugate focal plane and configured to pass a first part of the light received from an area on the retina which overlaps said light pattern. This light may be used for confocal imaging of the retina. A second spatial filter is configured to pass a second part of the light from another area on the retina, e.g. the central spot which is laterally distanced from the ring shaped illumination. In other words, this second part of the light is received from an area which was not directly illuminated. This light may be used to provide additional information on surrounding tissue, e.g. the light scattering and absorbing properties of a tissue volume related to the second spatial filter. By combining the measurements in a single device, a more complete image may be obtained with the benefits of (high spatial resolution) confocal imaging aligned with (lower spatial resolution) determination of other or further optical properties (scattering coefficient, scattering phase function, absorption coefficient).
In preferred embodiments, a single element detector is used to record a respective signal. Such detectors may have superior acquisition speed, e.g. compared to devices with a larger number of detection elements (pixels). Accordingly, problems associated with eye movement may be avoided. Preferably, the second filter is configured to allow accurate determination of the exact distance the light has travelled through the tissue before being retransmitted from the retina and collected. For example, a confocal laser scanning system can be combined with a ring-shaped light aperture that can be in the illumination or the detection path. In both cases the same scanning system can be used by both, the illumination and the detection path.
In one embodiment, e.g. with a ring shaped aperture in the illumination system, a second, confocal light source with a different wavelength can be combined using a mirror with a hole, or another beam splitting device based on polarization, or wavelength. In the detection path the two wavelengths can be separated by another beam splitter based on wavelength. For the detection then there can be two confocal detectors at conjugated position. The size of the detector for the ring illumination may have a different aperture/pinhole for the detection. The advantage of this solution is the simplicity in the detection path consisting in two confocal detectors. One can see the light from the center of the scanning, the other from the circular area around this central point.
Another or further embodiment may use a setup with a ring-shape aperture in the detection path. The illumination can be the same as in a standard confocal laser scanning system. In this case the system can work with a single wavelength. The beam splitting can be done spatially by a mirror with a pinhole for the confocal signal in the center or an active mirror with programmable mirror elements.
One embodiment may comprise a an active mirror in the projection optics to, e.g., control a radius of the projected light pattern. The programmable mirror can be also replaced by a transparent programmable screen like a LCD in the conjugated plane. In any case the lateral distance range or radius can be chosen by the geometrics of the inner and outer diameter of the aperture ring. For the case with the programmable mirror, it is also possible to toggle between two or more settings during the scanning—for every single position, for every line or a full frame. The ring shaped apertures can also be replaced by other shapes that allow to select light from a defined distance from the central spot.
These and other features, aspects, and advantages of the apparatus, systems and methods of the present disclosure will become better understood from the following description, appended claims, and accompanying drawing wherein:
Terminology used for describing particular embodiments is not intended to be limiting of the invention. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. The term “and/or” includes any and all combinations of one or more of the associated listed items. It will be understood that the terms “comprises” and/or “comprising” specify the presence of stated features but do not preclude the presence or addition of one or more other features. It will be further understood that when a particular step of a method is referred to as subsequent to another step, it can directly follow said other step or one or more intermediate steps may be carried out before carrying out the particular step, unless specified otherwise. Likewise it will be understood that when a connection between structures or components is described, this connection may be established directly or through intermediate structures or components unless specified otherwise.
The invention is described more fully hereinafter with reference to the accompanying drawings, in which embodiments of the invention are shown. In the drawings, the absolute and relative sizes of systems, components, layers, and regions may be exaggerated for clarity. Embodiments may be described with reference to schematic and/or cross-section illustrations of possibly idealized embodiments and intermediate structures of the invention. In the description and drawings, like numbers refer to like elements throughout. Relative terms as well as derivatives thereof should be construed to refer to the orientation as then described or as shown in the drawing under discussion. These relative terms are for convenience of description and do not require that the system be constructed or operated in a particular orientation unless stated otherwise.
In some embodiments, different part of the light are received and/or reflected along different light paths L1,L2, e.g. following at least partially distinct spatial trajectories. Preferably, the different light paths L1,L2 are recorded in distinct detection channels C1,C2, e.g. by different detectors (not shown here). In a preferred embodiment, all light corresponding to a respective detection channel C1,C2 is measured by a respective single element detector. It will be appreciated that a single element detector may typically be faster than a multi-pixel array and all light hitting the single detection element may be integrated.
