Interferometer-based synthetic multiple exposure speckle imaging (syMESI) method and system

Abstract

Synthetic multiple exposure speckle imaging (syMESI) methodology necessarily uses an optical interferometer device as part of the speckle imaging system to overcome photodetector noise that typically limits reliable and accurate determination of speckle contrast characteristics at low exposure times. The use of such methodology has made it possible to quantitatively determine absolute value(s) of motion changes (such as blood flow changes in tissue) in a target object with a low photon budget of less than 40 counts of average detection intensity, and / or to quantitatively image blood flow in an object in an intraoperative setting using a low-cost camera sensor.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This international patent application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 265,312, filed December 13, 2021, the disclosure of which is incorporated herein by reference.

[0002] Related Technology Blood flow through tissues serves as an important physiological indicator of tissue health, as it directly indicates the oxygen supply to the tissue and is critical for normal tissue function. For example, reduced blood flow to the brain has serious consequences, as even small changes in oxygen supply to the brain can dramatically affect normal physiological processes. Imaging of blood flow is therefore important for understanding the normal functioning of the physiology, monitoring disease progression, and tracking treatments.

[0003] In general, optical imaging methods, due to their superior spatiotemporal resolution characteristics, are more suitable for visualizing cerebral blood flow (CBF) dynamics (especially for applications requiring resolution of individual cerebral vessels) than magnetic resonance imaging (MRI), computed tomography (CT), diffuse optical tomography (DOT), etc. For example, optical imaging techniques based on photon correlation (e.g., laser speckle contrast imaging, or LSCI) are particularly well suited to assess CBF by utilizing the intrinsic contrast motion of red blood cells.

[0004] In particular, LSCI has been shown to be effective for imaging cerebral blood flow in small animal models. One of the main advantages of LSCI is that the imaging equipment used is simple and inexpensive, yet allows for the acquisition of wide-field CBF images with excellent spatial and temporal resolution. To date, LSCI has been utilized to image CBF dynamics during ischemia in the rat and mouse brain, for functional activation studies, and to model the progression of ischemic stroke.

[0005] As recognized in the related art, laser speckle is a random interference pattern generated by the coherent summation of light fields (e.g., laser light fields) backscattered from a sample along trajectories of slightly different path lengths. To this end, FIG. 1C shows a schematic of a typical LSCI setup. Here, slightly diverging light 104 from a visible or near-infrared diode laser source 110 is directed to impinge on a tissue sample 120, where the light 104 is scattered in the tissue and the light field components traveling along different paths through the tissue 120 undergo different phase shifts. The backscattered light 124 is collected through an imaging lens 128 and recorded on a camera sensor 130 in the form of a speckle image, which is then processed by appropriately configured electronics 130.

[0006] The motion of particles (e.g., red blood cells) within the sample tissue imprints spatial and temporal variations in the speckle pattern. Such effects manifest themselves as local blurring (or decorrelation) of the image (Figure 1A). Quantifying this blurring or decorrelation provides a measure of the flow of red blood cells in the vasculature of the tissue 120. Formally, the local speckle contrast is

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[0007] In particular, as recognized in the related art, the speckle contrast measured with the LSCI approach is only suitable for acute measurements of relative changes in CBF changes. In other words, the practical results of using conventional implementations of LSCI systems do not allow quantitative measurements of motion in the target tissue, but instead generate an evaluation of relative (e.g., on a scale of any unit from 0 to 1) contrast values ​​of the entire speckle image, which clearly gives only one concluding conclusion about the CBF changes, which can be expressed as follows: the motion of the target particle (e.g., blood flow) in a first region of the target tissue depicted in a first part of the image is occurring faster than the motion of the target particle in a second region of the target tissue depicted in a second part of the image. A quantitative (i.e., numerical) evaluation of the values ​​of the speeds of these two motions is simply not possible based on conventional LSCI, which gives relative (i.e., by comparison) results. As a result, the application of conventional LSCI systems has been limited to only very simple situations.

[0008] A methodology called multi-exposure speckle imaging (or MESI) was introduced to rectify the inability of conventional LSCI to perform quantitative measurements of blood flow by processing laser speckle images acquired with multiple camera exposures and fitting them to a quantitative speckle visibility model. To date, MESI has been achieved by time-gating the laser using relatively large and slow instruments such as acousto-optic modulators or rotating filter wheels (see, for example, Parthasarathy et al., “Robust flow measurement with multi-exposure speckle imaging,” Optics Express 16, 1975-1989;2008) or by using time-binning techniques (but using expensive high-speed detectors that are only suitable for low-resolution images such as 8 × 5 pixels; see, for example, Dragojevic et al., “High-speed multi-exposure laser speckle contrast imaging with a single-photon counting camera,” Biomedical Optics Express 6, 2865-2876;2015). Well-known drawbacks of the MESI approach are manifested in the need to use dedicated hardware to maintain a constant effective laser power at the investigated sample (tissue) and / or in the duration of the measurements, which is not short enough for several practical applications.

[0009] Recently, a software-based synthetic MESI (syMESI) methodology has been proposed (e.g., PCT / US2022 / 022734 has been published as WO2022 / 212636, the disclosure of which is incorporated herein by reference; or see Safi, Abdul Mohaimen, et al. "Quantitative Cerebral Blood Flow Imaging with Synthetic Single-Shot Multi-Exposure Laser Speckle Imaging." Optics and the Brain. Optical Society of America, 2021). This methodology, like traditional MESI approaches, utilizes the collection of only (single-beam) light scattered by a scene or sample of interest, and provides the user with the ability to perform quantitative blood flow imaging (i.e., determining absolute actual values ​​(not values ​​determined relative to some reference value) of a motion metric associated with a portion of a scene of interest across the entire scene of interest) without the hardware typically required to implement MESI. However, each of the traditional hardware-based multiple exposure speckle imaging (MESI) approach and the recently developed software-based synthetic multiple exposure (syMESI) approach requires acquiring speckle images with very short exposure times (on the order of about 50 μs). As one skilled in the art can easily appreciate, at such short exposure times, the noise associated with the operation of the photodetector used in the imaging process can and often does overwhelm the useful signal (the signal generated by the light backscattered from the sample and collected by the system), and under those conditions, it becomes mandatory to use high illumination optical power for imaging. However, such an unavoidable requirement may not be suitable for clinical settings such as intraoperative imaging or ophthalmology.

[0010] The current state of the art raises the question of how to avoid the use of high-power light sources (which would otherwise be impractical for use in the desired application) while at the same time maintaining the technical and / or operational advantages already demonstrated by related technologies. Summary of the Invention

[0011] An embodiment of the present invention provides a speckle imaging system configured to detect motion, the imaging system including an optical illumination system configured to generate an optical output at an output end, the imaging system including a light source, and an optical interferometer apparatus having a reference arm and a sample arm and optically coupled to the output end of the optical illumination system, the optical interferometer apparatus being configured to not require and / or tolerate a change in the optical phase difference between the sample light propagating through the sample arm and the reference light propagating through the reference arm. The speckle imaging system further incorporates an optical imaging system including a photodetector system in optical communication with the output end, and a computer system operably connected to the optical imaging system, the computer system being operable to detect and / or detect the motion of the optical imaging system.

