Light-efficient multispectral fluorescence imaging

Abstract

In certain embodiments, a system, computer-implemented method, and computer-readable medium for light-efficient fluorescence imaging are disclosed. The retina is flashed with broadband light, and the light returned after passing through one or more filters, such as a notch filter, a low-pass filter, and a high-pass filter, is imaged. Images may be captured by a single camera or by at least two cameras, one capturing the transmitted light from the filters and the other capturing the returned light. The images can be combined by subtraction and / or addition to obtain a composite image representing light within the passband without using passband filters during imaging.

Description

[Technical Field]

[0001] (Background technology) Diagnosis and treatment of many ocular diseases requires imaging of a patient's eye. The retina has many complex features that are imaged to diagnose ocular disorders and other disorders that cause physiological changes in the retina. Some features correspond to healthy ocular anatomical structures or pathological conditions that fluoresce when illuminated. The spectral "fingerprint" of this fluorescence may be used as a biomarker corresponding to a particular pathology. For example, fundus autofluorescence (FAF) is commonly used to diagnose retinal degenerative diseases. Summary of the Invention [Problem to be solved by the invention]

[0002] Traditional approaches to measuring fluorescence use complex and expensive spectrometers to detect the spectrum of reflected light, but have limited ability to detect spatial information in the retina. Thus, diagnosis of certain diseases requires expensive testing at relatively few institutions with the necessary expertise and equipment.

[0003] Making fluoroscopy more accessible and combining the fluorescence information with spatial information about the patient's retina would advance the field. [Means for solving the problem]

[0004] In certain embodiments, a system is provided that includes one or more processing devices and one or more memory devices coupled to the one or more processing devices. The one or more memory devices store executable code that, when executed by the one or more processing devices, causes the one or more processing devices to receive a first image of first light reflected from a patient's retina and filtered according to a first filtering. A second image is received of second light reflected from the patient's retina and filtered according to a second filtering. The first and second images are combined to obtain a composite image representing a portion of at least one of the first light and the second light within a passband, where neither the first filtering nor the second filtering includes passband filtering. The composite image may be output to a display device.

[0005] In order that the above-mentioned features of the present disclosure may be understood in detail, a more particular description of the present disclosure briefly summarized above can be had by reference to several embodiments thereof which are illustrated in the accompanying drawings. It should be noted, however, that the accompanying drawings depict only exemplary embodiments and therefore should not be considered as limiting the scope of the invention, as other equally effective embodiments are possible. [Brief explanation of the drawings]

[0006] [Figure 1] FIG. 1 illustrates an exemplary system for performing light-efficient fluorescence imaging, according to certain embodiments. [Figures 2A-2C] 2A-2C are plots of the wavelength response of the optical filters of the system of FIG. 1 and the spectrum of the combined returned light, according to certain embodiments. [Figure 2D] FIG. 2D shows the equivalent passband obtained using the system of FIG. [Figure 3] FIG. 3 illustrates an alternative system for performing light-efficient fluorescence imaging, according to certain embodiments. [Figure 4A-4B] 4A-4B are plots of the wavelength response of the notch filter and the spectrum of the combined return light for the system of FIG. [Figure 5]FIG. 5 illustrates the equivalent passbands shown in FIGS. 1 and 3 for the sensitivity spectrum of a sensor in a color camera, according to certain embodiments. [Figure 6] FIG. 6 is a process flow diagram of a method for performing light-efficient fluorescence imaging, according to certain embodiments. [Figure 7] FIG. 7 illustrates an exemplary computing device that at least partially implements one or more functions for implementing light-efficient fluorescence imaging, according to certain embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0007] For ease of understanding, wherever possible, the same reference numerals have been used to refer to identical elements common to the figures, and it is contemplated that elements and features of one embodiment may be incorporated into other embodiments, as appropriate, without further reference.

[0008] Fundus autofluorescence photography (FAF) is an important tool for diagnosing retinal degenerative diseases. FAF involves illuminating the retina with light and detecting the resulting autofluorescence. The excited autofluorescence may be emitted from multiple light sources (e.g., disease biomarkers). For early disease detection and better diagnosis, it is best to decompose the spectrum of the fluorescence to establish the spectral "fingerprints" of different biomarkers and determine which disease markers are the major contributors to the fluorescence.

