System and method for adaptive control of tissue vasculature imaging

Abstract

A system and method provided to acquire images of tissue vascularization in a patient. The system includes a laser arranged in an illumination arm of the system and configured to deliver an incident light to a region of tissue in the patient, a camera arranged in a detection arm of the system and configured to receive light from region of tissue in response to the incident light to acquire image data, a polarization controller arranged in the illumination arm and configured to adjust a polarization of the incident light delivered by the laser to the region of tissue in the patient, and a processor configured to control the polarization controller to adjust the polarization of the incident light delivered by the laser based to modulate vascular contrast in the region of tissue based on at least one of a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, frame rate, or acquisition time to generate images of tissue vascularization in the patient.

Description

Attorney Docket No. 125141.04955SYSTEM AND METHOD FOR ADAPTIVE CONTROL OF TISSUE VASCULATURE IMAGING CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 748,301, filed Jan 22, 2025, which is hereby incorporated by reference in its entirety.GOVERNMENT FUNDING STATEMENT

[0002] This invention was made with government support under award numbers FA9550-20-1-0063 (agreement 2019A006306) from the Air Force Office of Scientific Research. The government has certain rights in the invention.BACKGROUND

[0003] Microvasculature plays an important role in the development, progression, and monitoring of numerous pathological and physiological conditions, including but not limited to diabetes, sepsis, neurodegeneration, inflammation, wound healing, and cancer. Accordingly, there is substantial interest in imaging microvascular structure and activity across a range of tissues, such as brain, retina, oral mucosa, and skin. Skin microvascular imaging is of particular interest because the skin is readily accessible and because changes in skin microvascular activity may be indicative of local dermatologic disease processes (e.g., psoriasis, bum wounds, systemic sclerosis, and skin cancer) as well as systemic diseases that manifest vascular signatures in the skin (e.g., chronic kidney disease, diabetes, and peripheral vascular disease). A variety of optical imaging techniques have been proposed for in vivo assessment of skin microvasculature, including optical coherence tomography angiography (OCTA), reflectance confocal microscopy (RCM), photoacoustic imaging, and dynamic light scattering imaging (DLSI). While some cross-sectional imaging modalities can provide certain types of information about the imaged tissues, such approaches often require complex optical architecture, relatively expensive components, and substantial acquisition and processing time to image fields of view (FoV s) larger than a few millimeters in diameter. Laser speckle contrast imaging (LSCI), also referred to as laser speckle imaging (LSI) or laser speckle contrast analysis (LASCA), is an imaging technique that can employ comparatively simple hardware to image larger fields of view with relatively fast acquisition times. However, the application of LSCI in skin vascular imaging has been very limited due to practical and technical limitationssuch as insufficient resolution of small vessels, reduced performance on darker skin due to non-negligible melanin absorption at 700-800 nm, and long acquisition and processing times.

[0004] Thus, there is a continuing need for systems and methods for imaging microvascular structure and activity across a range of tissues.SUMMARY

[0005] The present disclosure overcomes the aforementioned drawbacks by providing systems and methods for reliable microvascular imaging that can support screening, diagnosis, therapy selection, treatment guidance, and longitudinal monitoring for a broad range of dermatologic and systemic conditions in both clinical and non-clinical settings. More particular, systems and methods are provided for enhancing vascular contrast and robustness across diverse tissue conditions based on configurable speckle-based imaging systems and methods. As one non-limiting example, systems and methods are provided that provides sufficient degrees of freedom to empower clinical imaging with vascular contrast in different skin areas, while minimizing acquisition and processing times. As just one example, tunable coherence length and / or polarization state of light may be controlled and the resulting imaging data processed to provide image data to clinicians that was previously unavailable.

[0006] In accordance with one aspect of the present disclosure, a system is provided for acquiring images of tissue vascularization in a patient. According to one non-limiting aspect of the present disclosure, the system may include a laser arranged in an illumination arm of the system and configured to deliver an incident light to a region of tissue in the patient, a camera arranged in a detection arm of the system and configured to receive light from region of tissue in response to the incident light to acquire image data, a polarization controller arranged in the illumination arm and configured to adjust a polarization of the incident light delivered by the laser to the region of tissue in the patient, and a processor configured to control the polarization controller to adjust the polarization of the incident light delivered by the laser to modulate vascular contrast in the region of tissue based on at least one of a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, frame rate, or acquisition time to generate images of tissue vascularization in the patient.

[0007] According to another aspect of the disclosure, a system is provided for acquiring tissue vascularization in a patient and may include a coherent light source arranged in an illumination arm of the system and configured to deliver an incident light to a region of tissue in a patient, a detector arranged in a detection arm of the system and configured to receive lightfrom the region of tissue in response to the incident light to acquire image data, a coherence controller configured to adjust an effective coherence length of incident light, and a processor configured to control the coherence controller to adjust the effective coherence length of the incident light to modulate vascular contrast in the region of tissue based on at least one of a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, frame rate, or acquisition time to generate images of tissue vascularization in the patient.

[0008] According to yet another aspect, a method is provided for acquiring images of tissue vascularization in a patient using a system that may include a light source arranged in an illumination arm to deliver an incident light to a region of tissue in the patient, a detector arranged in a detection arm to receive light from the region of tissue in response to the incident light to acquire image data, a coherence controller configured to adjust an effective coherence length of incident light, and a polarization controller arranged to adjust a polarization of the incident light or the light received from the region of tissue. The method may include controlling at least one of the coherence controller to adjust the effective coherence length of the incident light or the polarization controller to adjust the polarization of the incident light or the light received from the region of tissue to modulate vascular contrast in the region of tissue based on at least one of a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, frame rate, or acquisition time to generate images of tissue vascularization in the patient.

[0009] According to yet another aspect, a laser speckle imaging system is provided for acquiring tissue vascularization in a patient and may include a coherent light source arranged in an illumination arm of the system and configured to deliver an incident light to a region of tissue in the patient, a detector arranged in a detection arm of the system and configured to receive light from the region of tissue in response to the incident light to acquire image data, a tunable operating parameter controller configured to adjust at least one operational parameter associated with at least one of the incident light or the received light, and a processor configured to control the tunable operating parameter controller to adjust the at least one operational parameter based on at least one of a patient parameter or a clinical application to generate images of tissue vascularization in the patient.

[0010] The foregoing and other aspects and advantages of the disclosure will appear from the following description. In the description, reference is made to the accompanying drawings which form a part hereof, and in which there is shown by way of illustration a preferredconfiguration of the disclosure. Such configuration does not necessarily represent the full scope of the disclosure, however, and reference is made therefore to the claims and herein for interpreting the scope of the disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The invention will be better understood and features, aspects and advantages other than those set forth above will become apparent when consideration is given to the following detailed description thereof. Such detailed description makes reference to the following drawings.

[0012] FIG. 1 is a general illustration of a system for acquiring images of tissue vascularization in a patient, in accordance with some aspects of the present disclosure.

[0013] FIG. 2 illustrates a general illustration of a system for speckle imaging with tunable polarization state, in accordance with some aspects of the present disclosure.

[0014] FIG. 3 illustrates a general illustration of a system for speckle imaging with tunable coherence length, in accordance with some aspects of the present disclosure.

[0015] FIG. 4 a flowchart diagramming a method of for acquiring images of tissue vascularization in a patient, in accordance with some aspects of the present disclosure.

[0016] FIG. 5 is a flowchart diagramming an example polarization tuning procedure of the systems of FIGS. 1 and 2, in accordance w ith some aspects of the present disclosure.

[0017] FIG. 6 is a flowchart diagramming an example coherence length tuning procedure of the systems of FIGS. 1 and 3, in accordance with some aspects of the present disclosure.

[0018] FIG. 7 illustrates representative experimental results showing an impact of input polarization state on speckle-derived vascular maps using the system of FIG. 1, in accordance with some aspects of the present disclosure.

[0019] FIG. 8 illustrates representative experimental results showing an impact of coherence length on speckle-derived vascular maps using the system of FIG. 1, in accordance with some aspects of the present disclosure.

[0020] FIG. 9 an example of a system for acquiring images of tissue vascularization in a patient, in accordance with some configurations of the disclosed subject matter.