[0012] and configured to receive therefrom electrical signals representative of a raw speckle image formed at an optical output from the optical interferometer arrangement by the optical detector system. The optical output includes both a sample light (which interacts with a target sample in the sample arm and includes a speckle pattern representative of the target sample) and a reference light. Additionally, the speckle imaging system includes a computer readable tangible, non-transitory medium including computer readable program code having computer readable instructions stored thereon, the instructions, when executed by a processor of the computer system, causing the processor to at least determine and / or display speckle contrast characteristics of the raw speckle image. In at least one embodiment, the instructions are further configured to cause the processor to (a) display the speckle image as a spatial distribution of visually perceptible light irradiance, and / or (b) determine and / or display a speckle visibility curve of values ​​of a speckle contrast characteristic of the speckle image as a function of exposure time of the target sample, and / or (c) determine and / or display a number of speckle contrast images and / or speckle visibility curves as a map indicative of the spatial and / or temporal distribution of the changes in the motion in the target sample.

[0013] In substantially any embodiment, the speckle imaging system satisfies the following conditions: 1) the dynamic range of the measurement of the speckle contrast characteristic necessarily depends on the intensity of the reference light, and / or 2) the device includes at least one device configured to control the intensity of the sample light and / or the intensity of the reference light, and / or 3) the instructions incorporate instructions that cause the processor to ascertain a speckle variance of the raw speckle image while maintaining such variance greater than the variance of the noise of the photodetector, and / or 4) the instructions incorporate instructions that cause the processor to ascertain a speckle variance of the raw speckle image while maintaining such variance greater than the noise variance of the photodetector, substantially regardless of the level of non-zero intensity of the first portion of the light, and / or 5) the instructions incorporate instructions that cause the processor to ascertain a speckle variance of the raw speckle image while maintaining such variance greater than the noise variance of the photodetector, substantially regardless of the level of non-zero intensity of the first portion of the light, and / or 6) incorporate instructions that cause the processor to: (i) calculate, for each identified pixel or group of pixels of the photodetector, a speckle contrast value of the raw speckle image as a first ratio of a normalized value of the standard deviation of the intensity of light at pixels in a selected region of the photodetector surrounding the identified pixel to an average value of the intensity, or as a second ratio of the normalized value of the standard deviation of the intensity of light at the identified pixel to an average value of the intensity of light at the identified pixel calculated over multiple exposure times; and / or (ii) determine the first ratio and / or the second ratio in a time domain, a spatial domain, or a spatiotemporal domain.

[0014] In at least one of the above embodiments, the speckle imaging system may be configured as a multiple synthetic exposure time speckle imaging (syMESI) system, and the optical illumination system may not include a device configured to maintain the power of the light output substantially constant over an exposure time, and / or such a syMESI system may include instructions to cause a processor to: (i) acquire one or more raw speckle images formed on the light by an imaging system at only one fixed first empirical exposure time, and (ii) spatially average selected raw speckle images of the one or more raw speckle images using a plurality of binning apertures having spatially different dimensions to form corresponding modified speckle images, each such modified speckle image representing a speckle image corresponding to a corresponding second synthetic exposure time from a plurality of second synthetic exposure times (each second synthetic exposure time from the plurality of second synthetic exposure times is different from each other and different from the first empirical exposure time). In the latter case, the instructions may be further configured to cause the processor to convert each of the modified speckle images into a plurality of speckle contrast images corresponding to the same selected image and / or a respective corresponding speckle contrast image of the speckle visibility curve. Alternatively or additionally, the instructions may be configured to cause the processor to evaluate, based at least on the speckle visibility curve, a quantitative value of motion in a portion of a scene illuminated with the optical output during operation of the speckle imaging system and represented by one or more raw speckle images. Alternatively or additionally, the instructions may be configured to cause the processor to generate a visually perceptible image of a portion of a scene illuminated with the optical output during operation of the speckle imaging system and represented by one or more raw speckle images, where the visually perceptible image indicates a spatial distribution of a quantitative value of motion in said portion of the scene via a spatial distribution of an optical parameter throughout said visually perceptible image.Alternatively, or in addition, the instructions may be configured to cause the processor to acquire, with the imaging system, a sequence of raw speckle images at only one such fixed first empirical exposure time (wherein the constituent raw speckle images of the sequence are necessarily non-contiguous). In the latter case, the optical imaging system may be configured to acquire such necessarily non-contiguous raw speckle images with different time intervals between adjacent raw speckle images.

[0015] An embodiment of the present invention further provides a method of characterizing a scene using a speckle imaging system (which may, in at least one case, be configured according to any one of the embodiments described above). Such a method includes the steps of: a) coupling light generated by a light source of the speckle imaging system into an optical interferometer device of the speckle imaging system (wherein the speckle imaging system detects motion and the optical interferometer device does not require and / or tolerate changes in the optical phase difference between the sample arm and the reference arm); b) illuminating the scene with a first portion (of light generated by the light source) that propagates through a sample arm of the optical interferometer device; and c) spatially overlapping, at an optical detector of an optical detection system of the speckle imaging system, a second portion (of such light that propagated through a reference arm of the optical interferometer device) with the first portion of light that interacted with the scene, thereby forming an output light, the output light including both the first portion backscattered by the scene and the second portion. Furthermore, the method includes the step of acquiring a raw speckle image of the scene of the output light with the optical detector at a predetermined exposure time.

[0016] In at least one embodiment (where operating parameters of the optical interferometer apparatus do not include the intensity of the second portion of light generated by the light source), the method is configured to not alter such operating parameters of the optical interferometer apparatus during the combining, illuminating, and superimposing steps. In at least one particular instance of such an embodiment, the method can further include altering a dynamic range of a speckle contrast characteristic of the raw speckle image by altering the intensity of the second portion of light.

[0017] Alternatively or additionally, and in substantially all embodiments of the method, the method may include determining a speckle contrast characteristic of the raw speckle image as a function of a ratio of an intensity of the second portion of light to an intensity of the output light (such ratio optionally being time dependent), and / or may additionally include varying a dynamic range of the speckle contrast characteristic of the raw speckle image by altering an intensity of at least one of the first portion of light and the second portion of light.

[0018] Alternatively or additionally, and in substantially all embodiments, the method may be configured to include ascertaining a speckle variance of the raw speckle image while maintaining such speckle variance greater than the variance of the photodetector noise, (where such maintaining optionally includes maintaining the speckle variance greater than the variance of the photodetector noise substantially regardless of the level of non-zero intensity of the first portion of light generated by the light source.

[0019] Alternatively or additionally, and in substantially all embodiments, the method may be configured to satisfy at least one of the following conditions: (a) additionally including a step of quantitatively determining an absolute value of a motion indicator in a portion of the scene represented by a given pixel of the raw speckle image, and (b) such motion indicator is an indicator of blood flow when the scene is biological tissue.

[0020] Alternatively or additionally, and in substantially all embodiments, the method may include the steps of: (1) calculating, for each identified pixel of the photodetector, a speckle contrast value of the raw image as a first ratio of a normalized value of the standard deviation of the intensity of light at pixels within a selected region of the photodetector surrounding such identified pixel to an average value of the intensity, or as a second ratio of the normalized value of the standard deviation of the intensity of light at the identified pixel to an average value of such intensity of light at the identified pixel obtained over multiple exposure times; and / or (2) calculating the first ratio and / or the second ratio in a time domain, a spatial domain, or a spatiotemporal domain.

