WO2023283479A1 - Système d'imagerie de contraste à granularité laser et ses applications - Google Patents

Système d'imagerie de contraste à granularité laser et ses applications Download PDF

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Publication number
WO2023283479A1
WO2023283479A1 PCT/US2022/036633 US2022036633W WO2023283479A1 WO 2023283479 A1 WO2023283479 A1 WO 2023283479A1 US 2022036633 W US2022036633 W US 2022036633W WO 2023283479 A1 WO2023283479 A1 WO 2023283479A1
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Prior art keywords
light
images
tissue
camera
acquired
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PCT/US2022/036633
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English (en)
Inventor
Emmanuel A. Mannoh
Anita Mahadevan-Jansen
Han DONG
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Vanderbilt University
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Priority to EP22838511.8A priority Critical patent/EP4366609A1/fr
Priority to CN202280059741.XA priority patent/CN118234425A/zh
Publication of WO2023283479A1 publication Critical patent/WO2023283479A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/42—Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems
    • A61B5/4222—Evaluating particular parts, e.g. particular organs
    • A61B5/4227—Evaluating particular parts, e.g. particular organs endocrine glands, i.e. thyroid, adrenals, hypothalamic, pituitary
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4887—Locating particular structures in or on the body
    • A61B5/489—Blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2505/00—Evaluating, monitoring or diagnosing in the context of a particular type of medical care
    • A61B2505/05—Surgical care
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/02007—Evaluating blood vessel condition, e.g. elasticity, compliance

Definitions

  • the invention relates generally to optical assessments of bio-objects, and more particularly, to a laser speckle contrast imaging (LSCI) system that endures motion artefacts to enable intra-operative parathyroid identification and viability of assessment and applications of the same.
  • LSCI laser speckle contrast imaging
  • the endocrine system is a complex system of organs and glands which includes the thyroid and parathyroid.
  • the anatomy of the neck is illustrated in FIG. 1.
  • the thyroid gland regulates many developmental and metabolic processes. Common diseases of the thyroid include goiters, hyperthyroidism, hypothyroidism, benign and malignant nodules, and autoimmune diseases such as Graves' disease. Surgery is the most common treatment for Graves's disease, goiters, benign thyroid nodules, and thyroid cancers.
  • the parathyroid normally lies within the same region as the thyroid in the neck and functions to control calcium levels in the blood.
  • the most common parathyroid disorder is primary hyperparathyroidism, in which one or more of the parathyroid glands become enlarged and hyperactive. This causes excess secretion of parathyroid hormone and a disruption in normal bone and mineral metabolism.
  • the prevalence of primary hyperparathyroidism has been estimated at 21 cases per 100,000 person-years. In 80% of cases, primary hyperparathyroidism is caused by a single overactive parathyroid gland and surgical removal of the diseased parathyroid gland is the only definitive treatment.
  • tan parathyroid glands typically positioned within the neck but can vary in location within the body and are sometimes intra-thymic. Due to their small size and variability in position, the parathyroid glands and their blood supplies are often difficult to distinguish from surrounding tissue and thyroid in the neck. The parathyroid visually resemble its surrounding tissue and this can extend surgical time during thyroid and parathyroid related surgeries, during which the surgeon is need to locate the small organs and their blood supply. Accidental removal or damage to the healthy parathyroid and its blood supply during surgery can result in serious postsurgical complications such as hypocalcemia and hypoparathyroidism. Hypoparathyroidism may result from direct injury, devascularization, and/or disruption of the parathyroid glands. Statistics suggest that temporary and permanent hypoparathyroidism rates are between 4-20% during thyroid surgery. The most common complications of both parathyroid and thyroid surgery are postoperative hypocalcemia, vocal-cord paralysis, and hematoma.
  • the current surgical procedure for thyroid and parathyroid surgeries involves a systematic search within the neck and relying on visual inspection to assess parathyroids’ viability. Other methods such as lidocaine solution bathing and ICG are avoided due to their potential side effects. The incidence of complications occurring due to this subjective method is directly proportional to the extent of thyroidectomy and inversely proportional to the experience of the surgeon.
  • the disadvantages to the current method include the lengthy duration of the surgery, the exploratory and empirical nature of the surgery, and the lack of sensitive and applicable preoperative and intra operative imaging. Confirmation of removal of the diseased parathyroid relies on histopathology or post-operative diagnosis of symptoms.