In some embodiments, the different light paths L1,L2 are reflected from different areas Rc, Ro of the retina R. In one embodiment. e.g. as shown, the different light paths L1,L2 both originate from the same light pattern Ri. Alternatively, it also may be envisaged that the different light paths L1,L2 are reflected from the same area on the retina, e.g. originating from different illumination patterns (not shown here).
In a preferred embodiment, a first part of the light following the first light path L1 is directly reflected from a first area Re illuminated by the light pattern Ri. In another or further preferred embodiment, a second part following the second light path L2 is reflected via (multiple) scattering. For example, the second part may be laterally displaced away from the area of the retina R receiving the respective light pattern Ri which produces the scattered light.
In some embodiments, light entering the first detection channel C1 is used to perform a high resolution confocal measurement of the retinal surface while the second detection channel C2 is used to measure other or further properties of surrounding retinal tissue, e.g. the optical transport coefficients (scattering coefficient, scattering phase function and absorption coefficient). The tissue volume over which these properties are averaged depends on the selected radial distance dR, or range of radial distances. Typically, light which is recorded from a second areas Ro at a relatively large distance dR away from the originating light pattern Ri, may travel at relatively large depth dZ through the tissue of the retina R and the optical properties derived from such a measurement are average values of large retinal tissue volumes. Conversely, light received from the illuminated area, or in close proximity to this area, may correspond (mostly) to relatively small sampling volumes. By combining the measurements of the two or more detection channels C1,C2 a more informative lower spatial resolution optical property analysis of the retina R may be obtained without sacrificing the spatial resolution of the original confocal retinal image. For example, the information can be used to construct an image of the retina surface which is augmented by information of concentrations of absorbing molecules such as oxyhemoglobin, deoxyhemoglobin and carotenoids which can be obtained from a (multi-color) measurement of the absorption coefficient of the retinal tissue.
In some embodiments, e.g. as illustrated here, the light pattern Ri is formed by a ring-shaped pattern. In another or further embodiment, the light pattern Ri may have other forms, e.g. one or more focal spots or another pattern having a (radial) offset from an imaged location, preferably at a center or at least equal distance from each the focal spots. Typically, the ring-shaped pattern or other light pattern may be scanned over the retina R to form a spatially resolved image by combining measurements at different locations. In a preferred embodiment, light (resulting from the ring-shaped illumination) is exclusively collected (for at least one detection channel) from a central spot at a center of the ring-shaped pattern. For example, in at least one detection channel, direct light originating from the area around the central spot (where the ring-shaped pattern is projected) can be excluded in the detection, e.g. by means of a spatial filter, so only indirect light scattering via the retina and originating from the central spot enters that detection channel.
In some embodiments, light originating from a first area Re including or coinciding with the light pattern Ri (e.g. ring shape or other pattern) is recorded in a first detection channel C1. For example, the light from the retina is imaged by projection optics onto a first spatial filter (not shown here). For example, the first spatial filter comprises a ring-shape which exclusively passes light from the ring-shape to a respective light detector, at least does not pass light from a second area Ro which is noncontiguous with the first area Rc. In this way a confocal image of the retina may be recorded. Also other corresponding shapes of the light pattern and spatial filter may be envisaged.
In some embodiments, light originating from a second area Ro which does not include the ring-shape or other light pattern Ri, is recorded in a second detection channel C2. For example, the second area Ro is offset at a radial distance dR from the light pattern Ri, as illustrated in a center of the ring-shape. In some embodiments, light from the retina R is imaged on a second spatial filter (not shown here). For example, the second spatial filter comprises a pinhole or other transmissive or reflecting area having an offset to exclusively pass light from the second area Ro to a respective light detector, at least not pass light directly originating from the first area Re, e.g. ring shape.
In some embodiments, light entering the first detection channel C1 originates exclusively from within the ring overlapping the light pattern Ri. The closer, the recorded area matches the light pattern Ri, the more efficient the measurement while avoiding undesired (diffuse) light.
In some embodiments, light entering the second detection channel C2 originates from a specific distance dR (or range of distances) separated from the (inner) edge of the ring-shaped light pattern Ri. For example, in the embodiment shown, the second area Ro may be formed by a small circular area or focal spot on the retina which is separated from the inner ring radius R2 of the edge of the light pattern Ri e.g. ring-shape.
