JP2022537461A - Multimodal eye imaging technology and imaging device - Google Patents

Abstract

Aspects of the present disclosure provide improved techniques for imaging the retinal fundus of a patient. Some embodiments may be substantially binocular shaped and/or house multiple imaging devices configured to provide multiple corresponding modes of imaging the patient's retinal fundus. The present invention relates to an imaging device capable of Some embodiments use white light, fluorescence, infrared (IR), optical coherence tomography (OCT), and/or other imaging modalities that can be employed with a single imaging device to scan a patient's eye. It is related with the technique of imaging. Some aspects relate to improvements in white light, fluorescence, IR, OCT and/or other imaging techniques that may be employed alone or in combination with other techniques. Some aspects relate to multimodal imaging techniques that enable determination of a patient's health status. The imaging devices and imaging techniques described herein provide medical grade retinal fundus images and can be manufactured or implemented at low cost, thereby increasing access to medical grade imaging.

Description

Conventionally, the retinal fundus of the eye can be photographed using a conventional digital camera. This technique of imaging the retinal fundus would benefit from improvements.

Some aspects of the present disclosure relate to imaging and/or measurement devices for imaging and/or measuring the fundus retina of a patient, the imaging and/or measurement devices including white light imaging devices, fluorescence imaging devices, infrared imaging devices, and/or at least two imaging and/or measuring devices selected from the group comprising optical coherence tomography devices.

Some aspects of the present disclosure relate to methods of imaging and/or measuring a retinal fundus of a patient, the methods comprising at least one of a white light imaging device, an infrared imaging device, a fluorescence imaging device and/or an optical coherence tomography device. The two are used to image and/or measure the patient's fundus retina.

Some aspects of the present disclosure relate to an imaging device for measuring and/or imaging a patient's fundus retina, the imaging device comprising a first aperture configured to be placed proximate a first eye of the patient. a second housing portion comprising a second opening configured to be placed proximate a second eye of a patient; at least one imaging and/or measuring device supported by the body, the at least one imaging and/or measuring device imaging and/or measuring the patient's retinal fundus. configured as

Some aspects of the present disclosure relate to an apparatus for performing optical coherence tomography (OCT) on the retinal fundus of a patient, the apparatus comprising: a plurality of light sources configured to emit light; an interferometer configured to receive light from the component, split the light into a reference component and a sample component, illuminate the patient's eye through the sample component, and recombine the light from the reference and sample components. , and an image sensor configured to detect light recombined from the interferometer.

Some aspects of the present disclosure relate to an apparatus for performing optical coherence tomography of the retinal fundus of a patient, the apparatus comprising a light source configured to emit light, a light source receiving light from the light source, and a reference component for the light. and a sample component, illuminating the patient's eye by passing through the sample component, an interferometer configured to recombine light from the reference component and the sample component, and light recombined from the interferometer an image sensor configured to detect the

Some aspects of the present disclosure relate to an apparatus for performing time-domain optical coherence tomography of a patient's retinal fundus, the apparatus comprising a light source configured to emit light, a light source configured to receive light from the light source, and a a Michelson interferometer configured to split into a reference component and a sample component, illuminate the patient's eye through the sample component, and recombine light from the reference and sample components; and recombine from the Michelson interferometer. an image sensor configured to detect the emitted light in two image frames acquired less than 100 milliseconds apart.

Some aspects of the present disclosure relate to an apparatus for imaging and/or measuring a retinal fundus of a patient comprising a housing, a white light imaging device supported by the housing, and a white light imaging device supported by the housing. and a fluorescence imaging device, wherein the white light imaging device and the fluorescence imaging device share at least a portion of a common optical path within the housing.

Some aspects of the present disclosure relate to a method comprising imaging a retinal fundus of a patient with a white light imaging device and a fluorescence imaging device that at least partially share an optical path.
Some aspects of the present disclosure use an apparatus comprising at least two imaging and/or measurement devices selected from the group comprising a white light imaging device, a fluorescence imaging device and an optical coherence tomography device to image the retina of a patient. A method comprising imaging and/or measuring a fundus and determining a medical condition of a patient based on images captured during the imaging and/or measuring.

Some aspects of the present disclosure include imaging and/or measuring a patient's retinal fundus using an apparatus comprising at least two of a white light imaging device, a fluorescence imaging device, and an optical coherence tomography device. , identifying a patient based on images and/or measurements.

Some aspects of the present disclosure use an apparatus comprising at least two imaging and/or measurement devices selected from the group comprising a white light imaging device, a fluorescence imaging device and an optical coherence tomography device to image the retina of a patient. A method comprising imaging and/or measuring a fundus and obtaining patient security access based on the images and/or measurements.

Some aspects of the present disclosure use an apparatus comprising at least two imaging and/or measurement devices selected from the group comprising a white light imaging device, a fluorescence imaging device, an optical coherence tomography device to scan the patient's retina. A method comprising imaging and/or measuring a fundus and diagnosing a medical condition of a patient based on the images and/or measurements.

Some aspects of the present disclosure include imaging and/or measuring a patient's retinal fundus using fluorescence lifetime imaging and/or optical coherence tomography imaging; A method comprising identifying a person and/or obtaining security access to the person and/or determining a health condition of the person and/or diagnosing a medical condition of the person.

Some aspects of the present disclosure provide at least two imaging and/or measuring devices selected from the group comprising a white light imaging device, a fluorescence imaging component and an optical coherence tomography component, and at least two imaging and/or measuring A retinal imaging and/or measurement device comprising at least one modular light transmissive, reflective and/or refractive element in at least one optical path of the device.

Some aspects of the present disclosure provide at least one of a white light imaging and/or measurement device, a fluorescence imaging and/or measurement device, a white light imaging and/or measurement device and a fluorescence imaging and/or measurement device. A retinal imaging and/or measurement device comprising at least one modular light transmissive, reflective and/or refractive element in one optical path.

The above summary is not meant to be limiting. Also, various aspects of the disclosure may be practiced alone or in combination.

The accompanying drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component that is illustrated in various figures is represented by a like numeral. For clarity, not all components are labeled in all drawings.
1 is a front perspective view of a multimodal imaging device, according to some embodiments; FIG. 1C is a rear perspective view of the multimodal imaging device of FIG. 1B, according to some embodiments; FIG. FIG. 4B is a bottom perspective view of an alternative embodiment of a multimodal imaging device, according to some embodiments; FIG. 4B is a rear perspective view of another alternative embodiment of a multimodal imaging device, according to some embodiments; 3B is an exploded view of the multimodal imaging device of FIG. 3A, according to some embodiments; FIG. 3B is a side view of a patient operating the multimodal imaging device of FIGS. 3A-3B, according to some embodiments; FIG. FIG. 3C is a side perspective view of the multimodal imaging device of FIGS. 3A-3C supported by a stand, according to some embodiments; 1 is a top perspective view of a multimodal imaging apparatus comprising a combined optical coherence tomography (OCT) and infrared (IR) imaging device, according to some embodiments; FIG. 4B is a top view of the multimodal imaging apparatus of FIG. 4A with a portion of the housing and some of the imaging devices removed, according to some embodiments; FIG. 4B is a side perspective view of the multimodal imaging device illustrated in FIG. 4B, according to some embodiments; FIG. 4B is a top view of the multimodal imaging device of FIG. 4A with the top of the housing removed, according to some embodiments; FIG. 4A-4D are side perspective views of OCT and IR imaging device components of the multimodal imager of FIGS. 4A-4D, according to some embodiments; 4C is a top view of the light source component of the OCT imaging device of FIGS. 4A-4C, according to some embodiments; FIG. 5B is a side view of sample components of the OCT imaging device of FIG. 5A, according to some embodiments; FIG. 5B is a top view of the sample component illustrated in FIG. 5B, according to some embodiments; FIG. 5C is a perspective view of the light source and sample components illustrated in FIGS. 5A-5C, according to some embodiments; FIG. 4C is a perspective view of the reference components of the OCT imaging device of FIGS. 4A-4C, according to some embodiments; FIG. 5E is a perspective view of the light source and reference components illustrated in FIGS. 5A and 5E, according to some embodiments; FIG. 4A-4C are top views of detection components of the OCT imaging device of FIGS. 4A-4C, according to some embodiments; 5A and 5E-5G are perspective views of the source, reference, and detection components illustrated in FIGS. 5A and 5E-5G, according to some embodiments; FIG. 5D is a perspective view of the sample component of FIGS. 5B-5D coupled to an infrared (IR) camera and fixation component, according to some embodiments; FIG. FIG. 4 is a top perspective view of an alternative embodiment of a multimodal imaging apparatus comprising a combined optical coherence tomography (OCT) and infrared (IR) imaging device, according to some embodiments; 6B is a side perspective view of components of the OCT IR imaging device of FIG. 6A, according to some embodiments; FIG. 6B is an exploded view of alternative components that may be included in the OCT IR imaging device of FIGS. 6A-6B, according to some embodiments; FIG. 6B is a block diagram illustrating components of the OCT IR imaging device of FIGS. 6A-6B, according to some embodiments; FIG. 6B is a block diagram illustrating alternative components that may be included in the OCT IR imaging device of FIGS. 6A-6B, according to some embodiments; FIG. 7B is a top view of the sample and fixation components of the OCT-IR imaging device of FIGS. 6A-7A, according to some embodiments; FIG. 9 is a side view of an IR detection component that can be coupled to the sample component of FIG. 8, according to some embodiments; FIG. 9B is a side view of the pupil relay shown in FIG. 9A, and FIG. 9C is a top view of the pupil relay of FIGS. 9A-9B, according to some embodiments. 9 is a side view of an alternative IR detection component that can be coupled to the sample component of FIG. 8, according to some embodiments; FIG. 9 is a side view of another alternative IR detection component that can be coupled to the sample component of FIG. 8, according to some embodiments; FIG. 6B is a top view of the detection components of the OCT imaging device of FIGS. 6A-6B, according to some embodiments; FIG. 9 is a side view of the sample components of FIG. 8 illustrating the scan path of an OCT/IR imaging device, according to some embodiments; FIG. 11B is a side view of the sample components illustrated in FIG. 11A including a diopter correction component, according to some embodiments; FIG. 4 is a graph of light intensity over time of a light source of an imaging device as light source pulses synchronized with one or more cameras of the imaging device, according to some embodiments; FIG. 5 is a graph illustrating a retinal spot diagram of a pupil relay component that may be included in an imaging device, according to some embodiments; FIG. 4 shows individual interference amplitudes of three different light sources in an optical coherence tomography (OCT) device, according to some embodiments. FIG. 4 shows the combined interference amplitude of three different light sources in an optical coherence tomography device, according to some embodiments; FIG. 4 illustrates a light emitter with multiple light sources for use in an optical coherence tomography device, according to some embodiments; 4 illustrates a light emitter having multiple light sources emitting lines of light for use in an optical coherence tomography device, according to some embodiments; FIG. 4 is a top view of white light and fluorescence imaging components of a multimodal imaging device, according to some embodiments; 16B is a top view of the white light and fluorescence imaging components of FIG. 16A with portions of the imager removed, according to some embodiments; FIG. 16B is a perspective view of alternative white light and fluorescence imaging components that can be included in the imager of FIG. 16A, according to some embodiments; FIG. 16B is a perspective view of another alternative white light and fluorescence imaging component that can be included in the imager of FIG. 16A, according to some embodiments; FIG. FIG. 19 is a side view of alternative sample and detection components that can be included in the white light and fluorescence imaging components of FIG. 17 or FIG. 18, according to some embodiments; FIG. 20A is a graph of optical patterns generated using two Airy disks separated by a distance of 1.22 wavelengths, according to some embodiments; FIG. 20C is a graph of an optical pattern generated using two Airy disks separated by a distance of 1.41 wavelengths, and FIG. 20C is a distance separated by 2.44 wavelengths, according to some embodiments 1 is a graph of an optical pattern produced using two Airy discs laid together;

Aspects of the present disclosure provide improved techniques for imaging a patient's fundus retina. Some embodiments may be substantially in the form of binoculars and/or may house multiple imaging devices configured to provide multiple corresponding modes of imaging the patient's retinal fundus. It relates to an imaging device. Some aspects include white light, fluorescence, infrared (IR), optical coherence tomography (OCT), and/or other imaging modalities that can be employed by an imaging device. ) to image a patient's eye. Some aspects relate to improvements in white light, fluorescence, IR, OCT and/or other imaging techniques that may be employed alone or in combination with other techniques. Certain aspects relate to multi-modal imaging techniques that enable determination of a patient's health status. The imaging devices and imaging techniques described herein provide medical-grade imaging quality and can be manufactured or implemented at low cost, thereby improving access to medical-grade imaging.

The inventors have discovered a window into the human body in which a person's eyes can be used not only to determine whether the person has eye disease, but also to determine the general health of the person. I came to recognize and understand that it would be. However, conventional fundus imaging systems provide only superficial information about a patient's eye and do not provide sufficient information to diagnose certain diseases. Accordingly, in some embodiments, multiple imaging modes are used to more completely image the patient's fundus. For example, the fundus can be imaged simultaneously using two or more techniques. In some embodiments, optical imaging, fluorescence imaging, and optical coherence tomography techniques can also be used to provide multimodal imaging of the fundus. The inventors have found that by using multimodal imaging compared to conventional two-dimensional imaging, a greater amount of information about the fundus can be obtained than can be used to determine patient health. I have come to realize that I can In some embodiments, multidimensional imaging of the fundus oculi using two or more of two-dimensional optical imaging, optical coherence tomography (OCT), fluorescence spectral imaging, and fluorescent lifetime imaging (FLIM). can be provided. As an example, a device that uses two-dimensional optical imaging, optical coherence tomography (OCT), fluorescence spectral imaging and fluorescence lifetime imaging (FLIM) together provides a five-dimensional image of the fundus.

The inventors have realized and come to appreciate that the limitations of conventional two-dimensional optical imaging of the fundus can be overcome by providing one or more of the additional imaging modes described above. For example, OCT provides information about fundus features that lie below the surface of the fundus. This information is not accessible with conventional imaging techniques. Similarly, fluorescence imaging (using spectral and/or lifetime differences) can detect molecular consistency and/or biomarkers of the fundus that cannot be distinguished using conventional optical imaging or OCT. (if used).