  • one of the objectives of this invention is to provide a portable, miniaturized imaging system capable of performing LSCI measurements intraoperatively for intraoperative assessment of parathyroid gland vascularity and reducing motion artifact introduced to the image during the intraoperative LSCI measurements.
  • the LSCI system is developed to guide surgeons performing thyroid and parathyroid surgeries, which allows a surgeon to objectively assess a parathyroid gland’s viability with LSCI during surgery. It should be appreciated that the LSCI system can be applied to not only endocrine tissues such as thyroid or parathyroid but also other tissues such as pancreas gland or adrenal gland.
  • the imaging system comprises a light source for emitting a beam of light; a light delivery member coupled to the light source for delivering the beam of light onto a tissue surface of the living subject to illuminate the tissue surface; a light collection member configured to collect light from the illuminated tissue surface responsive to the illumination; a detector coupled to the collection member for acquiring images of the light from the illuminated tissue surface, wherein each of the acquired images comprises a speckle pattern; and a controller arranged to operate the detector to acquire the images of the light from the illuminated tissue surface, receive the acquired images from the detector, and process the acquired images to obtain speckle contrast images for the intraoperative assessment of tissue viability.
  • the light source comprises a laser.
  • the light source comprises an infrared laser.
  • the light source comprises a diode laser emitting the beam of light at a wavelength of about 785 nm.
  • the light delivery member comprises at least one optical fiber optically coupled to the light source for delivering the beam of light emitted from the light source.
  • a diffuser placed at a distal end of the at least one optical fiber for diffusing the beam of light onto the tissue surface.
  • the diffuser is a hollow center diffuser.
  • a beam shaper is placed at a distal end of the at least one optical fiber for focusing or collimating or directing the beam of light onto the tissue surface.
  • the beam shaper comprises a biconvex lens.
  • the beam shaper comprises a ball lens.
  • the light delivery member further comprises a linear polarizer placed at the front of the optic.
  • the collection member comprises one or more optical fibers, including a fiber bundle.
  • the collection member further comprises a rod lens placed on a distal end of the one or more optical fibers to optimize the collection of light and image formation at a predetermined working distance.
  • the collection member further comprises a polarizer placed on a distal end of the one or more optical fibers for reduction of spectral reflection.
  • the system further comprises at least one lens placed in an optical path between the collection member and the detector for collecting and focusing light from the one or more optical fibers onto the detector.
  • the detector comprises at least one camera.
  • a high-speed camera is deployed for motion error control.
  • a camera that is capable of capturing moving images with exposures of less than 1/20 second or frame rates in excess of 20 fps is deployed for motion error control.
  • the at least one camera comprises an infrared camera or a near- infrared camera.
  • the at least one camera comprises a charge-coupled device (CCD) camera or a complementary metal oxide semiconductor (CMOS) camera.
  • CCD charge-coupled device
  • CMOS complementary metal oxide semiconductor
  • the system further comprises a display for displaying the speckle contrast images of the tissue in real-time.
  • a perfused parathyroid gland has low speckle contrast
  • a devascularized parathyroid gland has high speckle contrast
  • the tissue is a parathyroid gland, a pancreas gland, or an adrenal gland.
  • the invention in another aspect, relates to a system for assessment of a tissue of a living subject, comprising a light source for emitting a beam of light to illuminate the tissue; and an imaging head positioned over the tissuefor acquiring laser speckle contrast imaging (LSCI) images of light from the illuminated tissue responsive to the illumination.
  • LSCI laser speckle contrast imaging
  • the light source comprises an infrared laser.
  • the imaging head comprises: an illumination channel coupled to the light source for delivering the beam of light onto the tissue surface to illuminate the tissue surface; and an imaging channel positioned in relationship to the illumination channel for acquiring images of the light from the illuminated tissue surface, wherein each of the acquired images comprises a speckle pattern.
  • the light source is placed in the illumination channel.
  • a diffuser is placed at a distal end of the illumination channel for diffusing the beam of light onto the tissue surface.
  • a beam shaper is placed at a distal end of the illumination channel for focusing or collimating or directing the beam of light onto the tissue surface.
  • the beam shaper comprises a ball lens.