In a preferred embodiment, the inner ring radius R2 is larger than the outer spot radius R1. In other words, the second area Ro is preferably noncontiguous or disjoint from the first area Rc. Accordingly, there can be a non-imaged area Rn on the retina separating the second area Ro from the first area Rc. For example, the hatched areas in the figure indicate areas of the retina from which light may be blocked to reach any detector, e.g. neither the first nor the second detection channel. For example, the light is blocked by one or more spatial filters in a respective light path. For example, a spatial filter comprises an absorptive coating in a corresponding area between the outer spot radius R1 and inner ring radius R2. Accordingly, light entering the second channel C2 has preferably traveled at least some minimum distance (R2−R1) from the point of illumination through the tissue, but no more than the maximum distance (R3−R1).
In some embodiments, the minimum distance (R2−R1) between the non-contiguous areas Ro and Rc imaged on respective spatial filters is more than ten micrometer, more than fifty micrometer, more than hundred micrometer, more than a few hundred micrometers, more than one millimeter, or more. In other or further embodiments, the maximum distance (R3−R1) between the second area Ro and the first area Re is less than two millimeter, less than one millimeter, less than five hundred micrometer, less than two hundred micrometer, or less. These minimum and maximum distances may correspond to typically desired photon path lengths for probing the retinal tissue. Radial distances may also be determined in relative proportion. In a preferred embodiment, the inner ring radius R2 is larger than the outer spot radius R1 by at least a factor 1.1 (ten percent), 1.5 (fifty percent), 2 (two hundred percent), 3 (three hundred percent), 5 (five hundred percent), or more.
In some embodiments, a difference between the outer ring radius R3 and inner ring radius R2 is relatively small. In other words, the range of radial distances dR entering the second detection channel C2 is relatively narrow. For example, R3 is larger than R2 by at least a factor 1.01, 1.1, or 1.5, but less than a factor two or three. Alternatively, or additionally, the thickness of the ring (R3−R2) may be compared relative to a distance (R2−R1) between the ring and the illuminated area, e.g. (R2−R1)≥N*(R3−R2) where the factor N is at least half, preferably at least one, or even more than two. These or other measures may ensure, light entering the second channel C2 originates from a well-defined yet sufficiently broad band of radial distances dR and can be correlated with corresponding path lengths.
It will be understood that the absolute distances dR on the retina may be related to corresponding, but possibly different distances dR′ on the respective spatial filter, depending on the magnification of the projection system. On the other hand, relative distances may be the same or similar for features on the corresponding spatial filters (at least assuming the same magnification is used for different filters).
Some embodiments for imaging the retina R comprise projecting a respective light pattern Ri of source light Li from onto a retinal focal plane Pr coinciding with the retina R. Other or further embodiments comprise measuring light from the retinal focal plane Pr resulting from the source light Li of the respective light pattern Ri interacting with the retina R. Other or further embodiments comprise measuring a first part of the light received in a first detection channel C1 from a first area Rc on the retina R which first area Rc overlaps the respective light pattern Ri from which said first part of the light originates. Other or further embodiments comprise measuring a second part of the light received in a second detection channel C2 of the respective light detector 22 from a second area Ro on the retina R which second area Ro is offset by a lateral distance dR with respect to the respective light pattern Ri from which said second part of the light originates. Preferably, the first and second parts of the light are measured simultaneously. It can also be envisaged to measure only the second part, e.g. using a ring-shaped illumination and measuring only scattered light at a central spot within the ring.
In some embodiments, the measurements of the first and second detection channels C1,C2 are combined to form one or more overlapping images I of the retina R. In other or further embodiments, a position of the light pattern Ri is scanned over the retina R, wherein the measurements of the first and second detection channels C1,C2 at each position are combined to form a pixel of the image I at that position. In other or further embodiments, respective overlapping images of the retina surface and retinal optical properties are constructed based on the respective detection channels C1,C2, wherein pixels are aligned across the images based on a corresponding position of the same light pattern Ri used for measuring those pixels. In other or further embodiments, an image of tissue optical properties of the retina is calculated based on respective measurements in the second detection channel C2, wherein the averaged tissue volume is controlled by setting a radial distance dR between a ring of the light pattern Ri and the second area Ro at a center of the ring from which light is received in the second detection channel C2.