The inventors believe that these extra dimensions of information can be used by experts and/or machine learning techniques to diagnose a wide range of diseases, including the general health of patients, not limited to eye health. I acknowledge and understand that it contains additional information that may be Thus, some embodiments measure an individual's susceptibility to certain diseases, including, for example, ophthalmic health, vitals, infection status, cardiovascular health, inflammation, and/or neurological health, and a person's susceptibility to certain diseases. It is directed to a real-time universal diagnostic device that can determine the health status of a person. As an example, 34% of cardiovascular diseases can be effectively treated by identifying at-risk patients in their early stages. Visual impairment in children can be diagnosed and prevented by screening premature infants for glaucoma and other eye diseases. The inventors believe that diagnostic tools, such as the devices described in some embodiments, are non-invasive techniques for determining whether a patient has a disease or is susceptible to such a disease. I came to realize that I would provide

The inventors have also further recognized and came to appreciate that making devices portable, handheld and affordable would have a tremendous impact on the health of people around the world. Countries and regions that do not have specialized facilities to diagnose specific diseases and/or lack medical professionals to analyze data from imaging tests often leave the health of the population as a whole compromised. A mobile device that can be delivered to low-income communities will enable increased access to critical health checks. Accordingly, some embodiments are directed to an apparatus that includes multiple modes of imaging the fundus in a mobile, in some example handheld, housing. In some embodiments, the device has a binocular form factor so that the patient can hold the device over both eyes for fundus imaging. In some embodiments, one or more of the multiple imaging modes can share optical components to make the device more compact, efficient, and cost effective. For example, an optical imaging device and a fluorescence imaging device can be housed in the first half of the binocular housing of the apparatus, and an OCT device can be housed in the second half of the binocular housing. Using such an apparatus, both eyes of a patient can be imaged simultaneously using different devices. For example, the patient's left eye can be imaged using an optical imaging device and/or a fluorescence imaging device while the patient's right eye is imaged using an OCT device. After the first imaging is completed, the patient flips the orientation of the binocular apparatus so that each eye is now measured with a device placed on the other half of the binocular housing, e.g. The eye can be imaged and the right eye can be imaged using an optical imaging device and/or a fluorescence imaging device. The front face of the device placed near the patient's eyes can be substantially symmetrical to ensure that the device can operate in both orientations. Additionally or alternatively, the two halves of the device housing may be connected by a hinge that allows the two halves to be adjusted in either orientation.

The inventors further recognized that providing a device having an interface with a deep learning system that enables the system to be learnable and smarter makes it easier for non-professional use, I came to understand. In low-income communities, access to professionals who can operate sophisticated equipment and/or analyze the resulting images acquired by such equipment is limited. Furthermore, since the device can communicate in either direction with a smart device (e.g., mobile phone or tablet) and/or cloud-based storage, the device can be controlled by the smart device and/or the cloud, and /Or images may be uploaded to a smart device and/or the cloud. By providing a device that interfaces with a deep learning system, the multimodal images acquired by the device of some embodiments can be automatically analyzed to identify one or more patients in a medical setting without the need for an expert. of health indicators can be determined.

I. Multi-Modal Imaging Apparatus
The inventors have developed a new and improved imaging device with enhanced imaging functionality and a flexible form factor. In some embodiments, the imaging apparatus described herein includes multiple imaging devices, such as at least two devices selected from OCT, IR, white light and/or FLIM devices within a common housing. can be done. For example, a single imaging device may include a housing shaped to support various imaging devices (such as white light, IR, fluorescence and/or OCT) within the housing. In some embodiments, different imaging devices can be separated on either side of the housing, with the imaging device on each side of the housing configured to image one of the patient's eyes. In some embodiments, all of the imaging devices may be configured to image the same one of the patient's eyes. In some embodiments, a single multimodal imaging device positioned on a portion of the housing may be configured to support multiple imaging modes (eg, IR and OCT, white light and FLIM, etc.). can. In some embodiments, the housing can further include electronics for capturing, processing or pre-processing images and/or accessing the cloud for image storage and/or transmission. In some embodiments, the electronics embedded in the imaging device can also be configured to determine the health or medical condition of the user.

In some embodiments, the imaging devices described herein may have a form factor suitable for imaging both (eg, simultaneously) a person's eyes. In some embodiments, the imaging devices described herein can be configured to image each eye with a different imaging device of the imaging device. For example, as described in more detail below, the imaging device may include a pair of lenses held within a housing of the imaging device for alignment with a person's eyes, the pair of lenses also are aligned with the respective imaging devices of the . In some embodiments, the imaging device can include a substantially binocular form factor with an imaging device positioned on each side of the imaging device. During operation of the imager, a person can easily flip the vertical orientation of the imager (eg, by rotating the device about an axis parallel to the direction in which the image is taken). Accordingly, the imaging apparatus can transition from imaging a person's right eye using a first imaging device to imaging a person's right eye using a second imaging device; can transition from imaging a person's left eye using the first imaging device to imaging the left eye using the first imaging device. In some embodiments, the imaging devices described herein are configured to be placed on a table or desk, eg, placed on a stand. For example, the stand can allow the imaging device to be rotated about one or more axes to facilitate user rotation during operation.

It should be appreciated that aspects of the imaging device described herein can be implemented using form factors substantially different than binoculars. For example, embodiments having form factors substantially different from the binocular shape can be configured differently in the manner described herein in connection with the exemplary imaging devices described below. . For example, the imager may be configured to simultaneously image one or both of a person's eyes using one or more imaging devices of the imager.

One example of an imaging device according to the techniques described herein is illustrated in FIGS. 1A-1B. As shown in FIG. 1A, imaging device 100 includes housing 101 having first housing portion 102 and second housing portion 103 . In some embodiments, the first housing portion 102 can house the first imaging device 122 of the imaging apparatus 100 and the second housing portion 103 can house the second imaging device 123 of the imaging apparatus. can. As illustrated in FIGS. 1A-1B, housing 101 is substantially binocular shaped.

In some embodiments, first and second imaging devices 122 and 123 can include optical imaging devices, fluorescence imaging devices, and/or OCT imaging devices. For example, in one embodiment, first imaging device 122 may be an OCT imaging device and second imaging device 123 may be an optical and fluorescence imaging device. In some embodiments, imaging apparatus 100 may include only a single imaging device 122 or 123, such as only optical imaging devices or only fluorescence imaging devices. In some embodiments, first and second imaging devices 122 and 123 share one or more optical components such as lenses (eg, converging, diverging lenses, etc.), mirrors, and/or other imaging components. can do. For example, in some embodiments, first and second imaging devices 122 and 123 can share a common optical path. It is envisioned that the devices can operate independently or cooperatively. Each device may be an OCT imaging device, each device may be a fluorescence imaging device, or both may be one or the other. Both eyes may be imaged and/or measured simultaneously, or each eye may be imaged and/or measured separately.

Housing sections 102 and 103 may be connected to the front end of housing 101 by front housing section 105 . In an exemplary embodiment, the front housing portion 105 is shaped to accommodate the contours of a person's face, such as having a shape that conforms to the person's face. When receiving a person's face, the front housing portion 105 may further provide a line of sight from the person's eyes to the imaging devices 122 and/or 123 of the imaging apparatus 100 . For example, the front housing portion 105 includes the first housing portion 102 and the second housing portion 102 to provide a minimally obstructed optical path between the first and second optical devices 122 and 123 and the human eye. A first opening 110 and a second opening 111 corresponding to respective openings in portion 103 may be included. In some embodiments, openings 110 and 111 are covered with one or more transparent windows (eg, each having its own window, having a common window, etc.) made of glass or plastic.

First and second housing parts 102 and 103 can be connected to the rear end of housing 101 by rear housing part 104 . The rear housing portion 104 covers the ends of the first and second housing portions 102 and 103 so that light in the environment of the imaging device 100 does not enter the housing 101 and interfere with the imaging device 122 or 123. can be shaped like

In some embodiments, imaging device 100 can be configured to communicatively couple to another device such as a mobile phone, desktop, laptop, or tablet computer and/or smartwatch. For example, imaging device 100 can be configured to establish wired and/or wireless connections to the device, such as by USB and/or a suitable wireless network. In some embodiments, housing 101 can include one or more openings to accommodate one or more electrical (eg, USB) cables. In some embodiments, housing 101 is mounted with one or more antennas for transmitting wireless signals to and/or receiving wireless signals from the device. In some embodiments, imaging devices 122 and/or 123 can be configured to interface with electrical cables and/or antennas. In some embodiments, imaging devices 122 and/or 123 can receive power from cables and/or antennas, such as to charge rechargeable batteries located within housing 101 .

During operation of the imaging device 100, the person using the imaging device 100 can place the front housing 105 against the person's face such that the person's eyes are aligned with the openings 110 and 111. FIG. In some embodiments, the imaging device 100 can include a gripping member (not shown) coupled to the housing 101 and configured to be gripped by a human hand. In some embodiments, the gripping member can be formed using a soft plastic material and can be ergonomically shaped to accept a person's finger. For example, a person can grasp the gripping members with both hands and place the front housing portion 105 against the person's face such that the person's eyes are aligned with the openings 110 and 111 . Alternatively or additionally, the imaging device 100 is coupled to the housing 101 and a mounting device configured to mount the imaging device 100 on a mounting arm, such as for mounting the imaging device 100 on a table or other equipment. A member (not shown) can be included. For example, when installed using a mounting member, imaging device 100 can be stabilized in one position for use by a person without the need for the person to hold imaging device 100 firmly.

In some embodiments, imaging device 100 projects visible light from imaging device 100 toward the person's eyes, e.g., along the direction in which openings 110 and 111 are aligned with the person's eyes. fixator can be employed. According to various embodiments, the fixation means may be a bright spot, such as a circular or elliptical spot, or an image or image such as a house or some other object. The inventors have recognized that people generally move both eyes in the same direction to focus on an object, even when only one eye perceives the object. Accordingly, in some embodiments, imaging device 100 may be configured to provide fixation to only one eye, such as by using only one aperture 110 or 111 . In other embodiments, fixation objects can be provided to both eyes, such as by using both apertures 110 and 111 .

FIG. 2 illustrates a further embodiment of imaging device 200, according to some embodiments. As shown, the imaging apparatus 200 includes a housing 201 within which one or more imaging devices (not shown) can be placed. Housing 201 includes a first housing portion 202 and a second housing portion 203 connected to a central housing portion 204 . Central housing portion 204 can include and/or act as a hinge connecting first and second housing portions 202 and 203 . The first and second housing portions 202 and 203 are rotatable about this hinge. Rotating the first and/or second housing portions 202 and/or 203 relative to the central housing portion 204 increases or decreases the distance separating the first and second housing portions 202 and 203 accordingly can be made Before and/or during operation of the imaging device 200, a person rotates the first and second housing portions 202 and 203 so that the person's eyes are positioned between the first and second housing portions 202 and 203. It can be adapted to the distance separating the person's eyes, such as for easy alignment with the aperture.

The first and second housing portions 202 and 203 can be configured as described for the first and second housing portions 102 and 103 with respect to FIGS. 1A-1B. For example, each housing portion can house one or more imaging devices therein, such as an optical imaging device, a fluorescence imaging device and/or an OCT imaging device. In FIG. 2, each housing portion 202 and 203 is coupled to a respective one of front housing portions 205A and 205B. The front housing portions 205A and 205B may be shaped to fit the contours of a person's face using the imaging device 200, such as to fit the portion of the person's face near the person's eyes. In one embodiment, the front housing portions 205A and 205B can be formed using a flexible plastic that can conform to the contours of a person's face when placed against the person's face. Front housing sections 205A and 205B are aligned with the openings of first and second housing sections 202 and 203 to provide minimally obstructed optical paths from both human eyes to the imaging device of imaging apparatus 200. can have respective openings 211 and 210 corresponding to openings in the first and second housing portions 202 and 203, such as being aligned with each other. In some embodiments, openings 210 and 211 are covered with transparent windows made of glass or plastic.

In some embodiments, central housing portion 204 may include one or more electronic circuits (eg, integrated circuits, printed circuit boards, etc.) for operating imaging device 200 . In some embodiments, one or more processors can be located in the central housing portion 204, such as for analyzing data imaged using an imaging device. The central housing portion 204 may include wired and/or wireless means for electrically communicating with other devices and/or computers, as described for imaging device 100 . For example, other processing may be performed by a device and/or computer communicatively coupled to imaging device 200 . In some embodiments, electronic circuitry contained within imaging device 200 can process captured image data based on instructions received from the communicatively connected device or computer. In some embodiments, imaging device 200 can initiate an image capture sequence based on instructions received from a device and/or computer communicatively coupled to imaging device 200 .

As described herein, including in relation to imaging device 100, imaging device 200 may include grasping and/or locating members and/or fixation means.
3A-3D illustrate further embodiments of an imaging device 300 according to some embodiments. As shown in FIG. 3A, the imaging device 300 has a housing 301 that includes a plurality of housing portions 301a, 301b, and 301c. Housing portion 301a has a control panel 325 that includes a plurality of buttons for turning imaging device 300 on or off and for initiating a scanning sequence. FIG. 3B is an exploded view of imaging device 300 illustrating several components located within housing 301 , such as imaging devices 322 and 323 and electronics 320 . Imaging devices 322 and 323 may include one or more of a white light imaging component, a fluorescence imaging component, an infrared (IR) imaging component, and/or an OCT imaging component, according to various embodiments. In one example, imaging device 322 can include an OCT imaging component and/or an IR imaging component, and imaging device 323 can include a white light imaging device and/or a fluorescence imaging device. The imaging device further includes a front housing portion 305 configured to receive a human eye for imaging, eg, as illustrated in FIG. 3C. FIG. 3D shows imaging device 300 seated on stand 350, as described in detail herein.

As shown in FIGS. 3A-3D, housing portions 301a and 301b can substantially accommodate imaging device 300, such as by placing all or most of the components of imaging device 300 between housing portions 301a and 301b. can be stored in Housing portion 301c can also be mechanically coupled to housing portions 301a and 301b, such as by using one or more screws that fasten housing 301 together. As illustrated in FIG. 3B, housing portion 301 c can have multiple housing portions therein, such as housing portions 302 and 303 for housing imaging devices 322 and 323 . For example, in some embodiments, housing portions 302 and 303 can be configured to securely hold imaging devices 322 and 323 . Housing portion 301c further includes a pair of lens portions in which lenses 310 and 311 are positioned. Housing portions 302 and 303 and lens portions can be configured to hold imaging devices 322 and 323 in alignment with lenses 310 and 311 . Housing portions 302 and 303 can house focusing components 326 and 327 for adjusting the focus of lenses 310 and 311 . Some embodiments can further include securing tabs 328 . Housing portions 301a, 301b and/or for accessing multiple components of imaging device 300 for maintenance and/or repair purposes, such as by adjusting (e.g., squeezing, pulling, pushing, etc.) securing tabs 328. Or 301c can be disconnected from each other.

Electronics 320 may be configured as described for electronics 320 with respect to FIG. A control panel 325 can be electrically connected to the electronics 320 . For example, a scan button on control panel 325 can be configured to communicate a scan command to electronics 320 to initiate a scan using imaging devices 322 and/or 323 . As another example, a power button on control panel 325 can be configured to communicate a power on or power off command to electronic device 320 . As illustrated in FIG. 3B, the imaging device 300 can further include an electromagnetic shield 324 configured to isolate the electronics 320 from electromagnetic interference (EMI) sources in the surrounding environment of the imaging device 300. . Including electromagnetic shield 324 may improve the operation (eg, noise performance) of electronic device 320 . In some embodiments, electromagnetic shield 324 may be connected to one or more processors of electronic device 320 to dissipate heat generated within the one or more processors.

In some embodiments, the imaging devices described herein can be configured to be mounted on a stand, as illustrated in the example of FIG. 3D. In FIG. 3D, imaging device 300 is supported by stand 350 including base 352 and holding portion 358 . Base 352 is shown to include a substantially U-shaped support portion and has a plurality of legs 354 attached to the underside of the support portion. As shown, the base 352 can be configured to support the imaging device 300 on a table or desk. The holding portion 358 may be shaped to accommodate the housing 301 of the imaging device 300 . For example, the exterior of retaining portion 358 can be shaped to fit housing 301 .

