Systems and methods for label-free short-wave infrared (SWIR) nerve imaging

Abstract

Systems and methods for visualization of nerves are disclosed. A tissue region is illuminated with short-wave infrared (SWIR) light and reflected light is captured to form images in which nerve substructures, including bands of Fontana, are resolved. In some embodiments, nerve contrast is enhanced by dynamic polarization modulation, achieved by rotating polarizing elements or by electronically altering illumination polarization using liquid-crystal or photoelastic devices. A polarization-resolving camera may detect polarization-dependent reflectance, enabling extraction of periodic modulation unique to birefringent nerve tissue. The disclosed techniques improve nerve visibility relative to conventional imaging and may be used for surgical navigation, robotic surgery safety, or other in vivo applications.

Description

Attorney Docket No.: 16569-20011.40SYSTEMS AND METHODS FOR LABEL-FREE SHORT-WAVE INFRARED (SWIR) NERVE IMAGINGCROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 735,252, filed December 17, 2024, the entire contents of which are incorporated herein by reference for all purposes.FIELD

[0002] This is directed generally to systems and methods for label-free SWIR-based imaging of nerves or nerve substructures.BACKGROUND

[0003] Peripheral nerve damage is a common surgical complication that can lead to patient morbidity, mortality, and poor quality of life. Certain imaging techniques have been used to attempt to identify nerves in medical images. For example, certain imaging systems have relied on complex optical systems and / or time-intensive image processing algorithms to generate images in which nerves can be visually distinguished from other tissue. However, these techniques are cumbersome, inefficient, time-consuming, and not suitable for use in real-time and in vivo surgical imaging. Some imaging systems have used SWIR illumination to visualize peripheral nerves. However, these imaging systems produce SWIR illumination by isolated SWIR wavelengths from a polychromatic light source, rely on an optical spectrometer, rely solely on differentiating nerves by contrast from surrounding tissue, and are not able to effectively image nerve substructures such as bands of Fontana.SUMMARY

[0004] As discussed, current medical imaging modalities are unsuitable for real-time nerve visualization during surgery; these imaging modalities are either unable to resolve nerve substructure such as bands of Fontana, or require complex optical systems and / or time -intensive image processing algorithms making them unsuitable for real-time in vivo applications. Accordingly, improved techniques for imaging nerve and nerve substructures during surgery and during manipulation of tissue samples are needed. Specifically, improved techniques that do not require exogeneous imaging agents and that can accurately optically resolve nerves and nerve substructures in real time are required. Disclosed herein are systems and methods that may address one or more of the aboveidentified needs.

[0005] Disclosed herein are systems and methods to image a region of biological tissue, wherein at least one nerve or nerve substructure is present, using narrow bandwidth, high-power SWIR illumination. SWIR illumination may be directed to the region of biological tissue and the portion of1MF-364871974Attorney Docket No.: 16569-20011.40SWIR illumination reflected from the nerve or nerve substructure may be captured in real-time by an optical sensor system and used to generate one or more images of the nerve or nerve substructure (e.g., as part of a real-time video feed of the tissue region being imaged). The image may exhibit a pattern formed by a plurality of high-intensity regions and a plurality of low-intensity regions, wherein the pattern is indicative of the presence and / or location of a nerve (e.g., a peripheral nerve) or nerve substructure, such as the bands of Fontana in a peripheral nerve. The image may allow an observer to visually identify the presence and location of a peripheral nerve based on the characteristic intensity pattern indicative of the bands of Fontana.

[0006] In some embodiments, an image analysis algorithm may be applied to automatically detect the presence and / or location of a nerve in the image based on the characteristic intensity pattern indicative of the bands of Fontana. Based on automatic detection of the presence and / or location of the nerve, an imaging system and / or surgical system may be configured to automatically control functionality of one or more components of the imaging system, to automatically generate one or more outputs for a user, to automatically annotate the image, and / or to automatically control one or more components of the surgical system (e.g., to prevent a robotic surgical system from contacting or damaging the identified nerve).

[0007] The provided systems and methods may use a combination of imaging optics and techniques that are configured to allow for effective and efficient visual resolution of nerve substructures such as bands of Fontana in real time, without the need for exogeneous imaging agents, and without the need for optical microscopes. In some variations, the systems and methods provide spatial resolution that is equal to or better than 200 micrometers. The high spatial resolution offered by the systems and methods herein allows for visualization of nerve substructures, such as the bands of Fontana.

[0008] The techniques disclosed herein may use illumination in the SWIR wavelength range to visually resolve nerve substructures using reflectance imaging. For example, the extent to which SWIR light is absorbed, scattered, and reflected by different portions of the nerve substructure may allow for visual resolution of an intensity pattern in an image captured by reflectance imaging at the appropriate SWIR wavelengths. In some embodiments, illumination may be in the range of 1000- 2000 nm. In certain embodiments, illumination may be in the range of 1000-1750 nm or 1300-1750 nm. In other embodiments, illumination may be in a narrow bandwidth within that range, for example over a bandwidth of equal to or less than 200 nm, 100 nm or less, 50 nm, 25 nm, 10 nm, 5 nm, or 1 nm.

[0009] Furthermore, use of achromatic optics such as an achromatic lens in the optical path of the reflected light may improve spatial resolution of the nerve substructures by allowing a wider range of SWIR illumination wavelengths to be collected without blurring of the collected image being imparted by chromatic effects of optics. Achromatic lenses used in the systems and methods described2MF-364871974Attorney Docket No.: 16569-20011.40 herein may be achromatic in that they do not impart focal shift (or do so only negligibly) for different portions of the wavelength range being imaged.

[0010] Furthermore, use of polarization-dependent imaging modalities may allow for effective visual resolution of nerve substructures that are located at different depths within the tissue being imaged. For example, use of cross-polarized (or predominantly cross-polarized) imaging may allow for visualization of nerve substructures located deeper within the tissue being imaged (by prioritizing collection of light that is more heavily scattered by passage through a longer path length within the tissue), while use of parallel-polarized (or predominantly parallel-polarized) imaging may allow for visualization of nerve substructures located closer to the surface of the tissue being imaged (by prioritizing collection of light that is less heavily scattered, due to it only passing through a shallow surface layer of the tissue).

[0011] Images captured in the manner described herein may have patterns of high-intensity and low- intensity regions that are indicative of neve substructures such as bands of Fontana. These substructures may be visible in the captured images with no image postprocessing or minimal image postprocessing, and may be visible in a real-time stream (e.g., video stream) of captured images.

[0012] In some embodiments, the image may be provided to an image processing algorithm, and the results of the image processing algorithm may also be used to optimize the visibility of the pattern formed by the high-intensity and low-intensity regions.

[0013] In some embodiments, the systems and methods described herein may further enhance nerve and nerve -substructure visibility by dynamically modulating the polarization state of the illumination and / or detected light. For example, rotating short-wave infrared orthogonal polarization imaging (r- SWIR-OPI) may be used to leverage the strong birefringence of nerves. By rotating two polarizers in a synchronized manner while maintaining a fixed angular relationship (e.g., an orthogonal polarization configuration of an illumination polarizer and a detection polarizer), the reflected SWIR intensity from birefringent nerve tissue may be caused to vary periodically in time, producing a characteristic flashing or strobing appearance distinguishable from surrounding non-birefringent tissues. This time-dynamic polarization effect may provide a temporally varying contrast mechanism that complements the spatial reflectance-based contrasts described above and may enable robust realtime identification of nerves and nerve substructures during surgical procedures.

[0014] In some embodiments, the polarization-based nerve -modulation effect may be generated electronically and without mechanical rotation. For instance, electronically controllable polarization modulators (e.g., twisted-nematic liquid crystal devices, ferroelectric liquid crystal devices, and / or photoelastic modulators) may be used to vary the polarization state of SWIR illumination at user- selected and / or high-frequency modulation rates. When combined with a pixel-level polarizationresolving camera capable of capturing multiple polarization components in a single frame, this3MF-364871974Attorney Docket No.: 16569-20011.40 electronically modulated approach may provide a fully solid-state mechanism for generating and detecting the birefringence-based nerve signal. Such embodiments may support compact, integrated, or high-speed imaging configurations without moving parts. These electronic and mechanical polarization-modulation techniques may be used independently or together and may further enhance the ability of the disclosed systems and methods to detect, classify, localize, and visualize nerves and nerve substructures in real time. In some embodiments, the methods and systems disclosed herein can be used to identify peripheral and / or central nerves.

[0015] In some embodiments, a method for in vivo medical imaging of nerves is provided, comprising: illuminating, by an illumination system, a tissue region with a short-wave infrared (SWIR) illumination light; detecting, by an optical sensor system, a reflected portion of the illumination light; and generating, by one or more processors, an image based on the detected reflected portion of the illumination light, wherein the generated image comprises a plurality of higher-intensity regions and a plurality of lower-intensity regions that form a pattern indicative of a substructure of a nerve in the tissue region.

[0016] In some embodiments, a system for in vivo medical imaging of nerves is provided, the system comprising: an illumination system configured to illuminate a tissue region with a short-wave infrared (SWIR) illumination light; an optical sensor system configured to detect a reflected portion of the illumination light; and one or more processors configured to generate an image based on the detected reflected portion of the illumination light, wherein the generated image comprises a plurality of higher-intensity regions and a plurality of lower-intensity regions that form a pattern indicative of a substructure of a nerve in the tissue region.

[0017] An exemplary method for in vivo medical imaging of nerves comprises: illuminating, by an illumination system, a tissue region with a short-wave infrared (SWIR) illumination light; detecting, by an optical sensor system, a reflected portion of the illumination light; and generating, by one or more processors, an image based on the detected reflected portion of the illumination light, wherein the generated image includes a plurality of higher-intensity regions and a plurality of lower-intensity regions that form a pattern indicative of a substructure of a nerve in the tissue region.

[0018] In some embodiments, the SWIR illumination light is in a range of 1000 to 1750 nm. In some embodiments, a method, wherein the detected reflected portion of the illumination light is reflected from a depth in the tissue of greater than or equal to 2 mm. In some embodiments, the SWIR illumination light is pulsed. In some embodiments, the SWIR illumination light is constant. In some embodiments, the tissue is free of exogeneous imaging agents. In some embodiments, the optical sensor system includes an achromatic lens configured to focus the reflected portion of the illumination light onto the optical sensor. In some embodiments, the optical sensor system includes a bandpass filter configured to transmit a wavelength range of the reflected portion of the illumination light onto4MF-364871974Attorney Docket No.: 16569-20011.40 an optical sensor. In some embodiments, the optical sensor system includes a lens configured to focus the reflected portion of the illumination light transmitted by the bandpass filter onto the optical sensor. In some embodiments, the illumination system includes a polarizer configured to polarize the illumination light. In some embodiments, the optical sensor system includes a polarizer configured to polarize the reflected portion of the illumination light.

[0019] In some embodiments, the illumination system includes a first polarizer configured to polarize the illumination light with a first polarization; and the optical sensor system includes a second polarizer configured to polarize the reflected portion of the illumination light with a second polarization that is orthogonal to the first polarization, such that the reflected portion of the illumination light after the second polarizer is cross-polarized with respect to the illumination light after the first polarizer. In some embodiments, the illumination system includes a first polarizer configured to polarize the illumination light with a first polarization; and the optical sensor system includes a second polarizer configured to polarize the reflected portion of the illumination light with a second polarization that is parallel to the first polarization, such that the reflected portion of the illumination light after the second polarizer is parallel -polarized with respect to the illumination light after the first polarizer.

[0020] In some embodiments, a power of the SWIR illumination light is greater than or equal to 5 mW at a wavelength range of less than or equal to 5 nm. In some embodiments, the method includes automatically detecting the nerve in the image of the tissue region by detecting the patterns of higher- intensity and lower intensity regions. In some embodiments, the method includes generating an output indicative of the detection of the nerve. In some embodiments, the method includes annotating the image based on the detection of the nerve. In some embodiments, automatically detecting the nerve in the image of the tissue region includes: providing the image of the tissue region to a machine -learning algorithm trained to detect a presence of the pattern indicative of a location of the nerve; and receiving, from the machine-learning algorithm, output data indicative of the detection of the nerve in the image of the tissue region. In some embodiments, the SWIR illumination light has a bandwidth of 200 nm or less. In some embodiments, the substructure of the nerve includes bands of Fontana. In some embodiments, a spatial resolution of the image is equal to or finer than 200 micrometers.