  • the illumination channel further comprises a linear polarizer placed at the front of the optic.
  • the imaging channel comprises at least one camera.
  • the at least one camera comprises a charge-coupled device (CCD) camera or a complementary metal oxide semiconductor (CMOS) camera.
  • CCD charge-coupled device
  • CMOS complementary metal oxide semiconductor
  • the imaging channel further comprises a polarizer placed the front of the at least one camera for reduction of spectral reflection.
  • the imaging channel is 1.5 mm in diameter.
  • the system further comprises a controller configured to control operations of the imaging head for acquiring the LSCI images of the illuminated tissue, receiving the acquired LSCI images from the at least one camera, and processing the acquired LSCI images to obtain speckle contrast images for the intraoperative assessment of tissue viability.
  • the invention in yet another aspect, relates to a method for assessment of a tissue of a living subject, comprising: directing a beam of light onto a tissue surface to illuminate the tissue surface; acquiring laser speckle contrast imaging (LSCI) images of light from the illuminated tissue responsive to the illumination; and processing the acquired LSCI images for the intraoperative assessment of tissue viability.
  • LSCI laser speckle contrast imaging
  • said processing the acquired images comprises calculating a plurality of speckle contrasts from the acquired images of the tissue.
  • said calculating plurality of speckle contrasts comprises: defining a window with a number of pixels over which a speckle contrast is to be calculated; moving the window across the acquired image of the speckle pattern; and at each location, calculating the speckle contrast as a standard deviation of pixel intensity values a s within the window divided by a mean intensity value (/) as follows: wherein the resultant speckle contrast image has values that range from 0 to 1, with values closer to 0 representing regions of greater motion (perfusion) and 1 representing regions with no motion.
  • said processing the acquired images comprises an LSCI threshold mechanism for frame selection that removes frames that contain excessive motion, thereby realizing the intraoperative assessment of tissue viability.
  • a frame selection code is applied to selection frames with tolerable motion.
  • a universal mean of the contrast value over each frame is threshold with a calculated number based on the acquired video and threshold applied, such that when a frame is below the threshold, there exists excessive amount of motion artifact that confounds with the blood flow information in the frame; and when a frame are above the threshold, the frame is acquired in relative stillness and the motion artifact that is introduced during the exposure time is tolerable by the LSCI.
  • said processing the acquired images comprises discarding a frame out of the video when the frame is below the threshold, and preserving a frame when the frame is above the threshold and using the preserved frame an indicator of whether the target of interest is well vascularized.
  • a machine learning algorithm is applied to reduce motion artifact on the acquired LSCI images.
  • the method further comprises displaying the speckle contrast images of the tissue in real-time.
  • FIG. 1 shows a general view of the anatomy of human thyroid/parathyroid glands.
  • FIG. 2 shows schematically a laser speckle contrast imaging (LSCI) system according to embodiments of the invention.
  • LSCI laser speckle contrast imaging
  • FIG. 3 shows schematically an LSCI system according to embodiments of the invention.
  • FIG. 4 shows schematically an LSCI system according to embodiments of the invention.
  • FIG. 5 shows schematically an LSCI system according to embodiments of the invention.
  • FIGS. 6A-6C show schematically an LSCI system according to embodiments of the invention.
  • FIG. 6 A a perspective view
  • FIG. 6B a transparent view
  • FIG. 6C a lateral cross section.
  • FIG. 7 shows a flowchart of automated image processing according to embodiments of the invention.
  • Automated imaging processing for laser speckle contrast imaging can be done in many other ways.
  • the flow chart shows one way to overcome the movement artifact that are introduced by the device being handheld.
  • a user needs to start the laser for speckle illumination and the camera for image streaming; aim the camera at the target parathyroid at a distance that the camera can be in focus, which one can either use computer for focus check or just via a display connected to the computer with human eyes; an automated program runs and checks for the optimum exposure time for laser speckle contrast imaging; with the optimum exposure time determined, the camera starts to acquire a speckle video.
  • the computer processes the raw video to a laser speckle contrasting video.
  • Another program is ran to determine a threshold of the contrast value. The threshold is then applied to the laser speckle contrast video that only frames that are held rather stationary remain.