[0021] Alternatively or additionally, and in substantially all embodiments, the acquiring step may include acquiring one or more raw speckle images of the scene in the output light at only one fixed first empirical exposure time, and the method additionally includes, for each of a plurality of binning apertures having different spatial dimensions, modifying a selected image of the one or more raw speckle images into a corresponding one of a plurality of modified speckle images by spatially averaging the irradiance distribution of the selected image with a respective corresponding binning aperture of the plurality of binning apertures, thereby generating a plurality of modified speckle images each representing a speckle image of the scene corresponding to a second composite exposure time of the plurality of second composite exposure times (wherein all second composite exposure times from the plurality of second composite exposure times are different from each other and different from the first empirical exposure time). In certain versions of the latter, the method may ensure that each of the plurality of modified speckle images is converted into a respective corresponding speckle contrast image of the plurality of speckle contrast images corresponding to the same selected image, and / or that the light source is a laser light source, and / or that for each modified speckle image from the plurality of modified speckle images, a numerical relationship between the first empirical exposure time and the corresponding second composite exposure time depends on a dimension of a predetermined binning aperture, and / or that at least one of one or more of the raw speckle images, the selected image, and at least one of the plurality of speckle contrast images is visually perceptible. Optionally, the at least one or more raw speckle images include only one raw speckle image, or two raw speckle images of such one or more consecutively acquired images are not acquired immediately one after the other, but with any time delay between such two images.In at least one embodiment, the method satisfies one or more of the following two conditions: (i) the step of acquiring (one or more raw speckle images at only one fixed first exposure time) comprises acquiring only one raw speckle image, and (ii) the step of modifying a selected one of the one or more initial speckle images is a step of modifying only one image of the one or more raw speckle images. In at least one embodiment, the method satisfies at least one of the following conditions: (1) the method further comprises quantitatively determining an absolute value of a motion indicator in a portion of the scene represented by a given pixel of the selected image, and (2) such motion indicator is an indicator of blood flow when the scene is biological tissue.

[0022] Alternatively or additionally, and in at least one embodiment, the acquiring step may include acquiring a plurality of raw speckle images at only one fixed first empirical exposure time with time intervals therebetween to form a sequence of raw speckle images whose constituent raw speckle images are necessarily non-contiguous. In at least one case, the acquiring step may include acquiring such necessarily non-contiguous raw speckle images having time intervals of different durations between different immediately adjacent raw speckle images.

[0023] For a more complete understanding of the present disclosure, please see the following detailed description and the accompanying drawings. [Brief description of the drawings]

[0024] [Figure 1]A, B, and C show an illustration of the laser speckle contrast imaging (LSCI) methodology, where A shows a "raw" speckle image acquired by a camera. The raw image displays random interference patterns; B is a processed "speckle contrast" image (based on the image in A), highlighting spatial regions of high and low blood flow; and C shows a schematic of a typical LSCI device configured for two-dimensional imaging of cerebral blood flow. [Diagram 2] Results of multiple exposure speckle imaging (MESI) of a rat brain are shown. The speckle variance as a function of the camera exposure time T is fitted to a speckle visibility equation to derive quantitative estimates of CBF in four regions of interest. The inset is a speckle contrast image of CBF in the mouse cortex. The visibility of blood vessels is modulated by the camera exposure time. [Diagram 3] A typical setup for multiple exposure speckle imaging (MESI) is shown diagrammatically. An acousto-optical modulator (AOM) is required to modulate the intensity of the laser over different exposure times. The camera and AOM are typically triggered by the data acquisition electronics (processor). [Figure 4] 1 illustrates a schematic of a speckle imaging system constructed in accordance with the concepts of the present invention. [Diagram 5] A synthetic multiple exposure speckle imaging methodology is used while collecting optical data in the embodiment of FIG. 4. Raw speckle images at longer exposures can be synthesized by spatially averaging images at shorter exposures. For example, a speckle image at 1 ms exposure time is synthesized by spatially averaging 4 pixels of a 0.25 ms speckle image. Averaging can be achieved by a 2×2 moving window or 2×2 binning. At each exposure time, the speckle contrast is calculated at each image pixel in the time domain by calculating the ratio of the standard deviation and mean of the intensity. [Figure 6]Characterization and comparison of synthetic multiple exposure speckle imaging results performed with related art system 300 (see FIG. 3) and a system constructed in accordance with the concepts of the present invention (see system 400 in FIG. 4). Histograms of pixel intensity for these two measurements, with the corresponding intensity map of the raw speckle image displayed in the inset. [Figure 7] A,B show a comparison of speckle contrast maps obtained by speckle imaging performed using a conventional embodiment 300 of the speckle imaging system of FIG. 3 (single exposure) with that performed using an embodiment of the present invention (400 in FIG. 4, synthetic multiple exposure), with a flow rate of 5 mm / s and a scale bar of 50 μm. [Figure 8] FIG. 8A shows the fit to a speckle model of synthetic MESI data obtained using the embodiment 400 of FIG. 4, the speckle variance as a function of synthetic exposure time at different velocities. Measurements were made on samples without a static scattering layer. FIG. 8B is the ability of the MESI model using the conventional embodiment 100 of FIG. 1 (curve 820) and the syMESI model using the embodiment 400 of FIG. 4 (curve 810) to determine the relative change in motion in an object. Baseline velocity: 1 mm / sec. Plot of relative τc against relative velocity. The plot should ideally be a straight line (shown as a dashed line). The embodiment of the present invention clearly improves / extends the linear range of the relative τc estimates compared to using the conventional embodiment of FIG. 3 or the conventional embodiment of FIG. 1. Error bars indicate the standard error of the relative correlation time estimate. Measurements were made using a microfluidic phantom without a static scattering layer. Detailed Description of the Invention

[0025] In general, the size and relative scale of elements in the drawings may be set differently from the actual ones in order to appropriately promote conciseness, clarity and understanding of the drawings. For the same reason, not all elements present in one drawing are necessarily shown in another drawing. Although specific embodiments are shown in the figures, with the understanding that the present disclosure is intended to be illustrative, these specific embodiments are not intended to limit the scope of the embodiments of the invention described and illustrated herein.

[0026] As mentioned above, a related art speckle imaging technique currently in use is called multiple exposure speckle imaging (or MESI), and another called synthetic MESI (or syMESI), which combines a more complex instrument design (compared to traditional LSCI systems) with a new but different mathematical model for converting speckle contrast into a quantitative index of blood flow.

[0027] Conventional LSCI methodology, which images speckles generated by light backscattering with a single fixed exposure time, is suitable for measuring relative flow changes. As a result, the application range of conventional LSCI is limited to very simple situations. In conventional LSCI, the speckle contrast depends on the camera exposure time. That is, the camera exposure time adjusts the "visibility" of blood vessels with different flow velocities. While a short exposure time can detect high-velocity motion and flow, a longer exposure time is required to detect the slow-velocity speckle intensity fluctuations associated with slow motion and flow.

[0028] Hardware-based MESI exploits this phenomenon and has been experimentally adapted to record speckle images with camera exposures of various durations (50 μs to 80 ms as shown in Figure 2). In practice, this is achieved by externally triggering the camera acquisition and the laser while ensuring that the illumination power remains relatively constant over the dynamic range of the measurement.