[0021] FIG. 10 show s an example of hardware that can be used to implement a computing device and server in accordance with some configurations of the disclosed subject matter.DETAILED DESCRIPTION

[0022] In speckle-based imaging, a coherent illumination directed to tissue can produce a speckle pattern formed by the light scattered from the tissue, and motion of scattering particles (e.g., blood cells) can induce spatial and temporal intensity fluctuations that may be captured by a detector and processed to derive perfusion and / or vasculature-related information. In practice, conventional laser speckle imaging approaches may fail to provide clinically useful vascular images across the range of patient-to-patient variability and clinical use cases. For example, vascular contrast may be insufficient or inconsistent due to differences in skin pigmentation, anatomical site, surface reflections, tissue scattering / absorption properties, imaging geometry, and / or the target tissue being non-skin (e.g.. subsurface or ocular tissue).

[0023] The present disclosure provides systems and methods for laser speckle imaging that are configured to produce clinically useful vascular images of tissue by enabling the imaging system to be adaptable to the patient and / or the clinical application. In particular, the disclosed systems can provide sufficient degrees of freedom to enable clinically useful vascular contrast in different tissue regions while minimizing acquisition and processing times. Rather than relying on a single fixed operating configuration, the disclosed systems may be configured to adapt operational parameters to the tissue site and / or patient-specific optical conditions, and a processor may be configured to assist in determining and applying the operating parameters that yield improved vascular visibility for a region of interest. In some configurations, and with reference to the figures described herein, a disclosed system may include an illumination arm (e.g., a laser source with optional tunable coherence length) configured to deliver light to tissue of interest and a detection arm configured to receive light scattered from the tissue and to acquire speckle images. The systems and methods provided may be configured to actively vary at least one acquisition degree of freedom that influences speckle formation including a polarization state associated with illumination and / or detected light and / or a coherence characteristic (e.g., coherence length or effective coherence length) of the delivered illumination. As one non-limiting example, the disclosed systems may provide sufficient degrees of freedom to empower clinical imaging with vascular contrast in different tissue areas (including different skin areas and / or non-skin tissues), while minimizing acquisition and processing times. By tuning one or both of these degrees of freedom via tunable coherence length controller, polarization controller, and / or other optical and opto-mechanical components, the systems and methods provided herein can be configured to enhance anobjective vascular contrast metric for a selected region of interest, to reveal different subsets of vasculature, and / or to reduce sensitivity’ to conditions that degrade contrast in conventional designs.

[0024] In further configurations, a processor may receive speckle frames acquired by a detector and generate one or more vascular images and / or extract perfusion information based on one or more speckle-derived metrics, for example, a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, frame rate, acquisition time to generate images of tissue vascularization in the patient, and / or combinations thereof. The processor may be configured to assist in determining and / or selecting operating parameters suitable for the patient and / or clinical application, including selecting and / or recommending an operating setting (e.g.. polarization state, coherence length setting, exposure setting, aperture setting, acquisition frame rate, and / or combinations thereof) that can improve vascular visibility’ for a target tissue region. The processor may further determine whether the vascular images have achieved at least a threshold value of a vascular contrast metric and, based on the determination, adjust one or more operating settings to increase the vascular contrast metric. The processor may additionally generate multiple vascular images corresponding to different operating settings and combine or fuse such images to provide an enhanced vascular representation.

[0025] As will be described, the disclosed systems and methods may be configured to reveal in-vivo vasculature in a plurality of organs and tissue types, and are not limited to skin. For example, the disclosed system may be configured for vascular imaging and / or perfusion assessment in skin, brain, retina, and other subsurface tissue beds, depending on the selected optical configuration, operating wavelength(s), and region-of-interest characteristics. The disclosed system may be adapted for different optical responses encountered across tissues (e.g., superficial skin, subdermal tissue, ocular tissue), rather than relying on a single fixed operating configuration.

[0026] In a non-limiting configuration, the disclosed system may be configured for skin microvascular imaging, where perfusion can play a significant role in the development and progression of various conditions. By enabling improved visualization and / or quantification of vascular features, the disclosed system may support monitoring and / or treatment of dermatologic conditions including, by way of non-limiting example, psoriasis, bum wounds, vascular malfonnations such as port wine stain birthmarks, inflammatory and fibrotic diseases such as systemic sclerosis, and malignant or premalignant lesions. Additionally, becausesystemic diseases can manifest vascular signatures in the skin, the disclosed system may be used to monitor diseases affecting other organs that induce changes in skin vascular activity, including, for example, chronic kidney disease, diabetes, and peripheral vascular disease.

[0027] In some configurations, the disclosed system may include and / or be compatible with a near-infrared illumination source that operates at a wavelength selected to reduce melanin absorption relative to shorter wavelengths commonly used in speckle imaging, thereby improving performance across a wider range of skin pigmentation. In one exemplary use case, the disclosed system may be employed as a tool for skin cancer assessment and / or detection based on vascular contrast associated with tumor-triggered angiogenesis. For instance, malignant lesions may exhibit abnormal microvasculature relative to benign lesions in terms of microvessel density, morphology, and / or spatial pattern. The disclosed system may be configured to generate one or more vascular images of a lesion and adjacent tissue, and a processor may be configured to extract one or more vascular network metrics (e.g., density, and / or perfusion heterogeneity measures). In further embodiments, the processor may apply a machine learning or artificial intelligence framework to such metrics and / or to the vascular images to facilitate automated classification, triage, and / or decision support. Such configurations may be suitable for deployment in point-of-care or primary care settings, where trained staff (e.g., nurses or technicians) may use the disclosed system to rapidly examine lesions and identify subjects for further evaluation in specialized clinics.

[0028] Unlike conventional LSI devices that rely on fixed operating parameters, the disclosed systems can adapt one or more operational parameters to the patient and / or the clinical application to obtain clinically useful vascular images. In some configurations, adaptability may be provided by tuning polarization state (in an illumination path and / or a detection path) and optionally tuning coherence length (or effective coherence length), while the processor assists in selecting operating settings that increase a vascular contrast metric for a region of interest. In further embodiments, the system may acquire speckle data at multiple polarization states and / or multiple coherence settings, generate a plurality7of vascular images (e.g., including images based on ASDI and / or BFI), and select, combine, or fuse such images to provide an enhanced vascular representation with reduced acquisition and processing time relative to repeated trial-and-error operation.

[0029] FIG. 1 illustrates an example laser speckle imaging (LSI) system 100 configured for in vivo vascular imaging of tissue 128 (e.g., skin). The system 100 may include an illumination arm configured to deliver an illumination light path 152 to a tissue 128 and adetection arm configured to receive a detection light path 124 backscattered (e.g., in response to the incident light) from the tissue 128 to form speckle images suitable for perfusion and / or vascular visualization. Although FIG. 1 depicts a benchtop / free-space optical layout, in other configuration, one or more components may be integrated into a handheld housing, a probe, an endoscopic / dermoscopic form factor, or a cart-based clinical instrument, and optical coupling may be via free-space optics, fiber delivery / collection, or combinations thereof.

[0030] In the illustrated non-limiting configuration, the illumination arm may include a light source 132, which may be a coherent or partially coherent source such as a near-infrared illumination source, a laser diode, fiber laser, or other narrowband source. The light source 132 may operate in a band selected to improve performance across a range of tissue pigmentation levels, for example, the light source 132 may emit near about 980 nm, although other wavelengths and wavelength bands may be used. Light emitted by the light source 132 may be coupled into a collimator 136 configured to collimate and / or shape the output beam for dow nstream optics. In some configurations, the collimator 136 may include one or more lenses, fiber collimators, and / or adjustable mounts to set beam diameter, divergence, and alignment.