  • a screen that connects to the computer displays the selected frames. Subsequently, about 10 successive selected frames are averaged for their area of interest's average contrast value and finally, a value for the parathyroid speckle contrast is obtained and fitted to a logistic regression model to determine the likelihood of devascularization.
  • a logistic regression model to determine the likelihood of devascularization.
  • FIG. 8A-8B show phantom data according to embodiments of the invention.
  • this is one embody of color hue that blue indicate motion of the object in the image and yellow represent static of that.
  • the color choice does not affect the result of laser speckle contrast imaging.
  • the lower the value of the pixel (contrast value) corresponds to the faster in motion and vice versa.
  • the contrast value can be converted into the speed of the flow (blood flow in this case).
  • the LSCI can be converted into a speed map.
  • FIG 8 A Indicating that there are flow in the blood vessel phantom.
  • FIG 5B Indicating that there are no flow in the blood vessel phantom.
  • first, second, third, etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another element, component, region, layer or section. Thus, a first element, component, region, layer or section discussed below can be termed a second element, component, region, layer or section without departing from the teachings of the present invention.
  • relative terms such as “lower” or “bottom” and “upper” or “top,” may be used herein to describe one element's relationship to another element as illustrated in the figures. It will be understood that relative terms are intended to encompass different orientations of the device in addition to the orientation shown in the figures. For example, if the device in one of the figures is turned over, elements described as being on the “lower” side of other elements would then be oriented on the “upper” sides of the other elements. The exemplary term “lower” can, therefore, encompass both an orientation of lower and upper, depending on the particular orientation of the figure. Similarly, if the device in one of the figures is turned over, elements described as “below” or “beneath” other elements would then be oriented “above” the other elements. The exemplary terms “below” or “beneath” can, therefore, encompass both an orientation of above and below.
  • “around”, “about”, “approximately” or “substantially” shall generally mean within 20 percent, preferably within 10 percent, and more preferably within 5 percent of a given value or range. Numerical quantities given herein are approximate, meaning that the term “around”, “about”, “approximately” or “substantially” can be inferred if not expressly stated.
  • the phrase “at least one of A, B, and C” should be construed to mean a logical (A or B or C), using a non-exclusive logical OR.
  • the term “and/or” includes any and all combinations of one or more of the associated listed items.
  • the term “living subject” refers to a human being such as a patient, or a mammal animal such as a monkey.
  • charge-coupled device refers to an analog shift register that enables the transportation of analog signals (electric charges) through successive stages (capacitors), controlled by a clock signal.
  • Charge-coupled devices can be used as a form of memory or for delaying samples of analog signals.
  • a CCD for capturing images there is a photoactive region (an epitaxial layer of silicon), and a transmission region made out of a shift register (the CCD, properly speaking).
  • An image is projected through a lens onto the capacitor array (the photoactive region), causing each capacitor to accumulate an electric charge proportional to the light intensity at that location.
  • a one-dimensional array used in line-scan cameras, captures a single slice of the image, while a two-dimensional array, used in video and still cameras, captures a two- dimensional picture corresponding to the scene projected onto the focal plane of the sensor.
  • a control circuit causes each capacitor to transfer its contents to its neighbor (operating as a shift register).
  • the last capacitor in the array dumps its charge into a charge amplifier, which converts the charge into a voltage.
  • the controlling circuit converts the entire semiconductor contents of the array to a sequence of voltages, which it samples, digitizes and stores in some form of memory.
  • Laser speckle contrast imaging is a widefield imaging technique capable of assessing superficial blood flow of parathyroid gland vascularity during endocrine surgery, which utilizes intrinsic tissue contrast from dynamic light scattering and provides a relatively simple technique for visualizing detailed spatiotemporal dynamics of blood flow changes in real time.
  • Laser speckle is the random interference pattern produced when coherent light scatters from a random medium and can be imaged onto a detector. Motion from scattering particles, such as red blood cells in the vasculature, leads to spatial and temporal variations in the speckle pattern. Speckle contrast analysis quantifies the local spatial variance, or blurring, of the speckle pattern that results from blood flow. Areas with greater motion have more rapid intensity fluctuations and therefore have more blurring of the speckles during the camera exposure time. LSCI can be used to quantify relative changes in blood flow.