[0029] In practice, such utilization is achieved by externally triggering the camera acquisition and the laser source such that the power level of the sample illumination remains substantially constant over the entire dynamic range of the measurement (see, for example, Parthasarathy, AB, et al., Optics Express 16, 1975-1989;2008). The relationship between speckle contrast and camera exposure time can be characterized by the speckle visibility equation, which in its simplest form is

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[0030] The recently developed and published software-based single-shot synthetic MESI (syMESI) methodology (see, e.g., PCT / US2022 / 022734) solves the problems associated with multi-exposure-time time-averaged MESI-based implementations of LSCI by circumventing the need to control the power of the laser light illuminating the target scene (thus allowing the user to return to the practical use of the basic, simpler LSCI system, e.g., shown diagrammatically in Figure 1), while at the same time conveying a quantitative assessment of the target's particulate motion that cannot be provided by conventional single-exposure-time LSCI approaches. Thus, syMESI allows one to emulate the same results achieved with MESI using conventional LSCI equipment, but using only one single exposure. A typical hardware / software configuration of syMESI has been described with reference to Figures 5A, 5B, and 5C of PCT / US2022 / 022734, and therefore will not be described in detail here either. As explained in PCT / US2022 / 022734, data representing raw speckle images recorded at longer exposure times in a conventional MESI scheme need not be empirically recorded, but instead can be numerically synthesized or generated by spatially averaging raw speckle image(s) recorded at substantially shorter exposure times. (Experimentally recorded raw speckle images are those directly acquired / read by a photodetector in a snapshot and not yet modified after acquisition). For example, a speckle image at a 1 ms exposure time can be synthesized by spatially averaging 4 pixels of a 0.25 ms speckle image. In one example, the averaging can be performed by a 2x2 moving window or 2x2 binning. At each exposure period (whether the speckle image was empirically acquired or the speckle image was numerically synthesized), the speckle contrast is calculated at that time using a temporal, spatial, or spatiotemporal speckle image processing scheme. The synthetic speckle contrast for the corresponding synthetic exposure time is fitted to the conventional MESI equation for estimating flow.Both the MESI and syMESI methodologies provide quantitative imaging of absolute flow values ​​(as opposed to relative values ​​determined against some reference value) or baselines, and have expanded the dynamic range of flow detection compared to conventional LSCI techniques. (In particular, the term "absolute value" is defined herein not in the mathematical sense as the absolute value of such a value, but as a value that represents the inherent magnitude of the parameter being measured without comparison to any other, whereas a "relative value" of a parameter is determined based on a comparison to a reference magnitude of a similar parameter.)

[0031] Those skilled in the art will immediately appreciate that both the conventional hardware-based multiple exposure speckle imaging (MESI) approach and the software-based synthetic multiple exposure (syMESI) approach utilize a single category, single type of light (light scattered by the scene or object of interest) to form the raw speckle image(s), and both require acquisition of the speckle image(s) with short exposure times (50 μs-80 ms for MESI, and approximately 50 μs for syMESI). Acquiring images with short exposure times is a notoriously significant instrumental challenge. Since speckle contrast is typically calculated as the variance of intensity normalized to the mean value of the intensity, the average intensity of the backscattered light at the camera sensor (photodetector) must necessarily be large enough to overcome the detector noise and utilize the entire dynamic range of the detector (e.g., 127 arbitrary units for an 8-bit camera, 32768 arbitrary units for a 16-bit optical camera). This necessarily results in high and / or expensive target irradiance powers of light produced by the laser source used, or the requirement that highly sensitive optical cameras / detectors must be used. (A "high" target irradiance laser power in the present context is one that produces a local irradiance that exceeds the ANSI-recognized limits for laser / skin exposure, or other conventional limits for laser tissue exposure.)

[0032] This limitation of having to use high-power laser sources reduces the importance of MESI / syMESI in clinical applications, since the damage caused by the laser irradiation would simply not allow working with such high target irradiation powers, especially for sensitive tissues such as intraoperative brain imaging or ophthalmology. In particular, the detection sensitivity can of course be improved by using SPAD arrays or EMCCD cameras, but their use also increases the cost, form factor, and complexity of the overall instrument.

[0033] Embodiments of the present invention avoid the above-mentioned limitations and problems inherent in related art methodologies by devising a speckle imaging system that employs an optical interferometer apparatus (wherein the light acquired by the optical imaging portion of the overall speckle imaging system is a composite of multiple light rays reaching the optical imaging portion from two different sources, only one of which represents the light backscattered by the target object or scene) and a novel speckle visibility algorithm for fast quantitative imaging of motion present in an object or scene while utilizing optical image transformation following the teachings of either the conventional LSCI, MESI, or syMESI methods.

[0034] It will be understood that implementations of the discussed concepts of the present invention are directed to non-invasive imaging of and determining the motion present in a variety of objects, whether inanimate or spatial, including certain moving parts or elements, or living objects, such as biological tissue with blood flow, all of which are within the scope of the present invention, although for simplicity and clarity of presentation, the following description of embodiments of the present invention will be described in terms of specific, non-limiting examples in which the object is biological tissue.

[0035] The idea of ​​the present invention comes from the realization of using an optical interferometer device between an optical illumination system (including, in certain cases, a light source such as a laser light source) and an optical imaging system (including a photodetector) under the condition that a target object or scene (which serves as a backscattered source of laser speckles to be imaged) is placed in the sample arm of such an interferometer (where the useful light (collected by the optical imaging system at the output of the interferometer device) includes not only the backscattered light by the target object but also the light propagating through the reference arm of the interferometer) to enhance the weak dynamic signal caused only by the backscattered light itself. By using such a configuration of the embodiments of the present invention, it has been shown that the entire speckle imaging system can be operated substantially always in such a state that the speckle variance value of the raw speckle image (empirically obtained at the detector at the optical output from the optical interferometer device) can be reliably and accurately ascertained or determined while this speckle variance value remains larger than the variance value of the noise of the photodetector, substantially regardless of the intensity level of the light illuminating the target object or scene placed in the sample arm of the interferometer device of the speckle imaging system. By using the embodiments of the present invention to increase the speckle variance above the noise level, the signal-to-noise ratio of the measurement is advantageously increased. Such an operating regime, formed by the use of an optical interferometer apparatus as part of an overall speckle imaging system, provides clear operational advantages to embodiments of the present invention, which stand in stark contrast to the operation of any speckle imaging system of the related art, which necessarily and indisputably does not allow for any reliable, reproducible, accurate, and / or precise determination of the speckle variance, which is dominated by the variance of the photodetector noise, as soon as the intensity level of the light illuminating the object / scene falls below a certain level.

[0036] Moreover, as empirically demonstrated by practical implementations of the inventive concept, the time resolution of the proposed speckle imaging methodology was limited only by the frame rate of the camera, and no high frame rate optical camera / detector was required for the methodology to work. As a result, the proposed methodology can be used to perform quantitative video-rate multiple exposure speckle imaging (approximately 10 times faster than the current state of the art). Implementations of the inventive concept provide the additional advantage that the intensity of the interference fringes collected at the optical output from the optical interferometer device of the system, and thus the overall measurement dynamic range, can be freely adjusted or changed, for example, by adjusting the intensity of the light in the reference arm (in one particular non-limiting case using a neutral density filter).

[0037] In particular, and in pure contrast to acquiring laser speckle under different circumstances, for example when using an optical coherence tomography (OCT) system, embodiments of the present invention are configured such that the optical interferometer apparatus does not require or even tolerate changes in the optical path difference (e.g., OPD, which would otherwise be caused by a change in phase difference) between the portions of light propagating through the sample arm and the reference arm.

[0038] An exemplary embodiment 400 of a speckle imaging system constructed in accordance with the teachings of the present invention is shown generally in FIG. 4 and includes, as shown, an optical interferometer arrangement, in this particular case configured as a Mach-Zehnder interferometer (it will be understood that in related embodiments the interferometer may be configured differently, for example according to a Michelson configuration).