The base 352 can be connected to a retaining portion 358 by a hinge 356, as shown in FIG. 3D. Hinge 356 may be configured to rotate about an axis parallel to the surface supporting base 352 . For example, during operation of imaging device 300 and stand 350, a person can rotate holding portion 358 with imaging device 300 to an angle suitable for the person to image one or both eyes. For example, a person sits at a table or desk supporting stand 350 . In some embodiments, a person can rotate the imaging device 300 about an axis parallel to the optical axis along which an imaging device within the imaging device images the person's (both) eyes. For example, in some embodiments, the stand 350 can alternatively or additionally include hinges parallel to the optical axis.

In some embodiments, holding portion 358 (or other portion of stand 350) can include charging hardware configured to deliver power to imaging device 300 via a wired or wireless connection. In one example, the charging hardware of stand 350 can include a power supply connected to one or more wireless charging coils, and imaging device 300 is configured to receive power from the coils in stand 350. A charging coil may be included. In another embodiment, the charging hardware in stand 350 is configured so that when imaging device 300 is seated in holding portion 358, a complementary connector on imaging device 300 interfaces with a connector on stand 350. can be connected to an electrical connector on the outside of the According to various embodiments, the wireless charging hardware includes one or more power converters (e.g., AC to DC, DC to DC, etc.). In some embodiments, stand 350 can house at least one rechargeable battery configured to supply wired or wireless power to imaging device 300 . In some embodiments, stand 350 can include one or more power connectors configured to receive power from a standard wall outlet, such as a single phase wall outlet.

In some embodiments, the front housing portion 305 can include multiple portions 305a and 305b. The front portion 305a can be formed using a mechanically resilient material, while the front portion 305b can be formed using a mechanically flexible material, thus making the front housing portion 305 is comfortable for the user. For example, in some embodiments, portion 305a can be formed using plastic and portion 305b can be formed using rubber or silicone. In other embodiments, front housing portion 305 can be formed using a single material that is mechanically resilient or mechanically flexible. In some embodiments, portion 305b can be positioned outside front housing portion 305 and portion 305a can be positioned within portion 305b.

II. Optical Coherence Tomography and/or Infrared (IR) Imaging Techniques The inventors have developed improved OCT and IR imaging techniques that can be implemented singly or in combination within a multimodal imaging device. In some embodiments, the combination of OCT and IR imaging components detailed herein can be housed together in one or both of the first and second housing portions of the multimodal imaging device. In some embodiments, the OCT imaging component can be located in one of the first or second housing portions and the IR imaging component can be located in the other housing portion. The inventors have found that combining OCT and IR components such that at least a portion of multiple components share an imaging path reduces the form factor and cost of manufacturing a multimodal imager. recognized.

In some embodiments, the OCT technique focuses broadband light on the patient's retinal fundus and also strikes a reference surface, and then combines the light reflected from the patient's retinal fundus with the light reflected from the reference surface. It is possible to obtain information about the structure of the retinal fundus. This information can be determined based on the detected interference between light received from the patient's fundus retina and light received from a reference surface. In some embodiments, OCT techniques can provide depth imaging information about structures beneath the surface of the fundus retina. In some embodiments, the beamsplitter splits source light into a sample component that provides light to the patient's retinal fundus and a reference component that provides light to a reference surface. The beamsplitter then combines the light reflected from the sample and reference components and provides the combined light to the interferometer. In some embodiments, an interferometer can detect interference by determining the phase difference between the sampled light and the reference light.

In some embodiments, OCT can be performed in the time domain to scan the depth of the patient's fundus retina. For example, in some embodiments, differences in optical path lengths between the reference and sample components may be accommodated. In some embodiments, OCT can be performed in the frequency domain by using an interferometer to detect interference in specific optical spectra. Embodiments described herein can be configured to perform time-domain and/or frequency-domain OCT.

In some embodiments, the IR imaging component can perform IR imaging of the patient's retinal fundus and can provide information regarding the depth and/or temperature of the patient's retinal fundus. In some embodiments, at least some of the IR and OCT imaging components described herein can share optical paths. For example, in some embodiments IR imaging and OCT imaging can be performed at different times using at least some of the same optical components as described herein.

It should be understood that the OCT and IR techniques described herein can be used alone or in combination within a single-modal or multi-modal imaging device. Also, some embodiments may include only an OCT component or only an IR component, as the techniques described herein may be implemented singly or in combination.

4A-4C illustrate combined OCT/IR with multiple OCT source components 410, multiple sample components 420, multiple reference components 440, and multiple detection components 450, according to some embodiments. A multimodal imaging apparatus 400 comprising an imaging device is illustrated. 4A is a top perspective view of the imaging device 400, FIG. 4B is a top view of the imaging device 400, and FIG. 4C is a side perspective view of the imaging device 400. FIG. In some embodiments, light source component 410 can include one or more light sources, such as superluminescent diodes, and multiple optical components configured to collect light from the light sources. . Light source component 410, light source 412, cylindrical lens 416 and beam splitter 418 are shown in FIGS. 4A-4C. In some embodiments, the sample component 420 can be configured to provide light from the light source component 410 through one or more optical components to the patient's eye. Of the sample components 420, scanning mirror 422 and fixation dichroic 424 are shown in FIGS. 4A-4C. In some embodiments, reference component 440 can be configured to provide light from light source component 410 through one or more optical components to one or more reference surfaces. A dispersion compensator 442, a cylindrical lens 444, a plurality of fold mirrors 446 and a reference surface 448 of the reference component 440 are shown in FIGS. 4A-4C. In some embodiments, detection component 450 is configured to receive reflected light from sample component 420 and reference component 440 in response to providing light from source component 410 to sample component 420 and reference component 440 . can Aspheric lens 452, plano-concave lens 454, achromatic lens 456, transmission grating 458 and achromatic lens 460 of detection component 450 are shown in FIGS. 4A-4C.

FIG. 4D is a top view of imaging device 400 with the top portion of the housing removed, according to some embodiments. Some of the plurality of reference components 450, such as the plurality of fold mirrors 446 and reference surfaces 448, are shown in FIG. 4D. FIG. 4E is a side perspective view of multiple components of the OCT and IR imaging device of imaging apparatus 400, according to some embodiments. IR camera 470, light source 412, scanning mirror 422 and OCT motor scanning window 451 are shown in FIG. 4E.

Further examples of light source components 410, sample components 420, reference components 440 and detection components 450 that may be included in imaging device 400 are described herein, including with reference to FIGS. 5A-5I. explained in writing.

FIG. 5A is a top view of an exemplary light source component 510, according to some embodiments. In some embodiments, light source component 510 can be included in OCT imaging device 400 as light source component 410 . In some embodiments, the light source component 510 can be configured to provide light to other OCT components, such as sample and/or reference components. For example, the light source component 510 provides light to the sample component for delivery to the patient's eye, provides light to the reference component for delivery to the reference surface, and responds to delivery of light through the sample component. can be configured so that light detected from the patient's eye can be compared with light delivered to the reference surface.

5A, light source component 510 includes light source 512, beam spreader 514, cylindrical lens 516 and beam splitter 518. In FIG. In some embodiments, light source 512 can include a superluminescent diode. In some embodiments, light source 512 can be configured to provide polarized light (eg, linear, circular, elliptical, etc.). In some embodiments, light source 512 can be configured to provide broadband light, such as including white light and IR light. In some embodiments, light source 512 can include a superluminescent diode with a spectral width greater than 40 nm and a center wavelength between 750 nm and 900 nm. In one example, light source 512 can have a center wavelength of 850 nm, which is less scattered by patient tissue than other wavelengths. In some embodiments, light source 512 can include a superluminescent diode with a single lateral spatial mode. In some embodiments, light source 512 can include a vertical-cavity surface-emitting laser (VCSEL) with an adjustable mirror on one side. In some embodiments, the VCSEL can have a tuning range greater than 100 nm using micro-mechanical movement (MEM). In some embodiments, light source 512 can include multiple light sources that together have a wide spectral width. In one embodiment, light source 512 may include multiple laser diodes in close proximity. Laser diodes are less expensive than superluminescent diodes and have higher brightness and shorter pulse durations than superluminescent diodes, making them cost effective. In some embodiments, the spectrum of each laser diode may be superimposed by a diffraction grating at the individual wavelengths of the CMOS sensor.

In some embodiments, beam spreader 514 can include a cylindrical beam spreader. In some embodiments, beam spreader 514 can include an aspheric lens. In some embodiments, beam spreader 514 and/or cylindrical lens 516 can be configured to direct light from light source 512 into an elongated line for scanning the patient's fundus retina. For example, when light reaches the patient's fundus retina, the light may be focused in a first direction and stretched in a second direction perpendicular to the first direction. In some embodiments, a fold mirror can be positioned between beam spreader 514 and cylindrical lens 516 . In some embodiments, cylindrical lens 516 can be configured to spatially focus the light source onto scanning mirror 522 , which can be included along with other sample components coupled to light source component 510 . In some embodiments, scanning mirror 522 uses one or more stepper motors, galvanometers, polygon scanners, micro-electromechanical switch (MEMS) mirrors, and/or other movable mirror devices. can be started by As shown in FIG. 5A, the cylindrical lenses 516 face in opposite directions, with curved surfaces facing each other.

In some embodiments, beamsplitter 518 can be configured to couple light from light source 512 to other OCT components, such as sample and/or reference components. In some embodiments, beamsplitter 518 can be configured to couple light to a sample component, such as scanning mirror 522, which in turn provides light to other sample components. can be done. In some embodiments, beamsplitter 518 can be configured as a longpass filter. In some embodiments, beam splitter 518 can be configured to reflect white light source light and transmit IR light source light incident from light source 512 . In some embodiments, beamsplitter 518 can be configured to transmit IR light to the sample component and reflect white light toward the reference component. In some embodiments, beam splitter 518 can be configured to provide half of the source light to the sample component and half of the source light to the reference component. In some embodiments, beamsplitter 518 can be configured to provide more source light to the sample component than to the reference component. In some embodiments, beamsplitter 518 can be further configured to provide coherent light from the sample and reference components to the detection component. In some embodiments, beam splitter 518 can be a plate beam splitter.

FIG. 5B is a side view of an exemplary sample component 520 and FIG. 5C is a top view of sample component 520, according to some embodiments. In some embodiments, sample component 520 can be included in OCT imaging device 400 as sample component 420 . 5B-5C, sample components include scanning mirror 522, fixation dichroic 524, IR fundus dichroic 526, plano-convex lens 528, bi-concave lens 530, plano-concave lens 532 and plano-convex lens 534. FIG. In some embodiments, fixation dichroic 524 can be configured to reflect some of the source light toward a fixation component, such as a fixation display. In some embodiments, the fixation dichroic 524 can be configured as a long pass filter so that short wavelength (eg, visible) light is reflected by the fixation dichroic 524 . In some embodiments, IR fundus dichroic 526 can be configured as a short-pass filter so that long wavelength (eg, IR) light is reflected by IR fundus dichroic 526 . In some embodiments, the IR fundus dichroic 526 can be configured to reflect IR light and transmit white light. In some embodiments, lenses 528, 530, 532 and/or 534 can be adjusted to provide dioptric correction. In some embodiments, these lenses can be adjusted to correct patients with different corrections, hyperopia or presbyopia. Figures 5B and 5C further illustrate how the sample component 520 can focus source light onto the patient's retina. As shown in FIG. 5B, the light provided by sample component 510 can be focused to a point in the back of the eye when viewed from the side. As shown in FIG. 5C, the light provided by the sample component 510 is directed to a point on the front of the eye (eg, the pupil) such that the light spreads to a line of points at the back of the eye when viewed from above. can focus.

FIG. 5D is a perspective view of source component 510 and sample component 520 in an optically coupled configuration, according to some embodiments. In FIG. 5D, scanning mirror 522 is shown configured to couple light from source component 510 to sample component 520 . In some embodiments, scanning mirror 522 can be configured to couple IR light from source component 510 to sample component 520 . In some embodiments, sample component 520 can collect light reflected back from the patient's eye onto scanning mirror 522 and provide reflected light to beam splitter 518 . In some embodiments, beamsplitter 518 can be further configured to provide reflected light to a detection component.

FIG. 5E is a perspective view of an exemplary reference component 540, according to some embodiments. In some embodiments, reference component 540 can be included in OCT imaging device 400 as reference component 440 . The reference component 540 includes a dispersion compensator 542, a collimating lens 544, a fold mirror 546 and a reference surface 548, as shown in FIG. 5E. As shown in FIG. 5E, beam splitter 518 of source component 510 can be configured to reflect white light toward reference component 540 . In some embodiments, dispersion compensator 542 can include a mirror. In some embodiments, dispersion compensator 542 is configured to provide the same amount of dispersion to light passing through reference component 540 as is provided to light passing through sample component 520 by the patient's eye. can In some embodiments, collimating lens 544 can include a cylindrical plano-convex lens. In some embodiments, reference surface 548 can include wedge glass. In some embodiments, reference surface 548 can include a diffuse reflector configured to reflect similarly to the human eye as each reflection point acts as a point source. In some embodiments, reference surface 548 can include a mirror. In some embodiments, reference component 540 has an adjustable optical path length of +/−5 mm.

FIG. 5F is a perspective view of source component 510 and reference component 540 in an optically coupled configuration, according to some embodiments. In FIG. 5F, beamsplitter 518 is shown configured to couple light from light source 512 of light source component 510 into reference component 540 . In some embodiments, reference component 540 can be configured to return light from reference surface 548 to beam splitter 518, which can provide the returned reference light to the detection component.

FIG. 5G is a top view of an exemplary detection component 550, according to some embodiments. In some embodiments, detection component 550 can be included in OCT imaging device 400 as detection component 450 . As shown in FIG. 5G, detection component 550 includes aspheric lens 552, plano-concave lens 554, achromatic lens 556, transmissive grating 558, achromatic lens 560, polarizer 562, plano-convex lens 564 and plano-concave lens 566. , as well as an OCT camera 568 . In some embodiments, aspheric lens 552 , plano-concave lens 554 and achromatic lens 556 can be configured to magnify detected light received from beam splitter 518 . For example, the received light can include light reflected from the patient's eye from the sample component, light reflected by the reference surface 548 of the reference component 540 . In some embodiments, OCT camera 568 can include an interferometer such as a Mach-Zehnder interferometer and/or a Michelson interferometer.

In some embodiments, transmission grating 558 can improve the spectral signal-to-noise ratio of light received by OCT camera 568 . In some embodiments, transmission grating 558 can be configured to provide light to OCT camera 568 at normal incidence. In some embodiments, the transmission grating 558 can improve the noise performance of the OCT camera 558 transfer function.

In some embodiments, transmission grating 558 can be configured to increase the symmetry of the received light and reduce aberrations. In some embodiments, transmission grating 558 can be configured to transmit received light at the Littrow angle. In some embodiments, transmission grating 558 can be configured to split the received light by wavelength. In some embodiments, transmission grating 558 can have a dispersion grating of 1200-1800 lines/mm. In some embodiments, transmission grating 558 can have a dispersion grating of 1500-1800 lines/mm. In some embodiments, transmission grating 558 can have a dispersion grating of 1800 lines/mm.