  • the LSCI technique analyzes the interference pattern produced when coherent light is incident on a surface. Minute differences in path length created by the light waves scattering from different regions of the surface produce bright and dark spots of constructive and destructive interference respectively, termed as a speckle pattern. This speckle pattern fluctuates depending on how fast particles are moving within a few microns of the surface. Blurring of the speckle pattern occurs when the motion is fast relative to the integration time of the detector. Analyzing this spatial blurring provides contrast between regions of faster versus slower motion and forms the basis of LSCI.
  • This technique is sensitive to microvascular perfusion and has been employed in a variety of tissues where the vessels of interest are generally superficial, such as the retina, skin and brain. Parathyroid glands are densely packed with blood vessels, given that they secrete PTH to the entire body. Furthermore, their small size (3-8 mm) makes many of these vessels superficial, making these glands suitable targets for assessment using LSCI.
  • Certain aspects of this invention disclose a combined auto-fluorescence and LSCI system for assessment of parathyroid gland vascularity during endocrine surgery.
  • LSCI is an effective method for evaluating blood flow in parathyroid glands, and measurements made by this technique are strongly related to the postoperative outcomes of total thyroidectomy patients.
  • the previous work involved a static imaging device that is not always ideal for small surgical incisions and to image hard-to-reach parathyroid glands.
  • one of the objectives of this invention is to provide a portable, miniaturized imaging system capable of performing LSCI measurements intraoperatively for intraoperative assessment of parathyroid gland vascularity and reducing motion artifact introduced to the image during the intraoperative LSCI measurements.
  • the LSCI system is developed to guide surgeons performing thyroid and parathyroid surgeries, which allows a surgeon to objectively assess a parathyroid gland’s viability with LSCI during surgery. It should be appreciated that the LSCI system can be applied to not only endocrine tissues such as thyroid or parathyroid but also other tissues such as pancreas gland or adrenal gland. In addition to laser speckle contrast imaging system, the invention can also be applied to other motion sensitive optical systems that may suffer from motion artefacts, such as laser Doppler imaging (LDI), multi-spectral laser speckle contrast images, speckle interferometry, etc.
  • LPI laser Doppler imaging
  • multi-spectral laser speckle contrast images multi-spectral laser speckle contrast images
  • speckle interferometry etc.
  • the LSCI system in one exemplary embodiment includes an imaging fiber bundle, which is used to relay images from a surgical site to a detector.
  • the end of the fiber bundle at the surgical site is referred to as the distal end, and the end connected to the detector is the proximal end.
  • a rod lens is placed on the distal end of the fiber bundle to optimize the collection of light and image formation at the chosen working distance.
  • an objective lens is adapted to collect light from the fiber bundle and image it through a secondary lens or system of lenses onto the detector. The lenses are chosen to magnify the image from the distal end of the fiber bundle to fill the detector. For example, as shown in FIG.
  • a 20x objective (the objective lens) is paired with an 80 mm focal length converging lens (the secondary lens) to magnify the image from a 1 mm diameter fiber bundle onto an 8.7 mm diameter CMOS sensor (the detector).
  • the secondary lens the focal length converging lens
  • an optical fiber is connected to a light source of a laser module of any wavelength and is run alongside the fiber bundle.
  • the light source is an infrared laser, e.g., a single mode 785 nm diode laser, or the like. It should be noted that any other wavelengths can also be used to practice the invention.
  • a diffuser e.g., hollow center diffuser shown in FIG. 2
  • a beam shaper is placed at a distal end of the illumination channel for focusing or collimating or directing the beam of light onto the tissue surface.
  • the beam shaper can be a lens tube having a biconvex lens coupled to the light source for directing the beam of light onto a tissue surface of a parathyroid gland (e.g., object) of a patient to illuminate the tissue surface.
  • the beam shaper can be a ball lens.
  • the detector includes a camera, such as an infrared camera or a near-infrared (NIR) camera.
  • the camera can be a charge-coupled device (CCD) camera or a complementary metal-oxide-semiconductor (CMOS) camera.
  • the detector further includes a focus tunable lens (e.g., a zoom lens) attached to the front end of the camera.
  • a high-speed camera is deployed for motion error control.
  • a camera that is capable of capturing moving images with exposures of less than 1/20 second or frame rates in excess of 20 fps is deployed for motion error control.
  • the camera is adapted to individually acquire the LSCI images.