[0039] Light from a light source 410 (which in one practical embodiment was a single mode laser diode, LD, generating linearly polarized CW light at λ=638 nm and 150 mW) in an optical illumination system 414 was spatially transformed using an optical system 418 (collimated aspheric lens L1, Thorlabs C171TMD-B, f=6.20 mm, NA=0.30, as shown in the figure) to generate an input beam 422, which was then split into a sample light beam 426S and a reference light beam 426R using a non-polarizing beam splitter 420. In general, the value of the light split ratio did not affect the working principle of the embodiment. However, in the illustrated case, a Thorlabs BS076 model of beam splitter 430 is used, such that approximately 10% of the input optical power of beam 422 is coupled into the reference arm 432R of the interferometer (here shown to include a step-index multimode fiber optic patch cable 424, Thorlabs M124L01, diameter Φ400 μm, NA 0.50) as reference light 422A, and approximately 90% of the optical power of beam 422 is sent to the sample arm 432S as sample light 422S, to substantially spatially uniformly illuminate the target sample 434.

[0040] The particular geometry of the illumination of the sample with the sample light 426S has proven not to affect the operation of the embodiment, but in the illustrated case, such illumination was at an angle of about 30-45 degrees with respect to a normal drawn to the surface of the sample 434. Similarly, the particular content of the reference arm 432R of the interferometer device has proven not to affect the operation of the embodiment 400 (related embodiments can be implemented, for example, without the use of the fiber optic cable 424). In the specific example of FIG. 4, the reference light at the output of the multimode fiber 424 was collimated by a fiber collimator FC2, 424B (Thorlabs F230FC-780-780 nm, f=4.51 mm, NA=0.55). Optionally, at least one of the sample arm 432S and the reference arm 432S can be equipped with a device configured to control the intensity of the light propagating in such arm. As shown in the example of FIG. 4, such a device is configured as a spatially relocatable neutral density filter ND444.

[0041] The sample light 426S backscattered upon interaction with the sample 434 was collected by a lens 438 (here shown as an optical objective lens, 4X, NA=0.10, Olympus). The backscattered light 442S collected by the sample beam 426S and the light 442R of the reference beam 426R at the output end of the reference arm 432R were then spatially superimposed by another beam splitter 446 (here a 50 / 50 beam splitter from Thorlabs, CCM1-BS013) to form light 450 at the output of the optical interferometer device, which was imaged by an optical imaging system 454 of embodiment 400, which in one particular case includes a CMOS camera (Basler acA2000-165umNIR). In one implementation, the operation of the speckle imaging system was performed without changing the operating parameters of the optical interferometer device (with the optional exception of varying the intensity of the reference light 442R). In one embodiment, raw speckle images were recorded continuously at a frame rate of 100 Hz and an exposure time of 100 μs.

[0042] The embodiment 400 was equipped with a computer processor (or computer system, or data processing electronics, not shown in FIG. 4 ) configured to at least convert images acquired by the photodetectors of the optical imaging system 454 and, at least optionally, control the operation of the optical illumination system 414 and / or a light intensity control device (such as device 444, if present). Such a computer processor is operatively connected to the optical imaging system 454 to receive the electrical signal(s) from the system 454, and is complemented by a computer readable tangible, non-transitory medium carrying computer readable program code. The code included instructions for causing the processor to determine and / or display at least speckle contrast characteristics (e.g., speckle variance and / or that of a raw speckle image acquired by system 454 at the optical output 450 from the optical interferometer device), and optionally perform additional optical image transformation steps, such as, for example, determining the speckle contrast characteristics of the empirically acquired raw speckle image as a function of the ratio of the intensity of reference light 442R and the intensity of light 450 at the output of the interferometer device (discussed in more detail below). The instructions provided to the processor by the code included in a storage medium associated with the computer processor are configured to enable calculation of the speckle contrast characteristics, in some cases, in either the time domain, the spatial domain, or the spatiotemporal domain, and / or using conventional MESI or syMESI algorithms. For example, in one embodiment, the instructions provided to the processor are configured to cause the processor to calculate, for each identified pixel (or group of pixels) of the photodetector of system 454, a speckle contrast value of the raw speckle image acquired with light 450 as a ratio of a normalized value of the standard deviation of the light intensity at pixels within a selected region of the photodetector surrounding the identified pixel to the average value of such intensity, or as a ratio of a normalized value of the standard deviation of the light intensity at the identified pixel to the average value of said light intensity at the identified pixel calculated over multiple exposure times.

[0043] Those skilled in the art having the benefit of the above discussion can readily appreciate that the effect of using the proposed embodiment of the invention is to ensure operation of the system with a useful and / or informative signal (i.e., the signal representing that which is backscattered by the sample light always exceeds the noise of the photodetector) at short exposure times (typically at or around 100 μs), thereby enabling quantitative determination of absolute values ​​(absolute measurements, not relative values) and / or imaging of movements in the sample (e.g., in the case of biological tissue, of blood flow movements). The use of an optical interferometer arrangement allows for a higher signal-to-noise ratio than previously possible, even in situations of low signal and high noise background, since the measured signal is increased (by increasing the power of the reference arm) while the noise remains relatively constant.

[0044] For laser speckle imaging performed using embodiment 400, for example, the electric field of light 450 at the output of the optical interferometer device can be expressed as:

number

[0045] Where:

number

number

number

[0046] For example, following the Sigert relation described by R. Bandyopadhyay et al. (Speckle-visibility spectroscopy: A tool to study time-varying dynamics,” Rev. Sci. Instrum. 76, 1-11, 2005), the autocorrelation of the measured intensity can now be expressed as:

number

[0047] Where:

number

number

[0048] Lorentz distribution

number

number

[0049] Thus, in an embodiment of the present invention, the speckle contrast characteristic of the acquired raw speckle image is determined as a function of the (time-dependent) ratio of the intensity of the reference light 442R to the intensity of the total output light 450. This Equation 8, which describes the speckle visibility obtained using embodiment 400 of the present system, can be further adapted by performing hardware-based multiple exposure (MESI) or software-based synthetic multiple exposure (syMESI) data processing.

[0050] For example, consider an embodiment of speckle imaging using system 400 and the syMESI approach and algorithm described with reference to FIG. 4 of PCT / US2022 / 022734, reproduced here as FIG. 5. Here, using speckle imaging system embodiment 400 (which does not necessarily include an apparatus configured to maintain the power of optical output 450 substantially constant over the exposure time), at least one or a series of multiple raw speckle images 528 can be acquired by the photodetector with only a single fixed exposure time (empirical acquisition of raw speckle data, here 0.25 ms). In any case, each of these selected (or alternative) raw speckle images is modified / transformed / converted into a corresponding composite multiple exposure time image (i.e., an image corresponding to multiple composite exposure times) by spatially averaging selected images 528(j) recorded by the camera using an appropriate spatial window or aperture (alternatively, a binning aperture). The shape of the aperture is preferably polygonal (given the pixelated nature of the raw speckle image 528), and in certain cases the averaging spatial aperture can have the shape of a concave polygon, i.e., a polygon with at least one angle greater than 180 degrees. Now, as shown in the example of FIG. 5, a selected raw speckle image 528(j) obtained with an empirical exposure time of 0.25 ms is spatially averaged with a 2×2 square window / binning aperture to produce a modified image, which is a synthetic exposure image 538(j). This image 538(j) is a speckle image of the scene 120 corresponding to a synthetic (non-empirical) exposure time of 1 ms. Each pixel of the synthetic 1 ms 1 ms image 538(j) is the average of 2×2=4 adjacent pixels of the 0.25 ms empirical exposure time image 528(j) acquired by the camera. In this way, FIG. 5 also shows how a modified speckle image 548(j) corresponding to a synthetic exposure time of 2.25 ms can be formed.By repeating this process multiple times using binning windows of various shapes and / or sizes on at least one (or more than one, if desired) empirically recorded raw speckle image from set 528, as shown by the ellipses in FIG. 5, the user or system generates multiple modified speckle images representing speckle images of the scene corresponding to corresponding composite exposure times (of the determined multiple composite exposure times).