In some embodiments, the achromatic lens 560 and field lens can be configured to collect light from the transmission grating 558 towards an OCT camera 568, which collects the collected light. can be configured to detect A polarizer 562 is shown positioned between the achromatic lens 560 and the field lens. In some embodiments, the polarizer 562 can have the same polarization as the light source 512 of the light source component 510, so that light with a different polarization than the light source 512 can be filtered out. In some embodiments, polarizer 562 has a different polarization than light source 512, such as to transmit light received from the patient's eye that is reflected by an eye having a different (eg, opposite) polarization. be able to. In some embodiments, the field lens can be configured to flatten the field of received light. In some embodiments, the field lens can be configured to adjust the chief ray angle of the received light. In some embodiments, the field lens can be configured to obtain a diverging ray of received light.

FIG. 5H is a perspective view of source component 510, reference component 540 and detection component 550 in an optically coupled configuration, according to some embodiments. In FIG. 5H, beamsplitter 518 is shown configured to couple light from source component 510 to reference component 540 and to provide light received from reference component 540 to detection component 550 .

FIG. 5I is a perspective view of sample component 520 coupled to detection component 550, IR camera 570, and fixation components including focusing lens 574 and fixation display 576, according to some embodiments. Lenses 528, 530 and 534 can be configured as a pupil relay component 590, as shown in FIG. 5I. In some embodiments, biconcave lens 530 can be configured to provide a negative focal length. In some embodiments, the pupil relay component can provide equivalent spectral and spatial spread and/or have reduced spatial spread. In one example, the pupil relay component can reduce spatial spread by a factor of five.

As shown in FIG. 5I, at least some IR light received from the patient's eye through lenses 534, 530 and 528 can be reflected off IR fundus dichroic 526 and delivered to IR camera 570 by collecting lens 527. . In some embodiments, collection lens 572 can be configured with ring illumination. For example, the condenser lens 572 can include a ring of multiple IR light emitting diodes (LEDs). In some embodiments, the IR LED can have a wavelength of 910 nm. In some embodiments, the IR LED can have a wavelength of 940nm. As also shown in FIG. 5I, at least some visible light received from the patient's eye can be reflected off the fixation dichroic 524 and delivered to the fixation display 576 by the condenser lens 574 . As shown in FIG. 5I, some visible and IR light is also provided through scanning mirror 522 to detection component 550 for OCT imaging. In FIG. 5I, lenses 528, 530 and 534 provide a common optical path for OCT and IR imaging.

FIG. 6A is a top perspective view of an alternative embodiment of a multimodal imaging apparatus 600 comprising a combined optical coherence tomography (OCT) and infrared (IR) imaging device, according to some embodiments. In some embodiments, the components of imaging device 600 can be configured as described in connection with FIGS. 4A-4C and 5A-5I. As shown in FIG. 6A, the imaging device 600 includes a plurality of OCT/IR components 602 including a plurality of source components, a plurality of sample components, a plurality of reference components and a plurality of detection components. Among the sample components, beamsplitter 618, scanning mirror 622 and IR fundus dichroic 626 are shown in FIG. 6A. In some embodiments, beam splitter 618 can be a plate beam splitter. Among the detection components, achromatic lenses 654 and 656, transmission grating 658, and OCT camera 668 are shown in FIG. 6A. FIG. 6A also shows a fixation display 674 and a diopter component that includes a diopter motor 682 and a diopter mechanism 684 . In some embodiments, OCT camera 668 can include an interferometer such as a Mach-Zehnder interferometer and/or a Michelson interferometer. In some embodiments, scanning mirror 622 can be actuated using one or more stepper motors, galvanometers, polygon scanners, micro-electromechanical switch (MEMS) mirrors, and/or other movable mirror devices. . As shown in FIG. 5A, the cylindrical lenses 516 face in opposite directions, with the curved surfaces facing each other.

FIG. 6B is a side perspective view of components 602 of imaging device 600, according to some embodiments. FIG. 6B shows fixation components including OCT/IR component 602 , IR camera 664 , and fixation lens 672 and fixation display 674 . The OCT/IR component 602 includes a source component, a sample component, a reference component and a detection component. Among the light source components, light source 612 and beam splitter 618 are shown in FIG. 6B, light source 612 can be a superluminescent diode. Among the sample components, scanning mirror 622, plano-convex lens 630, bi-concave lens 632 and plano-convex lens 634 are shown in FIG. 6B. Lenses 630 , 632 and 634 are diopter adjustable component 690 . In some embodiments, these lenses can be adjusted to correct patients with different corrections, hyperopia or presbyopia. Among the detection components, transmission grating 658 and OCT camera 668 are shown in FIG. FIG. 6B also shows motor and scanning window 651 .

FIG. 6C is an exploded view of alternative components 602' that may be included in imaging device 600, according to some embodiments. FIG. 6C illustrates the light source 612 and collimating lens 616 of the source component 610, the dispersion compensator 642, collimating lens 644 and reference surface 648 of the reference component 640, the pickoff mirror 652 of the detector component 650, the reflective grating 658', the field Lens 666 and OCT camera 668 are shown. In some embodiments, cylindrical lens 616, alone or in combination with a cylindrical or aspherical beam spreader, is configured to direct light from light source 612 into an elongated line for scanning the patient's retinal fundus. can For example, when light reaches the patient's fundus retina, the light can be focused in a first direction and stretched in a second direction perpendicular to the first direction.

FIG. 6C also shows pupil relay lens 690a of sample component 620 and pupil relay lens 690c of detection component 690c. In some embodiments, pupil relay lens 690c can include a first lens positioned near beamsplitter 618 and a second lens positioned near reflective grating 658'. The first lens has a smaller focal length than the second lens so that the two lenses magnify the interfering light from beamsplitter 618, thereby reducing the angular extent of the interfering light. In some embodiments, reflective grating 658' can be configured to reflect and diffract interfering light, causing different wavelengths of light to propagate in different directions towards the second lens. In some embodiments, the direction of diffusion of different wavelengths can be perpendicular to the direction of the elongated axis of the line of light. The second lens can focus the diffracted light onto a pickoff mirror 652, which reflects the diffracted light toward the OCT camera 668, as shown in FIG. 6C. In some embodiments, light reflected from pickoff mirror 652 can pass through cylindrical lens pair 666 toward OCT camera 668 . In some embodiments, the cylindrical lens pair 666 flattens the light field to equalize the focal length between the spectral light spread by the reflective grating 658′ and the spatial light spread of the lines. can be configured.

In some embodiments, OCT camera 668 can be configured to capture two-dimensional images using the received light. In some embodiments, the OCT camera 668 can be configured to spread the light in two directions, the first direction corresponding to the spectral spread of the light by the reflective grating 658' and the second direction Corresponds to the spatial diffusion of the light by the cylindrical lens 616 used to form the line of light. In some embodiments, OCT camera 668 can be configured to perform a Fourier transform along the spectral direction to obtain depth information. In some embodiments, a two-dimensional image of the portion of the patient's fundus retina that the line illuminates can be obtained corresponding to the elongated direction of the line and depth. In some embodiments, OCT camera 668 can be configured to capture three-dimensional images. In some embodiments, OCT camera 668 can be configured to capture multiple images as component 602' scans a line across the patient's retinal fundus. In some embodiments, each acquired image can correspond to a slice of the retinal fundus in a direction perpendicular to the elongate direction of the line and perpendicular to the depth direction. In one example, 15-30 images can be taken, each image corresponding to a different slice of the retinal fundus.

In some embodiments, component 602' can be configured to scan a line across the patient's retinal fundus to acquire multiple images. In some embodiments, a scanning mirror (eg, scanning mirror 622) can be positioned between beam splitter 618 and pupil relay lens 690c. In some embodiments, the scanning mirror has a stepper motor (e.g., motor and scanning window) configured to rotate the scanning mirror such that the line illuminates different slices of the patient's retinal fundus at different orientations of the scanning mirror. 651). In other embodiments, no moving parts may be used to scan the line across the eye. In one embodiment, the fixation display can include a moving fixation object so that scanning can occur as the patient's eyes follow the fixation object.

FIG. 7A is a block diagram illustrating OCT component 602 of imaging device 600, according to some embodiments. 7A, OCT components 602 include source component 610, sample component 620 (shown in more detail in FIGS. 8 and 11A), reference component 640 and detection component 650 (shown in more detail in FIG. 10). . Light source component 610 includes light source 612 , shown as superluminescent diode, collimating lens 616 and beam splitter 618 . In some embodiments, collimating lens 616 can include a cylindrical collimating lens and/or an aspheric lens. In FIG. 6, beamsplitter 618 is configured to split light from light source 612 into sample component 620 and reference component 640 and to direct reflected light from sample component 620 and reference component 640 to detection component 650 . Scanning mirror 622 of sample component 620 is also shown in FIG. 6B. Reference component 640 includes dispersion compensator 642, collimating lens 644, which in some embodiments may be a cylindrical collimating lens, and reference surface 648a, shown as a single mirror. In some embodiments, reference surface 648a can include a diffuse reflector configured to reflect similarly to the human eye since each reflection point acts as a point light source.

Figure 7B is a block diagram illustrating alternative components 602'' that may be included in the OCT IR imaging device of Figures 6A-6B, according to some embodiments. In some embodiments, component 602'' can be configured to perform an off-axis scan of the patient's fundus retina. For example, in some embodiments, the fold mirror of reference surface 648b can be oriented off-axis with multiple reflections to provide reflected light along multiple optical paths of detection component 650. . As shown in FIG. 7B, component 602'' can be configured similarly to component 602, except that reference surface 648b of reference component 640'' includes a pair of fold mirrors. Reference surface 648 b is shown reflecting light toward detection component 650 along multiple optical paths, at least one of which is spatially offset from light received through sample component 620 . FIG. 7B further shows achromatic lens 556 and OCT camera 668 of detection component 650 .

In some embodiments, off-axis illumination can provide a means of removing DC and/or autocorrelation components that interfere with OCT imaging. In some embodiments, off-axis illumination enables complex analytic signal recovery for full-range imaging by enabling complex spectral recovery. In some embodiments, the imaging range can be increased and the imaging speed can be decreased (including sampling less spectral signals and vice versa).

In some embodiments, the relative orientation angles of the illumination received by the camera can modulate the spatial direction of the light. In some embodiments, the cross-correlation modulation can be represented by the following equation.

In some embodiments, α can be set to an angle that provides spatial frequencies between 50% and 90% of the Nyquist rate (eg, 1 degree to 6 degrees). In some embodiments, oversampling by a factor of 1.2 or more in both directions can provide better signal-to-noise ratio and improved demodulation. In some embodiments, pre-processing of the OCT image includes cropping, subtracting the mean spectrum (eg, DC component), and/or employing one or more window functions. In some embodiments, processing the OCT image includes one or more of Fast Fourier Transform (FFT, e.g., x-spatial FFT), demodulation (e.g., shifting spatial frequencies of interest to baseband), and/or or trimming the DC and AC components of the received signal. In some embodiments, the processing can further include applying inverse FF and/or k-space resampling and fast Fourier transforms.

FIG. 8 is a top view of sample component 620 and fixation component 670, according to some embodiments. As shown in FIG. 8, the sample component 620 includes a scanning mirror 622, an IR fundus dichroic 624, a fixation dichroic 626, and an objective lens 628, which may be an achromatic lens. Also shown in FIG. 8 is diopter adjustable component 680a, which includes plano-convex lenses 630 and 634 and biconcave lens 632 shown in FIG. In some embodiments, dioptric adjustable component 680a can be configured to accommodate dioptric adjustment up to +/−10 diopters. In some embodiments, diopter adjustable component 680a can be configured to prevent inducing excessive pupil de-space that can interfere with image quality. . For an IR fundus examination system, an imaging system is assumed that views the image sensor and fixation target through a scanning window. In some embodiments, the diopter-adjustable component 680a can be configured to substantially reduce the effects of back reflections from the IR component and the patient's cornea. In some embodiments, the diopter-adjustable component 680a can be configured to eliminate or substantially reduce the visibility of fluorescence from the lens of the patient's eye. In some embodiments, diopter-adjustable component 680a can employ Schweitzer technology.

As shown in FIG. 8, fixation component 670 includes fixation dichroic 626 and fixation indicator 674 . In some embodiments, the fixation dichroic is a long pass that reflects short wavelength (eg, visible) light and transmits long wavelength (eg, IR) light through the fixation lens toward the fixation display 674. It can be configured as a filter. In some embodiments, fixation display 674 can be configured to display a visible fixation image. In some embodiments, fixation display 674 can be a color display configured to display a visible fixation image. In some embodiments, the fixation display 674 can be a New Haven Display International model NHD 0.6-6464G display. In some embodiments, the fixation display 674 can be a monochrome Sony IMX273 sensor with a resolution of 1440×1080 at 3.45 square microns. In some embodiments, the fixation component 670 can include a Sony IMX273 sensor with a resolution of 1440×1080 at 3.45 square microns. In some embodiments, the short dimension of fixation display 674 (eg, vertical for 4:3, 16:9, or 16:10 aspect ratios) maps to a 30 degree field of view examining the eye. In some embodiments, the fixation display portion 674 can have a full circular 30 degree diameter field of view, or other suitable field of view, substantially free of blurring. In some embodiments, the fixation display 674 (eg, a square array) maps to a 20 degree by 20 degree field of view as seen by the eye.

In some embodiments, some IR light can also be transmitted to detection component 650 . In some embodiments, fixation lens 672 can be adjustable to provide dioptric correction. The IR fundus dichroic 624 reflects long wavelength (eg, IR) light toward an IR detection component (shown in FIGS. 9A and 9D-9E) and short wavelength (eg, visible) light to the detection component 650. It is shown as a short-pass filter that propagates to .

Figure 9A is a side view of an IR detection component 660a that can be coupled to a sample component 660a, according to some embodiments. As shown in FIG. 9A, IR detection components 660a include IR fundus dichroic 624, IR pupil relay 690b, astigmatism corrector 662, diopter-adjustable lens 680c and IR camera 664. As shown in FIG. FIG. 9B is a side view of pupil relay 690b and fiber 692, including according to some embodiments. FIG. 9C is a top view of pupil relay 690b and fiber 692, according to some embodiments.

FIG. 9D is a side view of an alternative IR detection component 660B that can be coupled to sample component 620, according to some embodiments. Similar to IR detection component 660 a , IR detection component 660 b includes astigmatism corrector 662 , diopter-adjustable lens 680 b and IR camera 664 . IR detection component 660b further includes a pupil relay 690b that includes a plurality of off-axis LEDs 694. In some embodiments, pupil relay 690b can further include a holographic plate to provide a low-intensity spot in the reflective portion of the front objective lens, thereby reducing the distance between the reflective portion and the imaging surface. reduce coupling.

FIG. 9E is a side view of another alternative IR detection component 660c that can be coupled to sample component 620, according to some embodiments. Similar to IR detection components 660 a and 660 b , IR detection component 660 c includes astigmatism corrector 662 , diopter-adjustable lens 680 b and IR camera 664 . IR detection component 660c further includes a pupil relay 690c that includes a plurality of off-axis LEDs 694 and a diffraction plate 696. FIG. In some embodiments, the diffractive plate 696 can be configured to provide a low intensity spot in the reflective portion of the front objective lens, thereby reducing coupling between the reflective portion and the imaging plane.