[0021] An exemplary system for in vivo medical imaging of nerves includes: an illumination system configured to illuminate a tissue region with a short-wave infrared (SWIR) illumination light; an optical sensor system configured to detect a reflected portion of the illumination light; and one or more processors configured to generate an image based on the detected reflected portion of the illumination light, wherein the generated image includes a plurality of higher-intensity regions and a plurality of lower-intensity regions that form a pattern indicative of a substructure of a nerve in the tissue region.5MF-364871974Attorney Docket No.: 16569-20011.40

[0022] An exemplary method for in vivo medical imaging of nerves or nerve substructures includes: directing, by an illumination system, short-wave infrared (SWIR) illumination through a first polarizing element toward a tissue region including nerves or nerve substructures, while rotating the first polarizing element through a plurality of angular positions; polarizing, by a second polarizing element, a reflected portion of the SWIR illumination from the tissue region, while rotating the second polarizing element in synchrony with the first polarizing element such that the first and second polarizing elements maintain a fixed angular offset during rotation; receiving, by an optical sensor system, the polarized reflected portion of the SWIR illumination after passage through the second polarizing element; and generating, by one or more processors, a time series of images of the tissue region during rotation, the plurality of images exhibiting a periodic modulation in reflected intensity from birefringent nerve tissue, wherein the periodic modulation corresponds to a location of the nerve or the nerve substructure.

[0023] In some embodiments, the fixed angular offset between the first and second polarizing elements is approximately 90 degrees. In some embodiments, rotating the first and second polarizing elements includes rotating each element using a gear-driven synchronization mechanism. In some embodiments, rotating the first and second polarizing elements includes rotating each element using a belt-driven synchronization mechanism. In some embodiments, the first and second polarizing elements are fixed together in a pre-assembled orthogonal polarizer unit that rotates as a single structure. In some embodiments, the pre-assembled orthogonal polarizer unit includes a ring-shaped illumination polarizer surrounding a disk-shaped analyzer polarizer positioned coaxially with a camera lens. In some embodiments, the method includes preventing illumination from bypassing the tissue region by disposing a light-blocking barrier between the camera lens and an illumination ring associated with the ring-shaped illumination polarizer.

[0024] In some embodiments, rotating the first polarizing element and the second polarizing element includes rotating the elements at a speed in a range of about 3 to about 6000 revolutions per minute (RPM). In some embodiments, the optical sensor system acquires images at a frame rate in a range of about 10 to about 200 frames per second. In some embodiments, the method includes synchronizing image acquisition with the rotational position of the first polarizing element and the second polarizing element using an encoder or a phase-locking mechanism. In some embodiments, the method includes automatically detecting, by the one or more processors, the periodic modulation in the time series of images. In some embodiments the method includes generating, by the one or more processors, at least one of an alert and an annotation indicating at least one of a presence and a location of the nerve or the nerve substructure based on the detected periodic modulation.

[0025] An exemplary system for in vivo medical imaging of nerves or nerve substructures includes: an illumination system configured to direct short-wave infrared (SWIR) illumination toward a tissue6MF-364871974Attorney Docket No.: 16569-20011.40 region through a first polarizing element, the first polarizing element configured to rotate through a plurality of angular positions; an optical sensor system including: a second polarizing element disposed in a detection path of reflected SWIR illumination from the tissue region, the second polarizing element configured to rotate in synchrony with the first polarizing element such that the first and second polarizing elements maintain a fixed angular offset during rotation; and a camera positioned to receive the SWIR illumination after passage through the second polarizing element; and one or more processors configured to generate a time series of images of the tissue region during rotation of the first polarizing element and the second polarizing element, the plurality of images exhibiting a periodic modulation in reflected intensity from birefringent nerve tissue, wherein the periodic modulation corresponds to a location of the nerve or the nerve substructure.

[0026] An exemplary method for in vivo medical imaging of nerves or nerve substructures includes: directing, by an illumination system, short-wave infrared (SWIR) illumination toward a tissue region; electronically modulating, by an electronically controllable polarization modulator disposed in an illumination path, a polarization orientation of the SWIR illumination incident on the tissue region, the electronically controllable polarization modulator being driven to vary the polarization orientation overtime; receiving, by an optical sensor system, a reflected portion of the SWIR illumination from the tissue region; detecting, by a polarization-resolving camera of the optical sensor system, polarization-dependent intensity components of the reflected SWIR illumination at a plurality of polarization orientations; and generating, by one or more processors, a time series of images based on the detected polarization-dependent intensity components, the time series of images including a periodic modulation in reflected intensity from birefringent nerve tissue corresponding to the electronically modulated polarization orientation, wherein the periodic modulation corresponds to a location of the nerve or the nerve substructure.

[0027] In some embodiments, the electronically controllable polarization modulator includes a twisted-nematic liquid crystal (TN-LC) device configured to rotate the polarization orientation continuously. In some embodiments, the electronically controllable polarization modulator includes a ferroelectric liquid crystal (FLC) device configured to switch the polarization orientation between two polarization states. In some embodiments, the two polarization states correspond to different reflected-intensity responses from birefringent nerve tissue such that alternating between the states produces a flickering or strobing appearance of the nerve. In some embodiments, the electronically controllable polarization modulator includes a photoelastic modulator (PEM) configured to oscillate the polarization orientation of the SWIR illumination at a frequency in a range of about 10 kHz to about 100 kHz. In some embodiments, electronically modulating the polarization orientation includes using two or more cascaded liquid crystal modulators to generate a plurality of discrete polarization orientations. In some embodiments, the polarization-resolving camera includes a micro-polarizer array including pixels or pixel groups having a plurality of polarization orientations.7MF-364871974Attorney Docket No.: 16569-20011.40

[0028] In some embodiments, the method includes synchronizing a polarization modulation waveform of the electronically controllable polarization modulator with an exposure timing of the polarization-resolving camera using phase-locking or encoder-based synchronization. In some embodiments, the method includes applying, by the one or more processors, lock-in detection, frequency-domain filtering, or Fast Fourier Transform (FFT) analysis to isolate periodic intensity modulation associated with birefringent nerve tissue. In some embodiments, the method includes automatically detecting, by the one or more processors, the periodic modulation in the time series of images. In some embodiments, the method includes generating, by the one or more processors, at least one of an alert and an annotation indicating at least one of a presence or a location of the nerve or the nerve substructure based on the detected periodic modulation.

[0029] An exemplary system for in vivo medical imaging of nerves or nerve substructures includes: an illumination system configured to direct short-wave infrared (SWIR) illumination toward a tissue region; an electronically controllable polarization modulator disposed in an illumination path and configured to vary a polarization orientation of the SWIR illumination incident on the tissue region over time; an optical sensor system configured to receive a reflected portion of the SWIR illumination from the tissue region, the optical sensor system including a polarization-resolving camera configured to detect polarization-dependent intensity components of the reflected SWIR illumination at a plurality of polarization orientations; and one or more processors configured to generate a time series of images based on the detected polarization-dependent intensity components, the time series of images including a periodic modulation in reflected intensity from birefringent nerve tissue, wherein the periodic modulation corresponds to a location of the nerve or the nerve substructure.

[0030] In some embodiments, any of the above embodiments may be combined in whole or in part with one another and / or with any other embodiments, claims, and / or other disclosure(s) herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0031] The present application can be understood by reference to the following description taken in conjunction with the accompanying figures.

[0032] FIG. 1 shows a schematic illustration of an exemplary imaging system with different light polarization configurations, according to some embodiments.

[0033] FIG. 2A shows an image captured using a first polarization scheme (cross-polarization), wherein the image is of a region of biological tissue comprising a nerve with the bands of Fontana.8MF-364871974Attorney Docket No.: 16569-20011.40

[0034] FIG. 2B shows an image captured using a second polarization scheme (parallel-polarization), wherein the image is of the same region of biological tissue comprising the nerve with the bands of Fontana as shown in FIG. 2A.

[0035] FIG. 3A shows an exemplary dual-rotating-polarizer configuration, according to some embodiments.

[0036] FIG. 3B shows an exemplary gear-driven mechanism for synchronizing rotation of two polarizers in a dual -rotating-polarizer configuration, according to some embodiments.

[0037] FIG. 3C shows an exemplary belt-drive mechanism for synchronizing rotation of two polarizers in a dual -rotating-polarizer configuration, according to some embodiments.

[0038] FIG. 4A shows an exemplary pre-assembled orthogonal polarizer unit system, according to some embodiments

[0039] FIG. 4B shows an exemplary belt-drive mechanism configured to rotate a pre-assembled orthogonal polarizer unit, according to some embodiments.

[0040] FIG. 4C shows an exemplary gear-drive mechanism configured to rotate a pre-assembled orthogonal polarizer unit as a single assembly, according to some embodiments.

[0041] FIG. 4D shows another exemplary pre-assembled orthogonal polarizer unit system, according to some embodiments.

[0042] FIG. 5 shows an exemplary electronic polarization modulation system, according to some embodiments.

[0043] FIG. 6 shows a computer system, according to some embodiments.DETAILED DESCRIPTION

[0044] The following description sets forth exemplary systems, parameters, and the like. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure but is instead provided as a description of exemplary embodiments.

[0045] Although the following description uses terms “first,” “second,” etc. to describe various elements, these elements should not be limited by the terms. These terms are only used to distinguish one element from another. For example, a first graphical representation could be termed a second graphical representation, and, similarly, a second graphical representation could be termed a first graphical representation, without departing from the scope of the various described embodiments. The first graphical representation and the second graphical representation are both graphical representations, but they are not the same graphical representation.9MF-364871974Attorney Docket No.: 16569-20011.40

[0046] The terminology used in the description of the various described embodiments herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used in the description of the various described embodiments and the appended claims, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will also be understood that the term “and / or” as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items. It will be further understood that the terms “includes,” “including,” “comprises,” and / or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0047] The term “if’ is, optionally, construed to mean “when” or “upon” or “in response to determining” or “in response to detecting,” depending on the context. Similarly, the phrase “if it is determined” or “if [a stated condition or event] is detected” is, optionally, construed to mean “upon determining” or “in response to determining” or “upon detecting [the stated condition or event]” or “in response to detecting [the stated condition or event],” depending on the context.

[0048] In some embodiments, the systems and methods described herein can leverage the distinct absorption and scattering characteristics of biological tissues in the short-wave infrared (SWIR) range. SWIR light can exhibit different interaction profiles with water, lipids, proteins, and / or other biochemical components than visible and near-infrared (NIR) light. Thus, utilizing SWIR light in imaging can provide enhanced contrast between tissues and deeper penetration into biological structures. For example, water-rich structures may strongly absorb SWIR illumination while lipid-rich structures may reflect more, thereby providing multiple intrinsic contrast mechanisms that can be used to distinguish nerves from surrounding tissues such as fat and muscle. Such enhanced contrast can provide valuable visual guidance to surgeons, pathologists, and other clinicians.

[0049] Nerves can be highly birefringent, due to their highly anisotropic microstructure. As used herein, birefringence can refer to an optical property of a material in which the material exhibits different refractive indices for light polarized along different directions. Two contributors to this birefringence are the myelin sheath (which comprises concentric, lipid-rich bilayers disposed around axons) and the collagen-rich epineurium (a fibrous outer covering of the nerve). The highly ordered, multilayer myelin structure may produce strong form birefringence. The aligned collagen fibers of the epineurium may further increase the overall optical anisotropy of the nerve. Accordingly, nerve tissue has among the highest birefringence of all soft tissues. In larger animals and in humans, thicker myelin and more robust epineural collagen may cause nerves to stand out even more distinctly under polarized SWIR illumination.10MF-364871974Attorney Docket No.: 16569-20011.40

[0050] The internal components of a nerve may also differ in chemical composition. For example, myelin may be relatively rich in lipids and thus lower in water content, whereas axons may be relatively rich in water and thus lower in lipid content, and both may contain proteins and other biomolecules. These compositional differences may result in distinct short-wave infrared (SWIR) response spatial profiles; for instance, structures having higher water content may exhibit stronger SWIR absorption, whereas lipid-rich structures may reflect more of the SWIR illumination. In this manner, both compositional and structural differences between the nerve and other tissues may be leveraged to generate high-contrast SWIR images that reveal nerve macro-structure and / or microstructure.

[0051] In some embodiments, SWIR imaging of nerves using the systems described herein may reveal multiple, distinct types of contrast that collectively facilitate robust nerve identification. At a macro-structural level (e.g., at the organ / tissue level), nerves may display characteristic brightness differences compared to surrounding tissues when illuminated with SWIR wavelengths. For example, when a nerve is surrounded by adipose tissue, the nerve may appear darker than the surrounding fat because, although myelin within the nerve is lipid-rich, the overall nerve structure includes water-rich axons that reduce net SWIR reflectance relative to pure fat. Conversely, when a nerve is adjacent to muscle tissue, the nerve may appear brighter because muscle typically contains a high water content and therefore strongly absorbs SWIR illumination, while the nerve (with its lipid-bearing myelin) reflects more light relative to muscle. This gross contrast in SWIR may allow the nerve to visually stand out from both fatty and muscular backgrounds in real time.