[0009] In traditional approaches, fluorescence imaging uses single-wavelength (narrowband) light to excite retinal tissue and broadband detection of the fluorescence emission. In traditional approaches, the spectrum of the fluorescence signal is measured using a spectrometer at the detector. However, simultaneously achieving spectral resolution and capturing spatial information of the fundus is often difficult. The systems and methods disclosed herein enable imaging of ocular fluorescence with high spatial precision using relatively simple equipment that does not include a spectrometer.

[0010] Multispectral imaging (MSI) is another conventional approach to imaging the retina in multiple wavelength bands. Typical MSI techniques illuminate the eye with multiple different bands of narrow-band light. This light is detected by a detector after passing through a transmission filter that matches the narrow-band light. However, in the case of fluorescence imaging, such techniques are not directly applicable. Fluorescence imaging is performed by flashing high-intensity excitation light. Collecting only a narrow band of fluorescence signal that passes through a transmission filter, as used in MSI, is light inefficient. Capturing fluorescence in multiple wavelength bands in this manner requires multiple flashes, which can lead to phototoxicity. The systems and methods disclosed herein enable fluorescence imaging with high light efficiency without causing phototoxicity.

[0011] FIG. 1 illustrates an exemplary system 100 for performing light-efficient fluorescence imaging of a retina 102 of a patient's eye 104 without the use of a spectrometer. The system 100 includes a light source 106. The light source 106 may be implemented as one or more light-emitting diodes (LEDs) or other types of light sources. The light source 106 may be narrow-band (e.g., a −3 dB bandwidth of less than 100, 50, 25, or 10 nm) or single wavelength, or a combination thereof. The light from the light source may be in the visible spectrum (e.g., 380-700 nm) or the infrared spectrum. A filter 106a can filter the light from the light source 106 to reduce light that does not contribute to exciting fluorescence.

[0012] Light from the light source 106 may be transmitted to the interior of the eye 104 via a beam splitter 110, which may be implemented as a dichroic mirror. The beam splitter 110 may act as a filter for light returned from the eye 104, attenuating light within the passband of the filter 106a (e.g., by at least 10 dB) without substantially attenuating (e.g., by less than 3 dB) light within one or more other wavelength bands corresponding to fluorescence from the retina 102. A portion of the light returned from the retina 102 passes through the beam splitter 110. As used herein, "returned light" refers to light that has been filtered by the beam splitter 110 (by transmission in the illustrated example) and / or one or more other filtering steps and that primarily comprises light emitted as fluorescence by the retina 102, e.g., light other than fluorescence that is attenuated by at least 6 dB more than the fluorescence in the returned light.

[0013] The returning light is incident on optical filter 112. A portion of the returning light is filtered out by optical filter 112 and incident on camera 114. A portion of the returning light is transmitted through optical filter 112 and incident on camera 116. Cameras 114, 116 may be color (red, green, blue) cameras, monochrome cameras, infrared cameras, or other types of cameras. Other optical elements, such as lenses, pinhole filters, mirrors, etc., may be present in system 100 to focus the light on retina 102, suppress reflections from structures other than retina 102 (e.g., the cornea), and focus the light on detectors of cameras 114, 116.

[0014] The optical filter 112 may be implemented as a dichroic mirror or other type of optical filter. The optical filter 112 may be a low-pass filter, a high-pass filter, a notch filter, or other type of filter. As seen in FIG. 1 , the optical axis of the optical filter 112 may be at a non-parallel angle to the optical axis of the cameras 114, 116, such as an angle of 42-48 degrees, 44-46 degrees, or 45 degrees. The system 100 may include multiple optical filters 112 that may be selectively positioned at the positions shown or other positions to perform fluorescence imaging, as described in more detail below.

[0015] 2A-2D illustrate the operation of system 100. Figures 2A-2D are described with reference to the spectrum R of light returned from a point on retina 102, such as the fluorescence spectrum returned from that point on retina 102. The spectrum is approximated by cameras 114, 116 as a single monochrome pixel or red, green, and blue intensities according to the sensitivity spectrum of cameras 114, 116 (see Figure 5 and corresponding discussion).