[0031] Downstream of the collimator 136, the illumination arm may include a first polarization element 140 (also referred to herein as a first polarization controller or tunable polarization controller / module). The polarization element 140 may be configured to define and / or adjust a polarization state of illumination delivered to the tissue 128. In some configurations, the polarization element 140 may include a linear polarizer set to provide S-polarization, P-polarization, or an intermediate linear polarization orientation with respect to a plane of incidence, and / or may be configured to generate, provide or select linear, elliptical or circular polarization states. For example, light can be polarized parallel or perpendicular, respectively, to the plane of incidence (e.g., the XZ -plane), or light may be polarized at any intermediate angle between 0° and 90°. Alternatively, the polarization element 140 can be configured to illuminate the tissue 128 with right- or left-handed circularly or elliptically polarized light. Various polarization states of the incident light may reveal different subsets of blood vessels, as will be discussed in details. Accordingly, by tuning the polarization of the incident light, the vascular contrast in the resulting images can be modulated. In some configurations, the polarization element 140 may be implemented as a tunable polarization controller / module including, by way of non-limiting examples, a rotating waveplate, a liquid crystal polarization rotator, an electro-optic modulator, or a liquid crystal spatial light modulator configured to impose spatially varying polarization across the illuminated field. Inthe example of the polarization element 140 implemented as rotating waveplates, the system 100 can tune the polarization state of the light incident on the tissue 128 (e.g., mechanically or via software), and can illuminate the tissue 128 with different polarization states. In the example of the polarization element 140 implemented as liquid crystal polarization rotators, the system 100 can adjust the polarization state of the light incident on the tissue 128 via software by controlling the voltage of the liquid crystal polarization rotators. In the example of the polarization element 140 implemented through liquid crystal spatial light modulators (SLM), the polarization state of the light incident on the tissue 128 can be spatially encoded, such as each pixel of the SLM can achieve a different polarization state. Therefore, the system 100 can use different polarization states for different subregions (e.g., region of interests) of the illuminated area, thus optimizing the polarization state for each subregion.

[0032] The illumination arm may further include a beam expansion and / or beam shaping subsystem, which may include one or more optical elements 144 and 148 (e.g., beam expander / focusing lenses) configured to expand, collimate, homogenize, and / or shape the illumination beam to cover a desired field of view on the tissue 128. In some configurations, the beam expansion subsystem may be removed depending on clinical workflow requirements.

[0033] A stabilizing and / or coupling window 156 may be positioned between the optics and the tissue 128. The window 156 may include a transparent plate (e.g., glass, polymer) configured to provide a controlled working distance and / or to mechanically stabilize the tissue surface to reduce motion artifacts. In some configurations, the window 156 may be configured with anti -refl ection coatings, index-matching features (e.g., gel), disposable covers, and / or sterility barriers. In further configurations, the window 156 may be removed or replaced by a contact ring or spacer depending on clinical workflow requirements.

[0034] The detection arm may be arranged to receive light backscattered from the tissue 128 (optionally through the window 156) and to image the resulting speckle pattern onto a detector 104. In the illustrated non-limiting configuration, the detector 104 may include a camera, such as a two-dimensional image sensor configured to acquire speckle frames at one or more exposure times and frame rates suitable for speckle-based vascular imaging. In some configurations, the detector 104 may be implemented as a black silicon camera to enhance quantum efficiency at near-infrared wavelengths (e g., around 980 nm), although other detector technologies may be used, including conventional CMOS, sCMOS, CCD, EMCCD, InGaAs, and / or other photosensor arrays depending on wavelength and sensitivity targets. The detector 104 may also be replaced by a ID photosensor, accordingly, the illumination arm may includea line illumination coupled with galvos for scanning across the area of interest on the tissue 128.

[0035] The detection arm may include one or more imaging optics 112 and 116 configured to collect scattered light and form an image on the detector 104, which may include one or more focusing lenses arranged as a relay system (e.g., a 4-f system) or other imaging configuration. The detection arm may further include an aperture stop 120 (e.g., an iris) positioned to control numerical aperture and / or speckle size at the detector 104. By adjusting the aperture stop 120, the system 100 may be configured to tune speckle grain size relative to detector pixel size, thereby improving speckle contrast estimation and / or reducing spatial averaging artifacts. In other configurations, speckle size control may be achieved using fixed apertures, variable zoom optics, or adjustable working distance.

[0036] A second polarization element 108 (also referred to herein as a second polarization controller or tunable polarization controller / module) may be positioned in the detection arm to select and / or filter the polarization state of light incident on the detector 104. Any of the structures, configurations, and alternative implementations described herein with respect to the first polarization control element 140 as well as their associated functions (e.g., selecting, filtering, and / or tuning polarization among linear / elliptical / circular states and operating in parallel / crossed / intermediate orientations), may likewise be used for and are equally applicable to the second polarization control element 108. In some embodiments, the second polarization element 108 may be oriented relative to the first polarization element 140 to implement parallel-polarized detection, crossed-polarized detection, or intermediate polarization filtering. The second polarization element 108 may be configured to filter light scattered by the tissue 128 so as to select only light having a desired polarization relationship with respect to the incident light, for example, using crossed or parallel polarizers to reject or preserve light scattered from the tissue 128 surface. In alternative embodiments, the second polarization element 108 may be omitted in configurations that rely on illumination-side polarization control only. Although FIG. 1 illustrates polarization control in both the illumination and detection arms, in some embodiments only one polarization controller (e.g., 140 or 108) may be provided. Further, the polarization state may be actively varied among a plurality of polarization states during imaging, and the resulting speckle datasets may be processed to generate corresponding vascular images. The system 100 may be configured to select a polarization state that increases an objective vascular contrast metric (e.g., a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters,frame rate, or acquisition time) for a selected region of interest, and / or to combine vascular images obtained at different polarization states to yield an enhanced vascular representation.

[0037] In addition to polarization control, the system 100 may be configured with an adaptive coherence control mechanism 164 (e.g., a coherence controller) operatively coupled to the light source 132 or the detector 104 to adjust a coherence characteristic of illumination delivered to the tissue 128, such as coherence length or effective coherence length. The adaptive coherence length control mechanism 164 can be used alone or combined with the adaptive polarization controls. In some configurations, the coherence controller 164 may be implemented using a rotating diffuser configured to reduce spatial coherence of the light source 132 and / or a wavelength-swept source in which sweep parameters can be adjusted during one or more detector 104 exposure intervals to vary the effective coherent length by changing the speed of the sweep. The system 100 may be configured to vary coherence settings to reveal different vascular features and / or to reduce artifacts, and may select a coherence setting based on a vascular contrast metric (e.g., a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, frame rate or acquisition time) and / or combine information obtained from multiple coherence settings. In some configurations, the adaptive coherence length control mechanism 164 may be implemented by using a variable wavelength light source by changing the output wavelength during the integration time of the detector 104, obtained an effective coherence length. In another example, the light source 132 may be a broadband light source provided with a spectral filter with variable bandwidth, various coherence lengths can be achieved by adjusting the bandwidth of the spectral filter. In yet another configuration, the broadband light source 132 may be pulsed, and by stretching the pulse and the use of an intensity modulator, pulses of different spectral w idths can be achieved.

[0038] In operation, the detector 104 may acquire a plurality of speckle frames while the tissue 128 is illuminated. The acquired speckle frames may be provided to a processor configured to compute one or more speckle-derived metrics and generate one or more vascular images. Such metrics may include, by w ay of non-limiting examples, a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, acquisition time, frame rate, speckle contrast metrics, temporal autocorrelation and / or decorrelation metrics, adaptive speckle decorrelation indices (ASDI), and blood flow indices (BFI). The processor may further be configured to generate multiple vascular images using different metrics (e.g., a first metric that preferentially reveals smaller and / or superficial vessels with slower blood flow and a second metric that preferentially reveals larger and / or deeper vesselswith faster blood flow), and may fuse or otherwise combine such outputs. For each imaged area (e.g., face, arms, hands, legs), the system 100 may select predetermined operational parameters (e.g., coherence length and polarization state) that can maximize vascular contrast. In some configurations, a machine learning model or artificial intelligence framework may be applied to the vascular images and / or derived vascular network metrics to support automated classification, operational parameter recommendation, and / or decision support (e.g., lesion screening or triage).

[0039] Alternatively, the system 100 may employ an LSI device with a pulsed light source to achieve adaptive pulse width and / or adaptive timing control. In some configurations, the system 100 may employ a pulsed light source (e.g., the light source 132 operated in a pulsed mode or replaced by a pulsed laser) to provide improved control of speckle blurring relative to continuous-wave (CW) illumination, particularly where the relationship between detector integration time and frame rate influences speckle-derived vascular metrics such as a blood flow index (BFI) and an adaptive speckle decorrelation index (ASDI). In such non-limiting configuration, the pulsed light source may be configured to deliver one or more illumination pulses during an exposure interval of the detector 104 such that the amount of speckle blurring may be set by pulse duration, pulse timing, and / or pulse repetition characteristics, optionally independent of (or in addition to) the detector integration time. For example, as many cameras exhibit a duty cycle less than 100% (e.g., having deadtime between successive exposures), a pulsed illumination scheme may reduce wasted irradiation by delivering light primarily or exclusively during active integration periods, thereby increasing acquired signal efficiency while maintaining compliance with maximum permissible exposure limits. The pulse timing and / or pulse width may be selected to match the duty cycle of the detector 104, or may intentionally be set higher or lower than the duty cycle to modulate the effective speckle integration window and thereby adjust vascular contrast.