[0052] At a finer micro-structural level (e.g., at a nerve fiber bundle and vessel level), SWIR imaging performed at higher magnification and / or resolution may reveal striation patterns that extend along the longitudinal axis of the nerve. In some embodiments, a first type of striation may correspond to the nerve’s internal axon-bundle architecture. Axons are bundled and aligned with the length of the nerve, and the alternating arrangement of water-rich axons and lipid-rich myelin sheaths may create repeating light-and-dark stripe patterns under SWIR illumination. These internal fascicular striations may become apparent at higher magnification or spatial resolution and may exhibit substantially greater contrast than in visible-light or conventional near-infrared imaging modalities. In some embodiments, a second type of striation may correspond to small blood vessels located on the nerve surface (e.g., the vasa nervorum). These vessels, due to their high water content and associated strong SWIR absorption, may appear dark under SWIR illumination and form a separate set of thin lines that traverse or partially encircle the nerve. Accordingly, the nerve may exhibit two superimposed sets of striations, internal fascicular bands and external vascular traces, which are more readily discernible under SWIR imaging than under visible-light imaging.11MF-364871974Attorney Docket No.: 16569-20011.40

[0053] In some embodiments, SWIR imaging may also enhance visualization of microscopic repeating patterns known as bands of Fontana, which arise from the highly organized myelin microstructure within the nerve fascicles. Under conventional visible-light microscopy, these bands may be observable primarily in excised or thinly sectioned nerve specimens and typically only at high magnification, such as in rodent or other small-animal nerves. Prior techniques have generally not been able to visualize bands of Fontana reliably in larger animals or humans in situ. By contrast, due to the strong SWIR sensitivity to myelin and the reduced scattering at SWIR wavelengths, the systems described herein may allow bands of Fontana to be visualized with substantially enhanced contrast, including in intact tissue and at macroscopic scales suitable for surgical guidance. In this manner, SWIR imaging as disclosed herein may reveal fine fascicular patterns in real time, without the need for exogenous contrast agents or high-magnification optical microscopes.

[0054] In addition to absorption-based and structural contrast, nerves may provide a birefringence- based signal under polarized SWIR illumination. Because nerves include highly ordered, linearly arranged microstructures (e.g., aligned myelin sheaths, axonal fibers, and / or collagen within the epineurium) the refractive index experienced by incident light may differ depending on the polarization orientation of that light. Accordingly, nerves are strongly birefringent, and more birefringent than surrounding tissues like muscle or blood vessels, which are not birefringent. As a result, the intensity of SWIR light reflected from a nerve may vary as the incident polarization angle changes. In some embodiments, by varying the polarization of the illumination and / or the polarization of the detected reflected light, the nerve may exhibit a time-varying or angle -dependent modulation in its reflected intensity, whereas surrounding non-birefringent tissues may remain substantially constant in intensity. This polarization-dependent modulation may manifest as a flashing, strobed, or periodically brightening-and-darkening appearance of the nerve in real time, thereby providing a fourth, temporally varying type of intrinsic contrast that can facilitate rapid identification and localization of nerves (e.g., peripheral and / or central nerves) and their substructures.

[0055] In some aspects, provided herein are systems and methods for imaging micro-structures of the nerves, such as bands of Fontana, as the characteristic feature for differentiating nerves from other surrounding tissues. Bands of Fontana are light and dark stripes or spirals that appear on the surface of peripheral nerves. Rather than focusing on differentiating the contrast between the nerves and the surrounding tissues as a way to image the nerve, in some embodiments, the systems and methods herein focus on visualizing and imaging the micro-structures, such as bands of Fontana, as a feature of the nerves themselves, independent of the tissues surrounding the nerves.

[0056] In some embodiments, the systems herein use light sources with narrow bandwidths, which may confer an advantage with respect to the power level at individual wavelengths. The more power there is from the illumination, the more reflected photons can reach the detector, resulting in higher12MF-364871974Attorney Docket No.: 16569-20011.40 signal -to-noise levels for a higher quality image. For instance, SWIR cameras are generally more noisy than regular visible light cameras, and thus may require more photons for them to form a high- quality image. With either parallel polarization or cross-polarization, which are helpful for imaging nerve substructures such as bands of Fontana, the power level from the illumination may be further decreased by 10 or 100 times. Thus, use of narrow-band (e.g., “single wavelength”) illumination with higher optical powers at a narrower wavelength band may be advantageous.

[0057] In some variations, the system may employ a halogen light bulb as a light source, and a bandpass filter with a wider allowed wavelength range may be used to increase power level. This can result in a less drastic tissue contrast, because the tissue contrast is associated with the absorption peaks of different biological components, such as water, lipid, collagen, etc. This van also result in decreased spatial resolution because achromatic aberrations may also occur. However, achromatic aberrations can be mitigated or avoided, in some embodiments, by using achromatic imaging lenses and optics with no focus shift between different wavelengths.

[0058] In some embodiments, advantages of using light sources with narrow bandwidth may be understood with reference to power level at certain narrow wavelength ranges. For example, if a Halogen light bulb with 10 W optical power is used (this is considered a very high power), and a 1470 nm bandpass filter is used, the power that can be isolated to be in a 1470 nm + / - 10 nm window may be less than 5 mW. On the other hand, if illumination with a narrower bandwidth, such as single-color LEDs and / or lasers, is used, powers in the range of 100 mW to 20 W at specifically 1470 nm wavelength can be achieved.

[0059] In some embodiments, an exemplary system 104 configured for imaging of nerves or nerve substructures is provided. The system includes one or more light sources (e.g., including one or more laser light sources and / or one or more LED light sources) configured to provide SWIR illumination. The light source may be configured to provide pulsed or constant SWIR illumination.

[0060] In some embodiments, the one or more light sources may provide narrow-bandwidth (e.g., “single wavelength”) illumination using LEDs and / or lasers. The power output of the light source may be higher than power output levels that have been used in known nerve imaging systems. The power of the light source may be greater than or equal to 5 mW, 50 mW, 100 mW, 1 W, 10 W, or 20 W at a wavelength range of less than or equal to 10 nm, 5 nm, or 1 nm.

[0061] In some embodiments, a narrow-bandwidth (e.g., “single wavelength”) light source may be understood to be different from light sources that produce a continuous spectrum of light, such as tungsten halogen lamp, incandescent lamp, infrared heat lamp, sunlight, etc.

[0062] SWIR illumination may be in the wavelength range of about 1000 to 2000 nm, for example approximately 900 nm, 1000 nm, 1100 nm, 1200 nm, 1300 nm, 1400 nm, 1500 nm, 1600 nm, 170013MF-364871974Attorney Docket No.: 16569-20011.40 nm, 1800 nm, 1900 nm, 2000 nm, or 2100 nm. In some embodiments, the wavelength may be greater than or equal to 900 nm, 1000 nm, 1100 nm, 1200 nm, 1300 nm, 1400 nm, 1500 nm, 1600 nm, 1700 nm, 1800 nm, 1900 nm, 2000 nm, or 2100 nm. In some embodiments, the wavelength may be less than or equal to 900 nm, 1000 nm, 1100 nm, 1200 nm, 1300 nm, 1400 nm, 1500 nm, 1600 nm, 1700 nm, 1800 nm, 1900 nm, 2000 nm, or 2100 nm. The light source may be configured to emit SWIR illumination at any of the wavelengths described herein. In some embodiments, the light source is configured to emit a bandwidth of SWIR illumination, wherein any of the wavelengths described herein are within the bandwidth. In some embodiments, the bandwidth may be about 50 nm to 200 nm or less in width, for example approximately 25 nm, 50 nm, 75 nm, 100 nm, 125 nm, 150 nm, 175 nm, 200 nm, or 225 nm in width. In some embodiments, illumination may be in the wavelength range of about 1300 to 1750 nm. It has been found in experiments that the wavelength range of 1300 to 1750 nm may be particularly effective at capturing reflectance images as described herein that effectively resolve nerve substructures such as the bands of Fontana.

[0063] The SWIR illumination may be delivered to and incident on the nerve or nerve substructure to be imaged. Reflected light from the nerve or nerve substructure to be imaged may then be collected by an optical sensor system (e.g., including optional focusing optics and one or more optical sensors). The reflected portion of the SWIR illumination may be in the SWIR wavelength range recited above for the SWIR illumination, or in any sub-portion thereof.

[0064] In some embodiments, the optical sensor system comprises at least one camera sensor and at least one lens, wherein the lens is used to focus the reflected portion of the SWIR illumination onto the camera sensor. The camera may include any one or more of the following types of cameras: a silicon camera, an indium-gallium-arsenide camera, a black silicon camera, a germanium camera, a germanium-tin on silicon camera, a quantum dot short-wave infrared camera, or a mercury-cadmium- telluride camera.

[0065] The lens may have a focal length in a range of about 10 mm to 100 mm, for example, approximately 20 mm, 30 mm, 40 mm, 50 mm, 60 mm, 70 mm, 80 mm, or 90 mm.

[0066] The lens may be an achromatic lens, which may allow for a broad range of wavelengths emitted by the light source and reflected by the tissue to be clearly resolved into an image that effectively visualizes fine nerve substructures such as bands of Fontana. In some embodiments, achromatic lenses used here may provide for no focal shift across a wide range of wavelengths, for example across the range of 400 nm to 1700 nm, 400 nm to 1750 nm, 1300 nm to 1700 nm, or 1300 to 1750 nm. Lenses may include, for example, Computar Hyper APO series, which includes M1618- APVSW, M2518-APVSW, M3518-APVSW, M5018-APVSW.

[0067] In some embodiments, at least one bandpass filter is used as part of (or in addition to) the optical sensor system. A bandpass filter may select for a narrower range of wavelengths and may14MF-364871974Attorney Docket No.: 16569-20011.40 therefore mitigate or obviate the need to use an achromatic lens. The bandpass fdter may be configured to transmit a specific wavelength of light or a smaller wavelength range of light to the camera sensor, wherein the specific wavelength of light or the smaller wavelength range of light may be filtered from the broad range of wavelengths emitted from the light source. A specific wavelength of light or a smaller wavelength range of light may be more easily focused onto the focal point of the camera sensor with an achromatic lens with reduced achromaticity or with a non-achromatic lens. The bandpass filter may be centered at 1450 nm, 1470 nm, 1550 nm, 1650 nm, 1710 nm, or 1750 nm. The bandpass filter may have a width of 1 nm, 5 nm, 10 nm, 25 nm, 50 nm, 100 nm, or 200 nm.

[0068] In some embodiments, the image generated by the optical sensor system may comprise a plurality of high-intensity regions and a plurality of low-intensity regions. The plurality of the high- intensity and the low-intensity regions may form a pattern indicative of a location and / or a presence of the nerve or nerve substructure within the biological tissue. The effective visualization of the pattern of varying-intensity regions in the image may be provided by the specific combinations of polarization schema, illumination wavelengths, optical powers, illumination pulse schema, achromatic lens configurations, and / or one or more additional parameters as provided herein. In some embodiments, the pattern formed by the plurality of the high-intensity and the low-intensity regions represents bands of Fontana in a peripheral nerve. The pattern in the image may be perceptible in realtime by a human operator such as a surgeon. In some embodiments, the pattern may be detected by one or more image analysis algorithms, and the output of said algorithms may be used in real time to automatically generate one or more outputs or alerts, annotate the image, control components of the illumination and / or image capture devices, and / or control one or more components of a related surgical system or medical device.

[0069] In some embodiments, the systems described herein may polarize light with at least one polarizer in the optical path of the system. For example, system 100 in FIG. 1 shows an embodiment in which the system uses SWIR imaging wherein the SWIR illumination light is polarized; system 102 in FIG. 1 shows an embodiment in which the system uses SWIR imaging wherein the reflected portion of the SWIR illumination light is polarized; and system 106 in FIG. 1 shows an embodiment in which the system uses system SWIR imaging wherein the light is cross-polarized or parallel- polarized using multiple polarizers. Cross-polarized imaging may be used when the system is arranged such that the SWIR illumination source has a first polarizer configured to impart a first polarization and the optical sensor system has a second polarizer configured to impart a second polarization that is orthogonal to the first polarization, such that the light after the second polarizer is cross-polarized light with respect to the illumination light after the first polarizer. Cross-polarization, as used herein, may refer to polarizations that are orthogonal to each other within a tolerance of 5% or less from orthogonal. Parallel-polarized imaging may be used when the SWIR illumination source has a first polarizer configured to impart a first polarization and the optical sensor system has a second15MF-364871974Attorney Docket No.: 16569-20011.40 polarizer configured to impart a second light polarization that is parallel to the first light polarization, such that the light after the second polarizer is parallel-polarized light with respect to the illumination light after the first polarizer. Parallel-polarization, as used herein, may refer to polarizations that are parallel to each other within a tolerance of 5% or less from parallel.