[0016] 2A , when optical filter 112 is a high-pass or low-pass filter, one of cameras 114, 116 (the “first camera”) captures light primarily within the low-pass wavelength band LPA, and light with wavelengths above the low-pass wavelength band LPA is attenuated by optical filter 112. The other camera 116, 114 (the “second camera”) captures light primarily within the high-pass wavelength band HPA, and light with wavelengths below the high-pass wavelength band HPA is attenuated by optical filter 112. Optical filter 112 can define a cutoff wavelength COA (e.g., a −3 dB cutoff wavelength) that defines the boundary between the wavelength bands LPA and HPA.

[0017] 2B and 2C, other optical filters 112 may be used that have different cutoff wavelengths COB and COC between the corresponding low passbands LPB and LPC and the different high passbands HPB and HPC. For example, the cutoff wavelengths COA and COB may be different from each other. <COB<COCであってよい。

[0018] Although the wavelength responses of three different filters 112 are shown, more or fewer filters 112 may be used. For each filter 112, the system 100 may be used to flash the retina 102 with the light source 106 to capture an image with the cameras 114, 116. Thus, the intensity of the light source 106 and the number of filters 112 may be selected to avoid phototoxicity.

[0019] 2D, images captured using cameras 114, 116 for each filter 112 can be combined to produce an estimated image representing light within equivalent passbands PB1-PB4, which are greater than the number of filters 112. Furthermore, note that when capturing images using filters 112, the range of wavelengths collected by each camera 114, 116 is wider than the equivalent passbands PB1-PB4, resulting in greater light efficiency. That is, the amount of returned light collected relative to the amount of light illuminating retina 102 is greater than with passband filters having equivalent passbands PB1-PB4. Therefore, the degree of phototoxicity relative to the amount of spectral information acquired is lower than with passband filters.

[0020] The images acquired using the filter 112 and the cameras 114, 116 may be combined in a variety of ways. The following notation is used in the following description: ILA represents the image acquired by the first camera in the low pass wavelength band LPA (e.g., captured by camera 114 when filter 112 is a high pass filter or captured by camera 116 when filter 112 is a low pass filter). ·IHA represents the image acquired by the first camera in the low pass wavelength band HPA (e.g., captured by camera 114 when filter 112 is a low pass filter or captured by camera 116 when filter 112 is a high pass filter). ·ILB represents the image acquired with the first camera in the low pass wavelength band LPB. ·IHB represents the image acquired with the first camera in the low pass wavelength band HPB. ·ILC represents the image acquired with the first camera in the low pass wavelength band LPC. ·IHC represents the image acquired with the first camera in the low pass wavelength band HPC. ·IP1, IP2, IP3, and IP4 represent images estimating the light in the equivalent passbands PB1, PB2, PB3, and PB4, respectively.

[0021] In the first approach, a first image of a low pass wavelength band having a first cutoff wavelength is subtracted from an image of a low pass wavelength band having a second cutoff wavelength higher than the first cutoff wavelength to obtain pass band images corresponding to wavelength bands between the first and second cutoff wavelengths. For example, IP1, IP2, IP3, and IP4 can be obtained as follows: IP1 may be equivalent to ILA IP2:ILB-ILA IP3:ILC-ILB IP4 may be equivalent to IHC

[0022] In the second approach, a first image of a high pass band having a first cutoff wavelength is subtracted from an image of a high pass band having a second cutoff wavelength that is lower than the first cutoff wavelength to obtain pass band images corresponding to wavelength bands between the first and second cutoff wavelengths. For example, IP1, IP2, IP3, and IP4 can be obtained as follows: IP1 may be equivalent to ILA IP2:IHA-IHB IP3:IHB-IHC IP4 may be equivalent to IHC