FIG. 10 is a top view of detection component 650 coupled to beam splitter 618, according to some embodiments. As shown in FIG. 10, detection components 650 include aspheric lens 653 , achromatic lenses 654 and 656 , transmission grating 658 , field lens 666 and OCT camera 668 . In some embodiments, transmission grating 658 can be configured as described for transmission grating 558 . In some embodiments, transmission grating 558 can improve the spectral signal-to-noise ratio of light received by OCT camera 568 . In some embodiments, transmission grating 558 can be configured to provide light to OCT camera 568 at normal incidence. In some embodiments, the transmission grating 558 can improve the noise performance of the OCT camera 558 transfer function. In some embodiments, the aspheric lens 653 can be configured to provide a pupil relay 690c before the achromatic lens 654. In some embodiments, aspheric lens 653 can be configured to reduce spatial diffusion by a factor of five. In some embodiments, achromatic lens 654 can be configured to collimate received light toward transmission grating 658 . In some embodiments, achromatic lens 656 can be configured to focus light onto OCT camera 668 . In some embodiments, the field lens 666 can be configured to flatten the field and adjust the chief ray angle to obtain a diverging chief ray.

FIG. 11A is a side view of sample component 620 illustrating the scan path of an OCT/IR imaging device, in some embodiments. Horizontal scan path 798a and vertical scan path 798b from scanning mirror 622 through lenses 630, 632 and 634 are shown.

FIG. 11B is a side view of sample component 620 including scanning mirror 622, fixation dichroic 624, IR fundus dichroic 626, and diopter-adjustable lenses 630, 632, 634 and 636. FIG. In some embodiments, lenses 630, 632, 634 and/or 636 may be movable from scanning mirror 622 along the optical axis to the patient's eye to provide dioptric correction. In some embodiments, IR camera 664 and/or lens 666 can include IR LEDs, such as 910 nm LEDs or 940 nm LEDs.

It should be appreciated that in some embodiments, the imaging devices described herein (eg, in connection with FIGS. 4A-11B) can be configured to perform time-domain OCT. In some embodiments, the scanning mirror of the imaging device can be configured to scan the depth of the patient's fundus retina. In some embodiments, the scanning mirror can serve as reference surface 548 or 648 in reference component 540 or 640, respectively. In some embodiments, a piezoelectric actuator of the imaging device can be configured to control scanning of the scanning mirror.

In some embodiments, the imaging devices described herein (eg, in connection with FIGS. 4A-11B) capture two images in rapid succession to form a single depth image. can be configured as In some embodiments, the two images captured in rapid burst are captured sufficiently close together in time to ensure that no eye movement occurs between the two images. The inventors have recognized that the frame rate of conventional cameras may be too slow to guarantee this. For example, in order to keep the cost of imagers low, cameras with frame rates of less than 276 frames per second may be used. In some embodiments, such cameras can be configured to operate at much higher frame rates by limiting the field of view. To overcome the drawbacks associated with the use of slow frame rates, the imager's light source is turned off near the end of one frame and at the beginning of the next frame, as described herein, including with reference to FIG. Pulse transmission is possible.

FIG. 12 illustrates light over time for a light source of an imaging device (eg, of FIGS. 4A-11B) as multiple light source pulses synchronized with one or more cameras of the imaging device, according to some embodiments. It is a graph of intensity. In FIG. 12, dotted line 1202 represents the duration of an imaging frame and solid line 1204 represents the duration of a light pulse. By synchronizing the light pulses with the frame rate of the image sensor, two images of the fundus taken less than 1 ms apart can be obtained using an image sensor with a much longer frame period (e.g., 10 ms).

FIG. 13 is a graph illustrating a retinal spot diagram of a pupil relay component that may be included in an imaging device (eg, of FIGS. 4A-11B), according to some embodiments. In FIG. 13, the scale is 1 mm per grid, and a 30 mm diameter field of view corresponds to an 8.5 mm diameter disk. In some embodiments, the pupil relay components described herein can be configured to provide 50% peak reduction. In some embodiments, the pupil relay component can include two Airy disks separated by a distance of 1.41 wavelengths as a baseline interpretation of resolution, rather than a 2× Rayleigh reference of 2.44 wavelengths. In one example, the nominal IR imaging wavelength is 910 nm, the pupil diameter is 2.5 mm, and the focal length of the eye in air is 22.2 mm, which provides a diffraction limited resolution of 11 um. In another example, the central white light wavelength is 550 nm, which would reduce the resolution to 7 um. The desired imaging of an 8.5 mm disk of the retinal fundus into a 1080-row camera yields a Nyquist limit of 1 cycle per 16 um, yielding an imaging quality target of 50% MTF. Exemplary optical patterns for various Airy disk separations are illustrated in FIGS. 20A-20C. FIG. 20A is a graph of optical patterns generated using two Airy disks separated by a distance of 1.22 wavelengths, according to some embodiments. FIG. 20B is a graph of optical patterns generated using two Airy disks separated by a distance of 1.41 wavelengths, according to some embodiments. FIG. 20C is a graph of optical patterns generated using two Airy disks separated by a distance of 2.44 wavelengths, according to some embodiments.

In some embodiments, the scanning mirror can be placed in a conjugate position with the pupil of the patient's eye and configured to relay the parallel beam produced by the imager to the parallel beam of the patient's pupil. In one example, the scanning mirror can be configured to produce a first surface reflection at an incident angle of 45+/-6 degrees and a scanning thickness of 3 mm. In some embodiments, the scanning mirror can be configured as a variable angle window.

FIG. 14A illustrates the combined interference amplitude of three different light sources that can be included in an OCT imaging device (eg, of FIGS. 4A-11B). FIG. 14B illustrates the individual interference amplitudes of three different diode lasers that can be included in an OCT imaging device (eg, of FIGS. 4A-11B). As shown in FIG. 14B, the depth resolution of the three combined laser diodes is greater than that of any of the individual laser diodes.

FIG. 15A illustrates one possible technique for combining multiple diode lasers to form a broadband radiator 1501. FIG. Broadband emitter 1501 includes first diode laser 1501 , second diode laser 1502 and third diode laser 1503 . The first diode laser 1501 emits light of a first wavelength that is larger than the wavelength of the light emitted by the second diode laser 1502, and the wavelength of the light emitted by the second diode laser 1502 itself is the wavelength of the light emitted by the third diode laser 1503. greater than Light from first diode laser 1501 is combined with light from second diode laser 1502 at first dichroic mirror 1504 . The light from the first diode laser 1501 and the light from the second diode laser 1502 are combined with the light from the third diode laser 1503 at the second dichroic mirror 1505 . Thus, the output obtained from the second dichroic mirror 1505 is broadband light that can be used in an imager. FIG. 15B illustrates each of the laser diodes feeding the imaging system.

In some embodiments, the laser wavelengths are separated by no more than 1.5 times the spectral width of adjacent lasers. In one example, a 40 nm bandwidth emitter can be made with each of the three lasers having a 10 nm bandwidth and a 5 nm gap between the spectral peaks of adjacent lasers.

III. Fluorescence and/or White Light Imaging Techniques The inventors have developed improved white light and fluorescence imaging techniques that can be implemented alone or in combination with multimodal imaging devices as described herein. . In some embodiments, one or more white light and/or fluorescence imaging devices can be included in one or both of the first and second housing portions of the apparatus. In some embodiments, the fluorescence imaging device and the white light imaging device are included in the same housing so that both imaging devices image one eye in a short period of time (eg, seconds). In some embodiments, the devices described herein are configured to capture white light and fluorescence images without the patient moving or redirecting the patient's eyes. can be done. According to various embodiments, the white-light and fluorescence imaging devices can be configured to capture white-light and fluorescence images, respectively, for periods of less than 5 seconds, less than 3 seconds, and/or less than 1 second. . Also, in embodiments in which the imaging devices are included in two housing portions of the imaging apparatus, the imaging components within each housing portion are configured to capture images simultaneously and/or over a short period of time, as described above. be able to.

In some embodiments, white-light imaging involves illuminating the patient's retinal fundus with light from a white light source (or multiple colored LEDs) and sensing reflected light from the retinal fundus using a white-light camera. can be done by In one example, multiple colored LEDs can illuminate the patient's retinal fundus at different times, the camera can capture multiple images corresponding to the different colored LEDs, and the images can be combined to form the patient's retinal fundus. can produce a color image of In some embodiments, fluorescence imaging uses an excitation light source (e.g., one or more narrowband LEDs) to illuminate the patient's retinal fundus and a fluorescence sensor and/or camera to illuminate the patient's retinal fundus. This can be done by sensing fluorescent light from the For example, the wavelength of the excitation light source can be selected to cause one or more target molecules in the patient's retinal fundus to fluoresce so that detection of the fluorescent light can indicate the location of the molecule within the image. . According to various embodiments, the fluorescence of a particular molecule can be determined based on the lifetime, intensity, spectrum and/or other attributes of detected light.

As described herein, an imaging device can include fluorescence and white light imaging components configured to share at least some components such that the imaging components share at least a portion of the optical path. . As a result, imaging devices including such components can be made smaller and less expensive to manufacture while still providing high quality medical images. Although the techniques described herein can be implemented singly or in combination, it should be understood that some embodiments may include only a fluorescence imaging component or only a white light imaging component. .

16A-16B are top views of the white light and fluorescence imaging component 1604 of the multimodal imaging device 1600, according to some embodiments. 16A is a top view of the multimodal imaging device 1600 with a partial view of the white light and fluorescence imaging component 1604, and FIG. 16B is a top view of the white light and fluorescence imaging component 1604 with portions of the imaging device 1600 removed. It is a diagram. As shown in FIGS. 16A-16B, the white light and fluorescence imaging component 1604 includes a white light source component 1610, an excitation light source component 1620, a sample component 1630, a fixation display 1640 and a detection component 1650. FIG. In some embodiments, the white light source component 1610 and the excitation light source component 1620 are coupled to the sample component such that reflected light and/or fluorescent light from the patient's retinal fundus can be imaged using the detection component 1650. It can be configured to illuminate the patient's retinal fundus through 1630 . In some embodiments, the fixation display 1640 can be configured to provide a fixation target for the patient to focus on during imaging.

In some embodiments, the white light source component 1610 is applied to the patient so that light reflected and/or scattered by the retinal fundus can be captured and imaged by the detection component 1650, as described herein. can be configured to illuminate the retinal fundus of the The white light source component 1610 includes a white light source 1612, a collimating lens 1614 and a laser dichroic 1616, as shown in FIGS. 16A-16B. In some embodiments, white light source 1612 can include white LEDs. In some embodiments, the white light source 1612 can include multiple colored LEDs that combine to substantially cover the visible spectrum, thereby approximating a white light source. In some embodiments, the white light source 1612 can include one or more blue or ultraviolet (UV) lasers.

In some embodiments, excitation light source component 1620 can be configured to excite fluorescence of one or more target molecules in the patient's fundus retina such that the fluorescent light can be captured by detection component 1650 . As shown in FIGS. 16A-16B, the fluorescence light source components include a laser 1622, a collimating lens 1624 and a mirror 1626. FIG. In some embodiments, laser 1622 can be configured to generate light at one or more wavelengths corresponding to the fluorescence properties of one or more respective target molecules in the patient's fundus retina. In some embodiments, the molecule may occur naturally in the fundus retina. In some embodiments, the molecule can be a biomarker configured for fluorescence imaging. For example, laser 1622 can be configured to generate excitation light having a wavelength between 405 nm and 450 nm. In some embodiments, laser 1622 can be configured to generate light having a bandwidth of 5-6 nm. Some embodiments can include multiple lasers configured to generate light having different wavelengths.

A white light source 1612 is configured to generate white light and transmit the white light through a collimating lens 1614 to a laser dichroic 1616, as shown in FIGS. 16A-16B. Laser 1622 is configured to generate excitation light and transmit the excitation light through collimating lens 1624 to mirror 1626 , which reflects the excitation light toward laser dichroic 1616 . Laser dichroic 1616 can be configured to transmit white light and reflect excitation light such that the white light and excitation light share an optical path to the patient's fundus retina. In some embodiments, laser dichroic 1616 can be configured as a longpass filter.

In some embodiments, the fixation display 1640 can be configured to display a fixation target for the patient to focus on during imaging. The fixation display 1640 can be configured to provide fixation light to a fixation dichroic 1642 . In some embodiments, the fixation dichroic 1642 transmits fixation light such that the fixation light, white light, and excitation light all share an optical path from the fixation dichroic 1642 to the patient's retinal fundus; It can be configured to reflect white light and excitation light.

In some embodiments, sample component 1630 is configured to provide white light and excitation light to the patient's retinal fundus and to provide reflected light and/or fluorescent light from the patient's retinal fundus to detection component 1650. can As shown in FIGS. 16A-16B, sample component 1630 includes achromatic lens 1632, iris diaphragm 1634, illumination mirror 1636 and achromatic lens 1638. FIG. In some embodiments, achromatic lenses 1632 and 1638 can be configured to focus white light, excitation light, and fixation light onto the patient's fundus retina. In some embodiments, the iris diaphragm 1634 scatters some of the white light, the excitation light, and/or the fixation light such that light from different sources is focused onto respective portions of the patient's fundus retina. can be configured to In some embodiments, illumination mirror 1636 can be adjustable, such as by moving positioning component 1637 in a direction parallel to the imaging axis. In some embodiments, achromatic lens 1638 can be further configured to provide reflected and/or fluorescent light from the patient's retinal fundus to detection component 1650 .

The detection component 1650 can be configured to collect and capture light from the patient's fundus retina and create an image using the received light. As shown in FIGS. 16A-16B, detection component 1650 includes achromatic lens 1652, dichroic 1654, condenser lens 1656 and camera 1658. FIG. In some embodiments, achromatic lens 1652 and condenser lens 1656 are configured to focus received light onto camera 1658 such that camera 1658 can use the received light to capture an image. can be configured. In some embodiments, dichroic 1654 can be configured to transmit white and fluorescent light and reflect excitation light so that the excitation light does not reach camera 1658 .

FIG. 17 is a perspective view of an alternative fluorescence and white light imaging component 1704 that can be included in an imaging device, according to some embodiments. For example, in some embodiments, the fluorescence and white light imaging component 1704 can be located in the first and/or second housing portions of the imaging device, as described above. As shown in FIG. 17, fluorescence and white light imaging components 1704 include white light imaging components including white light source component 1710 and white light camera 1760, and fluorescence imaging components including excitation light source component 1720 and fluorescence detection component 1770. . Fluorescence and white light imaging component 1704 further includes sample component 1730 and detection component 1750, which include a common imaging path for fluorescence and white light imaging. In some embodiments, the white light source component 1710 and the excitation light source component 1720 can be configured to provide light to the sample component 1730, which can focus light onto the patient's retinal fundus. can. In some embodiments, detection component 1750 receives light reflected and/or emitted from the patient's retinal fundus and transmits the received white light to white light camera 1760 and the fluorescent light to fluorescence detection component 1770 . can be configured to supply

In some embodiments, the white light source component 1710 is used by the patient so that light reflected and/or scattered by the retinal fundus can be captured and imaged by the white light camera 1760, as described herein. can be configured to illuminate the retinal fundus of the In FIG. 17, white light source component 1710 includes white light source 1712 and collimating lens 1714 . In some embodiments, the white light source 1712 can include white LEDs. In some embodiments, the white light source 1712 can include multiple colored LEDs that combine to substantially cover the visible spectrum, thereby approximating a white light source.