[0070] In some embodiments, the at least one polarizer is configured to adjust polarization of the illumination light and / or the captured reflected portion of the imaging light. That is, polarization may be imparted on the illumination light before it reaches the tissue, and / or on the reflected light after it is reflected from the tissue and before it reaches the imaging sensor. Using different polarizations for illumination and / or capture of reflected light may allow for cross-polarization and / or parallel polarization imaging modalities to be applied. The configuration of the one or more polarizers may be used to control the relative intensity of the different regions in the image of the nerve or nerve substructure. For example, one polarization of light generated by the polarizer may produce the SWIR image of the nerve or nerve substructure shown in FIG. 2A, and another polarization of light generated by the polarizer may produce the SWIR image of the nerve or nerve substructure shown in FIG. 2B. In some embodiments, a SWIR image with a less contrast between nerve substructures (e.g., FIG. 2A) is produced by system 106, wherein the light in the optical path is cross-polarized. In some embodiments, a SWIR image with more contrast between nerve substructures (e.g., FIG. 2B) is produced by system 106, wherein the light in the optical path is parallel-polarized. Parallel polarized light is known to be more responsive to birefringent materials, such that if a material is structured in a highly organized or directional manner, it will have an enhanced contrast with polarized light. Cross- polarization removes surface glare and is not sensitive to birefringence. However, cross-polarization imaging produces the most accurate absorption-based image. In the case of peripheral nerves, a crosspolarized image may highlight the water and lipid contrast content the best because water and lipid components that have very different light absorption characteristics in the SWIR range.

[0071] In some embodiments, nerve substructures located deeper within the tissue are more effectively visualized using cross-polarized image capture. In some embodiments, nerve substructures located closer to the surface of the tissue are more effectively visualized using parallel-polarized image capture. Bands of Fontana may not be particularly deep in the tissue (e.g., 0-5 mm in depth), as an entire nerve structure may be less than 2 mm in thickness. Cross-polarization imaging in the SWIR range may help penetrate into tissue structure by greater than or equal to 0.5 mm, 1 mm, 2 mm, 3 mm, 4 mm, or 5 mm.

[0072] In some embodiments, the nerve or nerve substructure patterns are more effectively differentiated from one another (e.g., with more contrast within the generated image) using a certain polarization configuration. (Other factors such as lens chromaticity, illumination power, illumination pulse patter, and / or illumination wavelength may also contribute to the effective differentiation of16MF-364871974Attorney Docket No.: 16569-20011.40 nerves and nerve substructures in the captured image.) In some embodiments, effective visualization of the nerve substructure patterns, such as the bands of Fontana, is able to be achieved in multiple polarization configurations, including in some embodiments in all polarization configurations.

[0073] In some embodiments, one or more of the polarizers may be adjustable, for example by being automatically or manually rotated to change the polarization of the illumination and / or collection light. In some embodiments, one or more processors and controllers may automatically control polarization of the light by adjusting one or more of the polarizers, for example in response to detection (or lack of detection) of patterns indicative of bands of Fontana in one or more images (e.g., images in a captured stream).

[0074] The one or more light sources and / or the optical sensor may be electronically coupled to and controlled by one or more controllers of the system. The one or more controllers may be configured to synchronize functionality between the optical sensor system and the one or more light sources.

[0075] The controller may control the optical sensor system such that SWIR image frames are captured. These frames may be used to generate separate images or video in real-time and / or in postprocessing. These frames may also be used to adjust the polarization of the light in the optical path for better visualization of the nerve or nerve substructure. The SWIR image frames may be displayed and / or stored separately.

[0076] In some embodiments, an image processing algorithm may be configured to identify the nerve or nerve substructure in the field-of-view of the camera in the optical sensor system. The image processing algorithm may identify the pattern formed by the high-intensity regions and the low- intensity regions of the nerve or nerve substructure. The image processing algorithm may use the pattern to determine the presence and / or location of the peripheral nerve or nerve substructure. For instance, the image processing algorithm may identify one or more nerve substructures such as the bands of Fontana. In some embodiments, machine learning may be configured to identify the nerve or nerve substructure in a SWIR image based on the pattern formed by the high-intensity and the low- intensity regions. The machine learning may be trained on a plurality of SWIR images exhibiting the pattern.

[0077] The results of the image processing algorithm and / or the results of the machine learning may be used to adjust the field-of-view of the camera (e.g., by automatically controlling the physical position and / or optical configuration of the camera), the polarization of the light in the optical path for better visualization of the nerve or nerve substructure (e.g., by automatically, physically, and / or optoelectronically controlling one or more polarizers), the illumination wavelength, illumination pulse characteristics, the optical power, the image processing settings, and / or any one or more additional device settings.17MF-364871974Attorney Docket No.: 16569-20011.40Rotating Shortwave Infrared Orthogonal Polarization Imaging (r-SWIR-OPI)

[0078] While the foregoing embodiments describe the use of fixed or selectively adjustable polarization states for enhancing visualization of nerve substructures, in some embodiments the systems and methods described herein may further employ dynamic polarization modulation to exploit the strong birefringence of nerves. Because nerves exhibit polarization-dependent reflectance that varies predictably with the orientation of incident and detected polarization, actively modulating the polarization state (e.g., mechanically and / or electronically) can cause the reflected nerve signal to oscillate in intensity over time. This time-varying signal can provide an additional, temporally distinct contrast mechanism that may not be available through static polarization alone. Accordingly, in some embodiments, the systems described herein can include rotating polarizer assemblies, electronically controlled polarization modulators, polarization-resolving sensors, and / or synchronized detection schemes configured to generate, detect, and / or analyze such dynamic polarization-dependent nerve signals. These dynamic polarization imaging modalities can enable real-time visualization of nerves through a periodic flashing, strobing, and / or intensity-modulated appearance and can further support algorithmic detection techniques such as frequency-domain filtering and lock-in amplification.

[0079] In some embodiments, the systems and methods described herein may implement a rotating short-wave infrared orthogonal polarization imaging (r-SWIR-OPI) modality to exploit the intrinsic birefringence of nerves. In such embodiments, the illumination system may include a first linear polarizer disposed in the illumination path, and the optical sensor system may include a second linear polarizer (analyzer) disposed in front of the camera sensor. The first and second polarizers may be oriented to impart orthogonal polarization states to the illumination light and to the detected reflected light, respectively. The first and second polarizers may be rotated together in synchrony at substantially the same angular speed while maintaining this orthogonal relationship, thereby preserving an orthogonally polarized configuration during rotation.

[0080] Because strongly birefringent structures such as nerves modify the polarization state of incident light in a direction-dependent manner, the reflected intensity from the nerve varies systematically as a function of the instantaneous polarization angle during rotation. In contrast, surrounding non-birefringent tissues (e.g., muscle or blood vessels) do not impart a polarizationdependent phase delay and therefore remain substantially constant in intensity over the rotation cycle. As a result, rotation of the polarizers produces a periodic, time-varying intensity modulation from the nerve. In some embodiments, this may manifest as a perceptible flashing or strobed appearance of the nerve in real time, providing a dynamic contrast mechanism that is not available using static polarization alone.

[0081] As the polarizers rotate, birefringent structures such as nerves may exhibit strong, periodic modulation in reflected intensity, whereas surrounding non-birefringent tissues may remain18MF-364871974Attorney Docket No.: 16569-20011.40 substantially constant in intensity and may remain dark under orthogonal polarization. For a birefringent nerve, the reflected intensity depends on the relative angle between the incident polarization and the nerve’s principal optic axes (e.g., its fast and slow axes). When the incident polarization aligns with one of these axes (e.g., approximately 0° or 180° for the fast axis, or at approximately 90° or 270° for the slow axis) the light emerging from the nerve remains polarized along that same principal axis. Because the analyzer is oriented orthogonally to the illumination polarization, these orientations yield extinction conditions, producing intensity minima. Thus, during a full 360° rotation, the polarizer aligns with a principal axis four separate times, producing four extinction minima spaced 90° apart. In some embodiments, the polarizers may rotate continuously through a full 360° cycle, while in other embodiments the polarizers may move back and forth through an angular sweep of less than 360°, such as by oscillating between two angular limits to periodically vary the polarization orientation without completing a full rotation. For example, the polarizers may move back and forth through an angular sweep of about 90°, about 180°, or about 270°.

[0082] When the polarizer is oriented approximately 45° relative to the nerve’s principal axes (e.g., at about 45°, 135°, 225°, or 315°), the incident light has equal components along the fast and slow axes. The nerve introduces a differential phase delay between these components, causing them to recombine into a polarization state that is rotated away from the incident orientation. The 45° orientation maximizes this phase-retardation effect. In the case of approximately half-wave retardation (5 « 7i), the outgoing polarization may be rotated by nearly 90° relative to the incident polarization, aligning it with the analyzer and producing a bright transmitted signal. More generally, when 5 differs from n, the outgoing polarization may be elliptically polarized but still include a substantial component aligned with the analyzer; thus, these 45° orientations can yield the intensity maxima.

[0083] There can be two distinct 45° orientations per principal axis in each full turn of the polarizer, one on either side of each extinction alignment. For example, if the nerve’s fast axis lies at 0°, then polarizer angles of +45° and -45° (i.e., 45° and 315°) yield strong transmission. Likewise, for the slow axis at 90°, orientations of 90°±45° (i.e., 45° and 135° relative to that axis, corresponding to overall angles 45° and 135°) produce maxima. When mapped over a full 360° rotation, these relationships yield four bright peaks located at approximately 45°, 135°, 225°, and 315°.

[0084] This phenomenon may also be interpreted via the “halfway-between” principle of polarized- light microscopy, in which a birefringent sample appears darkest when one of its optic axes aligns with the polarizer or analyzer and brightest when the sample is oriented at approximately 45° relative to them. As the polarizer rotates, each passage through an extinction alignment is followed 45° later by a brightness maximum, yielding four maxima per 360° rotation. Mapping these over a full 0°-360°19MF-364871974Attorney Docket No.: 16569-20011.40 range yields bright peaks at approximately 45°, 135°, 225°, and 315°, and extinction minima at approximately 0°, 90°, 180°, and 270°.

[0085] The periodic modulation produced by the r-SWIR-OPI technique can also facilitate effective differentiation between true birefringence-based nerve signals and artifacts introduced by system components or the surgical environment. Any artifacts caused by rotation of the polarizers (e.g., slight intensity fluctuations arising from polarizer imperfections, variations in illumination, jitter or wobble in the mechanical assembly, and / or transient glare from blood, fluid films, or debris on the tissue surface) tend to occur at the fundamental rotation frequency R. These artifacts therefore manifest as a relatively slow flicker or periodic change. By contrast, the birefringent nerve signal varies at approximately four times the rotation frequency (4R), owing to the four brightness maxima per full rotation described above. This frequency separation can enable the nerve’s modulation pattern to be distinguished from rotation-derived artifacts. In practice, for example, motion blur or movement of surface fluids typically produces a slow oscillation matching the rotation speed R, whereas the nerve appears as a distinctly faster strobe, allowing robust discrimination between true nerve signal and noise.

[0086] In some embodiments, the known frequency relationship may be exploited using frequencydomain filtering and / or lock-in amplification to enhance nerve visibility. Because the rotation speed of the polarizers is user-controlled and therefore known, the expected nerve flicker frequency (4R) is also known and can be used as a target frequency for isolation. One or more processors may apply a Fast Fourier Transform (FFT), a discrete Fourier decomposition, and / or other spectral analysis techniques to identify components of the image signal oscillating at or near the 4R frequency. In some embodiments, a band-pass filter may be applied to the video stream so that intensity variations occurring within a narrow band centered on the nerve flicker frequency are retained, thereby highlighting pixels exhibiting sinusoidal modulation at 4R while suppressing static, low-frequency, or irregularly varying background pixels. In some embodiments, a lock-in detection scheme may be employed to compute the amplitude of the periodic modulation at the expected frequency. This can produce an image in which pixels corresponding to nerve tissue (e.g., those exhibiting a strong periodic response) are bright, while surrounding tissues lacking such modulation remain dark.