[0051] Further, optionally, referring back to FIG. 5, in at least one particular embodiment of the present invention, information about motion present in the imaged sample / object / scene 434 (as a non-limiting example, information about blood flow in biological tissue) can be quantified, in at least one case, by determining the temporal speckle contrast of each image pixel for all composite exposure times, i.e., by calculating the value of K for each pixel according to Equation 8. This converts the set(s) of modified speckle images 538(j), 548(j), etc. into corresponding images that contain information about speckle contrast. See speckle contrast image 578(0.25), which represents the spatial distribution of speckle contrast within image(s) 528 empirically acquired with an exposure time of 0.25 ms. See also speckle contrast image 578(1.0), which represents the spatial distribution of speckle contrast within composite image(s) 538(j) (corresponding to a composite exposure time of 1.0 ms) generated by spatial binning averaging. See also speckle contrast image 578(2.25), which depicts the spatial distribution of speckle contrast within the composite image(s) 448(j) (corresponding to a composite exposure time of 2.25 ms) generated by spatial binning averaging.Additionally, at each pixel of such speckle contrast image(s), speckle visibility (represented in at least one example as a plot or curve of speckle variance vs. synthetic exposure time, e.g., in FIG. 2) can be assessed, which can be further fitted to either a single scattering quantitative speckle contrast spectroscopy model (see Parthasarathy, AB, et al., in Optics Express 16, 1975-1989;2008) or a diffuse scattering quantitative speckle contrast spectroscopy model (see Valdes, CP et al. in Biomedical optics express 5, 2769, doi:10.1364 / BOE.5.002769(2014)) to estimate an indication of motion in the portion of the interrogated scene 434 represented by a particular pixel of the selected raw speckle image (if the scene is biological tissue, an indication of blood flow in the corresponding portion of the tissue).

[0052] In particular, spatial averaging can be performed using various approaches appropriate for the application. This includes pixel-wise binning using spatial windows or apertures of various sizes and / or shapes that are placed at approximately the same location on the selected raw speckle image (as explicitly shown in FIG. 5), or binning using spatial windows or apertures of fixed sizes and / or shapes that are relocated across the selected raw speckle image. The latter can maintain high spatial resolution of the image. These operations can be performed using standard image processing algorithms. Furthermore, as those skilled in the art will already understand from the above description, spatial averaging is not limited to rectangular spatial windows or binning apertures. For example, referring to FIG. 5, a 3×2 spatial window can be used to synthesize a 0.25×6=1.5 ms exposure image. Windows of any (optionally polygonal) shape and size can be used as required by the application. Discussion of the experimental results

[0053] As already mentioned above, one of the practical advantages obtained by the use of an embodiment of a speckle imaging system incorporating an optical interferometer device characterized by a substantially unchanged OPD between the sample arm and the reference arm is the ability of the system to acquire / amplify weak dynamic signals, especially against the background of the always present noise of the photodetector. The use of the embodiment 400 has experimentally verified this advantage, demonstrating that imaging and quantification of absolute numerical parameters of the motion present in the target object can be performed virtually regardless of how low the intensity of the sample illumination light 426S is. For this purpose, starting from raw speckle image(s) acquired with a single exposure time, synthetic MESI images and speckle visibility curves were calculated (according to the algorithm referenced above with respect to FIG. 5) for additional multiple exposures varying from 100 μs to 10 ms. The raw speckle image(s) were collected from tissue simulating a flow phantom, with flow velocities of 1-7 mm / s, while flowing 20% ​​Intralipid through a 200 μm × 150 μm channel.

[0054] The results shown in FIG. 6 attest to the fact that system 400 necessarily operates in a regime where the weak dynamic signal representing light 442S is amplified to overcome the noise of the photodetector. Here, FIG. 6 compares the intensity histograms of raw speckle images acquired with system 100 of FIG. 1 and system 400 of FIG. 4. Using embodiment 100, the average intensity of light at the imaging camera's photodetector is 33.75 (arbitrary units), which is one-quarter of the intensity required to fill the dynamic range of an 8-bit camera sensor. Also, due to the low photon count, the imaged speckle is underdeveloped. Histogram 100 and inset

number

number

number

[0055] 7A, 7B show a comparison of quantitative speckle contrast image reconstruction according to an embodiment of the present invention (FIG. 7B) with results produced by using conventional speckle imaging (embodiment 100, low photon counts typical for short exposure times <1 ms). FIG. 7A shows that the average intensity detected by the photodetector of embodiment 100 is low, and the image is dominated by photodetector noise. Applying MESI / syMESI data processing to raw images acquired with conventional embodiment 100 can result in artificially high speckle contrast values. The resulting image of object movement (in this case, an image of blood flow in biological tissue) had low sensitivity to blood flow in the channels present in the center of the image, and the entire image in FIG. 7A resembled a static speckle pattern. However, using embodiment 400, this issue was overcome by amplifying the low average intensity of light backscattered by the sample through interference between this backscattered light and light propagating through the reference arm, allowing accurate evaluation of speckle contrast images with relatively short exposure times(s). From several images in Fig. 7B, it is clear that the speckle contrast at, for example, an exposure time of 100 μs is incomparably higher than that in Fig. 7B, and at the same time, the absolute value of the speckle contrast can be accurately measured despite the presence of photodetector noise.

[0056] Furthermore, use of embodiment 400 demonstrated linearity of large changes in motion in a sample (e.g., large changes in blood flow in biological tissue) in the presence of photodetector noise, in contrast to results obtained using the conventional embodiment 100 (see Figures 8A, 8B).

[0057] Here, we used the experimental setup 400 (Figure 4) in combination with the synthetic exposure technique to perform controlled experiments on microfluidic samples. Intralipid 20% was injected into the sample at various speeds ranging from 1 mm / s to 7 mm / s in 1 mm / s increments using a syringe pump. 100 raw speckle images were captured for each flow rate with an exposure time of 100 μs. A synthetic multiple exposure algorithm was used to calculate the average heterodyne speckle contrast of the flow region as a function of exposure time. The synthetic multiple exposure speckle contrast data thus obtained were then calculated as β and

number

number

[0058] FIG. 8B shows that the proposed speckle model, when used in combination with the speckle imaging system 400 and the synthetic multiple exposure speckle imaging scheme, easily overcomes the presence of photodetector noise while achieving linearity of the relative correlation estimate over a wide flow range (about 6 times, compare data curve 810 with the straight dashed line). At the same time, using the conventional single exposure scheme of embodiment 100 (see curve 820), it was not possible to obtain any relative change of motion in the imaged object / scene, since the useful (backscattered by the object) signal was completely buried by the photodetector noise. In fact, to evaluate the linearity of the relative motion change (blood flow in one particular example), the average detection intensity had to be at least 127 (arbitrary units) for an 8-bit photodetector and 32768 (arbitrary units) for a 16-bit photodetector. This allowed the full use of the dynamic range of the optical imaging system and allowed the speckle to be fully developed. On the other hand, using embodiment 100, such short exposure times (<1 ms) were insufficient to achieve this dynamic range in each case unless high power lasers and sensitive detectors were used.