[0040] In one implementation, the system 100 may vary one or more detector settings (e.g., integration time and / or frame rate) while also adapting a pulse duration (and optionally pulse energy) of the light source 132 to increase signal-to-noise ratio and / or vascular contrast for a selected region of interest. In another implementation, the pulsed light source may be synchronized to detector readout such that pulses are delivered at selected times relative to successive frames, thereby effectively changing an inter-frame sampling interval even when the nominal detector frame rate remains fixed. By way of example, a first pulse may be timed to occur near an end portion of a first acquired frame and a second pulse may be timed to occurnear a beginning portion of a subsequent acquired frame, such that the effective time separation between the two pulses can differ from the nominal frame period. In this manner, the system 100 may adjust an effective frame rate (or effective sampling delay) via pulse-to-pulse timing, and the pulse timing offset may be adapted for a given tissue site to modulate BFI, ASDI, and / or other speckle-derived contrast metrics. In further embodiments, the pulsed illumination may be combined with tunable polarization control (e.g., polarization elements 140 and / or 108) and / or tunable coherence control 164 (if provided) so that timing, polarization state, and coherence characteristics may be jointly adjusted to improve vascular visibility and robustness.

[0041] FIG. 2 illustrates an example laser speckle imaging (LSI) system 200 that may be configured similarly to system 100 of FIG. 1, with adaptive polarization control provided in one or both of an illumination arm and a detection arm. In the illustrated embodiment, a light source 232 (e.g., a laser) may provide illumination that can be shaped by a collimator 236 and then may pass through a first polarization controller 240 disposed in the illumination path 252. The first polarization controller 240 may be configured to set and / or vary7a polarization state of an illumination light path 252 delivered to tissue 228 (e.g., skin), including, for example, linear, elliptical, and / or circular polarization states, and may be implemented using any suitable tunable or non-tunable polarization elements (e.g., a linear polarizer with a rotatable mount, one or more waveplates, a liquid crystal polarization rotator, an electro-optic modulator, and / or a spatial light modulator). The illumination arm may further include a beam-expanding and / or beam-shaping subsystem, which may include one or more optical elements 244, 248 configured to expand and / or condition the beam to illuminate a desired field of view on the tissue 228.

[0042] In the detection arm, light backscattered from the tissue 228 may propagate along a detection light path 224 and may be collected and imaged by one or more imaging optics 216 and 212 onto a detector 204 (e.g., a camera). An aperture stop 220 (e.g.. an iris) may be positioned in the detection path to control numerical aperture and / or speckle size at the detector 204. A second polarization controller 208 may be positioned in the detection arm and configured to filter and / or select a polarization component of the detected light prior to detection, for example in a parallel-polarized, crossed-polarized, or intermediate orientation relative to the polarization set by the first polarization controller 240. In this manner, the system 200 may be configured to acquire speckle datasets under different polarization conditions, thereby enabling generation, selection, and / or combination of vascular images corresponding to different polarization states based on a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, frame rate, and / or acquisition time. Inalternative configurations, one of the polarization control modules 240 or 208 may be omitted such that polarization control is provided only in the illumination arm or only in the detection arm. Further, the polarization control of FIG. 2 may be used alone or combined with coherence control (e.g., as shown in FIG. 3) in other configurations.

[0043] FIG. 3 illustrates an example laser speckle imaging (LSI) system 300 that may be configured similarly to system 100 of FIG. 1, with an adaptive coherence length control mechanism. In the illustrated non-limiting configuration, a light source 332 may include a laser source coupled with an adaptive coherence controller (e.g., a coherence length controller, a spatial coherence reduction element and / or a spectral / temporal control mechanism) configured to vary a coherence characteristic of light delivered to tissue 328 (e.g., skin), such as coherence length and / or effective coherence length. The illumination arm may further include a beamexpanding and / or beam-shaping subsystem, which may include one or more optical elements 344, 348 configured to expand and / or condition an illumination light path 352 to illuminate a desired region of interest on the tissue 328.

[0044] Light backscattered from the tissue 328 may propagate along a detection light path 324 and may be collected and imaged by one or more imaging optics 316 and 312 onto a detector 304 (e.g., a camera). An aperture stop 320 (e.g., an iris) may be provided in the detection arm to adjust numerical aperture and / or speckle size at the detector 304. By vary ing coherence characteristics using the light source module 332, the system 300 may be configured to acquire speckle datasets under different coherence settings, which can reveal different vascular features and / or improve a vascular contrast metric for a selected region of interest. In some embodiments, vascular images obtained under different coherence settings may be compared, selected, and / or combined to yield an enhanced vascular representation. In this manner, the system 300 may be configured to acquire speckle datasets under different coherence conditions, thereby enabling generation, selection, and / or combination of vascular images corresponding to different effective coherence length based on a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, frame rate and / or acquisition time. In alternative configurations, the adaptive coherence-length control of the module 332 may be implemented using, by way of non-limiting example, a rotating diffuser or mode-mixing element to reduce spatial coherence, a wavelength-swept source in which sweep parameters are adjusted to create different effective coherence lengths during an exposure, a broadband source with a bandwidth-tunable spectral filter, and / or temporally modulated or pulsed illumination configured to control effective coherence and / or speckleintegration time. Further, the coherence control approach of FIG. 3 may be used alone or combined with polarization control (e.g., as shown in FIG. 2) in other configurations.

[0045] Referring now to FIG. 4, a flowchart is illustrated setting forth steps of an example method of operation 400 for acquiring images of tissue vascularization in a patient. The method 400 may be performed or operated using one or more of the systems described herein, including laser speckle imaging systems described herein, including, by way of non-limiting example, systems 100, 200, and / or 300. The systems provided herein and, thus, the method of operation 400, are designed to allow selection or adjustment of operational parameters for imaging to create images of tissue showing vascularization or vascular structures that are suitable for clinical use. As will be described, operational parameters can include coherence length or selection or coordination of polarization. In one non-limiting example, adjusting coherence length, or effective coherence length, and / or using different polarization states for the illumination (and optionally for the detected light) can enable visualization of different vascular structures and / or vascular contrast. Thus, operational parameters can be used to modulate or maximize vascular contrast to create clinically useful vascular images.

[0046] The method 400 may be executed by a processor (e.g., processor of computing device and / or processor of server) in communication with a laser speckle system (e.g., laser speckle system 100, 200, 300) that may include a light source (e.g., light source 132, 232, or 332), one or more polarization control controllers (e.g., polarization element / controller 140, 108, 240 and / or 208). an coherence controller (e.g., coherence-related control within light source and / or a coherence control mechanism operatively coupled to the light source), and a detector (e.g., camera 104, 204, or 304). In some configurations, the method 1000 may be executed locally on computing device, and additionally or alternatively one or more steps may be executed, in whole or in part, on server, with information communicated over communication network, and with results presented via a display (e.g., a user interface) and / or received via one or more inputs from the user. In some configurations, the processor may control at least a portion of system to generate control signals for one or more tunable components (e.g., polarization controller, coherence controller, etc.) of the laser speckle system. It should be appreciated that method 400 is presented as a workflow in which one or more operational parameters (e g., polarization state, coherent length) of speckle imaging may be adapted to improve clinical utility of vascular image data for a given patient parameter and / or clinical application, as will be described further below. As used herein, a patient parameter may include any information associated with a patient that is relevant to selectionand / or adjustment of one or more operational parameters for acquiring clinically useful vascular images, including, by way of non-limiting example, categorical skin tone, estimated melanin content, an inferred absorption characteristic at one or more wavelengths, skin pigmentation, tissue absorption and / or scattering characteristics, or anatomical location of a region of interest. As used herein, a clinical application (also referred to as a clinical condition or imaging task condition) may include any suspected, known, or monitored disease state for which vascular imaging is relevant and any information associated with an intended clinical use, workflow, or target imaging objective that is relevant to selecting and / or adjusting one or more operational parameters for acquiring clinically useful vascular images including, by way of non-limiting example, dermatologic conditions such as psoriasis, bum wounds, port wine stain birthmarks or other vascular malformations, systemic sclerosis, and skin cancer, as well as systemic diseases that may induce changes in skin vascular activity such as chronic kidney disease, diabetes, and peripheral vascular disease.