[0087] In some embodiments, the optical sensor system may capture multiple sequential SWIR images while the polarization state of the illumination and / or detection path is varied. The captured images may form a continuous sequence, such as a video stream or a set of consecutively acquired frames. The resulting sequence of images may be analyzed collectively to observe polarizationdependent changes in reflected intensity from birefringent nerve tissue. Accordingly, the images generated during rotation or electronic modulation may be understood as a time-ordered set of frames that together reveal the periodic modulation characteristic of nerves.20MF-364871974Attorney Docket No.: 16569-20011.40

[0088] For the flashing nerve effect produced by r-SWIR-OPI to be observable in real time (e.g., visually on a surgical monitor or through immediate or near-immediate computational processing) the rotation speed of the polarizers may be selected within an appropriate operational window. If the rotation speed is too high, the nerve’s intensity modulation may complete a full bright-dark cycle within a single camera exposure. In such cases, the rapid oscillation may be temporally averaged by the sensor, causing the flicker to diminish or disappear. In practical terms, the polarization should generally not rotate more than approximately 180° during a single camera exposure frame. In some embodiments, a camera can operate at approximately 10 to 200 frames per second (i s) or approximately 10 to 180 ips. For example, for a camera operating at approximately 200 ips, corresponding to an exposure duration of about 5 ms, this consideration corresponds to a maximum practical rotation speed of about 6000 revolutions per minute (RPM). Rotation speeds beyond this threshold may under sample the modulation and fail to satisfy a Nyquist-type sampling condition in which the flicker frequency should remain below approximately one -half of the camera frame rate.

[0089] If the rotation speed is too low, the intensity changes may occur so gradually that they are not perceived as a flashing or strobing effect by a human observer. When consecutive frames show only minimal differences in brightness, the modulation may not be readily discernible in real time. In many embodiments, rotation speeds of at least approximately 3 RPM may be desirable to ensure that the modulation is perceptible during live viewing. At rotation speeds below this range, the modulation may still be present and detectable through accelerated playback or temporal analysis, but may not produce an immediately visible flicker to a user.

[0090] Accordingly, for practical real-time surgical use, the rotation speed may be selected within a range of approximately 3 RPM to 6000 RPM, with specific values chosen based on factors such as the camera frame rate, sensor exposure time, and desired flicker characteristics. In many implementations, rotation speeds within a narrower range (e.g., tens to a few hundred RPM) may be advantageous, as they remain well within typical sampling capabilities of SWIR cameras and may produce a flicker rate that is comfortable and easy to interpret visually (for example, corresponding to a nerve flashing at a frequency of a few Hertz to several tens of Hertz). In some embodiments, the rotational speed of one or more polarizers (e.g., rotating illumination and / or analyzer polarizers) may be selected from a wide operational range. For example, the polarizer rotation speed may be in a range of about 3 revolutions per minute (RPM) to about 6000 RPM, for example approximately 3 RPM, 5 RPM, 10 RPM, 25 RPM, 50 RPM, 75 RPM, 100 RPM, 150 RPM, 250 RPM, 500 RPM, 750 RPM, 1000 RPM, 2000 RPM, 3000 RPM, 4000 RPM, 5000 RPM, or 6000 RPM. In some embodiments, the rotation speed may be greater than or equal to 3 RPM, 5 RPM, 10 RPM, 25 RPM, 50 RPM, 75 RPM, 100 RPM, 150 RPM, 250 RPM, 500 RPM, 750 RPM, 1000 RPM, 2000 RPM, 3000 RPM, 4000 RPM, 5000 RPM, or 6000 RPM. In some embodiments, the rotation speed may be less than or equal to 6000 RPM, 5000 RPM, 4000 RPM, 3000 RPM, 2000 RPM, 1000 RPM, 750 RPM, 500 RPM, 250 RPM,21MF-364871974Attorney Docket No.: 16569-20011.40150 RPM, 100 RPM, 75 RPM, 50 RPM, 25 RPM, 10 RPM, or 3 RPM. In some embodiments, the rotational speed may be selected within a narrower range, such as about 3 RPM to 150 RPM, for example approximately 3 RPM, 5 RPM, 10 RPM, 25 RPM, 50 RPM, 75 RPM, 100 RPM, or 150 RPM. Selecting a rotation speed within any of these ranges may support real-time visualization of polarization-dependent modulation of birefringent nerve tissue and / or may satisfy sampling constraints associated with the frame rate of the optical sensor system.

[0091] In some embodiments, the system may be configured to synchronize camera frame capture with the rotational position of the polarizer assembly. Such synchronization may be achieved, for example, by using an encoder mechanically or optically coupled to the rotating polarizers, and / or by using timing or positional information derived from a motor driver signal. Synchronization may allow the imaging system to acquire frames at predetermined angular increments or at fixed phase positions within each rotation cycle. Sampling the polarization state at known angular positions may be particularly advantageous in embodiments that perform temporal averaging over multiple cycles, reconstruct the full modulation waveform across the rotation period, and / or apply lock-in detection or phase-sensitive signal extraction at each pixel. Phase-locked acquisition may also reduce temporal jitter and improve the accuracy of frequency-domain filtering, thereby enhancing the reliability and contrast of nerve identification.

[0092] Such synchronization may further support operation in multiple imaging modes. For example, in a static mode, the polarizers may remain stationary and the system may operate as a conventional orthogonally polarized SWIR imager. In a dynamic r-SWIR-OPI mode, the polarizers may rotate continuously to produce real-time intensity modulation of birefringent nerve tissue. In a data- acquisition mode, the system may capture frames at defined rotational angles or phases for subsequent computational analysis, enabling reconstruction of modulation amplitude, phase maps, or other temporal descriptors of birefringence. Each of these modes may be selectable or automatically invoked by one or more controllers, depending on the imaging task or desired level of contrast enhancement. Dynamic polarization modulation as employed in r-SWIR-OPI may therefore supplement or enhance the spatial contrast mechanisms described previously, providing a temporally varying signal that is associated with birefringent nerve tissue. This additional temporal dimension of contrast may facilitate more robust, reliable identification and localization of nerves during surgical procedures or other in vivo imaging applications. Accordingly, the imaging system may be operated in multiple modes. A surgeon or operator may use the device in a static orthogonally polarized SWIR mode for baseline anatomical visualization and may then activate rotation to induce the dynamic flicker associated with r-SWIR-OPI when enhanced nerve contrast or real-time nerve discrimination is desired. This dual-mode capability can allow the system to provide both high-contrast anatomical imaging and dynamic birefringence-based nerve highlighting within the same platform.22MF-364871974Attorney Docket No.: 16569-20011.40

[0093] A significant advantage of the rotating r-SWIR-OPI configuration is that the system remains orthogonally polarized at all times during rotation. Because the illumination and detection paths maintain orthogonal polarization states throughout the rotation cycle, surface glare and specular reflections from wet tissue, bodily fluids, or surgical instruments may be substantially reduced in every frame. This reduction in specular contamination may improve image quality and enhance the visibility of weakly reflecting or subsurface structures.

[0094] Orthogonal polarization in the SWIR range may also improve imaging depth. Since SWIR photons scatter less than visible-light photons, an orthogonally polarized SWIR configuration may suppress superficially scattered light and thereby enhance visualization of features located beneath the tissue surface. Even when rotation of the polarizers is halted, the system may continue to function as a static orthogonally polarized SWIR imager, which can provide improved anatomical contrast (e.g., clearer differentiation of nerves, blood vessels, connective tissue, and / or adipose structures) relative to unpolarized or parallel-polarized configurations.

[0095] In some embodiments, the illumination system may include an illumination source that itself emits polarized short-wave infrared (SWIR) illumination. For example, a laser, super luminescent diode, and / or other polarized SWIR emitter may be used in place of, or in addition to, a separate polarizing element positioned in the illumination path. In embodiments using such an inherently polarized source, the illumination source itself may be mounted for rotation and rotated through a plurality of angular positions to vary the polarization orientation incident on the tissue region. Rotation of the inherently polarized illumination source may be synchronized with rotation of an analyzer polarizer in the detection path, thereby maintaining a fixed angular offset between illumination and detection polarizations during the imaging process. Such an arrangement may simplify system construction by reducing the number of discrete optical components while still enabling dynamic polarization modulation and the associated birefringence-based contrast.

[0096] In some embodiments, one or more controllers may be configured to operate the imaging system in multiple modes, including: (i) a static orthogonally polarized SWIR imaging mode that provides enhanced anatomical contrast; (ii) a dynamic r-SWIR-OPI mode in which the polarizers rotate continuously to generate the time-varying birefringence -based nerve signal; and / or (iii) a synchronized data-acquisition mode in which image frames are captured at predetermined rotational angles or phases for subsequent or real-time temporal -frequency analysis. The controller may automatically select among these modes based on user input, sensor feedback, or detection confidence levels from image-analysis algorithms.

[0097] In some embodiments, the one or more processors may be configured to automatically detect the periodic modulation of reflected SWIR intensity from birefringent nerve tissue in the time series of images generated during rotation of the polarization state. The processor(s) may implement a23MF-364871974Attorney Docket No.: 16569-20011.40 video-analysis algorithm configured to analyze temporal variations in pixel intensity across successive frames, and to identify pixels and / or regions exhibiting modulation amplitudes, phases, and / or frequency-domain characteristics consistent with the known modulation behavior of birefringent nerve tissue. The algorithm may utilize one or more techniques, such as temporal differencing, sinusoidal fitting, Fast Fourier Transform (FFT) analysis, band-pass filtering, and / or lock-in detection, to detect the presence and / or location of the nerve or nerve substructure within the field of view.

[0098] In some embodiments, based on detecting the periodic modulation associated with birefringent nerve tissue, the one or more processors may be further configured to generate one or more outputs indicating the presence or location of the nerve or nerve substructure. Such outputs may include, for example, generating an alert to a user, highlighting or annotating one or more frames of the time series of images to visually indicate the detected nerve, overlaying a graphical marker on a live or recorded video feed, and / or transmitting control signals to an external system. In certain embodiments, the one or more processors may annotate an image sequence by outlining, shading, labeling, and / or otherwise visually indicating the region exhibiting the detected modulation pattern. These outputs may assist a surgeon, operator, robotic system, and / or image -guidance platform in avoiding contact with or damage to sensitive nerve structures.

[0099] In some embodiments, the image-processing or machine -learning algorithms described herein may utilize temporal features of the reflected SWIR signal, in addition to the spatial patterns of high- and low-intensity regions described above. For example, the amplitude, phase, temporal waveform shape, or harmonic content of the periodic modulation at the nerve flicker frequency may be used as discriminative features to identify, classify, or track nerves and nerve substructures such as fascicles or bands of Fontana. Incorporating these temporal descriptors may improve robustness to noise, reduce false positives from non-birefringent tissues, and enhance automated nerve detection in realtime surgical or interventional settings.

[0100] FIGS. 3A-3C illustrate exemplary mechanical embodiments of imaging systems configured to implement the r-SWIR-OPI modality described above. In some embodiments, a first polarizer is positioned in the illumination path and a second polarizer is positioned in the detection path, and the two polarizers can be rotated together at substantially the same angular speed while maintaining a fixed angular relationship (e.g., approximately orthogonal). These structural configurations provide practical implementations of the dynamic polarization modulation techniques described above, enabling synchronized rotation, stable angular tracking, and consistent delivery of the polarizationdependent intensity modulation characteristic of birefringent nerve tissue.

[0101] As shown in FIG. 3A, an exemplary imaging system 300 may include an illumination source 310 configured to emit VIS and / or SWIR illumination, a rotating illumination polarizer 320, a tissue region 360 containing a nerve 362, a camera 330, and a rotating analyzer polarizer 340 positioned in24MF-364871974Attorney Docket No.: 16569-20011.40 front of a camera lens 332. The illumination emitted by source 310 passes through the illumination polarizer 320 and is directed toward the tissue region 360. Light reflected from the tissue passes through the analyzer polarizer 340 before reaching the camera 330. The illumination polarizer 320 and analyzer polarizer 340 may be rotated in synchrony to maintain the desired angular relationship between their polarization states. In some embodiments, each polarizer may be mounted to a rotating frame or holder driven by a shared mechanical linkage or motor assembly. This arrangement provides a structural basis for generating the time-varying polarization states required for r-SWIR-OPI.

[0102] In some embodiments, the illumination polarizer 320 and analyzer polarizer 340 may each be mounted in rotating holders or wheels configured to permit low-friction, low-wobble rotation. The two polarizers may be driven in synchrony by a variety of mechanisms. In some embodiments, a single motor may drive both polarizers through a shared mechanical linkage, such as gears, ring gears, belts, pulleys, or other transmission elements. In some embodiments, each polarizer may be attached to a separate motor, and the motors may be electronically synchronized such that the polarizers rotate at substantially the same angular speed. Regardless of the drive mechanism, the system may maintain a fixed angular offset between the two rotating polarizers (e.g., an approximately 90° orthogonal polarization relationship) throughout the rotation cycle. This may be achieved either by mechanically coupling the two polarizers so that they rotate together with a constant phase relationship, or by electronically monitoring and locking their relative angular positions when independent drive motors are used. In some embodiments, the rotational assemblies may include ball bearings, rotary stages, or precision bushings to minimize wobble, backlash, or mechanical jitter, thereby reducing intensity noise in the captured images. The rotation speed may be user-controlled and adjustable over the full operational range described above (e.g., approximately 3 RPM to 6000 RPM), allowing the system to accommodate different camera frame rates, exposure times, and desired flicker frequencies.