In some embodiments, the excitation light source component 1720 is configured to generate light that excites fluorescent molecules in the patient's retinal fundus such that the fluorescent light can be captured and imaged with the fluorescence detection component 1770. can be done. In FIG. 17, excitation source component 1720 includes first and second lasers 1722a and 1722b, first and second collimating lenses 1724a and 1724b, and first and second laser dichroics 1726a and 1726b. In some embodiments, the first and second lasers 1722a and 1722b can be configured to generate light at wavelengths corresponding to fluorescence properties of one or more respective target molecules of the patient's retinal fundus. can. In some embodiments, the molecule may be naturally occurring in the fundus retina. In some embodiments, the molecule can be a biomarker configured for fluorescence imaging. In some embodiments, the first and second lasers 1722a and 1722b are configured to generate light at wavelengths that can be combined into a single optical path for imaging the patient's retinal fundus. can be done. In some embodiments, first laser 1722a can be configured to generate excitation light having a wavelength of 405 nm. In some embodiments, the second laser 1722b can be configured to generate excitation light having a wavelength of 450 nm. In some embodiments, first laser 1722a and/or second laser 1722b can be configured to generate light having a bandwidth of 5-6 nm. It should be understood that some embodiments may include fewer or more lasers than shown in FIG. According to various embodiments, excitation light source component 1720 can include three to six lasers configured to generate light at wavelengths of 405 nm, 450 nm, 473 nm, 488 nm, 520 nm and 633 nm, respectively. In some embodiments, excitation light source component 1720 can be configured to provide excitation light suitable for fluorescence intensity measurements. In one example, the excitation light source component 1720 can include a range of LEDs spanning the visible light spectrum.

As shown in Figure 17, a first laser 1722a is configured to emit excitation light through a collimating lens 1724a toward a first laser dichroic 1726a. In some embodiments, the first laser dichroic 1726a is a white light source such that light from the first laser 1722a shares an optical path with light from the white light source 1712 from the first laser dichroic 1726a to the second laser dichroic 1726b. It can be configured to transmit light from 1712 and reflect light from the first laser 1722a. In some embodiments, the first laser dichroic 1726a can be configured as a longpass filter. As also shown in FIG. 17, a second laser 1722b is configured to emit excitation light through a collimating lens 1724b toward a second laser dichroic 1726b. In some embodiments, the second laser dichroic 1726b directs light from the white light source 1712 and the first laser 1722a such that the light from the second laser 1722b shares an optical path with the light from the white light source 1712 and the first laser 1722a. can be configured to transmit light from the second laser 1722b and reflect light from the second laser 1722b. In some embodiments, the second laser dichroic 1726b can be configured as a longpass filter. In FIG. 17, light from white light source 1712, first laser 1722a and second laser 1722b share an optical path from second laser dichroic 1726b to beam splitter 1754, at which point the received fluorescent light and white light are fluorescent light. It is divided into a detection component 1770 and a white light camera 1760 respectively.

As shown in FIG. 17, mirror 1728 is configured to reflect the coupled light towards sample component 1730 . In some embodiments, mirror 1728 can be a flat mirror. In some embodiments, mirror 1728 can be a spherical mirror configured to adjust the size and/or divergence of reflected light.

In some embodiments, sample component 1730 can be configured to focus white light and excitation light from white light source component 1710 and excitation light source component 1720 onto the patient's retinal fundus. As shown in FIG. 17, sample component 1730 includes first achromatic lens 1732 and scattering component 1734 . Scattering component 1734 can be configured to reflect light from mirror 1728 toward first achromatic lens 1732 . In some embodiments, scattering component 1734 can be a plane mirror. In some embodiments, scattering component 1734 can be a mirror having a scattering surface configured to provide more uniform illumination of the patient's retina fundus than a flat mirror. In some embodiments, scattering component 1734 can have a 1200-grit scattering surface. According to various embodiments, the scattering component 1734 can have an 800-grit, 1000-grit, 1400-grit or 1600-grit scattering surface.

As shown in FIG. 17, scattering component 1734 includes holes 1736 configured to allow some light to pass through scattering component 1734 . In some embodiments, light received through second laser dichroic 1726b passing through hole 1736 may not be used for imaging. In some embodiments, hole 1736 can be configured to pass scattered light received from the patient's fundus retina through scatter component 1734 toward white light camera 1760 and fluorescence detection component 1770 . In some embodiments, hole 1736 can be cylindrical. In some embodiments, holes 1736 can be configured to prevent noise light from reaching white light camera 1760 and fluorescence detection component 1770 . For example, hole 1736 may be configured to block light entering scatter component 1734 from directions other than the direction in which light is received from the patient's fundus retina from reaching white light camera 1760 and fluorescence detection component 1770. can be done. In some embodiments, at least a portion of the inner walls of hole 1736 can include a black material configured to reduce reflection. In some embodiments, the black material can be black tape. In some embodiments, holes 1736 can have a shape to reduce reflection. For example, in some embodiments, hole 1736 can have a conical shape.

The first achromatic lens 1732 can be configured to focus light received through the scattering component 1734 onto the patient's fundus retina. In some embodiments, the first achromatic lens 1732 can be configured to collimate light received from the patient's retinal fundus. In some embodiments, the first achromatic lens 1732 can be positioned at a distance from the retinal fundus where the received light will be approximately collimated. In one example, the focal length of the first achromatic lens 1732 can be 20 mm, and the distance from the first achromatic lens 1732 to the front of the patient's eye can be 37 mm.

In some embodiments, the excitation light source component 1720 can be configured to produce fluorescence in the patient's retinal fundus when light is focused onto the retinal fundus by the sample component 1730 . In some embodiments, fluorescence can produce light at the patient's fundus retina at a wavelength different from the wavelength of the excitation light. For example, depending on the target molecule being excited by the excitation light and responding by emitting fluorescent light, the fluorescent light may have a wavelength 30-50 nm, 50-70 nm or 70-80 nm longer than the wavelength of the excitation light. can. In some embodiments, the sample component 1730 can be configured to receive both excitation light and fluorescence light from the patient's retinal fundus and provide the received light to the detection component 1750 .

In some embodiments, detection component 1750 can be configured to receive light from sample component 1730 and provide received white light to white light camera 1760 and fluorescence light to fluorescence detection component 1770 . can. As shown in FIG. 17, detection component 1750 includes second achromatic lens 1752 and beam splitter 1754 . In some embodiments, the second achromatic lens 1752 can be configured to further collimate light received from the patient's fundus retina through the sample component 1730 . In some embodiments, the received light can have greater diffusion at the second achromatic lens 1752 than at the first achromatic lens 1732 . Therefore, in some embodiments, second achromatic lens 1752 can have a larger diameter than first achromatic lens 1732 . In one example, the first achromatic lens 1732 can have a half inch diameter and the second achromatic lens 1752 can have a one inch diameter.

In some embodiments, beam splitter 1754 can be configured to reflect some of the received light toward white light camera 1760 and transmit some of the received light to fluorescence detection component 1770 . In some embodiments, beam splitter 1754 can be configured to reflect half of the received light toward white light camera 1760 and transmit half of the received light to fluorescence detection component 1770 . In some embodiments, the light level can be lower at fluorescence detection component 1770 than at white light camera 1760 . Thus, in some embodiments, beamsplitter 1754 can be configured to transmit more received light to fluorescence detection component 1770 than it reflects toward white light camera 1760 . In some embodiments, beamsplitter 1754 transmits 90%, 95%, 99% or 99.9% of the light to fluorescence detection component 1770 and 10%, 5%, 1% or 0.1% of the light. can be configured to reflect toward the white light camera 1760 . As shown in FIG. 17, beam splitter 1754 separates the optical paths for fluorescence imaging and white light imaging.

In some embodiments, white light camera 1760 can be configured to detect light reflected from beam splitter 1754 and store image data for analysis. In some embodiments, white light camera 1760 can be a high resolution color digital camera. In some embodiments, white light camera 1760 can have a resolution of 3-10 megapixels. In some embodiments, white light camera 1760 can be a high resolution monochrome digital camera. In some embodiments, the white light source 1712 can include multiple colored LEDs and the white light camera 1760 can be configured to capture a color image of the patient's retinal fundus. In one embodiment, light source 1712 includes a red LED, a blue LED and a green LED, each LED configured to emit light sequentially in time, and white light camera 1860 captures a separate image for each of the sequential emissions. can be configured to White-light camera 1760 and/or processing circuitry coupled to white-light camera 1760 can be configured to combine the images captured for each of the sequential flashes to produce a color image of the retinal fundus.

In some embodiments, fluorescence detection component 1770 can be configured to detect fluorescence light transmitted through beam splitter 1754 and obtain fluorescence information from the light. As shown in FIG. 17, fluorescence detection component 1770 includes spectral filter 1772 , field lens 1774 and fluorescence sensor 1776 . In some embodiments, spectral filter 1772 can be configured to block excitation light and transmit fluorescence light. In one example, spectral filter 1772 can be configured to block light having wavelengths of 405 nm and 450 nm. In some embodiments, field lens 1774 can be configured to focus received light onto fluorescence sensor 1776 .

In some embodiments, fluorescence sensor 1776 can be configured to distinguish fluorescence emissions from at least two different molecules. In some embodiments, fluorescence sensor 1776 can be configured such that the fluorescence emission distinguishes between molecules with different lifetimes. For example, in some embodiments, the fluorescence sensor 1776 can be configured to determine the location of different molecules in the patient's fundus retina by determining the lifetime of the received light. In some embodiments, fluorescence sensor 1776 can be configured to distinguish between molecules whose fluorescence emissions have different wavelengths. For example, in some embodiments, fluorescence sensor 1776 can be configured to determine the location of different molecules in the retinal fundus by determining the lifetime of light received. In some embodiments, fluorescence sensor 1776 can be configured to distinguish between molecules whose fluorescence emissions have different intensities. For example, in some embodiments, fluorescence sensor 1776 can be configured to determine the location of different molecules in the fundus retina by determining the intensity of light received. It should be appreciated that fluorescence sensors 1776 may be configured for lifetime, spectral, intensity and/or other measurements, alone or in combination, according to various embodiments.

FIG. 18 is a perspective view of another alternative fluorescence and white light imaging component 1804 that can be included in an imaging device, according to some embodiments. As shown in FIG. 18, fluorescence and white light imaging component 1804 includes white light source component 1810 , excitation light source component 1820 , sample component 1830 and detection component 1850 . In some embodiments, the white light source component 1810 and the excitation light source component 1820 can be configured to provide light to the sample component 1830 for imaging the patient's retinal fundus. In some embodiments, the sample component 1830 is configured to focus light onto the patient's retinal fundus and receive light reflected and/or emitted by the patient's retinal fundus in response. can be done. In some embodiments, detection component 1850 can be configured to capture an image using light received through sample component 1830 . Fluorescence and white light component 1704 includes white light camera 1760 and fluorescence detection component 1770 , while detection component 1850 includes combined white light and fluorescence sensor 1858 . Also shown in FIG. 18 is an excitation light source component 1820 that includes a single laser 1822, whereas the excitation light source component 1720 includes first and second lasers 1722a and 1722b. In the embodiment illustrated in Figure 18, the white light and fluorescence sensor 1858 is configured to distinguish between molecules having different fluorescence emission wavelengths. Fluorescence and white light imaging component 1804 further includes a fixation display 1840, which is configured to provide a fixation target for the patient to focus their view during imaging.

In some embodiments, the white light source component 1810 can be configured to provide white light for transmission to the patient's retinal fundus. As shown in FIG. 18, white light source component 1820 includes white light source 1812 and collimating lens 1814, which can be configured as described for white light source 1712 and collimating lens 1714 with respect to FIG.

In some embodiments, the excitation light source component 1820 can be configured to provide excitation light to excite fluorescence emission from one or more target molecules in the patient's fundus retina. As shown in FIG. 18, excitation source component 1820 includes laser 1822, collimating lens 1824, mirror 1826 and laser dichroic 1816. As shown in FIG. In some embodiments, the laser 1822 can be configured as described for the first and/or second lasers 1722a and/or 1722b, and the collimating lens 1824 is a first and/or second collimating laser. Lenses 1724a and/or 1724b can be configured as described, and laser dichroic 1816 can be configured as described for first and/or second laser dichroics 1726a and/or 1726b. Mirror 1826 can be configured to reflect light from laser 1822 toward laser dichroic 1816 . As shown in FIG. 18, excitation light and white light share an optical path from laser dichroic 1816 to white light/fluorescence sensor 1858 .

In some embodiments, the fixation display 1840 is configured to provide a fixation target for the patient to focus on during imaging such that the patient's eyes are oriented in the desired direction for imaging. can be done. For example, in some embodiments, fixation display 1840 can be configured to display a point or a house as a fixation target. As shown in FIG. 18, the fixation display is configured to provide fixation light to a fixation dichroic 1842 . In some embodiments, the fixation dichroic 1842 reflects the white light and the excitation light such that the white light, the excitation light and the fixation light are combined for transmission through the sample component 1830 to the patient's retinal fundus. and can be configured to transmit fixation light.

In some embodiments, the sample component 1830 can be configured to deliver white light, excitation light and fixation light to the patient's fundus retina. As shown in FIG. 18, sample component 1830 includes first achromatic lens 1832 , iris diaphragm 1834 , entrance mirror 1836 and second achromatic lens 1838 . In some embodiments, the second achromatic lens 1838 receives light reflected and/or emitted from the patient's retinal fundus to collimate the received light for transmission to the detection component 1850 . configured to

In some embodiments, the detection component 1850 can be configured to capture images using light received from the patient's fundus retina. As shown in FIG. 18, the detection component 1850 includes an iris diaphragm 1852, a condenser lens 1854, a dichroic 1856, and a white light and fluorescence sensor 1858. FIG. In some embodiments, iris diaphragm 1852 can be configured to prevent light received from directions other than the direction in which light is received from the patient's retinal fundus from reaching white light and fluorescence sensor 1858 . In some embodiments, collection lens 1854 can be configured to collect light received from the patient's fundus retina onto white light and fluorescence sensor 1858 . In some embodiments, dichroic 1856 can be configured such that no reflected excitation light reaches white light and fluorescence sensor 1858 . In some embodiments, dichroic 1856 can be configured as a longpass filter.

FIG. 19 is a side view of an alternative sample component 1930 and detection component 1950 that can be included in combination with other white light and/or fluorescence imaging components of a multimodal imaging device, according to some embodiments. As shown in FIG. 19, sample component 1930 includes pupil relay lens 1990 , which includes plano-convex lenses 1932 and 1936 and bi-concave lens 1934 . In some embodiments, biconcave lens 1934 can be configured to provide negative dispersion and/or field flattening. In some embodiments, biconcave lens 1934 can be configured to provide a negative focal length. In some embodiments, sample component 1930 can further include other sample components, such as those described herein in connection with FIGS. 17-18. According to various embodiments, the sample component 1930 can be configured to illuminate the patient's retinal fundus from an on-axis or off-axis illumination ring.

As also shown in FIG. 19, detection component 1950 includes achromatic lenses 1952 and 1956 and camera 1958 . In some embodiments, achromatic lenses 1952 and 1956 can be configured to flatten the illuminated field and adjust the chief ray angle to obtain a diverging chief ray. In some embodiments, camera 1958 can be a white light and/or fluorescence imaging sensor. In some embodiments, pupil relay lens 1990 can be adjusted to correct for field curvature of camera 1958 . For example, as shown in FIG. 19, pupil relay lens 1990 is configured to spatially disperse light of different wavelengths at different angles. As shown, achromatic lenses 1952 and 1956 are configured to focus different wavelengths of light onto different portions of camera 1958 .