[0023] The third approach is a combination of the first and second approaches. An image corresponding to a wavelength passband from the first approach is added (or weighted added) to an image from the second approach in the same wavelength passband, and the resulting image may be scaled, such as divided by two or some other scaling factor. For example, IP1, IP2, IP3, and IP4 can be obtained as follows: IP1 may be equivalent to ILA IP2=(IHA-IHB+ILB-ILA) / 2 IP3=(IHB-IHC+ILC-ILB) / 2 IP4 may be equivalent to IHC

[0024] The third approach has the advantage of using information from four different images to reduce flash intensity with increased precision. In addition to reducing the number of flashes, the third approach offers an additional advantage over using an equivalent passband filter. Passband filters do not have a perfectly flat frequency response, meaning that light at wavelengths at the edges of the passband, even within the nominal passband, is attenuated more than light at the center of the passband. Using the third approach, light at wavelengths at the edges of the equivalent passband that are well off the cutoff wavelengths of the COA, COB, and COC are used, resulting in relatively less attenuation than with an equivalent passband filter.

[0025] As used herein, image addition and subtraction means that for images A and B, the value of pixel D(x,y) in difference (or sum) image D is equal to the difference (or sum) of pixel value A(x,y) and pixel value B(x,y) in image A, where x and y are the indices of the values ​​of the two-dimensional arrays of pixels contained in images A, B, and D.

[0026] Although the examples described herein use addition and subtraction, other pixel-by-pixel operations may be performed in a similar manner, for example, D(x,y) = A(x,y) / B(x,y), D(x,y) = A(x,y)*B(x,y), or D(x,y) = F(A(x,y), B(x,y)), where F() is a mathematical function chosen to enhance the visibility of retinal features.

[0027] In some embodiments, the images may be weighted before being combined. Such weighting can compensate for different sensitivities of the cameras 114, 116 or improve the ability of the combined image to approximate results obtained using a spectrometer. For example, system 100 can be used to acquire and process images of the retina 102 to obtain combined images IP1, IP2, IP3, and IP4. For the same retina 102, the spectrum of the returned light at a point on the retina 102 can be obtained, such as by using a spectrometer. The intensity of the returned light within each equivalent passband PB1, PB2, PB3, and PB4 can be integrated to compare the pixel intensities of a pixel representing that point or a block of pixels representing a region containing the point in images IP1, IP2, IP3, and IP4.

[0028] The weights of an image may be selected such that, following weighting, the relative intensities of that pixel or block of pixels in images IP1, IP2, IP3, IP4 correspond to the relative magnitudes of the integrals of the reflectance in each equivalent passband PB1, PB2, PB3, PB4. Multiple points within an image may be processed in a similar manner. Points from one or more other images may be processed in a similar manner to obtain a weight. The final weight may be obtained as an average or other combination of the weights obtained for multiple points in a single image or multiple images.

[0029] 3, in some embodiments, similar accuracy can be achieved using system 300. System 300 reduces complexity by using a single camera 302. System 300 requires exposing retina 102 to more flashes of light than system 100, while still providing an improvement over acquiring images using conventional MSI without a spectrometer.

[0030] The system 300 can illuminate the retina 102 using a light source 106 (and possibly a corresponding filter 106a, as described above) and a beam splitter 110. Light returning from the retina 102 passes through the beam splitter 110 (which may be a dichroic mirror that filters out the passband of the filter 106a, as described above), which produces light containing primarily fluorescent light (i.e., the "returned light," as described above). A single camera 302 detects the portion of the returned light that is transmitted or blocked by the optical filter 112. By selecting the optical filter 112 and the orientation of the optical filter 112, the system 300 can capture images in wavelength bands (LPA, LPB, LPC, HPA, HPB, HPB). For example, a low-pass optical filter 112 with a cutoff wavelength COA can be positioned to acquire an image ILA, with the camera 302 receiving the transmitted light. A high-pass optical filter 112 having a cutoff wavelength COA may be positioned with camera 302 receiving transmitted light to acquire image IHA. Alternatively, camera 302 may be moved to receive reflected light to acquire image IHA using the same optical filter 112 used to acquire ILA. Images ILB, IHB, ILC, and IHC may be acquired in a similar manner using filters having cutoff wavelengths COB and COC. Images ILA, IHA, ILB, IHB, ILC, and IHC acquired using system 300 may be processed in the same manner as images acquired using system 100 to acquire images corresponding to equivalent passbands PB1, PB2, PB3, and PB4.