[0103] In some embodiments, the rotation of one or more polarizing elements may be driven by a hollow-shaft motor, frameless brushless motor, hollow rotary actuator, and / or a printed-circuit board (PCB) motor. Such motors may include a central aperture through which optical components and / or illumination paths can pass, thereby allowing a rotating cross-polarization assembly to be mounted to the motor’s inner diameter. Hollow-shaft and frameless brushless motors may provide smooth, stable rotation of the polarizers while minimizing added system weight. PCB motors may also serve as lighter-weight alternatives.

[0104] FIG. 3B illustrates an embodiment in which the illumination polarizer 320 and analyzer polarizer 340 are rotated using a gear-driven synchronization mechanism 370. In this configuration, gears 372 mounted to the respective polarizer assemblies are coupled to one another, such that rotation of a drive interface 374 (e.g., a motor shaft driving a pinion gear) imparts coordinated rotation to both polarizers. The gear ratios may be selected such that the polarizers rotate at substantially the25MF-364871974Attorney Docket No.: 16569-20011.40 same angular velocity while preserving the fixed angular offset needed for orthogonal (or otherwise specified) polarization alignment. Gear-based synchronization may provide predictable motion, mechanical stability, and low angular error, thereby reducing jitter-induced artifacts in the captured images.

[0105] FIG. 3C illustrates an alternative embodiment in which the illumination polarizer 320 and analyzer polarizer 340 are rotated by a belt-driven synchronization mechanism 380. In this arrangement, belt pulleys 382 mounted on polarizer supports are coupled by a flexible belt 386, allowing rotation of a single pulley 384 to drive both polarizers simultaneously. Belt-driven systems may reduce mechanical backlash relative to gear-driven systems and may produce smoother rotational motion, which can improve temporal stability of the polarization modulation and reduce noise in the resulting r-SWIR-OPI signal. Such embodiments may be advantageous in applications requiring quiet operation or compact mechanical integration.

[0106] FIGS. 4A-4D illustrate embodiments in which the illumination and analyzer polarizers are pre-assembled into a single rotational unit. In these embodiments, two linear polarizers can be fixed, bonded, and / or otherwise secured together in a rigid structure such that their relative angular orientation (e.g., an approximately 90° orthogonal relationship) can be maintained. Rotating the entire unit can preserve the desired polarization relationship without requiring mechanical synchronization between two separate rotating components. This configuration can simplify alignment, reduce assembly tolerance requirements, and / or enable more compact system integration, particularly in hand-held, head-mounted, microscope-integrated, and / or endoscopic imaging devices. In some embodiments, the imaging device can include a relay lens and / or rod lens that extends through a ringshaped illumination assembly. As described with reference to FIG. 4D, the polarization optics may be arranged annularly around the relay lens to reduce the distal profile of the rotating assembly.

[0107] As seen in FIGS. 4A-4C, the pre-assembled orthogonal polarizer unit 410 may be configured in a concentric, ring-shaped geometry that is advantageous for imaging systems incorporating a coaxial or near-coaxial illumination arrangement, such as surgical scopes and / or devices employing a ring-light around the camera. In such embodiments, a first polarizer may be formed as an annular or ring-shaped polarizing film that surrounds the optical axis of the imaging system and polarizes illumination emitted radially inward toward the tissue. A second polarizer may be formed as a smaller disk positioned at the center of the ring, in front of the camera lens, such that the disk polarizes reflected illumination entering the camera. The ring-shaped illumination polarizer and disk-shaped analyzer polarizer may be bonded together (e.g., using an optical adhesive, mechanical frame, or integrated substrate) so that the two polarizers remain fixed at an approximately 90° relative orientation. When assembled in this manner, the resulting concentric, donut-shaped polarizer unit maintains its orthogonal alignment as a single rigid structure.26MF-364871974Attorney Docket No.: 16569-20011.40

[0108] This concentric configuration may simplify alignment and may ensure that the orthogonal polarization relationship is preserved during rotation without requiring two motors or electronic phase locking. The bonded donut-shaped polarizer assembly may be mounted on a rotating stage or turntable and driven by a motor or other actuator, such that the entire unit rotates as a single piece. In some embodiments, a light-blocking barrier may be disposed between the circumference of the camera lens and the surrounding illumination ring to prevent illumination light from bypassing the tissue and entering the camera directly. The barrier may take the form of a tubular sleeve, conical baffle, or other opaque structure configured to ensure that substantially all illumination light reaching the camera has interacted with the tissue and passed through both portions of the orthogonal polarizer unit. This arrangement may preserve the integrity of the orthogonally polarized SWIR illumination and detection geometry in a coaxial system and may reduce stray light, glare, and undesired reflections that could otherwise degrade nerve visualization.

[0109] As shown in FIG. 4A, an exemplary imaging system 400 configured to implement rotation of a pre-assembled orthogonal polarizer unit may include a camera 440, a camera lens 445, a ring-shaped illumination system 450, a motor 470, and an orthogonal polarizer unit 410 positioned between the ring-shaped illumination system 450 and a tissue region 460 containing a nerve 462. The ring-shaped illumination system 450 can emit SWIR and / or visible light illumination toward the tissue region 460 and nerve 462. The orthogonal polarizer unit 410 can include a ring-shaped polarizer 411 configured to polarize the illumination before it reaches tissue region 460. The orthogonal polarizer unit 410 can also include a disk-shaped analyzer polarizer 412 disposed along the optical axis of the camera 440. The disk-shaped analyzer polarizer 412 can be polarized orthogonally to the ring-shaped polarizer 411, and can be configured to polarize light reflected from the tissue region 460 before it is received by camera 440. The motor 470 can be coupled to the orthogonal polarizer unit 410 and can be configured to rotate the entire unit as a single assembly, thereby maintaining a fixed angular relationship between the ring-shaped polarizer 411 and the disk-shaped analyzer polarizer 412 throughout rotation. Light reflected from the tissue region 460 passes through the analyzer polarizer 412 and lens 445 before reaching the camera 440, enabling the system 400 to capture polarizationdependent variations in reflected SWIR intensity from birefringent nerve tissue during rotation.

[0110] As shown in FIG. 4B, a pre-assembled orthogonal polarizer unit 410 may be rotated using a belt-driven mechanism 420. In this embodiment, one or more belt pulleys 422 may be mounted to the outer surface or frame of the polarizer unit 410, and a flexible belt 424 may couple these pulleys to a motor or drive pulley 426. Rotation of the drive pulley therefore causes the entire polarizer unit 410 to rotate as a single assembly. This arrangement may produce smooth, low-backlash motion and may be advantageous in embodiments requiring low acoustic noise or vibration. Because the two polarizers remain fixed in their orthogonal relationship, rotation of the bonded unit automatically maintains the27MF-364871974Attorney Docket No.: 16569-20011.40 polarization geometry necessary for r-SWIR-OPI without the need for electronic or mechanical synchronization of separate shafts.

[0111] FIG. 4C illustrates an alternative embodiment in which the pre-assembled orthogonal polarizer unit 410 is rotated via a gear-driven mechanism 430. In this configuration, one or more gears 432 may be rigidly attached to or integrated into the frame of the polarizer unit. A drive gear or pinion 434, actuated by a motor or manual actuator, may engage the gear teeth and impart rotation to the polarizer unit 410. The drive gear or pinion 434 may include a motor shaft, gear head, or other actuator. Gear-driven rotation may provide highly stable angular motion and predictable rotational dynamics, making this embodiment suitable for applications requiring precise phase control, fast rotation acceleration, or tight integration with encoders for synchronized acquisition. As with the belt- driven version, rotation of the bonded assembly maintains the fixed orthogonal angular offset between the two polarizers.

[0112] FIG. 4D illustrates another embodiment of an imaging system 490 including a compact rotating cross-polarization unit 410 positioned at the distal end. System 490 can include a relay lens or glass-rod lens 480 (e.g., a portion of a laparoscope) positioned between the tissue region 460 and the remainder of the imaging system 490. The relay lens 480 can extend proximally through an aperture of the ring-shaped illumination system 450 and the ring-shaped illumination polarizer 411. This geometry can allow illumination to be delivered in an annular pattern surrounding the relay lens 480, while the relay lens 480 simultaneously collects reflected or scattered light returning from the illuminated tissue region.

[0113] The ring-shaped illumination system 450 can emit light that is polarized as it passes through the ring polarizer 411 before reaching the tissue. Reflected light from the tissue is collected by the relay lens 480 and directed proximally toward the imaging lens 445 and camera 440. A disk-shaped analyzer polarizer may be positioned at either location 412a or 412b in FIG. 4D. In the proximal configuration 412a, the analyzer polarizer can be positioned in between imaging lens 445 and relay lens 480. In the distal configuration 412b, the analyzer polarizer can be positioned in between relay lens 480 and the tissue region 460. Because typical imaging optics do not substantially alter the polarization state of light, both locations can provide effective cross-polarization detection.

[0114] In system 490, the components that may be assembled together to form the orthogonal polarizer unit 410 can include the analyzer polarizer at position 412a or 412b, the ring-shaped illumination polarizer 411, and / or the relay lens 480. In some embodiments, the ring-shaped illumination system 450 can remain fixed (e.g., not part of the rotating polarizer assembly 410). For example, the ring-shaped illumination system 450 may be fixed when it is powered or controlled using a fiber-optic bundle or electrical wiring, because rotation may interfere with those wired connections. In some embodiments, the ring-shaped illumination system 450 may be part of the28MF-364871974Attorney Docket No.: 16569-20011.40 orthogonal polarizer unit 410. For example, when the ring-shaped illumination system 450 is powered by an internal battery and / or by wireless charging, it may alternatively form part of the orthogonal polarizer unit 410.

[0115] By configuring the ring-shaped illumination components to use a relay lens 480, system 490 can enable the rotating cross-polarization unit 410 to be constructed with a reduced outer diameter. This compact geometry can provide significant clinical advantages: the imaging device may be maneuvered closer to the target anatomy and can occupy less space within an already crowded operative field. The improved proximity to tissue can also provide a more intuitive correspondence between the captured image and the anatomical region being visualized.Electronic Polarization Modulation

[0116] In some embodiments, the polarization-based flashing nerve effect described herein may be achieved without mechanically rotating polarizers by electronically modulating the polarization state of the illumination and using a polarization-resolving detector on the imaging side. In this approach, an electronically controllable polarization modulator, such as a liquid crystal (LC) polarization rotator, may be placed in the illumination path and driven by electrical signals to alter the polarization orientation dynamically. A pixel-level polarization-resolving camera may be used on the detection side to measure the polarization state of the reflected illumination at multiple orientations simultaneously. This method may eliminate (or reduce the number of) moving parts, reduce mechanical jitter, allow high-speed modulation, and provide rapid switching between polarization states.

[0117] Liquid crystal devices may function as electrically tunable waveplates or polarization rotators. By applying a voltage across the LC cell, the orientation of the LC molecules and the effective optical axis of the device may be varied, thereby rotating the polarization of the transmitted light by a controlled angle. Several types of LC polarization modulators may be used.

[0118] In some embodiments, a twisted-nematic liquid crystal (TN-LC) device may be used as an electronically tunable waveplate to modulate the polarization state of the illumination. A TN-LC modulator may rotate the polarization orientation of transmitted light as a function of the applied voltage, allowing the polarization angle to be adjusted in a continuous, analog manner. Thus, TN-LC devices may be capable of producing intermediate polarization orientations between two endpoints and, in some implementations, may sweep through a continuous range of polarization angles as the drive signal varies. TN-LC devices, however, may exhibit switching-speed limitations of tens of Hertz; for example, achieving a full 90° or 180° polarization rotation may use modulation rates of about approximately 5-50 Hz. Such modulation speeds may be suitable for slower polarization cycling, calibration routines, or applications in which continuous angular scanning is desired, but may29MF-364871974Attorney Docket No.: 16569-20011.40 be less suited for generating the higher flicker frequencies achievable with mechanically rotating polarizers or high-speed ferroelectric liquid crystal (FLC) devices.

[0119] In some embodiments, a ferroelectric liquid crystal (FLC) device may be used to provide high-speed electronic modulation of the illumination polarization. FLC modulators are characterized by rapid switching behavior (e.g., in the kilohertz range) and generally operate as binary polarization switches between two stable polarization orientations, such as approximately 0° and 90°, or approximately 0° and 45°. When driven by an oscillating electrical signal, the FLC may alternate the illumination polarization between its two stable states at rates substantially higher than those achievable with TN-LC devices. These two polarization orientations may be selected to correspond to different reflected-intensity responses from birefringent nerve tissue, such that one orientation produces a relatively bright reflected signal and the other produces a relatively dim reflected signal (e.g., driving the FLC between 0° and 45° states). Alternating the illumination between these orientations can therefore generate an effective flickering or strobing of the nerve signal, analogous to the modulation produced by mechanical rotation but occurring at substantially higher frequencies. FLC devices may readily achieve modulation frequencies of about 1-10 kHz, far beyond the temporal resolution of human vision, and thus may be advantageously paired with algorithmic detection approaches such as lock-in amplification and / or frequency-domain filtering to isolate the nerve’s birefringence-based response from background tissue.