[0047] Turning now to FIG. 4, at process block 402, the process may start with receiving or otherwise identifying a region of tissue for imaging of tissue vascularization. The region of tissue may be any of a variety of tissues and / or anatomical regions desired for imaging vascular structures and / or perfusion, including but not limited to skin (including, superficial skin, subdermal tissue, ocular tissue), brain, retina, and other subsurface tissue beds. At process block 404, inputs for the imaging process may be provided. These may include operating wavelength(s) and / or region-of-interest characteristics. At process block 406, the operational parameters for imaging may be selected and or adjusted.

[0048] For example, the system may illuminate tissue, for example, with coherent light by a coherent light source. For example, the tissue may be tissue 128, 228, or 328, and illumination may be provided by the coherent light source such as a laser (e.g., light source 132, 232, or 332) delivering illumination along an illumination light path (e.g., illumination light path 152, 252, or 352) to a region of tissue in a patient. The illumination may be delivered as a full-field beam (e.g., via beam expansion optics 144, 244, 344 and associated lenses 148, 248, 348) and / or may be delivered as scanned illumination (e.g., a line or spot) in configurations employing a one-dimensional photosensor and a scanning subsystem. The illumination wavelength may be selected based on desired penetration depth and tissue absorption characteristics, and in some configurations may be in a near-infrared band.

[0049] At process block 408, the system may acquire an imaging data from the region of tissue using the operational parameters. As shown, optionally, the process 400 may iterate toprocess block 406 to adjust operational parameters. In some configurations, the operational parameter may be polarization state or coherence length, or effective coherence length.

[0050] More particularly, in some example configurations, the operational parameter may be any controllable parameter associated with at least one of the incident light delivered by the coherent light source or in the illumination arm, the received light collected by the detection arm, and / or acquisition settings used to acquire the image data (e.g., integration time, frame rate, exposure timing, or other acquisition-time settings). In some configurations, process block 406 and 408 may iterate based on intermediate results. In one non-limiting example, the operational parameter selected or adjusted at step 406 may include a polarization-related parameter, and the system may include a polarization controller arranged in the illumination arm (e.g., polarization element / controller 140 or polarization controller 240) configured to adjust a polarization of the incident light delivered by the laser to the region of tissue in the patient. In such configuration, the processor may control the polarization controller to adjust polarization of the incident light to modulate vascular contrast in the region of tissue and generate images of tissue vascularization in the patient, including adjusting polarization while the camera acquires the image data. In some configurations, polanzation adjustment may include adjusting polarization on an illumination side (i.e., within the illumination arm) and additionally or alternatively adjusting polarization on a detection side (i.e., within the detection arm). For example, the system may include another polarization controller arranged in the detection arm (e.g., polarization element / controller 108 or polarization controller 208), and the processor may be configured to adjust polarization of the incident light in concert with polarization of light received from the region of tissue to select a desired vascular contrast. In further configurations, the processor may calibrate and / or coordinate illumination-side and detection-side polarization settings to complement one another for a particular clinical application, patient parameter, and / or tissue site, for example, to suppress surface reflections in some cases while preserving signal components that can improve visualization of targeted vessel sizes in other cases. The polarization state may be adjusted among a plurality of polarization states during imaging, including linear polarization, elliptical polarization, and / or circular polarization. In non-limiting implementations, the polarization controller may include a rotating waveplate, a liquid crystal polarization rotator, a liquid crystal spatial light modulator, and / or other tunable polarization devices. In some configurations, polarization selection may include setting relative orientations between illumination-side and detection-side polarization states (e.g., crossed, parallel, or intermediate), and / or selecting an absolutepolarization orientation relative to an incident plane and / or sample orientation to modulate vascular contrast.

[0051] Additionally or alternatively to polarization adjustment, the operational parameter selected or adjusted at step 406 may include a coherence-related parameter. For example, the system may include a coherence controller configured to adjust a coherence length and / or an effective coherence length of the incident light, and the processor may be configured to operate the coherence controller to modulate vascular contrast to generate images of tissue vascularization in the patient. In some configurations, coherence control may be implemented using a rotating diffuser to reduce spatial coherence, and in other configurations coherence control may be implemented using a variable-wavelength or wavelength-swept source in which the coherence controller varies a sweep parameter to change wavelength during an integration time of the camera to adjust the effective coherence length of the incident light. In further configurations, the processor may control the coherence controller and / or the polarization controller based on an integration time and / or a frame rate to modulate contrast of vessels in the images of tissue vascularization, including tailoring settings to emphasize different vessel sizes and / or depths within a selected region of tissue. Coherence tuning / adjusting may be performed sequentially across multiple coherence settings and / or dynamically during acquisition, and may be used alone or in combination with polarization tuning to improve vascular contrast for a selected region of interest.

[0052] Finally, at process block 410. the imaging data may be delivered as images showing tissue vascularization that enables clinically useful vascular imaging across variable tissue optical response. In some examples, the operational parameters may be adjusted or selected by the processor based on one or more inputs indicative of the location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters (e.g., absorption expected due to pigmentation or wavelength-dependent absorption), frame rate, or an acquisition time. The processor may determine and apply operational parameter settings in a variety of ways. In a non-limiting example, the operational parameter settings may be selected directly by a user through a user interface (e.g., via inputs and displayed via display), optionally using presets associated with clinical applications, clinical conditions, anatomical sites, or tissue types. In another non-limiting example, the user may provide one or more patient parameter- or tissue-related inputs (e.g., pigmentation category. estimated absorption / scattering, anatomical location, desired acquisition time), and the processor may determine corresponding operational parameter settings using a lookup table, rules engine,calibration data, and / or a predictive model. In yet another non-limiting example, the system may operate in a closed-loop mode in which the processor may acquire image data (or preliminary image data) and may evaluate whether the resulting vascular images are sufficient for clinical purposes, and may adjust one or more operational parameters accordingly. For example, the processor may compute a vascular contrast metric and determine whether one or more vascular images have achieved at least a threshold value of the vascular contrast metric; if not, the processor may automatically adjust operational parameters and / or prompt the user to approve an adjustment and re-acquire speckle frames. In certain configurations, an artificial intelligence or machine-learning model may be used to evaluate image adequacy for a stated clinical application (e.g., whether vascular contrast, vessel visibility, and / or artifact level meet a target), and to recommend or apply operational parameter adjustments to improve clinical usefulness while minimizing acquisition and processing time.

[0053] Thus, when implementing the method 400 of FIG. 4, the system may generate an image based on the speckle frames by a processor. The processor may receive the speckle frames captured by the detector and compute one or more speckle-derived metrics to generate one or more vascular images of the region of tissue. For example, the processor may generate a plurality of vascular images corresponding to different operational parameter settings, including different polarization states and / or different coherence settings, and may generate vascular images based on an adaptive speckle decorrelation index (ASDI), a blood flow index (BFI), and / or other speckle-derived metrics. In some configurations, the processor may compute a vascular contrast metric for each of a plurality of polarization states and control the polarization controller to modulate vascular contrast using the vascular contrast metric, and additionally or alternatively may compute a vascular contrast metric for each of a plurality of effective coherence lengths and control the coherence controller to modulate vascular contrast using the vascular contrast metric. In further configurations, the processor may combine vascular images obtained using different polarization states and / or different effective coherence lengths (e.g., by fusion, weighted combination, selection, or compositing), and may generate multiple output vascular images including a first vascular image produced using a first speckle-derived metric and a second vascular image produced using a second speckle-derived metric different from the first. The vascular images may be displayed via a display and / or stored in memory and / or transmitted over communication network.