IV. Applications The inventors have developed improved imaging techniques that can be implemented using the imaging devices described herein. According to various embodiments, such imaging techniques can be used for biometric authentication, health status determination, disease diagnosis, and the like.

The inventors have come to appreciate that the appearance of a person's retinal fundus in one or more images captured by the techniques described herein can indicate various ailments. For example, diabetic retinopathy may be indicated by small bulges or microaneurysms protruding from the walls of small blood vessels, sometimes leaking fluid and blood into the retina. Additionally, the larger retinal vessels can begin to swell and become uneven in diameter. Nerve fibers in the retina may begin to swell. Occasionally, the central portion of the retina (macula) begins to swell, such as macular edema. Injured blood vessels can become occluded, causing abnormal growth of new blood vessels in the retina. Glaucomatous optic neuropathy, or glaucoma, is suggested by peripapillary retinal nerve fiber layer (RNFL) thinning and optic disc recession as a result of loss of axons and secondary retinal ganglion cells. There is something. The inventors have come to recognize that RNFL deficiency, as suggested by OCT, for example, is one of the earliest manifestations of glaucoma. In addition, age-related macular degeneration (AMD) is characterized by detachment and/or elevation of the macula, disorders of macular pigmentation such as yellowish material under the pigment epithelial layer of the central retinal zone, and /or drusen such as macular drusen, peripheral drusen and/or granular type drusen. AMD may also be suggested by geographic atrophy, such as sharply delineated rounded areas of hyperpigmentation, atrophy round and/or subretinal fluid. Stargardt's disease may be indicated by the death of photoreceptor cells in the central portion of the retina. Macular edema may be suggested by grooves in the perifoveal area. A macular hole may be indicated by a hole in the macula. Floaters may be suggested by out-of-focus light path blurring. Retinal detachment may be indicated by severe optic disc damage and/or separation from the underlying pigment epithelium. Retinal degeneration may be suggested by degeneration of the retina. Central serous retinopathy (CSR) may be indicated by local detachment from the macular sensory retina and/or pigment epithelium. Choroidal malignant melanoma may be suggested by a melanocyte-derived malignancy that begins in the choroid. Cataracts may be indicated by an opaque lens and may result in blurred fluorescence lifetimes and/or 2D retinal fundus images. Macular telangiectasia may be indicated by a dramatically increased ring of fluorescence lifetime about the macula and deterioration of the small blood vessels in and around the fovea. Alzheimer's disease and Parkinson's disease may be suggested by thinning of RNFL. It should be understood that diabetic retinopathy, glaucoma and other such ailments can lead to blindness or severe visual impairment if not properly checked and treated.

Thus, in some embodiments, various pre-stages of a person's medical conditions can be determined based on one or more images of that person's retinal fundus taken by the techniques described herein. . For example, if one or more of the symptoms of a particular medical condition described above (e.g., macular detachment and/or lifting of age-related macular degeneration) are detected in the captured image, the person has the medical condition. it may be easy.

The inventors have also come to appreciate that several health conditions can be detected using the fluorescence imaging techniques described herein. For example, the macular hole is 340-500 nm excitation light to excite the retinal pigment epithelium (RPE) and/or macular pigment in the patient's eye with fluorescence emission wavelengths of 540 nm and/or 430-460 nm. can be detected using the wavelength of Fluorescence from RPE may be primarily due to lipofuscin from RPE lysomes. Retinal artery occlusion excites Flavin adenine dinucleotides (FAD), RPE and/or nicotinamide adenine dinucleotide (NADH) in the patient's eye with fluorescence emission wavelengths between 520 nm and 570 nm. Therefore, it can be detected using an excitation light wavelength of 445 nm. Drusen AMD can be detected using an excitation light wavelength of 340-500 nm to excite the RPE of the patient's eye with fluorescence emission wavelengths of 540 nm and/or 430-460 nm. AMD, including geographic atrophy, can be detected using an excitation light wavelength of 445 nm to excite the RPE and elastin in the patient's eye with fluorescence emission wavelengths of 520-570 nm. The neovascular form of AMD can be detected by exciting the patient's choroid and/or inner retina. Diabetic retinopathy can be detected using an excitation light wavelength of 448 nm to excite FAD in the patient's eye with fluorescence emission wavelengths of 590-560 nm. Central serous chorio-retinopathy (CSCR) is detected using an excitation light wavelength of 445 nm to excite the RPE and elastin in the patient's eye with fluorescence emission wavelengths of 520-570 nm. can do. Stargardt's disease can be detected using an excitation light wavelength of 340-500 nm to excite the RPE of the patient's eye with fluorescence emission wavelengths of 540 nm and/or 430-460 nm. Colloideremia can be detected using an excitation light wavelength of 340-500 nm to excite the RPE of the patient's eye with fluorescence emission wavelengths of 540 nm and/or 430-460 nm.

The inventors have also developed techniques for diagnosing various health problems of a person using captured images of the person's fundus retina. For example, in some embodiments any of the diseases mentioned above can be diagnosed.

In some embodiments, the imaging techniques described herein can be used to determine health conditions, including heart health, cardiovascular disease, anemia, retinal toxicity, body mass index, water weight , hydration status, muscle mass, age, smoking habits, blood oxygen levels, heart rate, white blood cell count, red blood cell count, and/or other health attributes such as. For example, in some embodiments, a light source with a bandwidth of at least 40 nm can be configured with sufficient imaging resolution to capture red blood cells with a diameter of 6 μm and white blood cells with a diameter of at least 15 μm. Accordingly, the imaging techniques described herein can be configured to facilitate classification and counting of red and white blood cells, estimation of their respective densities in blood, and/or other such determinations.

In some embodiments, the imaging techniques described herein enable tracking of blood cell migration to measure blood flow. In some embodiments, the imaging techniques described herein can enable tracking of vessel width to provide an estimate of blood pressure variation and abundance. For example, an imaging device as described herein, configured to resolve red and white blood cells using a three-dimensional (3D) spatial scan that completes within 1 μs, can detect blood cell motion at 1 meter per second. can be configured to capture. In some embodiments, light sources that can be included in the devices described herein, such as superluminescent diodes, LEDs, and/or lasers, are sub-microscopic so that images can be captured in less than 1 microsecond. It can be configured to emit seconds light pulses. Using the spectral linescan technique described herein, it is possible to image the entire scanned line-to-depth cross-section in sub-microseconds. In some embodiments, the two-dimensional (2D) sensors described herein can be configured to capture the image for internal or external readout at slow speeds and subsequent analysis. . In some embodiments, a 3D sensor can be used. The embodiments described below overcome the problem of obtaining a large number of high quality scans within 1 microsecond.

In some embodiments, the imaging devices described herein can be configured to scan lines aligned along the direction of the blood vessel. For example, after identifying the vascular configuration of the patient's retinal fundus and selecting the larger vessels for observation, the scan line can be rotated and positioned. In some embodiments, vessels may be selected that are small and allow only one cell to pass sequentially such that the selected vessel fits within a single scan line. In some embodiments, limiting the target imaging area to a smaller segment of the patient's eye can reduce the acquisition area of the imaging sensor. In some embodiments, using a portion of the imaging sensor helps increase the imaging frame rate to tens of KHz. In some embodiments, the imaging devices described herein can be configured to perform fast scans of small regions of a patient's eye while reducing spread spectrum interference. For example, each scanned line can use a different 2D cross-section of the imaging sensor array. Therefore, multiple line scans can be captured simultaneously, each line scan being captured by a respective portion of the imaging sensor array. In some embodiments, each 2D line scan can be measured independently, since magnifying each line scan can result in a wider spacing on the imaging sensor array, such as a wider spread spectrum. can.

Having thus described several aspects and embodiments of the technology described in this disclosure, it will be appreciated that various alterations, modifications, and improvements will readily occur to those skilled in the art. Such alterations, modifications and improvements are intended to be within the spirit and scope of the technology described herein. For example, those skilled in the art will readily envision a variety of other means and/or structures for performing the functions described herein and/or obtaining one or more of the results and/or advantages. Also, each such variation and/or modification is considered to be within the scope of the embodiments described herein. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments described herein. It is therefore to be understood that the above-described embodiments are presented by way of example only, and that within the scope of the appended claims and their equivalents, the inventive embodiments may be practiced other than as specifically described. It should be. Moreover, any combination of two or more features, systems, articles, materials, kits and/or methods described herein is not intended to be inconsistent with such features, systems, articles, materials, kits and/or methods. If not, it is included within the scope of this disclosure.

The embodiments described above can be implemented in any of a number of ways. One or more aspects and embodiments of the present disclosure that involve the performance of a process or method are directed to a device (e.g., computer, processor or other device) for performing or controlling the performance of that process or method. Program instructions executable by the . In this regard, the various inventive concepts can be directed to one or more methods that, when executed on one or more computers or other processors, perform methods that implement one or more of the various embodiments described above. computer readable storage medium (or any number of computer readable storage media) (e.g., computer memory, one or more floppy disks, compact disks, optical disks, magnetic tapes, flash memory, field programmable gate arrays) encoded with a program of or other semiconductor device circuitry, or other tangible computer storage medium). One or more computer-readable media can be loaded with one or more programs stored thereon into one or more different computers or other processors to implement various of the aspects described above. can be made transportable. In some embodiments, computer readable media may be non-transitory media.

As used herein, the term "program" or "software" refers to any type of computer code or set of computer readable instructions that can be employed to program a computer or other processor to implement the various aspects described above. used in a generic sense to refer to Additionally, according to one aspect, one or more computer programs that, when executed, perform the methods of the present disclosure need not reside on a single computer or processor to implement various aspects of the present disclosure. It should be understood that it may be modularly distributed among a number of different computers or processors.

Computer-executable instructions may be in many forms, such as program modules, executed by one or more computers or other devices. Generally, program modules include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. Typically the functionality of the program modules may be combined or distributed as desired in various embodiments.

Also, data structures may be stored in computer-readable media in any suitable form. For ease of explanation, data structures are sometimes shown to have fields that are related by position within the data structure. Such relationships may similarly be achieved by allocating field storage at locations within the computer-readable medium that convey the relationship between the fields. However, any suitable mechanism may be used to establish relationships between the information in the fields of the data structures, such as through the use of pointers, tags, or other mechanisms for establishing relationships between data elements.

When implemented in software, the software code can be executed on any suitable processor or collection of processors, whether hosted in a single computer or distributed among multiple computers. can.

Further, it should be understood that the computer may take any of a number of forms, such as a rackmount computer, desktop computer, laptop computer, or tablet computer, as non-limiting examples. Additionally, a computer is any device not generally considered a computer but having suitable processing power, including a personal digital assistant (PDA), smart phone or any other suitable portable or stationary electronic device. can also be embedded in

Also, a computer may have one or more input/output devices. These devices can be used, among other things, to present user interfaces. Examples of output devices that can be used to provide a user interface include printers or display screens for visual presentation of output, and speakers or other sound producing devices for audible presentation of output. be Examples of input devices that can be used for user interfaces include keyboards and pointing devices such as mice, touch pads, and digitizing tablets. As another example, the computer may receive input information through speech recognition or in other audible formats.

The computers may be interconnected by any suitable form of network or networks, including local or wide area networks, such as enterprise networks, and intelligent networks (IN) or the Internet. Such networks may be based on any suitable technology, may operate according to any suitable protocol, and may include wireless, wired or fiber optic networks.

The acts performed as part of the method may be ordered in any suitable manner. Thus, although illustrated as sequential acts in an exemplary embodiment, embodiments can be constructed in which the acts occur in a different order than that illustrated, and some acts may occur simultaneously. can also be included.

All definitions and definitions used herein supersede dictionary definitions, definitions in documents incorporated by reference and/or ordinary meaning of the defined terms.
As used in this specification and claims, "a" is understood to mean "at least one" unless the content clearly indicates otherwise.

As used in this specification and claims, the term "and/or" is understood to refer to "one or both" of the elements connected by this term, i.e., when understood conjunctively and when , may be understood disjunctively. Multiple elements listed with the term "and/or" should be construed in the same manner, meaning "one or more" of the listed elements. Elements other than those specifically identified with the "and/or" may optionally be present, regardless of whether related or unrelated elements specifically identified. Thus, as a non-limiting example, when "A and/or B" is used in combination with open-ended phrases such as "comprising," in one embodiment A alone (optionally elements other than B ), in another embodiment only B (optionally including elements other than A), in yet another embodiment both A and B (optionally also other elements) including).

In the specification and claims herein, the phrase "at least one" referring to a listing of one or more elements is selected from one or more of the listed elements. , but need not include at least one each of every element specifically recited in a recited element, and combinations of elements of the recited elements not excluded. Also in this definition, elements other than those specifically identified in a recited element to which the phrase "at least one" refers, whether or not they relate to the elements specifically identified, may optionally be present. Thus, as a non-limiting example, "at least one of A and B" (also "at least one of A or B" or "at least one of A and/or B") means, in one embodiment, means comprising at least one, optionally two or more A and no B (and optionally comprising elements other than B), in another embodiment at least one, optionally two means that it includes one or more Bs and that A is absent (and optionally includes elements other than A); means one and optionally including B (and optionally including other elements).

Also, the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The terms "including", "comprising", "having", "having", "using" and variations thereof herein are meant to encompass the items listed thereafter and their equivalents and additional items. .

In the claims and the above specification, all terms such as "comprising", "including", "having", "having", "consisting of", "accompanied", "holding", "consisting of", etc. is an open-ended phrase and is understood to mean including but not limited to. Only the transitional phrases “consisting of” and “consisting essentially of” are to be understood as restrictive or semi-limiting phrases.