[0031] 4A and 4B illustrate how optical filter 112 implemented as a notch filter may be used to obtain an image in a given passband. With specific reference to FIG. 4A, a first image of retina 102 may be obtained using system 100 or 300 by capturing returning light in the unfiltered wavelength band UF. The first image may be obtained either (a) without optical filter 112, or (b) with optical filter 112 that is substantially unattenuated (e.g., less than 1 dB) in a wavelength range that includes the entire stopband of the notch filter.

[0032] With specific reference to FIG. 4B, a second image of the retina 102 can be obtained using system 100 or 300 by capturing a portion of the returning light in the wavelength bands NFL and NFH and substantially excluding light having wavelengths within a rejection band RB between the passbands NFL and NFH (e.g., an attenuation of at least −3 dB and / or an average attenuation of at least −6 dB).

[0033] By subtracting the second image from the first image, an image representing the returned light within the stopband can be obtained. The first and second images may be weighted before subtraction, with the weights being determined as described above with respect to FIG. 2D.

[0034] Referring to FIG. 5 , camera 114, 116, or camera 302 may be a color camera, with red, green, and blue sensors having different sensitivity spectra. For example, any of cameras 114, 116, and 302 may be implemented as an NGENUITY 3D visualization system, available from Alcon, Inc., Fort Worth, Texas. Pixel values ​​of a given color in an image may be considered separate images that can be processed as described above. Equivalent passbands PB1, PB2, PB3, and PB4 may be selected with reference to the sensitivity spectra such that one or more sensitivity spectra (e.g., −3 dB bandwidth) of each sensor are divided into two or more passbands. Images in the equivalent passbands may be acquired as described above for the red, green, and blue images that make up a color image acquired using system 100 or 300. Thus, assuming four equivalent passbands, up to 12 images, each representing light from a different portion of the electromagnetic spectrum, may be acquired for a single color image. In practice, fewer images are acquired and used because images of a given color do not contain significant information in passbands far from the peak sensitivity of that color.

[0035] 5, the blue image can be used to obtain images corresponding to passbands PB1 and PB2, the green image can be split into images corresponding to PB2 and PB3, and the red image can be split into images corresponding to PB3 and PB4. Note that even if a blue image and a green image are both used to generate an image corresponding to, for example, PB2, these images may contain different information about the fluorescence because the sensitivity spectra of the blue and green sensors are not identical.

[0036] For a given equivalent passband PB1, PB2, PB3, PB4, the composite sensitivity spectrum of the sensor in the frequency domain is the product of the frequency response of the equivalent passband and the sensitivity of the sensor in the frequency domain. The frequency response of the equivalent passband may be determined from the frequency response of the optical filter 112 used to realize the equivalent passband.

[0037] The combined sensitivity of each color and each passband can be used to obtain more detailed spectral information for the red, green, and blue images. In particular, for each color and equivalent passband, the combined sensitivity of the sensor for that color and the frequency response of the equivalent passband can be used to find a spectral basis function (along with the spectrum of the light source 106). The spectral basis functions for the combinations of colors and equivalent passbands can then be used to obtain multispectral information from the images obtained for some or all combinations of colors and equivalent passbands.

[0038] 6 , method 600 may be performed by a computing system, such as computing system 700, that receives images from cameras 114, 116 of system 100 or camera 302 of system 300. Some of the embodiments described above use different filter configurations, such as different optical filters 112, different orientations of optical filters 112 relative to camera 302 (operating as high-pass or low-pass filters), and / or omit optical filters 112 in some configurations. In such embodiments, electronic actuators may be used to automatically move or rotate optical filters 112 and / or move or rotate camera 302 to achieve the different filter configurations. Computing system 700 may be coupled to electronic actuators to achieve the different filter configurations when performing method 600. Computing system 700 may also be coupled to light source 106 and configured to illuminate retina 102 with light source 106 when capturing images, as described above.