[0054] It should be appreciated that the steps of method 400 may be re-ordered, repeated, performed in parallel, and / or combined, and that one or more steps may be optional dependingon the implementation. For example, in polarization-focused configurations, coherence adjustment may be omitted while polarization state adjustment may be performed across a plurality of polarization states, and in coherence-focused embodiments, polarization state adjustment may be omitted while coherence adjustment is performed across a plurality of effective coherence lengths. In combined configurations, operational parameters (e.g., polarization states, coherence length) may be jointly optimized to determine an operating setting that increases vascular contrast for a selected region of interest, and the method 400 may thereby provide a configurable speckle imaging workflow suitable for revealing vasculature in vivo across different tissues and imaging conditions. For example, process block 406 may be performed before acquisition to set initial operational parameter values, during acquisition to vary operational parameters while speckle frames are acquired, and / or after an initial acquisition to adapt operational parameter values based on an image quality assessment. In all cases, method 400 may provide a configurable and adaptable speckle imaging workflow suitable for generating clinically useful vascular images across different tissues, skin tones, anatomical locations, and clinical applications.

[0055] FIG. 5 illustrates an example polarization tuning procedure 500 that may be performed by the disclosed LSI systems (e.g., system 200 of FIG. 2 and / or system 100 of FIG.1) to enhance vascular visualization by vary ing polarization state during acquisition, as described in process block 406 of FIG. 4. In the illustrated example, a set ofN polarization states of interest {1, ... , N} may be identified and an index n may be initialized (e.g.. n = 1). The polarization state may be defined relative to an incident plane and / or a sample orientation, and in some configurations may further be defined relative to a tissue surface normal, an illumination incidence angle, a detection axis, and / or a reference axis of the disclosed system.

[0056] For each polarization state n, the procedure 500 may set a first polarization controller (e.g., polarization controller / module in an illumination arm, such as element 240 in FIG. 2 and / or element 140 in FIG. 1) to achieve polarization state n. The procedure 500 may also set a second polarization controller (e.g., polarization controller 2 / module in a detection arm, such as element 208 in FIG. 2 and / or element 108 in FIG. 1) to filter backscattered light with a selected polarization orientation relative to the incident illumination, for example a crossed, parallel, or intermediate relative orientation. While the flow chart shows sequential control of the first and second polarization controllers, in other configurations, the controllers may be set jointly, synchronously, or adaptively (e.g., co-optimized using a contrast metric).

[0057] The procedure 500 may then acquire speckle data (e.g., one or more speckle frames) and generate one or more vascular maps using one or more speckle-derived metrics, including by way of non-limiting example ASDI and BFI calculations. The index n may be incremented (e.g., n = n + 1) and the procedure may repeat until the set of polarization states has been exhausted (e.g., n > N). Upon completion, information from one or more vascular maps may¬ be processed to generate one or more output vascular maps, which may include, for example, selection of a preferred polarization state, fusion or combination of maps acquired at different polarization states, and / or generation of a composite map that emphasizes complementary vascular features.

[0058] FIG. 6 illustrates an example coherence-length tuning procedure 500 that may be performed by the disclosed laser speckle imaging systems (e.g., system 300 of FIG. 3 and / or system 100 of FIG. 1) to enhance vascular visualization by varying a coherence characteristic of illumination, such as coherence length and / or effective coherence length, as described in process block 406 of FIG. 4. In the illustrated example, the procedure 600 may begin byspecifying a set of M coherence lengths (or coherence settings) of interest {1. ... , M} and initializing an index m (e.g., m = 1). The procedure 600 may then set a coherence length controller to achieve coherence length m, which may be performed in various ways depending on implementation, including, for example, setting a rotating diffuser speed and / or setting a wavelength-sweeping speed (or other sweep parameter) accordingly.

[0059] After setting the coherence length controller to the selected coherence length m. the procedure 600 may acquire data (e.g., a plurality of speckle frames) and generate one or more vascular maps through calculation of one or more speckle-derived metrics, including, by way of non-limiting example, ASDI and BFI. The index m may then be incremented (e.g., m = m + 1), and the procedure 500 may repeat the coherence-setting and acquisition / processing steps while m < M. When the set of coherence lengths has been exhausted (e.g., m > M), the procedure 600 may process information from one or more vascular maps generated using different coherence lengths and generate one or more output vascular maps. The output vascular maps may include, for example, selection of a preferred coherence length based on a vascular contrast metric, combination or fusion of vascular maps obtained at different coherence lengths, and / or generation of a composite vascular representation that emphasizes complementary' vascular features.

[0060] In alternative implementations, the coherence-length controller may include any mechanism capable of changing spatial coherence and / or temporal / spectral coherence,including a rotating diffuser, a multimode fiber segment, a bandwidth-tunable spectral filter used with a broadband source, a wavelength-swept source with adjustable sweep rate and / or sweep span, and / or temporally modulated or pulsed illumination configured to create different effective coherence lengths during an exposure interval. Further, the coherence-length tuning procedure 600 may be performed alone or in combination with polarization tuning (e.g., FIG.5), including alternating between coherence and polarization adjustments or jointly optimizing coherence and polarization settings for a selected region of interest.

[0061] FIG. 7 illustrates representative, non-limiting experimental results demonstrating that vary ing an input polarization state of illumination may change vascular contrast and / or reveal different subsets of vasculature in speckle-derived vascular images. In the illustrated example, the same tissue region (e.g., a pigmented lesion on skin) was imaged under multiple linearly polarized illumination conditions, including an S-polarized state, a P-polarized state, and an intermediate state oriented at approximately 45 degrees (with respect to the plane of incidence XZ in FIG. 1). For each polarization condition, a sample speckle frame is shown in a first column, a vascular map generated using an adaptive speckle decorrelation index (ASDI) is shown in a second column, and a vascular map generated using a blood flow index (BFI) is shown in a third column. In this example configuration, a detection-side polarizer may be oriented in a crossed configuration relative to an illumination-side polarizer, although other relative polarization relationships may be used. The results shown in FIG. 7 were obtained using a relatively short coherence-length illumination condition (e.g.. about 0.9 mm coherence length), and illustrate that different polarization states can lead to different vascular appearances in one or both of the ASDI-derived and BFI-derived maps, consistent with polarization-dependent scattering, for example, using different input polarization states can lead to the visualization of different vessels.

[0062] FIG. 8 illustrates representative, non-limiting experimental results demonstrating that varying an illumination coherence characteristic (e.g., coherence length or effective coherence length) may change vascular contrast and / or emphasize different vascular features in speckle-derived vascular images. In the illustrated example, the same tissue region (e.g., a pigmented lesion on skin) was imaged using two illumination conditions corresponding to a relatively short coherence length and a relatively long coherence length (e.g., about 0.9 mm and about 9 m, respectively). For each coherence condition, a sample speckle frame is shown in a first column, an ASDI-derived vascular map is shown in a second column, and a BFI-derived vascular map is shown in a third column. In this example, different detector exposuretimes may be selected for different coherence conditions to improve vascular contrast (e.g., a shorter exposure time for the short coherence length source and a longer exposure time for the long coherence length source), although exposure time, frame rate, and other acquisition parameters may be selected in other ways depending on desired contrast and motion robustness. The results shown in FIG. 8 illustrate that a shorter coherence length illumination condition may enhance vascular contrast for vessels emphasized by the ASDI-derived map (e.g., to reveal smaller superficial vessels with slower blood flow), while a longer coherence length illumination condition may improve visualization of vessels emphasized by the BFI-derived map (e.g., to reveal larger deeper vessels with faster flow), thereby indicating that coherence tuning can provide complementary vascular information that may be selected and / or combined.

[0063] In some examples, the experimental configurations used to obtain FIGs. 7-8 may be implemented using an LSI arrangement such as that shown in FIG. 1, for example employing a near-infrared illumination wavelength (e.g., around 976 nm) to mitigate melanin absorption relative to shorter wavelengths, an optical beam expansion arrangement to illuminate a centimeter-scale field of view (e g., approximately 1.5 cm diameter), and imaging optics (e.g., a relay such as a 4-f configuration) to image backscattered light onto a detector (e.g., a black silicon camera). An aperture stop (e.g., an iris) may be positioned to adjust speckle size at the camera sensor (e.g., by setting an aperture of approximately 3 mm), and polarization control may be provided by one or more polarization elements positioned in the illumination path and / or detection path. These results are provided as illustrative examples and are not intended to limit the disclosed systems and methods. In other implementations, different wavelengths, coherence settings, polarization states (including elliptical and / or circular polarization), acquisition parameters, and speckle-derived metrics may be employed, and the system may select, optimize, and / or fuse outputs across polarization and / or coherence settings to provide enhanced vascular representations.