[0120] In embodiments where more than two polarization orientations are desired (e.g., to accommodate different nerve orientations and / or to optimize contrast under varying anatomical conditions) multiple discrete polarization states may be generated using a combination of electronically controlled modulators. In some embodiments, two ferroelectric liquid crystal (FLC) devices may be cascaded in series. By selecting the respective two-state axes of the cascaded FLCs appropriately, the combined device may produce four effective polarization orientations (e.g., approximately 0°, 45°, 90°, and 135°) when the modulators are driven in different binary combinations. This arrangement may allow the system to cycle rapidly through several predetermined polarization angles without mechanical movement, thereby enabling multi-angle nerve interrogation at kilohertz-level switching rates.

[0121] In some embodiments, a slower analog polarization modulator (e.g., such as a TN-LC device or a motorized polarization rotator) may be used to identify or calibrate a polarization orientation that provides enhanced nerve visibility for a particular anatomical geometry. Once such an orientation is determined, a high-speed FLC device may rapidly switch between that orientation and one or more nearby orientations to provide dynamic modulation during the imaging procedure. Such a hybrid arrangement may combine the broad angular adjustability of analog modulation with the high-speed switching capability of FLC -based digital modulation. Additional variants may include mechanically30MF-364871974Attorney Docket No.: 16569-20011.40 rotating a FLC itself, or employing multiple preset LC devices arranged in parallel or in sequence to provide several predefined polarization states with minimal switching time.

[0122] In some embodiments, polarization modulation may be achieved using a photoelastic modulator (PEM). A PEM operates by driving a transparent optical element (e.g., a crystal such as fused silica or quartz) at a mechanical resonance frequency to induce a periodic strain. This strain produces oscillatory birefringence within the crystal, thereby causing the polarization state of the transmitted illumination to oscillate at the drive frequency. PEMs may achieve modulation rates of about tens of kilohertz to approximately 100 kHz, far exceeding the switching speeds of liquid crystal devices and enabling polarization modulation that is effectively continuous at the timescales relevant to video-rate imaging.

[0123] Such high-frequency modulation may be particularly advantageous for embodiments relying primarily on computational detection methods. For example, because the PEM-generated modulation occurs at a precise, stable, and known frequency, lock-in amplification, synchronous demodulation, and / or frequency-domain filtering may be applied to extract a nerve -specific birefringence signal from the reflected illumination. PEMs typically feature relatively small apertures and may require precise drive electronics, which may influence suitability for wide-field or hand-held imaging systems; however, for applications where ultrafast modulation is desired (e.g., high-speed scanning, algorithmic classification, and / or integration with polarization-resolving sensors) PEMs may provide an effective solid-state alternative to mechanically rotating polarizers.

[0124] In some embodiments, the detection-side optics may employ a pixel-level polarizationresolving camera, such as a division-of-focal-plane polarimeter. These cameras incorporate an array of micro-polarizers, each having a defined polarization orientation, such as approximately 0°, 45°, 90°, or 135°, patterned directly onto or integrated with the image sensor. In some embodiments, the micro-polarizers may be arranged in a repeating pattern, for example in 2x2 or 4x4 pixel groups, such that each group samples multiple polarization components at the same spatial location. As a result, a single image frame may simultaneously record several polarization-resolved views of the reflected illumination, with each pixel (or pixel cluster) effectively knowing the polarization angle to which it is sensitive.

[0125] This architecture can eliminate the need for a rotating analyzer in front of the camera and can allow polarization-dependent reflectance information to be captured without mechanical movement. For example, pixels associated with micro-polarizers oriented at 0° may measure the horizontal polarization component, pixels oriented at 90° may measure the vertical component, and pixels oriented at 45° or 135° may capture diagonal components, all in one frame. By comparing the intensities measured across these pixel groups, the system may infer the instantaneous polarization state of the reflected light and reconstruct polarization-resolved images at multiple orientations from a31MF-364871974Attorney Docket No.: 16569-20011.40 single exposure. This capability may substantially improve imaging efficiency, reduce mechanical complexity, and support real-time polarization analysis during surgical or interventional procedures.

[0126] When an electronically controlled illumination polarization modulator (e.g., an LC device or a photoelastic modulator) is used in combination with a pixel-level polarization-resolving camera, the system may achieve rapid and precisely timed polarization cycling. In some embodiments, the illumination modulator may be driven to sweep continuously through a range of polarization angles or to hop between a set of discrete orientations. Because each image frame captured by the polarizationresolving camera contains pixel groups that measure different polarization components, the system may reconstruct the equivalent of multiple polarization-resolved images from each exposure.

[0127] In some embodiments, the illumination modulation waveform and the camera exposure timing may be electronically synchronized. For example, the camera readout may be triggered at specific points in the modulation cycle, or the modulator’s drive signal may be phase-locked to the camera’s frame timing. Such synchronization may be accurate to the microsecond level, thereby ensuring that each frame corresponds to a well-defined polarization state of the illumination. Synchronization may also prevent drift between the modulator and the detector, which could otherwise degrade the fidelity of temporal demodulation or frequency-domain analysis.

[0128] Because both modulation and detection are electronically controlled, the system may perform real-time processing, such as continuously computing differences between polarization channels, reconstructing orthogonally polarized views, or applying lock-in amplification across the micropolarizer channels. This may enable the generation of enhanced, nerve-highlighted video streams at standard frame rates, without requiring mechanical rotation or multi -frame averaging.

[0129] In summary, the electronically modulated polarization approach described herein can provide a solid-state alternative to mechanically rotating polarizers for generating the polarization-dependent flashing nerve effect. Although the underlying source of contrast remains the nerve’s intrinsic birefringence, the polarization state of the illumination may be varied electronically rather than mechanically. This may eliminate moving parts, reduce mechanical jitter, minimize wear or alignment drift, and allow the system to operate at modulation frequencies that exceed those achievable through physical rotation.

[0130] Because liquid crystal devices and photoelastic modulators can be fabricated in compact form factors, and because polarization-resolving cameras can detect multiple polarization components in a single snapshot, electronically modulated systems may support small, integrated, and rugged imaging architectures suitable for surgical scopes, handheld devices, robotic systems, and other instrumentation. Electronic modulation may also achieve significantly higher flicker frequencies, limited primarily by modulator response time or camera frame rate, which can be leveraged by32MF-364871974Attorney Docket No.: 16569-20011.40 frequency-domain processing, synchronous detection, or lock-in amplification to enhance nerve discrimination beyond what is observable visually.

[0131] This electronic technique may complement the mechanically rotated r-SWIR-OPI modality. For example, mechanical rotation may be used initially for intuitive, visually interpretable nerve flashing, while electronic modulation may be activated for high-speed mapping, quantitative analysis, or operation in constrained form factors where mechanical rotation is impractical. In some embodiments, both methods may be integrated within a single imaging platform, allowing the user to transition between mechanical and electronic polarization modulation depending on the imaging conditions and the desired balance between visual feedback and computational sensitivity.

[0132] In some embodiments, one or more processors of the system may be configured to automatically detect the periodic modulation of reflected SWIR intensity from birefringent nerve tissue in the time series of images generated during electronic modulation of the polarization state. The processor(s) may implement a video-analysis algorithm configured to analyze temporal variations in pixel intensity across successive frames, and to identify pixels or regions exhibiting modulation amplitudes, phases, or frequency-domain characteristics consistent with the known modulation behavior of birefringent nerve tissue. The algorithm may utilize one or more techniques, such as temporal differencing, sinusoidal fitting, Fast Fourier Transform (FFT) analysis, band-pass filtering, and / or lock-in detection, to detect the presence and / or location of the nerve or nerve substructure within the field of view.

[0133] In some embodiments, based on detecting the periodic modulation associated with birefringent nerve tissue, the one or more processors may be further configured to generate one or more outputs indicating the presence or location of the nerve or nerve substructure. Such outputs may include, for example, generating an alert to a user, highlighting or annotating one or more frames of the time series of images to visually indicate the detected nerve, overlaying a graphical marker on a live or recorded video feed, and / or transmitting control signals to an external system. In certain embodiments, the one or more processors may annotate an image sequence by outlining, shading, labeling, and / or otherwise visually indicating the region exhibiting the detected modulation pattern. These outputs may assist a surgeon, operator, robotic system, and / or image-guidance platform in avoiding contact with or damage to sensitive nerve structures.

[0134] FIG. 5 illustrates an exemplary electronic polarization-modulation imaging system 500 configured to implement the electronic polarization modulation techniques described above. In some embodiments, an illumination source 510 is configured to emit short-wave infrared (SWIR) illumination toward a tissue region 560 containing a nerve 562. The emitted illumination passes through an electronically controllable polarization modulator 520, which may include, for example, a twisted-nematic liquid crystal device, a ferroelectric liquid crystal device, and or a photoelastic33MF-364871974Attorney Docket No.: 16569-20011.40 modulator, any of which may be driven electrically to alter the polarization orientation of the transmitted SWIR illumination at user-selected or predefined modulation frequencies.

[0135] The reflected portion of the illumination returning from the tissue region 560 is collected by imaging optics, such as a lens 530, and detected by a pixel-level polarization-resolving camera 540. The camera 540 may include an array of micro-polarizers, each oriented at a different polarization angle, allowing each frame to encode multiple polarization components of the reflected light. In some embodiments, the illumination modulator 520 and camera 540 are electronically synchronized (e.g., by phase-locking the camera exposure timing to the modulator’s drive signal such that that each captured frame corresponds to a known polarization state of the illumination. Using this configuration, the system 500 may generate polarization-resolved SWIR images in real time, reconstruct orthogonally polarized views, perform lock-in detection or other temporal demodulation, and produce enhanced nerve-highlighted image streams without requiring mechanical rotation of optical elements.

[0136] Although many of the embodiments described herein emphasize short-wave infrared (SWIR) illumination due to its advantageous penetration depth and contrast characteristics for nerve and nerve-substructure imaging, the disclosed systems and methods are not limited to SWIR wavelengths. In some embodiments, an illumination system as described herein may additionally or alternatively be configured to provide visible (VIS) and / or near-infrared (NIR) illumination. For example, a given imaging system may include separate VIS and SWIR light sources, a broadband source used in conjunction with wavelength-selective filters, and / or a multi-channel illumination module configured to operate in a plurality of modes, such as a SWIR-only mode, a VIS-only mode, an NIR-only mode, and / or combined or sequential VIS / SWIR / NIR modes. In certain embodiments, VIS and SWIR images of a common tissue region may be acquired concurrently or in rapid succession and displayed separately or as fused, co-registered images, thereby providing complementary anatomical and functional information while still leveraging the enhanced nerve and nerve-substructure contrast afforded by SWIR illumination.

[0137] The imaging techniques described herein may be performed without the use of any contrast agent in the nerve or nerve substructure. The imaging techniques described herein may be used to generate images without the use of reference light. The imaging techniques described herein may be used to generate images in the presence of ambient light surrounding the camera sensor. Bandpass and / or long-pass filters may be used to block out ambient light. The imaging techniques described herein may be used to image nerve or nerve substructures in-situ.

[0138] In some variations of the foregoing, the systems and methods described herein may further comprise or be combined with other systems and methods for one or more additional modalities.34MF-364871974Attorney Docket No.: 16569-20011.40

[0139] FIG. 6 shows an exemplary computer system 600 that may be used to generate images and / or video of biological tissue based on information received from a plurality of sensors in the imaging systems (e.g., systems 300 or 500). In other words, computer system 600 may be used to implement a controller in a system for imaging biological tissue using SWIR light. Computer system 600 can be any suitable type of microprocessor-based device, such as a personal computer, workstation, server, or handheld computing device (portable electronic device) such as a phone or tablet, or dedicated device. As shown in FIG. 6, computer system 600 may include one or more processors 602, an input device 604, an output device 606, storage 608 storing software 610, and a communication device 612.

[0140] Input device 604 and output device 606 can be connectable or integrated with the imaging systems disclosed herein. Input device 604 may be any suitable device that provides input, such as a touch screen, keyboard or keypad, mouse, or voice-recognition device. Likewise, output device 606 can be any suitable device that provides output, such as a display, touch screen, haptics device, or speaker.