[0039] Method 600 may include, in step 602, configuring one or more of the available optical filters 112, and, in step 604, capturing one or more images of retina 102 with the filter configuration from step 602 using camera 114, 116 or camera 302. Step 604 includes emitting a flash of light from light source 106 to activate fluorescence in retina 102. Steps 602 and 604 may be repeated, with each iteration of step 602 achieving a different filter configuration, such as some or all of the filter configurations described above with respect to FIGS. 2A-2C and 4A-4B.

[0040] Method 600 may include, in step 606, weighting the images acquired in one or more iterations of step 604. In some embodiments, step 606 is omitted. If step 606 is performed, the weights may be determined as described above.

[0041] The images, which may have been weighted in step 606, may then be combined in step 608 to obtain composite images, each corresponding to light having wavelengths within an equivalent passband. For example, step 606 may include combining images using the approaches described above to obtain images in some or all of IP1, IP2, IP3, IP4, or more equivalent passbands.

[0042] The composite image from step 608 may then be displayed in step 610, such as on a display device of the computing system 700. Other processing may be performed, such as feature identification using a machine learning model, processing the composite image and / or identified features using a machine learning model to identify diseases represented in the composite image, or other processing. The composite image may be displayed under control of an interface that allows a user to select an equivalent passband to activate the display of an image corresponding to the equivalent passband.

[0043] 7 illustrates an exemplary computing system 700 that may at least partially implement one or more of the functions described herein. Computing system 700 may be integrated with an imaging device that captures images according to one or more imaging modalities described herein, or may be a separate computing device.

[0044] As shown, computing system 700 includes a central processing unit (CPU) 702, one or more input / output device interfaces 704 that can enable various input / output devices 714 (e.g., keyboard, display, mouse device, pen input, etc.) to be connected to computing system 700, a network interface 706 that connects computing system 700 to a network 790, memory 708, storage 710, and an interconnect 712.

[0045] CPU 702 can read and execute programming instructions stored in memory 708. Similarly, CPU 702 can read and store application data in memory 708. Interconnect 712 transfers programming instructions and application data between CPU 702, input / output device interface 704, network interface 706, memory 708, and storage 710. CPU 702 is included to represent a single CPU, multiple CPUs, a CPU with multiple processing cores, etc.

[0046] Memory 708 represents volatile memory, such as random access memory, and / or non-volatile memory, such as non-volatile random access memory, phase change random access memory, etc. As shown, memory 708 can store executable code image capture logic 716, such as logic that performs steps 602 and 604 of method 600. Memory 708 can store executable code implementing combination logic 718 that combines images to obtain a passband image, as described above with respect to step 608 of Figures 2D, 4A, 4B, 5, and 6.

[0047] Storage 710 may be non-volatile memory such as a disk drive, a solid state drive, or a collection of storage devices distributed across multiple storage systems. Storage 710 may store images 720 acquired using system 100 or 300 and composite images 722 as described above with respect to step 608 of Figures 2D, 4A, 4B, 5, and 6.

[0048] (Additional considerations) The previous description is provided to enable those skilled in the art to practice various embodiments described herein. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other embodiments. For example, changes may be made to the function and arrangement of elements described above without departing from the scope of the disclosure. Various procedures or elements may be omitted, substituted, or added in various examples, as appropriate. Also, features described with respect to some examples may be combined with other examples. For example, an apparatus may be implemented or a method may be practiced using any number of aspects described herein. Furthermore, the scope of the disclosure is intended to encompass similar apparatuses or methods practiced using structure, functionality, or structure and functionality in addition to or other than various aspects of the disclosure described herein. It should be understood that any aspect of the disclosure disclosed herein may be realized by one or more elements recited in the claims.

[0049] As used herein, phrases referring to "at least one of" listed items refer to any combination of those items, including single members. As an example, "at least one of a, b, or c" is intended to encompass not only a, b, c, ab, ac, bc, and abc, but also any combination with multiples of the same element (e.g., aa, aaa, aab, aac, abb, acc, bb, bbb, bbc, cc, and ccc, or any other permutation of a, b, and c).