In some embodiments, the ophthalmoscope 100 comprises an illumination system. Preferably, the illumination system comprises at least one light source 11,12. e.g. laser. In some embodiments, e.g. as shown, a first set of projection optics 41-43 is configured to project a respective light pattern Ri of source light Li from the respective light source 11,12 onto a retinal focal plane Pr coinciding with the retina R.
In some embodiments, the ophthalmoscope 100 comprises a measurement system. Preferably, the measurement system comprises at one or more light detectors 21,22. In some embodiments, e.g. as shown, a second set of projection optics 42-45 is configured to measure light from the retinal focal plane Pr. The measured light results from the source light Li of the respective light pattern Ri interacting with the retina R.
In some embodiments, the ophthalmoscope 100 comprises a first spatial filter 31 disposed in a first light path L1 between a respective pair 11,21 of the at least one light source 11 and at least one light detector 21,22. Preferably, the first spatial filter 31 is configured to predominantly or exclusively pass a first part of the light received in a first detection channel C1 of the respective detector 21 from a first area Rc on the retina R. For example, the first area Re overlaps the respective light pattern Ri from which said first part of the light originates.
In some embodiments, the ophthalmoscope 100 comprises a second spatial filter 32, disposed in the second light path L2 between a respective pair 11,22 of the at least one light source 11 and at least one light detector 21,22. Preferably, the second spatial filter 32 is configured to predominantly or exclusively pass a second part of the light received in a second detection channel C2 of the respective light detector 22 from a second area Ro on the retina R. For example, the second area Ro is offset by a lateral distance dR with respect to the respective light pattern Ri from which said second part of the light originates.
In some embodiments, the projection optics 40-45 comprise one or more lenses and/or (curved) mirrors to form the light paths L1,L2; and project or image respective light patterns between the retinal focal plane Pr and its conjugate focal planes P0,P1,P2, e.g. planes where an image of the retina can be formed by the intermediate optics. In a preferred embodiment, the first and second spatial filters 31 are disposed in one or more of the conjugate focal planes designated as P1 and/or P2. In some embodiments, a third spatial filter 30 is arranged at another conjugate focal plane designated as P0.
In some embodiments, the first set of projection optics 40-43 is configured to project an image of one or more patterns arranged at an object plane onto the retinal focal plane Pr. In some embodiments, e.g. as shown in
In some embodiments, the second set of projection optics 42-45 is configured to project an image the retinal focal plane Pr onto a respective one or more image planes. Preferably, the image is projected on a respective spatial filter which is configured to pass (transmit or reflect) only the intended part of the image to a respective detector.
In some embodiments, one or more of the optical components 42,43 may be shared between the first and second sets of projection optics. In the embodiments shown, a beam splitter/combiner 42 acts as a reflector in the first set while acting as a transmitter in the second set. Of course this may also be reversed.
In some embodiments, beam steering optics 43 are configured to controllably vary a position of the light pattern Ri on the retina. For example, an illuminated spot may be scanned over the surface of the retina. In the embodiments shown, the steering optics 43 are arranged to both transmit and receive light to/from the retina. For example, the beam steering optics 43 comprise one or more controllable mirrors. Also other ways of controlling the position of the light pattern can be envisaged, e.g. moving the ophtalmoscope and/or retina.
In some embodiments, e.g. shown in
In some embodiments, e.g. as shown in
In some embodiments, a part of the first light path L1 overlaps a part of the second light path L2. In other words the first light path L1 and second light path L2 may travel together at least part of the way. This may be advantageous, e.g. in that at least some of the optical components (41-44), may be used to form both light paths L1,L2. In some embodiments, at least some of the first light path Li is distinct from the second light path L2. In other words the first light path Li may not completely overlap the second light path L2. This may be advantageous, e.g. in that the light can be well separated, e.g. in the detection. For example, it may be prevented that the first part of the light of the first light path L1 interferes with the second part of the light in the second light path L2, at least along the distinct path. Alternatively, or additionally, it may be envisaged that different light patterns are alternated or modulated, e.g. as shown in
In a preferred embodiment, e.g. as shown in
In another or further preferred embodiment, each of the separate light detectors 21,22 are single element detectors. Accordingly, all light entering a respective detection channel is measured by a respective single detection element. For example, when using two detection channels C1,C2 the detection system may be formed by only two single detector elements. For example, the single element detectors may be formed by two photodiodes. Alternatively, or additionally, the system may alternate between different types of measurements, e.g. as shown in
Also more than two detection channels may be envisaged, e.g. an additional third or fourth detection channel may be associated with other respective radial distances from the light pattern Ri. By measuring two, three, four, or more different radial distances in two or more separate detection channels, an even more complete analysis of the retinal tissue may be obtained. In some embodiments, a radial distance of light entering the second detection channel C2 may be varied while taking confocal measurements in the first detection channel C1. For example, a position of the second spatial filter 32 and/or shape of the projected light pattern Ri can be varied.