[0059] Those skilled in the art will now appreciate the practical advantages gained by using the proposed embodiments of the speckle imaging system compared to comparable optical instruments of the related art when imaging / measuring motion occurring in a target object or sample or scene.

[0060] The proposed setup simply requires the addition of a reference arm to a conventional speckle imaging setup. This can be realized in free space as shown in Figure 4, or using fiber optic components or other similar arrangements. Any low-power laser source and low-cost camera (1 megapixel or less, low bit depth and light sensitivity) can be used.

[0061] No special expensive high power lasers or equipment are required to overcome the noise of the photodetector.

[0062] When utilizing single-shot imaging, the temporal resolution of this approach is limited only by the frame rate of the photodetector. A high frame rate camera is not required for this methodology to work. As a result, the described embodiment can be used to perform quantitative video-rate multiple exposure speckle imaging (approximately 10x faster than the current state of the art).

[0063] The intensity of the acquired interference fringes, and therefore the dynamic range of the measurement, can be easily adjusted by adjusting the light intensity in the reference arm.

[0064] Embodiments of the present invention can be readily used in a wide variety of applications, for example, in applications utilizing laser speckle contrast imaging for blood flow imaging, including but not limited to imaging of skin microvascular function and dysfunction, wound healing angiogenesis, diagnosis of tissue burns, skin cancer, endoscopic and gastrointestinal surgery, ulcers and / or cardiovascular investigations, ophthalmology, diabetes, cerebrovascular investigations, and especially intraoperative surgery, and can also be advantageously used to quantify speckle fluctuation dynamics in any multi-speckle detection system, including those applied in diffuse speckle contrast analysis, laser speckle rheology, and speckle-based thrombus measurements.

[0065] The contents of each of the relevant technical documents and / or articles identified in this disclosure are hereby incorporated by reference.

[0066] Reference herein to "one embodiment," "an embodiment," "a related embodiment," or similar phrases means that the particular feature, structure, or characteristic described in connection with the referenced "embodiment" is included in at least one embodiment of the invention. Thus, appearances of phrases such as "in one embodiment," "in an embodiment," and the like throughout this specification can, but do not necessarily, all refer to the same embodiment. It is to be understood that no portion of the disclosure, by itself and in possible association with the figures, is intended to provide a complete description of all features of the invention.

[0067] For purposes of this disclosure and the appended claims, the use of the terms "substantially", "approximately", "about" and similar terms in reference to a descriptor of a value, element, property or characteristic at hand is intended to emphasize that the value, element, property or characteristic referred to is not necessarily exactly as described, but is nevertheless considered to be described by one of ordinary skill in the art for practical purposes. These terms, as applied to a particular property or quality descriptor, mean "mostly", "predominantly", "substantially", "approximately", "essentially", "to a great or substantial extent", "almost the same, but not necessarily completely", and provide a reasonable indication of approximation and a description of the range of the particular property or descriptor as would be understood by one of ordinary skill in the art. In one particular example, the terms "approximately", "substantially", and "about", when used in reference to a numerical value, represent a range of plus or minus 20% relative to the specified value, more preferably plus or minus 10%, even more preferably plus or minus 5%, and most preferably plus or minus 2% relative to the specified value. As a non-limiting example, two values ​​being "substantially equal" to one another means that the difference between the two values ​​can be within + / - 20% of the value itself, preferably within + / - 10% of the value itself, more preferably within + / - 5% of the value itself, and even more preferably within + / - 2% or less of the value itself.

[0068] The use of these terms in describing selected properties or concepts is not intended to imply or provide any basis for uncertainty or for adding numerical limitations to particular properties or descriptors. As will be understood by those skilled in the art, actual deviations from the stated exact values ​​or characteristics of such values, elements, or characteristics will fall within numerical ranges defined by typical experimental measurement error when using measurement methods accepted for such purposes in the art.

[0069] The term "image" generally refers to an ordered representation of detector outputs that correspond to spatial locations. For example, a visual image may be formed on a display device such as a video screen or printer in response to a pattern of light detected by a photodetector. The term "quantitative" is defined as being or capable of being represented by a quantity.

[0070] The invention(s) set forth in the claims appended to this disclosure are intended to be evaluated in light of this disclosure as a whole, including any features disclosed in the related art referenced.

[0071] Although the present invention has been described through the exemplary embodiments described above, those skilled in the art will appreciate that modifications and variations to the illustrated embodiments are possible without departing from the inventive concepts disclosed herein. The disclosed aspects, or portions of these aspects, may be combined in ways not described above. Thus, the present invention should not be considered as limited to the disclosed embodiment(s).

Claims

1. 1. A speckle imaging system, comprising: an optical illumination system of the speckle imaging system configured to generate a light output at an output end thereof, the optical illumination system including a light source, the speckle imaging system configured to detect motion; an optical interferometer device of the speckle imaging system, the optical interferometer device having a reference arm and a sample arm, the optical interferometer device optically coupled to an output end of the optical illumination system, the optical interferometer device not requiring and / or not allowing a change in the optical phase difference between sample light propagating through the sample arm and reference light propagating through the reference arm; an optical imaging system of the speckle imaging system, the optical imaging system including a photodetector system in optical communication with the output end; a computer system operably connected to the optical imaging system and configured to receive electrical signals therefrom, the computer system comprising: the electrical signal represents a raw speckle image formed by the photodetector system at the optical output from the optical interferometer device; the light output includes sample light that interacts with a target sample in the sample arm and includes a speckle pattern representative of the target sample and the reference light. A computer system; a computer-readable tangible, non-transitory medium including computer-readable program code having computer-readable instructions stored thereon, the instructions, when executed by a processor of the computer system, causing the processor to at least determine and / or display speckle contrast characteristics of the raw speckle image; and 1. A speckle imaging system comprising:

2. The instructions to the processor further include: Displaying the speckle image as a visually perceptible spatial distribution of light irradiance, and / or determining and / or displaying a speckle visibility curve of the speckle contrast characteristic values ​​of the speckle image as a function of exposure time of the target sample; and / or Determining and / or displaying a number of speckle contrast images and / or the speckle visibility curves as a map showing the spatial and / or temporal distribution of motion changes in the target sample. The speckle imaging system of claim 1 , wherein

3. The following conditions: (3a) the speckle imaging system is configured such that the dynamic range of the measurement of the speckle contrast characteristic is necessarily dependent on the intensity of the reference light; and / or (3b) the speckle imaging system includes at least one device configured to control the intensity of the sample light and / or the intensity of the reference light; and / or (3c) the instructions further cause the processor to verify the speckle variance of the raw speckle image while maintaining it greater than the variance of the noise of the photodetector; and / or (3d) the instructions cause the processor to ascertain a speckle variance of the raw speckle image while maintaining such speckle variance greater than a noise variance of the photodetector substantially regardless of a non-zero intensity level of the first portion of light; and / or (3e) the instructions further cause the processor to quantitatively determine an absolute value of a measure of motion across the portion of the scene or the entire scene represented by a given pixel of the raw speckle image; and / or (3f) the instructions to the processor further (i) for each identified pixel or group of pixels of the photodetector, determining a speckle contrast value of the raw speckle image; as a first ratio of a normalized value of the standard deviation of the light intensity at pixels within the selected region of the photodetector surrounding the identified pixel to the average value of the intensity; or as a second ratio of a normalized value of the standard deviation of the light intensity at the identified pixel to an average value of the light intensity at the identified pixel calculated over a plurality of exposure times; To calculate, and / or (ii) determining the first ratio and / or the second ratio in the time domain, the spatial domain, or the spatiotemporal domain; to give rise to The speckle imaging system according to claim 1 or 2, wherein at least one of the following is satisfied:

4. the speckle imaging system is configured as a multiple synthetic exposure time speckle imaging (syMESI) system, and the optical illumination system does not include a device configured to maintain the power of the optical output substantially constant over an exposure time; The instructions further include: acquiring one or more raw speckle images formed in the light by the imaging system using only one fixed first empirical exposure time; and spatially averaging selected raw speckle images of the one or more raw speckle images using a plurality of binning apertures having spatially different dimensions to form respective corresponding modified speckle images, each of the modified speckle images representing a speckle image corresponding to a respective second composite exposure time from a plurality of second composite exposure times, each second composite exposure time from the plurality of second composite exposure times being different from each other and different from the first empirical exposure time; The speckle imaging system according to claim 1 or 2, wherein

5. 5. The speckle imaging system of claim 4, wherein the instructions further cause the processor to convert each of the modified speckle images into a plurality of speckle contrast images and / or speckle visibility curves corresponding to the same selected image.