[0064] Turning to FIG. 9, an example 1400 of a system (e.g. a data collection and processing system) for acquiring images of tissue vascularization in a patient is shown in accordance with some configurations of the disclosed systems and methods. In some configurations, a computing device 1410 can execute at least a portion of a system for acquiring images of tissue vascularization in a patient 1404 and provide control signals to one or more optical components associated with a laser speckle imaging system 1402. Additionally or alternatively, in some configurations, computing device 1410 can communicate information regarding the control signals to or from a server 1420 over a communication network 1406,which can execute at least a portion of system for acquiring images of tissue vascularization in a patient 1404. In some such configurations, server 1420 can return information to computing device 1410 (and / or any other suitable computing device) relating to the control signals for system for acquiring images of tissue vascularization in a patient 1404. This information may be transmitted and / or presented to a user (e.g. a researcher, an operator, a clinician, etc.) and / or may be stored (e.g. as part of a research database or a medical record associated with a subject).

[0065] In some embodiments, computing device 1410 and / or server 1420 can be any suitable computing device or combination of devices, such as a desktop computer, a laptop computer, a smartphone, a tablet computer, a wearable computer, a server computer, a virtual machine being executed by a physical computing device, etc. As described herein, system for speckle imaging with tunable polarization state and coherence length 1404 can present information about the control signals to a user (e.g., researcher and / or physician). In some configurations, LSI system 1402 may include optical components such as those disclosed herein (e.g. see FIG. 1).

[0066] In some configurations, communication network 1406 can be any suitable communication network or combination of communication networks. For example, communication network 1406 can include a Wi-Fi network (which can include one or more wireless routers, one or more switches, etc.), a peer-to-peer network (e.g., a Bluetooth network), a cellular network (e.g., a 3G network, a 4G network, a 5G network, etc., complying with any suitable standard, such as CDMA, GSM, LTE, LTE Advanced, WiMAX, etc.), a wired network, etc. In some embodiments, communication network 1406 can be a local area network, a wide area network, a public network (e.g., the Internet), a private or semi-private network (e.g., a corporate or university intranet), any other suitable type of network, or any suitable combination of networks. Communications links shown in FIG. 9 can each be any suitable communications link or combination of communications links, such as wired links, fiber optic links, Wi-Fi links, Bluetooth links, cellular links, etc.

[0067] FIG. 10 shows an example 1500 of hardware that can be used to implement computing device 1410 and server 1420 in accordance with some embodiments of the disclosed systems and methods. As shown in FIG. 10, in some configurations, computing device 1410 can include a processor 1502, a display 1504 of a user interface, one or more inputs 1506, one or more communication systems 1508, and / ormemory 1510. In some configurations, processor 1502 can be any suitable hardware processor or combination of processors, such as a central processing unit, a graphics processing unit, etc. In some embodiments, display 1504 caninclude any suitable display devices, such as a computer monitor, a touchscreen, a television, etc. In some embodiments, inputs 1506 can include any suitable input devices and / or sensors that can be used to receive user input, such as a keyboard, a mouse, a touchscreen, a microphone, etc.

[0068] In some configurations, communications systems 1508 can include any suitable hardware, firmware, and / or software for communicating information over communication network 1406 and / or any other suitable communication networks. For example, communications systems 1508 can include one or more transceivers, one or more communication chips and / or chip sets, etc. In a more particular example, communications systems 1508 can include hardware, firmware and / or software that can be used to establish a Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, etc.

[0069] In some configurations, memory 1510 can include any suitable storage device or devices that can be used to store instructions, values, etc., that can be used, for example, by processor 1502 to present content using display 1504, to communicate with server 1420 via communications system(s) 1508, etc. Memory 1510 can include any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, memory 1510 can include RAM, ROM, EEPROM, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, etc. In some embodiments, memory71510 can have encoded thereon a computer program for controlling operation of computing device 1410. In such embodiments, processor 1502 can execute at least a portion of the computer program to present content (e g., images, user interfaces, graphics, tables, etc.), receive content from server 1420, transmit information to server 1420, etc.

[0070] In some configurations, server 1420 can include a processor 1512, a display 1514, one or more inputs 1516. one or more communications systems 1518. and / or memory 1520. In some embodiments, processor 1512 can be any suitable hardware processor or combination of processors, such as a central processing unit, a graphics processing unit, etc. In some embodiments, display 1514 can include any suitable display devices, such as a computer monitor, a touchscreen, a television, etc. In some embodiments, inputs 1516 can include any suitable input devices and / or sensors that can be used to receive user input, such as a keyboard, a mouse, a touchscreen, a microphone, etc.

[0071] In some embodiments, communications systems 1518 can include any suitable hardware, firmware, and / or software for communicating information over communication network 1406 and / or any other suitable communication networks. For example,communications systems 1518 can include one or more transceivers, one or more communication chips and / or chip sets, etc. In a more particular example, communications systems 1518 can include hardware, firmware and / or software that can be used to establish a Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, etc.

[0072] In some configurations, memory 1520 can include any suitable storage device or devices that can be used to store instructions, values, etc., that can be used, for example, by processor 1512 to present content using display 1514, to communicate with one or more computing devices 1410, etc. Memory 1520 can include any suitable volatile memory, nonvolatile memory, storage, or any suitable combination thereof. For example, memory 1520 can include RAM, ROM, EEPROM, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, etc. In some embodiments, memory 1520 can have encoded thereon a server program for controlling operation of server 1420. In such embodiments, processor 1512 can execute at least a portion of the server program to transmit information and / or content (e.g., results of a tissue identification and / or classification, a user interface, etc.) to one or more computing devices 1410. receive information and / or content from one or more computing devices 1410, receive instructions from one or more devices (e.g., a personal computer, a laptop computer, a tablet computer, a smartphone, etc.), etc.

[0073] In some configurations, any suitable computer readable media can be used for storing instructions for performing the functions and / or processes described herein. For example, in some embodiments, computer readable media can be transitory or non-transitory. For example, non-transitory computer readable media can include media such as magnetic media (such as hard disks, floppy disks, etc.), optical media (such as compact discs, digital video discs, Blu-ray discs, etc.), semiconductor media (such as RAM, Flash memory, electrically programmable read only memory (EPROM), electrically erasable programmable read only memory (EEPROM), etc.), any suitable media that is not fleeting or devoid of any semblance of permanence during transmission, and / or any suitable tangible media. As another example, transitory7computer readable media can include signals on networks, in wires, conductors, optical fibers, circuits, or any suitable media that is fleeting and devoid of any semblance of permanence during transmission, and / or any suitable intangible media.

[0074] It should be noted that, as used herein, the term mechanism can encompass hardware, software, firmware, or any suitable combination thereof.

[0075] The above discussion is presented to enable a person skilled in the art to make and use embodiments of the invention. Various modifications to the illustrated embodiments willbe readily apparent to those skilled in the art, and the generic principles herein can be applied to other embodiments and applications without departing from embodiments of the invention. Thus, embodiments of the invention are not intended to be limited to embodiments shown, but are to be accorded the widest scope consistent with the principles and features disclosed herein. The following detailed description is to be read with reference to the figures, in which like elements in different figures have like reference numerals. The figures, which are not necessarily to scale, depict selected embodiments and are not intended to limit the scope of embodiments of the invention. Skilled artisans will recognize the examples provided herein have many useful alternatives and fall within the scope of embodiments of the invention.

[0076] For any embodiments of the invention are explained in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the attached drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. For example, the use of '‘including / ’ "comprising,” or "having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.

[0077] In some implementations, devices or systems disclosed herein can be utilized, manufactured, or installed using methods embodying aspects of the invention. Correspondingly, any description herein of particular features, capabilities, or intended purposes of a device or system is generally intended to include disclosure of a method of using such devices for the intended purposes, a method of otherwise implementing such capabilities, a method of manufacturing relevant components of such a device or system (or the device or system as a whole), and a method of installing disclosed (or otherwise known) components to support such purposes or capabilities. Similarly, unless otherwise indicated or limited, discussion herein of any method of manufacturing or using for a particular device or system, including installing the device or system, is intended to inherently include disclosure, as embodiments of the invention, of the utilized features and implemented capabilities of such device or system.