In some embodiments, e.g. as shown in
In some embodiments, e.g. as shown in
In some embodiments, e.g. as shown in
In some embodiments. e.g. as shown in
In some embodiments, e.g. as shown in
In some embodiments, e.g. as shown in
Preferably, the beam splitting spatial filters are placed at a relatively small angle α with respect to the conjugate focal planes, e.g. less than thirty degrees (plane angle), preferably less than twenty or even less than ten degrees. Alternatively, or additionally, the image may be projected with a relatively large depth of focus. e.g. wherein the depth of focus is larger than a maximum difference in axial positions of the tilted spatial filter along the optical axis. In one embodiment, e.g. as shown, a shape of one or more of the spatial filters 31,32 is adapted to the angle α at which it is placed with respect to the conjugate focal planes. For example, the ring shape may be extended to form an ellipse, e.g. stretched inversely proportional to a cosine of the angle α. The ellipse may be asymmetric, e.g. to match a converging beam in which it is placed. Optionally, also the pinhole may be stretched and/or drilled through the plate at a corresponding angle α.
In some embodiments, a position of the light being passed by one or more of the spatial filters 31,32 to a respective detector 21,22 is controllable, e.g. determined by a controller [not shown] and/or program on the controller. For example, a position of a pinhole forming the second spatial filter 32, e.g. as shown in
In some embodiments, e.g. as shown in
In some embodiments, e.g. as shown in
In some embodiments. e.g. as shown in
In a preferred embodiment, a ring-shaped pattern light of having a wavelength λ2 is projected on the retina, while (simultaneously or consecutively) a (focal) spot of light having another wavelength λ1 is projected at the center of the ring-shaped pattern. In some embodiments, the light of different wavelengths λ1,λ2 is both collected from the same spot at the center of the ring-shaped illumination and separated by wavelength in different detection channels. As will be appreciated, measurement of the light with the wavelength λ1 (originating from the focal spot illumination) may correspond to a confocal measurement in a first detection channel C1, while the light with the wavelength λ2 may correspond to a scattering measurement in a second detection channel. Advantageously, both light can be spatially filtered, e.g. using a filter 30 with a pinhole that is confocal with the central spot. Instead of the single spatial filter 32 with a fixed radius dR″, as shown in
In some embodiments, e.g. as shown in
In one embodiment, the digital light projector is disposed as a spatial filter 32 in a path between a respective light source 11 and the retina R. In some embodiments, a radius dR″ of the ring-shaped pattern is varied by controlling the digital light projector. For example, the varying radius may correspond to different types of measurements of the same area. For example, when the radius dR″ is sufficiently small, this may effectively correspond to a confocal measurement. For example, a set of two or more different radii may correspond to different scattering measurements.
For the purpose of clarity and a concise description, features are described herein as part of the same or separate embodiments, however, it will be appreciated that the scope of the invention may include embodiments having combinations of all or some of the features described. For example, while embodiments were shown for simultaneously performing confocal and scattering measurements using a set op spatial filters, also alternative ways may be envisaged by those skilled in the art having the benefit of the present disclosure for achieving a similar function and result. E.g. optical components may be combined or split up into one or more alternative components. The various elements of the embodiments as discussed and shown offer certain advantages, such as quick and reliable measurement of the retinal surface and deeper tissue. Of course, it is to be appreciated that any one of the above embodiments or processes may be combined with one or more other embodiments or processes to provide even further improvements in finding and matching designs and advantages. It is appreciated that this disclosure offers particular advantages to retinal measurements, and in general can be applied also for contactless measurement of other tissue.
In interpreting the appended claims that follow, it should be understood that the word “comprising” does not exclude the presence of other elements or acts than those listed in a given claim; the word “a” or “an” preceding an element does not exclude the presence of a plurality of such elements; any reference signs in the claims do not limit their scope.
| Number | Date | Country | Kind |
|---|---|---|---|
| 19174087.7 | May 2019 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/NL2020/050304 | 5/13/2020 | WO |