6. 5. The speckle imaging system of claim 4, wherein the instructions are configured to cause the processor to further evaluate, based at least on the speckle visibility curve, a quantitative value of motion in a portion of a scene illuminated with the light output during operation of the speckle imaging system and represented by the one or more raw speckle images.

7. 5. The speckle imaging system of claim 4, wherein the instructions are configured to further cause the processor to generate a visually perceptible image of a portion of a scene illuminated with the light output during operation of the speckle imaging system and represented by the one or more raw speckle images, the visually perceptible image displaying a spatial distribution of quantitative values ​​of motion in the portion of the scene via a spatial distribution of an optical parameter across the visually perceptible image.

8. 5. The speckle imaging system of claim 4, wherein the instructions configure the processor to acquire a sequence of raw speckle images formed in the light by the imaging system using only the one fixed first empirical exposure time, and the constituent raw speckle images of the sequence are necessarily non-contiguous.

9. 10. The speckle imaging system of claim 8, wherein the optical imaging system is configured to acquire non-consecutive raw speckle images with different time intervals between immediately adjacent raw speckle images.

10. 1. A method for characterizing a scene using a speckle imaging system, the method comprising: coupling light generated by a light source of the speckle imaging system into an optical interferometer device of the speckle imaging system; the speckle imaging system detects motion; the optical interferometer device does not require and / or tolerate changes in the optical phase difference between the sample arm and the reference arm; And, illuminating the scene with a first portion of light propagating through a sample arm of the optical interferometer apparatus; spatially overlapping a second portion of the light that propagated through a reference arm of the optical interferometer apparatus with a first portion of the light that interacted with the scene at a photodetector of an optical detection system of the speckle imaging system, thereby forming an output light that includes both the first portion of the light backscattered by the scene and the second portion of the light; acquiring a raw speckle image of the output light scene with a photodetector at a predetermined exposure time; A method comprising:

11. 11. The method of claim 10, performed using the speckle imaging system of claim 1.

12. without changing the operating parameters of the optical interferometer apparatus during the combining, illuminating, overlaying, and acquiring; The method of claim 10 or 11, wherein the operating parameters do not include the intensity of the second portion of light.

13. Varying the intensity of the second portion of light to vary the dynamic range of the speckle contrast characteristic of the raw speckle image. The method of claim 12 further comprising:

14. determining a speckle contrast characteristic of the raw speckle image as a function of a ratio of an intensity of the second portion of light to an intensity of the output light; 12. The method of claim 10 or 11, further comprising:

15. The method of claim 14 , wherein the ratio is a time-dependent ratio.

16. Varying the dynamic range of a speckle contrast characteristic of the raw speckle image by varying the intensity of at least one of the first portion of light and the second portion of light.

15. The method of claim 14, further comprising:

17. determining the speckle variance of the raw speckle image while maintaining such speckle variance greater than the variance of the noise of the photodetector; 12. The method of claim 10 or 11, further comprising:

18. 18. The method of claim 17, wherein the maintaining comprises maintaining the speckle variance greater than the variance of the noise of the photodetector substantially regardless of a non-zero intensity level of the first portion of light.

19. The following conditions: (19a) The method further includes quantitatively determining an absolute value of a motion indicator in the portion of the scene represented by a given pixel of the raw speckle image; and (19b) the measure of motion is a measure of blood flow when the scene is a biological tissue; The method according to claim 12, wherein at least one of the following is satisfied.

20. (20a) for each identified pixel of the photodetector, a speckle contrast value of the raw image is calculated by: as a first ratio of a normalized value of the standard deviation of the light intensity at pixels within the selected region of the photodetector surrounding the identified pixel to the average value of the intensity; or as a second ratio of a normalized value of the standard deviation of the light intensity at the identified pixel to an average value of the light intensity at the identified pixel obtained over a plurality of exposure times; To calculate, and / or (20b) calculating the first ratio and / or the second ratio in the time domain, the spatial domain, or the spatiotemporal domain; 13. The method of claim 12, comprising:

21. acquiring includes acquiring one or more raw speckle images of the scene in the output light at only one fixed first empirical exposure time; moreover, for each of a plurality of binning apertures having different spatial dimensions, modifying a selected image of the one or more raw speckle images into a corresponding one of a plurality of modified speckle images by spatially averaging the irradiance distribution of the selected image with a respective binning aperture of the plurality of binning apertures, thereby generating a plurality of modified speckle images representing speckle images of the scene corresponding to second composite exposure times of a plurality of second composite exposure times, wherein all second composite exposure times from the plurality of second composite exposure times are different from one another and from the first empirical exposure time.

13. The method of claim 12, comprising:

22. converting each of the plurality of modified speckle images into a corresponding speckle contrast image of a plurality of speckle contrast images corresponding to the same selected image.

22. The method of claim 21 further comprising:

23. (23a) the light source is a laser light source, and / or (23b) for each modified speckle image from the plurality of modified speckle images, a numerical relationship between the first empirical exposure time and the corresponding second composite exposure time depends on a size of the predetermined binning aperture; and / or (23c) at least one of the one or more of the raw speckle images, the selected image, and at least one of the plurality of speckle contrast images is visually perceptible.

22. The method of claim 21.

24. (24a) the at least one or more raw speckle images includes only one raw speckle image; or (24b) Two raw speckle images of the one or more consecutively acquired raw speckle images are not acquired immediately one after the other, but are acquired with an arbitrary time delay between the two images.

22. The method of claim 21.

25. (25a) acquiring one or more raw speckle images at the only one fixed first exposure time includes acquiring only one raw speckle image; and / or (25b) modifying selected ones of the one or more initial speckle images includes modifying only one image of the one or more raw speckle images.

22. The method of claim 21.

26. The following conditions: (26a) the method further comprises quantitatively determining an absolute value of a motion indicator in the portion of the scene represented by a given pixel of the selected image; and (26b) the measure of motion is a measure of blood flow when the scene is a biological tissue; The method of claim 21 , wherein at least one of the following is satisfied:

27. 22. The method of claim 21 , wherein the acquiring comprises acquiring a plurality of raw speckle images at the single, fixed, first empirical exposure time with time intervals therebetween to form a sequence of raw speckle images whose constituent raw speckle images are necessarily non-contiguous.

28. 23. The method of claim 22, wherein said acquiring comprises acquiring said necessarily non-contiguous raw speckle images having time intervals of different durations between different immediately adjacent raw speckle images.

Images