[0078] The above discussion is presented to enable a person skilled in the art to make and use embodiments of the invention. Various modifications to the illustrated embodiments will be readily apparent to those skilled in the art, and the generic principles herein can be appliedto other embodiments and applications without departing from embodiments of the invention. Thus, embodiments of the invention are not intended to be limited to embodiments shown, but are to be accorded the widest scope consistent with the principles and features disclosed herein. The above detailed description is to be read with reference to the figures, in which like elements in different figures have like reference numerals. The figures, which are not necessarily to scale, depict selected embodiments and are not intended to limit the scope of embodiments of the invention. Skilled artisans will recognize the examples provided herein have many useful alternatives and fall within the scope of embodiments of the invention.

[0079] It is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the attached drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. For example, the use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.

[0080] Additionally, unless otherwise specified or limited, the terms “about” and “approximate,” as used herein with respect to a reference value, refer to variations from the reference value of ± 15% or less, inclusive of the endpoints of the range. Similarly, the term “substantially equal” (and the like) as used herein with respect to a reference value refers to variations from the reference value of less than ± 30%, inclusive. Where specified, “substantially” can indicate in particular a variation in one numerical direction relative to a reference value. For example, “substantially less” than a reference value (and the like) indicates a value that is reduced from the reference value by 30% or more, and “substantially more” than a reference value (and the like) indicates a value that is increased from the reference value by 30% or more.

[0081] Also as used herein, ordinal numbers are used for convenience of presentation only and are generally presented in an order that corresponds to the order in which particular features are introduced in the relevant discussion. Accordingly, for example, a "first" feature may not necessarily have any required structural or sequential relationship to a "second" feature, and so on. Further, similar features may be referred to in different portions of the discussion by different ordinal numbers. For example, a particular feature may be referred to in somediscussion as a "first" feature, while a similar or substantially identical feature may be referred to in other discussion as a "third" feature, and so on.

[0082] The description of the different advantageous embodiments has been presented for purposes of illustration and description and is not intended to be exhaustive or limited to the embodiments in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art. Further, different advantageous embodiments may provide different advantages as compared to other advantageous embodiments. The embodiment or embodiments selected are chosen and described in order to best explain the principles of the embodiments, the practical application, and to enable others of ordinary skill in the art to understand the disclosure for various embodiments with various modifications as are suited to the particular use contemplated.

[0083] The present invention has been described in terms of one or more preferred aspects, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention.

[0084] For the avoidance of doubt, aspects of the present disclosure described with respect to the systems are applicable to the methods and aspects described with respect to the methods are applicable to the systems.

[0085] Within this specification embodiments have been described in a way which enables a clear and concise specification to be written, but it is intended and will be appreciated that embodiments may be variously combined or separated without parting from the invention. For example, it will be appreciated that all preferred features described herein are applicable to all aspects of the invention described herein.

[0086] Thus, while the invention has been described in connection with particular embodiments and examples, the invention is not necessarily so limited, and that numerous other embodiments, examples, uses, modifications and departures from the embodiments, examples and uses are intended to be encompassed by the claims attached hereto. The entire disclosure of each patent and publication cited herein is incorporated by reference, as if each such patent or publication were individually incorporated by reference herein.

[0087] Various features and advantages of the invention are set forth in the following claims.

Claims

CLAIMS1. A system configured to acquire images of tissue vascularization in a patient, the system comprising:a laser arranged in an illumination arm of the system and configured to deliver an incident light to a region of tissue in the patient;a camera arranged in a detection arm of the system and configured to receive light from region of tissue in response to the incident light to acquire image data;a polarization controller arranged in the illumination arm and configured to adjust a polarization of the incident light delivered by the laser to the region of tissue in the patient; anda processor configured to control the polarization controller to adjust the polarization of the incident light delivered by the laser to modulate vascular contrast in the region of tissue based on at least one of a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, frame rate, or acquisition time to generate images of tissue vascularization in the patient.

2. The system of claim 1, wherein the tunable polarization controller is configured to adjust the polarization of the incident light delivered by the laser to the region of tissue in the patient while the camera acquires the image data to generate images of tissue vascularization in the patient.

3. The system of claim 1, wherein the tunable polarization controller comprises a rotating waveplate, a liquid crystal polarization rotator, or a liquid crystal spatial light modulator.

4. The system of claim 1, wherein the camera is configured to acquire one-dimensional speckle image data or two-dimensional speckle image data.

5. The system of claim 1, further comprising another polarization controller arranged in the detection arm and wherein the processor is configured to adjust the polarization of the incident light in concert with polarization of light received by the from region of tissue to select a desired vascular contrast.

6. The system of claim 5, wherein the processor is further configured to select the desired vascular contrast using the at least one of location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, frame rate, or acquisition time.

7. The system of claim 1, wherein the images of tissue vascularization in the patient include a plurality of vascular images based on adaptive speckle decorrelation index or blood flow index.

8. The system of claim 1, further comprising a coherence controller configured to adjust a coherence length of the incident light and wherein the processor is further configured to operate the coherence controller to adjust the coherence length of the incident light to modulate vascular contrast to generate images of tissue vascularization in the patient.

9. The system of claim 1, wherein the polarization controller includes rotating waveplates or liquid crystal polarization rotators (LCPR) configured to change a polarization state of the light incident.

10. The system of claim 9, wherein the polarization state includes at least one of parallel or crossed with respect to the incident light.

11. The system of claim 1, wherein the polarization controller includes liquid crystal spatial light modulators (SLM) configured to change and spatially encode a polarization state of the light incident.

12. A laser speckle imaging system configured to acquire tissue vascularization in a patient, the system comprising:a coherent light source arranged in an illumination arm of the system and configured to deliver an incident light to a region of tissue in a patient;a detector arranged in a detection arm of the system and configured to receive light from the region of tissue in response to the incident light to acquire image data;a coherence controller configured to adjust an effective coherence length of incident light; anda processor configured to control the coherence controller to adjust the effective coherence length of the incident light to modulate vascular contrast in the region of tissue based on at least one of a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, frame rate, or acquisition time to generate images of tissue vascularization in the patient.

13. The laser speckle imaging system of claim 12, wherein the coherence controller includes a rotating diffuser.

14. The laser speckle imaging system of claim 12, wherein the coherence controller is configured to control a variable wavelength of the coherent light source to change a wavelength of the incident light during an integration time of the camera to adjust the effective coherence length of the incident light.

15. The laser speckle imaging system of claim 12. further comprising a polarization controller arranged in the illumination arm and configured to adjust a polarization of the incident light under the control of the processor.

16. The laser speckle imaging system of claim 15. wherein the processor is configured to control the coherence controller or the polarization controller based on an integration time or a frame rate to modulate contrast of vessels in the images of tissue vascularization in the patient.

17. The laser speckle imaging system of claim 12. wherein the coherent light source comprises a wavelength-swept source and the coherence controller is configured to vary a sweep parameter to vary the effective coherence length.

18. A method acquiring images of tissue vascularization in a patient using a system that includes a light source arranged in an illumination arm to deliver an incident light to a region of tissue in the patient, a detector arranged in a detection arm to receive light from the region of tissue in response to the incident light to acquire image data, a coherence controller configured to adjust an effective coherence length of incident light, and a polarizationcontroller arranged to adjust a polarization of the incident light or the light received from the region of tissue, the method comprising:controlling at least one of the coherence controller to adjust the effective coherence length of the incident light or the polarization controller to adjust the polarization of the incident light or the light received from the region of tissue to modulate vascular contrast in the region of tissue based on at least one of a location of the region of tissue, vessel size within the region of tissue, tissue-light absorption parameters, frame rate, or acquisition time to generate images of tissue vascularization in the patient.

19. The method of claim 18, further comprising computing a vascular contrast metric for each of a plurality of polarization states and controlling the polarization controller to modulate vascular contrast in the region of tissue using the vascular contrast metric.

20. The method of claim 16, further comprising computing a vascular contrast metric for each of a plurality of effective coherence lengths and controlling the coherence controller to modulate vascular contrast in the region of tissue using the vascular contrast metnc.

21. A laser speckle imaging system configured to acquire images of tissue vascularization in a patient, the system comprising:a coherent light source arranged in an illumination arm of the system and configured to deliver an incident light to a region of tissue in the patient;a detector arranged in a detection arm of the system and configured to receive light from the region of tissue in response to the incident light to acquire image data; a tunable operating parameter controller configured to adjust at least one operational parameter associated with at least one of the incident light or the received light; and a processor configured to control the tunable operating parameter controller to adjust the at least one operational parameter based on at least one of a patient parameter or a clinical application to generate images of tissue vascularization in the patient.

Images