Claims (105)

An imaging and/or measuring device for imaging and/or measuring a patient's fundus retina, said imaging and/or measuring device comprising:
white light imaging device,
fluorescence imaging device,
Imaging and/or measuring apparatus comprising at least two imaging and/or measuring devices selected from the group comprising an infrared imaging device and/or an optical coherence tomography device. 2. The imaging and/or measuring device of claim 1, wherein the imaging and/or measuring device comprises the white light imaging device and the fluorescence imaging device. 2. The imaging and/or measuring apparatus of claim 1, wherein the imaging and/or measuring apparatus comprises the white light imaging device and the optical coherence tomography device. 2. The imaging and/or measurement apparatus of claim 1, wherein the imaging and/or measurement apparatus comprises the white light imaging device, the fluorescence imaging device, and the optical coherence tomography device. 2. Imaging according to claim 1, wherein the imaging and/or measurement apparatus comprises the fluorescence imaging device, the fluorescence imaging device being configured to determine spectral and lifetime information of received fluorescence emissions. and/or measurement equipment. Imaging and/or measuring apparatus according to any one of the preceding claims, further comprising a housing having at least two housing portions configured to support said at least two imaging devices. 7. The imaging and/or measurement device of claim 6, wherein the at least two housing parts comprise two housing parts having optical components configured to align with both eyes of a patient. 8. Imaging and/or measuring device according to claim 7, wherein the housing has the shape of a binocular. 8. Imaging and/or measuring apparatus according to claim 7, wherein said two housing parts are each configured to support at least one of said at least two imaging devices. 10. The at least two imaging units comprise at least four imaging devices, and the two housing portions are configured to support two of the at least four imaging devices, respectively. The imaging and/or measurement device according to . A method of imaging and/or measuring a patient's fundus retina, said method comprising:
white light imaging device,
infrared imaging device,
a fluorescence imaging device and/or an optical coherence tomography device,
imaging and/or measuring a patient's retinal fundus using at least two of: 12. The method of claim 11, wherein imaging and/or measuring comprises using the white light imaging device and the fluorescence imaging device. 12. The method of claim 11, wherein imaging and/or measuring comprises using the white light imaging device and the optical coherence tomography device. 12. The method of claim 11, wherein imaging and/or measuring comprises using the white light imaging device, the fluorescence imaging device, and the optical coherence tomography device. 12. Imaging and/or measuring comprises using the fluorescence imaging device, wherein the fluorescence imaging device is configured to determine spectral and lifetime information of received fluorescence emissions. The method described in . 16. The method of any one of claims 11-15, further comprising supporting the at least two imaging devices by a housing having at least two housing portions. 17. The method of Claim 16, further comprising aligning two of the at least two imaging devices with the patient's eyes. 18. The method of claim 17, wherein the housing has a binocular shape. 18. The method of Claim 17, wherein the two housing portions each support at least one of the at least two imaging devices. 20. The method of claim 19, wherein the at least two housing portions comprise at least four imaging devices, each of the two housing portions supporting at least two of the at least four imaging devices. Imaging device. An imaging and/or measurement device for measuring and/or imaging a patient's fundus retina, said imaging device comprising:
A housing having the shape of binoculars,
a first housing portion comprising a first opening configured to be placed proximate to a first eye of a patient;
a second housing portion comprising a second opening configured to be placed proximate to the patient's second eye;
the housing comprising
at least one imaging and/or measurement device supported by said first housing portion and/or said second housing portion and configured to image and/or measure a retinal fundus of a patient; Imaging and/or measurement equipment. 22. The imaging and/or measuring apparatus of Claim 21, wherein said at least one imaging and/or measuring device comprises a white light imaging device. 23. Imaging and/or measuring apparatus according to claim 21 or 22, wherein said at least one imaging and/or measuring device comprises a fluorescence imaging device. 24. The imaging and/or measurement apparatus of claim 23, wherein the fluorescence imaging device is configured for fluorescence spectral imaging. 24. The imaging and/or measurement apparatus of claim 23, wherein the fluorescence imaging device is configured for fluorescence lifetime imaging. 24. The imaging and/or measurement apparatus of claim 23, wherein the fluorescence imaging device is configured for fluorescence intensity imaging. 23. The at least one imaging and/or measuring device according to claim 21 or 22, wherein said at least one imaging and/or measuring device comprises a white light imaging device in said first housing part and an optical coherence tomography device in said second housing part. Imaging and/or measurement equipment. 28. The imaging and/or measuring apparatus of Claim 27, wherein said at least one imaging and/or measuring device further comprises a fluorescence imaging device within said first housing portion. The at least one imaging and/or measurement device displays a fixation target to the patient at different times through the first opening of the first housing part and the second opening of the second housing part. 29. An imaging and/or measuring device according to claim 28, further configured. 30. An imaging and/or measuring device according to claim 29, wherein the fixation target is an image of an object. 31. The imaging and/or measuring device according to claim 30, wherein the fixation target is a bright spot. The at least one imaging and/or measuring device provides a first fixation target to a patient through the first opening of the first housing and a second fixation to the patient through the second opening of the second housing. 29. The imaging and/or measurement device of claim 28, further configured to simultaneously display vision. further comprising a gripping member coupled to the housing,
23. Imaging and/or measuring device according to claim 21 or 22, wherein the gripping member is configured to be grasped by at least one hand of a patient. further comprising an installation member attached to the housing,
23. Imaging and/or measuring device according to claim 21 or 22, wherein the mounting member is configured to mount the device on a mounting arm and/or stand. 23. An imaging and/or measuring device according to claim 21 or 22, further comprising a hinge coupled between said first housing part and said second housing part. 1. An apparatus for performing optical coherence tomography (OCT) on the retinal fundus of a patient, said apparatus comprising:
a plurality of light sources configured to emit light;
an interferometer,
receiving light from the plurality of light source components;
splitting the light into a reference component and a sample component;
illuminating an eye of a patient through the sample component;
the interferometer configured to recombine light from the reference component and the sample component;
an image sensor configured to detect recombined light from the interferometer. 37. The apparatus of Claim 36, wherein said plurality of light sources are configured to emit light of a wavelength different from other wavelengths of said plurality of light sources. 37. The apparatus of claim 36, wherein said interferometer is a Michelson interferometer. 37. The apparatus of Claim 36, wherein said plurality of light sources comprise a plurality of light emitting diodes. 37. The apparatus of Claim 36, further comprising at least one dichroic configured to combine light from multiple light sources into a single optical path. 41. The apparatus of any one of claims 36-40, wherein the plurality of light sources comprises three light sources. The three light sources are
a first light source configured to emit light having a center wavelength between 620 nm and 630 nm;
a second light source configured to emit light having a center wavelength between 635 nm and 645 nm;
42. The apparatus of claim 41, comprising a third light source configured to emit light having a center wavelength between 650nm and 660nm. The first light source is configured to emit light with a center wavelength of 625 nm,
The second light source is configured to emit light with a center wavelength of 640 nm,
wherein the third light source is configured to emit light with a center wavelength of 655 nm;
43. Apparatus according to claim 42. 41. The apparatus of any one of claims 36-40, wherein the plurality of light sources are configured to emit light sequentially. 45. The apparatus of Claim 44, wherein the image sensor is configured to sequentially detect recombined light associated with each of the plurality of light sources. further comprising at least one processor;
The at least one processor
Receiving image data associated with recombined light from the image sensor, the image data comprising individual image data associated with each of the plurality of light source components. thing,
46. The apparatus of Claim 45, configured to perform combining the image data associated with each of the plurality of light sources into a single OCT image. A device for performing optical coherence tomography of a patient's retinal fundus, said device comprising:
a light source configured to emit light;
an interferometer,
receiving light from the light source;
splitting the light into a reference component and a sample component;
illuminating an eye of a patient through the sample component;
the interferometer configured to recombine light from the reference and sample components;
an image sensor configured to detect recombined light from the interferometer. 48. The apparatus of claim 47, wherein the sample component is configured to focus scan lines on a patient's fundus retina and the reference component is configured to focus scan lines on a reference plane. 48. The apparatus of claim 47, wherein said interferometer is a Michelson interferometer. 48. The apparatus of Claim 47, further comprising a first cylindrical lens pair positioned between said light source and said interferometer. 51. The apparatus of Claim 50, further comprising a second cylindrical lens pair positioned between said interferometer and said image sensor. 52. The apparatus of any one of claims 47-51, further comprising a transmission grating positioned between the interferometer and the image sensor. 48. The apparatus of claim 47, wherein the interferometer is configured to scan the scan line across the patient's fundus retina. 3. The image sensor is configured to detect recombined light from the interferometer such that different portions of the image sensor correspond to different scans of a portion of the fundus retina. 47. Apparatus according to 47. 1. An apparatus for performing time-domain optical coherence tomography of the retinal fundus of a patient, said apparatus comprising:
a light source configured to emit light;
A Michelson interferometer,
receiving light from the light source;
splitting the light into a reference component and a sample component;
illuminating an eye of a patient through the sample component;
the Michelson interferometer configured to recombine light from the reference component and the sample component;
an image sensor configured to detect recombined light from the Michelson interferometer in two image frames acquired less than 100 milliseconds apart. 56. The apparatus of Claim 55, wherein the light source is configured to emit multiple light pulses synchronized with a frame rate of the image sensor. The light source is
emitting a first light pulse of the plurality of light pulses at a first time point corresponding to the end of a first frame of the image sensor;
3. configured to emit a second light pulse of said plurality of light pulses at a second time point corresponding to the beginning of a second frame of said image sensor, which is the next frame after said first frame. 56. Apparatus according to 56. 57. The apparatus of claim 56, wherein each light pulse emitted by said light source has a duration less than a frame duration of said image sensor. the light source is configured to emit each light pulse of duration between 0.1 milliseconds and 5 milliseconds;
59. The apparatus of Claim 58, wherein the image sensor is configured to have a frame duration between 5ms and 20ms. the light source is configured to emit each light pulse of duration between 0.1 milliseconds and 1 millisecond;
56. The apparatus of Claim 55, wherein said image sensor is configured to have a frame duration between 9 ms and 11 ms. A device for imaging and/or measuring a retinal fundus of a patient, said device comprising:
a housing;
a white light imaging device supported by the housing;
a fluorescence imaging device supported by the housing;
The apparatus of claim 1, wherein the white light imaging device and the fluorescence imaging device share at least a portion of a common optical path within the housing. 62. The apparatus of Claim 61, wherein the white light imaging device and the fluorescence imaging device share an imaging sensor. The white light imaging device comprises a white light source,
the fluorescence imaging device comprises at least one laser;
The device comprises:
an optical path of light emitted from the white light source and an optical path of light emitted from the at least one laser such that light emitted from the white light source and light emitted from the at least one laser share the common optical path 63. The apparatus of claim 62, further comprising an optical element configured to couple with. the fluorescence imaging device comprising a first laser configured to emit light at a first wavelength and a second laser configured to emit light at a second wavelength;
The device comprises:
a first optical element configured to combine the optical path of light emitted from the white light source with the optical path of light emitted from the first laser;
The optical path of light emitted from the white light source and the first light source such that light emitted from the white light source, light emitted from the first laser and light emitted from the second laser share the common optical path. 64. The apparatus of claim 63, comprising a second optical element configured to combine the optical path of light emitted from a laser with the optical path of light emitted from the second laser. 64. The apparatus of claim 63, wherein the common optical paths include optical paths from the first optical element to the patient's eye and from the patient's eye to the imaging sensor. further comprising a reflector in the common optical path;
66. The apparatus of any one of claims 61-65, wherein the reflector comprises an aperture configured such that light reflected from the retinal fundus passes through the reflector. Claims 61-65 further comprising a beam splitter configured to transmit light for said fluorescence imaging device to a fluorescence imaging sensor and reflect light for said white light imaging device towards said white light imaging sensor. The apparatus described in . 68. The apparatus of claim 67, wherein the transmittance of the beam splitter is greater than the reflectance of the beam splitter. 69. The apparatus of Claim 68, wherein the fluorescence imaging sensor is configured to detect the fluorescence lifetime of at least one molecule in the patient's eye. 69. The apparatus of Claim 68, wherein the fluorescence imaging sensor is configured to detect fluorescence wavelengths of at least one molecule in the patient's eye. a method,
A method comprising imaging a patient's retinal fundus with a white light imaging device and a fluorescence imaging device that at least partially share an optical path. a method,
Imaging and/or measuring a patient's retinal fundus using a device, the device comprising:
white light imaging device,
imaging and/or measuring the patient's retinal fundus, comprising at least two imaging and/or measuring devices selected from the group comprising a fluorescence imaging device and an optical coherence tomography device;
determining a patient's medical condition based on images captured during imaging and/or measurements. 73. The method of claim 72, wherein determining the medical condition comprises determining whether the patient has an eye disease. 74. The method of claim 73, wherein said eye disease comprises age-related macular degeneration (AMD). 74. The method of claim 73, wherein said eye disease comprises Stargardt's disease. 74. The method of claim 73, wherein said eye disease comprises diabetic retinopathy. 74. The method of claim 73, wherein said eye disease comprises macular edema. 74. The method of claim 73, wherein said eye disease comprises macular hole. 74. The method of claim 73, wherein said eye disease comprises floaters. 74. The method of claim 73, wherein said eye disease comprises glaucoma. 74. The method of claim 73, wherein said eye disease comprises retinal detachment. 74. The method of claim 73, wherein said eye disease comprises cataracts. 74. The method of claim 73, wherein said eye disease comprises macular telangiectasia. 73. The method of claim 72, wherein determining the medical condition comprises determining whether the patient has a non-ocular disease. 85. The method of claim 84, wherein the non-ocular disease comprises Alzheimer's disease. 86. The method of claim 85, wherein determining whether the patient has Alzheimer's disease comprises using the image to determine the patient's retinal nerve fiber layer thickness. 85. The method of claim 84, wherein the non-ocular disease comprises Parkinson's disease. 88. The method of claim 87, wherein determining whether the patient has Parkinson's disease comprises using the image to determine the patient's retinal nerve fiber layer thickness. 88. The method of claim 87, wherein determining whether a patient has Parkinson's disease comprises using the image to determine a measure of eye tracking ability. 85. The method of claim 84, wherein said non-ocular disease comprises concussion. a method,
Imaging and/or measuring a patient's retinal fundus using a device, the device comprising:
white light imaging device,
imaging and/or measuring the patient's retinal fundus, comprising at least two of a fluorescence imaging device and an optical coherence tomography device;
identifying a patient based on said images and/or measurements. a method,
Imaging and/or measuring a patient's retinal fundus using a device, the device comprising:
white light imaging device,
imaging and/or measuring the patient's retinal fundus, comprising at least two imaging and/or measuring devices selected from the group comprising a fluorescence imaging device and an optical coherence tomography device;
obtaining patient security access based on said images and/or measurements. a method,
Imaging and/or measuring a patient's retinal fundus using a device, the device comprising:
white light imaging device,
imaging and/or measuring the patient's retinal fundus, comprising at least two imaging and/or measuring devices selected from the group comprising a fluorescence imaging device and an optical coherence tomography device;
diagnosing a patient's medical condition based on said images and/or measurements. a method,
imaging and/or measuring a human retinal fundus using fluorescence lifetime imaging and/or optical coherence tomography imaging;
identifying the person, obtaining security access to the person, determining a health condition of the person, and diagnosing a medical condition of the person based on said images and/or measurements; performing at least one. A device for retinal imaging and/or measurement, comprising:
at least two imaging and/or measuring devices,
white light imaging device,
the at least two imaging and/or measurement devices selected from the group comprising a fluorescence imaging component and an optical coherence tomography component;
at least one modular light transmissive, reflective and/or refractive element in the optical path of at least one of said at least two imaging and/or measuring devices. 96. The device of Claim 95, wherein said at least one modular element comprises a mirror. 96. The device of Claim 95, wherein said at least one modular element comprises a prism. 96. The device of Claim 95, wherein said at least one modular element comprises a lens. 96. The device of Claim 95, wherein said at least one modular element comprises a beam splitter. A device for retinal imaging and/or measurement, comprising:
a white light imaging and/or measurement device;
a fluorescence imaging and/or measurement device;
at least one modular light transmissive, reflective and/or refractive element in the optical path of at least one of said white light imaging and/or measuring device and said fluorescence imaging and/or measuring device. 101. The device of Claim 100, wherein the white light imaging device further comprises an optical coherence tomography imaging and/or measurement device. 101. The device of Claim 100, wherein the device is in the form of binoculars. said at least one modular element comprising:
eye relay,
scanning mirror,
light source,
cylindrical lens and/or plate beam splitter,
101. The device of claim 100, comprising at least one member selected from the group comprising: complementary metal oxide semiconductor (CMOS) image sensors;
infrared retinal fundus image sensor,
a fluorescence image sensor and/or a white light retinal fundus image sensor,
101. The device of claim 100, further comprising at least one member of the group comprising: 101. The device of Claim 100, further configured to display a fixation target comprising a two-dimensional (2D) screen and/or light emitting diodes (LEDs) mounted on said device.

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