[0141] Storage 608 can be any suitable device that provides storage, such as an electrical, magnetic, or optical memory, including a RAM, cache, hard drive, removable storage disk, or other non- transitory computer readable medium. Communication device 612 can include any suitable device capable of transmitting and receiving signals over a network, such as a network interface chip or device. The components of computer system 600 can be connected in any suitable manner, such as via a physical bus or via a wireless network.

[0142] Processor(s) 602 may be or comprise any suitable processor or combination of processors, including any of, or any combination of, a central processing unit (CPU), a field programmable gate array (FPGA), and an application-specific integrated circuit (ASIC). Software 610, which can be stored in storage 608 and executed by processor(s) 602, can include, for example, the programming that embodies the functionality of the present disclosure. Software 610 may be stored and / or transported within any non-transitory computer-readable storage medium for use by or in connection with an instruction execution system, apparatus, or device that can fetch instructions associated with the software from the instruction execution system, apparatus, or device and execute the instructions. In the context of this disclosure, a computer-readable storage medium can be any medium, such as storage 608, that can contain or store programming for use by or in connection with an instruction execution system, apparatus, or device.

[0143] Software 610 can also be propagated within any transport medium for use by or in connection with an instruction execution system, apparatus, or device, such as those described above, that can fetch instructions associated with the software from the instruction execution system, apparatus, or device and execute the instructions. In the context of this disclosure, a transport medium can be any medium that can communicate, propagate, or transport programming for use by or in connection with35MF-364871974Attorney Docket No.: 16569-20011.40 an instruction execution system, apparatus, or device. The transport readable medium can include, but is not limited to, an electronic, magnetic, optical, electromagnetic, or infrared wired or wireless propagation medium.

[0144] Computer system 600 may be connected to a network, which can be any suitable type of interconnected communication system. The network can implement any suitable communications protocol and can be secured by any suitable security protocol. The network can comprise network links of any suitable arrangement that can implement the transmission and reception of network signals, such as wireless network connections, T1 or T3 lines, cable networks, DSL, or telephone lines.36MF-364871974

Claims

Attorney Docket No.: 16569-20011.40CLAIMS1. A method for in vivo medical imaging of nerves or nerve substructures, comprising: directing, by an illumination system, short-wave infrared (SWIR) illumination through a first polarizing element toward a tissue region comprising nerves or nerve substructures, while rotating the first polarizing element through a plurality of angular positions; polarizing, by a second polarizing element, a reflected portion of the SWIR illumination from the tissue region, while rotating the second polarizing element in synchrony with the first polarizing element such that the first and second polarizing elements maintain a fixed angular offset during rotation; receiving, by an optical sensor system, the polarized reflected portion of the SWIR illumination after passage through the second polarizing element; and generating, by one or more processors, a time series of images of the tissue region during rotation, the plurality of images exhibiting a periodic modulation in reflected intensity from birefringent nerve tissue, wherein the periodic modulation corresponds to a location of the nerve or the nerve substructure.

2. The method of claim 1, wherein the fixed angular offset between the first and second polarizing elements is approximately 90 degrees.

3. The method of claim 1, wherein rotating the first and second polarizing elements comprises rotating each element using a gear-driven synchronization mechanism.

4. The method of claim 1, wherein rotating the first and second polarizing elements comprises rotating each element using a belt-driven synchronization mechanism.

5. The method of claim 1, wherein the first and second polarizing elements are fixed together in a pre-assembled orthogonal polarizer unit that rotates as a single structure.

6. The method of claim 5, wherein the pre-assembled orthogonal polarizer unit comprises a ringshaped illumination polarizer surrounding a disk-shaped analyzer polarizer positioned coaxially with a camera lens.

7. The method of claim 6, further comprising preventing illumination from bypassing the tissue region by disposing a light-blocking barrier between the camera lens and an illumination ring associated with the ring-shaped illumination polarizer.37MF-364871974Attorney Docket No.: 16569-20011.

408. The method of claim 1, wherein rotating the first polarizing element and the second polarizing element comprises rotating the elements at a speed in a range of about 3 to about 6000 revolutions per minute (RPM).

9. The method of claim 1, wherein the optical sensor system acquires images at a frame rate in a range of about 10 to about 200 frames per second.

10. The method of claim 1, further comprising synchronizing image acquisition with the rotational position of the first polarizing element and the second polarizing element using an encoder or a phase-locking mechanism.

11. The method of claim 1, further comprising automatically detecting, by the one or more processors, the periodic modulation in the time series of images.

12. The method of claim 11, further comprising generating, by the one or more processors, at least one of an alert and an annotation indicating at least one of a presence and a location of the nerve or the nerve substructure based on the detected periodic modulation.

13. A system for in vivo medical imaging of nerves or nerve substructures, the system comprising: an illumination system configured to direct short-wave infrared (SWIR) illumination toward a tissue region through a first polarizing element, the first polarizing element configured to rotate through a plurality of angular positions; an optical sensor system comprising: a second polarizing element disposed in a detection path of reflected SWIR illumination from the tissue region, the second polarizing element configured to rotate in synchrony with the first polarizing element such that the first and second polarizing elements maintain a fixed angular offset during rotation; and a camera positioned to receive the SWIR illumination after passage through the second polarizing element; and one or more processors configured to generate a time series of images of the tissue region during rotation of the first polarizing element and the second polarizing element, the plurality of images exhibiting a periodic modulation in reflected intensity from birefringent nerve tissue, wherein the periodic modulation corresponds to a location of the nerve or the nerve substructure.

14. A method for in vivo medical imaging of nerves or nerve substructures, the method comprising:38MF-364871974Attorney Docket No.: 16569-20011.40 directing, by an illumination system, short-wave infrared (SWIR) illumination toward a tissue region; electronically modulating, by an electronically controllable polarization modulator disposed in an illumination path, a polarization orientation of the SWIR illumination incident on the tissue region, the electronically controllable polarization modulator being driven to vary the polarization orientation over time; receiving, by an optical sensor system, a reflected portion of the SWIR illumination from the tissue region; detecting, by a polarization-resolving camera of the optical sensor system, polarizationdependent intensity components of the reflected SWIR illumination at a plurality of polarization orientations; and generating, by one or more processors, a time series of images based on the detected polarization-dependent intensity components, the time series of images comprising a periodic modulation in reflected intensity from birefringent nerve tissue corresponding to the electronically modulated polarization orientation, wherein the periodic modulation corresponds to a location of the nerve or the nerve substructure.

15. The method of claim 14, wherein the electronically controllable polarization modulator comprises a twisted-nematic liquid crystal (TN-LC) device configured to rotate the polarization orientation continuously.

16. The method of claim 14, wherein the electronically controllable polarization modulator comprises a ferroelectric liquid crystal (FLC) device configured to switch the polarization orientation between two polarization states.

17. The method of claim 16, wherein the two polarization states correspond to different reflected-intensity responses from birefringent nerve tissue such that alternating between the states produces a flickering or strobing appearance of the nerve.

18. The method of claim 14, wherein the electronically controllable polarization modulator comprises a photoelastic modulator (PEM) configured to oscillate the polarization orientation of the SWIR illumination at a frequency in a range of about 10 kHz to about 100 kHz.

19. The method of claim 14, wherein electronically modulating the polarization orientation comprises using two or more cascaded liquid crystal modulators to generate a plurality of discrete polarization orientations.39MF-364871974Attorney Docket No.: 16569-20011.4020. The method of claim 14, wherein the polarization-resolving camera comprises a micropolarizer array including pixels or pixel groups having a plurality of polarization orientations.

21. The method of claim 14, further comprising synchronizing a polarization modulation waveform of the electronically controllable polarization modulator with an exposure timing of the polarization-resolving camera using phase-locking or encoder-based synchronization.

22. The method of claim 14, further comprising applying, by the one or more processors, lock-in detection, frequency-domain filtering, or Fast Fourier Transform (FFT) analysis to isolate periodic intensity modulation associated with birefringent nerve tissue.

23. The method of claim 14, further comprising automatically detecting, by the one or more processors, the periodic modulation in the time series of images.

24. The method of claim 11, further comprising generating, by the one or more processors, at least one of an alert and an annotation indicating at least one of a presence or a location of the nerve or the nerve substructure based on the detected periodic modulation.

25. A system for in vivo medical imaging of nerves or nerve substructures, the system comprising: an illumination system configured to direct short-wave infrared (SWIR) illumination toward a tissue region; an electronically controllable polarization modulator disposed in an illumination path and configured to vary a polarization orientation of the SWIR illumination incident on the tissue region overtime; an optical sensor system configured to receive a reflected portion of the SWIR illumination from the tissue region, the optical sensor system comprising a polarization-resolving camera configured to detect polarization-dependent intensity components of the reflected SWIR illumination at a plurality of polarization orientations; and one or more processors configured to generate a time series of images based on the detected polarization-dependent intensity components, the time series of images comprising a periodic modulation in reflected intensity from birefringent nerve tissue, wherein the periodic modulation corresponds to a location of the nerve or the nerve substructure.

26. A method for in vivo medical imaging of nerves, comprising: illuminating, by an illumination system, a tissue region with a short-wave infrared (SWIR) illumination light;40MF-364871974Attorney Docket No.: 16569-20011.40 detecting, by an optical sensor system, a reflected portion of the illumination light; and generating, by one or more processors, an image based on the detected reflected portion of the illumination light, wherein the generated image comprises a plurality of higher-intensity regions and a plurality of lower-intensity regions that form a pattern indicative of a substructure of a nerve in the tissue region.

27. The method of claim 26, wherein the SWIR illumination light is in a range of 1000 to 1750 nm.

28. The method of claim 26, wherein the detected reflected portion of the illumination light is reflected from a depth in the tissue of greater than or equal to 2 mm.

29. The method of claim 26, wherein the SWIR illumination light is pulsed.

30. The method of claim 26, wherein the SWIR illumination light is constant.

31. The method of claim 26, wherein the tissue is free of exogeneous imaging agents.

32. The method of claim 26, wherein the optical sensor system comprises an achromatic lens configured to focus the reflected portion of the illumination light onto the optical sensor.

33. The method of claim 26, wherein the optical sensor system comprises a bandpass filter configured to transmit a wavelength range of the reflected portion of the illumination light onto an optical sensor.

34. The method of claim 33, wherein the optical sensor system comprises a lens configured to focus the reflected portion of the illumination light transmitted by the bandpass filter onto the optical sensor.

35. The method of claim 26, wherein the illumination system comprises a polarizer configured to polarize the illumination light.

36. The method of claim 26, wherein the optical sensor system comprises a polarizer configured to polarize the reflected portion of the illumination light.

37. The method of claim 26, wherein:41MF-364871974Attorney Docket No.: 16569-20011.40 the illumination system comprises a first polarizer configured to polarize the illumination light with a first polarization; and the optical sensor system comprises a second polarizer configured to polarize the reflected portion of the illumination light with a second polarization that is orthogonal to the first polarization, such that the reflected portion of the illumination light after the second polarizer is cross-polarized with respect to the illumination light after the first polarizer.

38. The method of claim 26, wherein: the illumination system comprises a first polarizer configured to polarize the illumination light with a first polarization; and the optical sensor system comprises a second polarizer configured to polarize the reflected portion of the illumination light with a second polarization that is parallel to the first polarization, such that the reflected portion of the illumination light after the second polarizer is parallel-polarized with respect to the illumination light after the first polarizer.

39. The method of claim 26, wherein a power of the SWIR illumination light is greater than or equal to 5 mW at a wavelength range of less than or equal to 5 nm.

40. The method of claim 26, comprising automatically detecting the nerve in the image of the tissue region by detecting the patterns of higher-intensity and lower intensity regions.

41. The method of claim 40, comprising generating an output indicative of the detection of the nerve.

42. The method of claims 40, comprising annotating the image based on the detection of the nerve.

43. The method of claim 40, wherein automatically detecting the nerve in the image of the tissue region comprises: providing the image of the tissue region to a machine-learning algorithm trained to detect a presence of the pattern indicative of a location of the nerve; and receiving, from the machine-learning algorithm, output data indicative of the detection of the nerve in the image of the tissue region.

44. The method of claim 26, wherein the SWIR illumination light has a bandwidth of 200 nm or less.42MF-364871974Attorney Docket No.: 16569-20011.4045. The method of claim 26, wherein the substructure of the nerve comprises bands of Fontana.

46. The method of claim 26, wherein a spatial resolution of the image is equal to or finer than 200 micrometers.

47. A system for in vivo medical imaging of nerves, the system comprising: an illumination system configured to illuminate a tissue region with a short-wave infrared (SWIR) illumination light; an optical sensor system configured to detect a reflected portion of the illumination light; and one or more processors configured to generate an image based on the detected reflected portion of the illumination light, wherein the generated image comprises a plurality of higher-intensity regions and a plurality of lower-intensity regions that form a pattern indicative of a substructure of a nerve in the tissue region.43MF-364871974

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