[0050] As used herein, the term "determining" encompasses a wide variety of actions. For example, "determining" may include calculating, computing, processing, deriving, examining, referencing (e.g., referencing a table, database, or another data structure), ascertaining, etc. "Determining" may also include receiving (e.g., receiving information), accessing (e.g., accessing data in memory), etc. "Determining" may also include resolving, selecting, choosing, establishing, etc.

[0051] The methods disclosed herein include one or more steps or actions that implement the method. Method steps and / or actions may be interchangeable without departing from the scope of the claims. In other words, unless a specific order of steps or actions is specified, the order and / or use of specific steps and / or actions may be changed without departing from the scope of the claims. Furthermore, various actions of the methods described above may be performed by any suitable means capable of performing the corresponding functions. These means may include various hardware and / or software elements and / or modules, including, but not limited to, circuits, application specific integrated circuits (ASICs), or processors. In general, where there are actions illustrated in the figures, these actions may include corresponding means-plus-function elements that are similarly numbered.

[0052] The various illustrative logic blocks, modules, and circuits described in connection with this disclosure may be implemented or performed by a general-purpose processor, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA) or other programmable logic device (PLD), discrete gate or transistor logic, discrete hardware elements, or any combination thereof designed to perform the functions described herein. A general-purpose processor may be a microprocessor, but alternatively, the processor may be any commercially available processor, controller, microcontroller, or state machine. A processor may also be implemented as a combination of computing devices, such as a DSP and a microprocessor, multiple microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.

[0053] The processing system may be implemented with a bus architecture. The bus may include any number of interconnected buses and bridges, depending on the particular application and overall design constraints of the processing system. The bus may interconnect various circuits, including, among other things, a processor, machine-readable media, and input / output devices. A user interface (e.g., keypad, display, mouse, joystick, etc.) may also be connected to the bus. The bus may also connect various other circuits, such as timing sources, peripherals, voltage regulators, power management circuits, etc., which are known in the art and will not be described further. The processor may be implemented with one or more general-purpose and / or special-purpose processors. Examples include microprocessors, microcontrollers, DSP processors, and other circuits capable of executing software. Those skilled in the art will recognize how to best implement the described functionality of a processing system depending on the particular application and the overall design constraints imposed on the overall system.

[0054] If implemented in software, the functions described above may be stored on or transmitted as one or more instructions or code on a computer-readable medium. Software should be broadly construed to mean instructions, data, or any combination thereof, whether referred to as software, firmware, middleware, microcode, hardware description language, or otherwise. Computer-readable media includes both computer storage media and communication media, such as any medium that facilitates transfer of a computer program from one place to another. A processor may be responsible for managing the bus and general processing, including the execution of software modules stored on the computer-readable storage medium. The computer-readable storage medium may be coupled to the processor such that the processor can read information from and write information to the storage medium. Alternatively, the storage medium may be integrated into the processor. By way of example, computer-readable media may include a transmission line, a carrier wave modulated with data, and / or a computer-readable storage medium on which instructions are stored separately from a wireless node, all of which may be accessed by the processor via a bus interface. Alternatively or additionally, the computer-readable medium, or any portion thereof, may be integrated into the processor, such as in the case of a cache and / or general-purpose register file. Examples of machine-readable storage media include, for example, RAM (random access memory), flash memory, ROM (read-only memory), PROM (programmable read-only memory), EPROM (erasable programmable read-only memory), EEPROM (electrically erasable programmable read-only memory), registers, magnetic disks, optical disks, hard drives, or any other suitable storage medium or any combination thereof. The machine-readable medium may be embodied in a computer program product.

[0055] A software module may include a single instruction or many instructions and may be distributed across several different code sections, across different programs, and across multiple storage media. A computer-readable medium may include many software modules. A software module contains instructions that, when executed by a device such as a processor, cause a processing system to perform various functions. A software module may include a transmit module and a receive module. Each software module may reside on a single storage device or may be distributed across multiple storage devices. For example, a software module may be loaded from a hard drive into RAM when a trigger event occurs. During execution of a software module, a processor may load some of the instructions into a cache to speed access. One or more cache lines may then be loaded into a general-purpose register file for execution by the processor. When referring to the functionality of a software module, it is understood that such functionality is implemented by the processor when executing instructions from that software module.

[0056] The following claims are not limited to the embodiments set forth herein but are to be accorded the full scope consistent with the claim language. In the claims, when an element is referred to in the singular, it does not mean "one" or "only one" unless specifically stated otherwise, but rather "one or more." The term "some" refers to one or more unless specifically stated otherwise. No element of a claim shall be construed under the provisions of 35 U.S.C. § 112(f) unless the element is expressly recited using the phrase "means for," or, in the case of a method claim, unless the element is recited using the phrase "step for." All structure and functionality equivalents to the elements of the various aspects described throughout this disclosure that are known or later become known to those skilled in the art are expressly incorporated herein by reference and are intended to be encompassed by the claims. Furthermore, nothing disclosed herein is intended as a public disclosure, regardless of whether such disclosure is expressly recited in the claims.

Claims

1. 1. A system including one or more processing units and one or more memory units coupled to the one or more processing units, the one or more memory devices, when executed by the one or more processing devices, to the one or more processing devices; receiving a first image of the first light reflected from the patient's retina and filtered according to the first filtering; receiving a second image of the second light reflected from the patient's retina and filtered according to the second filtering; combining the first image and the second image to obtain a combined image representing a portion of at least one of the first light and the second light within a passband, where neither the first filtering nor the second filtering includes passband filtering; outputting a representation of said composite image to a display device. Save the executable code system.

2. 2. The system of claim 1, wherein the executable code, when executed by the one or more processing units, further causes the one or more processing units to combine the first image and the second image by subtracting the first image from the second image.

3. 3. The system of claim 2, wherein the first filtering is high-pass filtering with a first cutoff wavelength, the second filtering is high-pass filtering with a second cutoff wavelength lower than the first cutoff wavelength, and the passband is between the first cutoff wavelength and the second cutoff wavelength.

4. 3. The system of claim 2, wherein the first filtering is low-pass filtering with a first cutoff wavelength, the second filtering is low-pass filtering with a second cutoff wavelength higher than the first cutoff wavelength, and the passband is between the first cutoff wavelength and the second cutoff wavelength.

5. a light source configured to illuminate the retina and coupled to the one or more processing devices; a camera coupled to the one or more processing devices; a first optical filter positionable between the camera and the retina; further comprising a second optical filter positionable between the camera and the retina; 2. The system of claim 1, wherein the executable code, when executed by the one or more processing devices, further causes the one or more processing devices to receive the first image when the first optical filter is positioned between the retina and the camera, and to receive the second image when the second optical filter is positioned between the retina and the camera.

6. a light source configured to illuminate the retina and coupled to the one or more processing devices; a first camera coupled to the one or more processing devices; a second camera coupled to the one or more processing devices; a first optical filter that is alignable with the first camera that receives transmitted light from the first optical filter and the second camera that receives reflected light from the first optical filter; a second optical filter alignable with the first camera to receive transmitted light from the second optical filter and the second camera to receive reflected light from the second optical filter; The executable code, when executed by the one or more processing units, further causes the one or more processing units to: receiving the first image from the first camera and the third image from the second camera with the first optical filter positioned between the first camera and the retina; receiving the second image from the first camera and a fourth image from the second camera with the second optical filter positioned between the first camera and the retina; combining the first, second, third, and fourth images to obtain the combined image; The system of claim 1 .

7. the first and second optical filters are low-pass filters, and the first optical filter has a higher cutoff wavelength than the second optical filter; the executable code, when executed by the one or more processing devices, further causes the one or more processing devices to combine the first, second, third, and fourth images by adding the first image and the fourth image and subtracting the second image and the third image to obtain a combined image. The system of claim 6.

8. the first optical filter and the second optical filter are high-pass filters, and the first optical filter has a higher cutoff wavelength than the second optical filter; the executable code, when executed by the one or more processing devices, further causes the one or more processing devices to combine the first, second, third, and fourth images by adding the third image and the second image and subtracting the first image and the fourth image to obtain a combined image. The system of claim 6.

9. The system of claim 6 , wherein the first and second optical filters are dichroic mirrors.

Images