  • the illumination channel and the imaging fiber bundle are bundled into one rigid or flexible probe, which can be hold by a user in the operating room.
  • the probe parathyroid glands can be more easily evaluated in cases with small surgical incisions.
  • a micro-camera can also be employed for performing LSCI measurements.
  • the camera is placed at the distal end of the probe, adjacent to the illumination channel, while the wiring connecting the camera runs to the distal end outside the surgical field where it is connected to the appropriate electronics for recording images.
  • a mini camera with 249x250 pixels is deployed at the distal end of the probe.
  • an optical fiber is connected to a laser module of any wavelength and runs alongside the imaging channel.
  • a diffuser can be attached at the distal end of the illumination optical fiber to produce a more uniform speckle pattern on the target tissue to be imaged.
  • An optional white light fiber can be attached to the bundle for white light illumination and better focusing experience. Bundling the imaging channel, fiber optics, and the optional white light fiber into one rigid or flexible probe, parathyroid glands can be more easily evaluated in cases with small surgical incisions.
  • FIGS. 3-4 shows two different embodiments of the laser speckle contrast imaging system.
  • the base laser speckle contrast system can be composed of the illumination, which in the two embodiments are the laser and optical fiber that deliver light to the region of interest, but the illumination can well be illuminated from a light source through free space and through other media.
  • Acquisition channel can be composed of optical fiber that collects data from the region of interest or be composed of a camera upfront with electronics or wireless connections that send data back to the process.
  • the data acquisition channel can be realized through other forms.
  • the handheld LSCI system (i.e., the probe) 100 is shown according to embodiments of the invention.
  • the LSCI system 100 includes a light source channel (i.e., illumination channel) 106 for emitting a beam of light to illuminate a target of interest 105; and an imaging channel 107 positioned next to the light source channel 106 aiming at the target of interest 105 for acquiring LSCI images of light from the illuminated target of interest 105 responsive to the illumination.
  • the imaging channel 107 is about 1.5 mm in diameter.
  • the light source is, but is not limited to, an infrared laser.
  • the infrared laser is a diode laser emitting a beam of light at a wavelength of about 785 nm.
  • the imaging channel 107 comprises a detector 103 with a metal ferrule for individually acquiring the LSCI images.
  • the detector 103 such as a camera is adapted for collecting the light from the illuminated target of interest 105 in a surgical field.
  • the distance, D, between the distal end of the probe 100 and the target of interest 105 is about 2 cm.
  • the choice of about 2 cm working distance is to keep the imaging probe relatively compact and friendly to use. It should be noted that such a distance D can be adjusted by refocusing with optical instrument.
  • a short focal length lens 102 is deployed in the front of the illumination fiber 101 to match the field of view of that of the detector 103.
  • a sapphire ball lens is deployed due to its power and compactness.
  • an alternative to the optical fiber 101 for illumination is a small laser diode placed at the distal end of the probe in a relationship to the ball lens 102 such that the ball lens 102 is between the target of interest 105 and the small laser diode 101.
  • channels of fibers 104 are installed for white light illumination pre-LSCI image acquisition. Such a design helps the user with the orientation of the device and image capturing.
  • polarizers are deployed in the front of the illumination channel and the imaging channel either separately or together to reduce the effect of spectral reflection.
  • a polarizer is placed in the front of the camera perpendicular to the polarization orientation of the illumination channel to reduce spectral reflection.
  • a linear polarizer is positioned in the front of the illumination.
  • FIGS. 5 and 6A-6C show the exemplary embodiments of the image system according to the invention, the imaging system is enclosed in a sealed and sterilizable probe that can be hold by the user in the operating room and reusable afterwards.
  • imaging head on the interface end of the probe is the imaging head, where imaging channel contains commercial camera Naneye (AMS, Premstaetten, Austria) for LSCI image acquisition as well as white light image acquisition.
  • Illumination channel contains single mode fiber with FC/PC connector (Thorlab, Newton, NJ) and a 6 mm diameter sapphire ball lens (Edmund Optics, Barrington, NJ), 5 mm apart from each other. Together, the illumination channel can illuminated the region of interested with good quality speckle pattern illumination that can be easily picked up by the built-in camera and thus analyzed by the computer mentioned previously.
  • the LSCI system further comprises a controller (alternative computer) configured to control operations of the imaging head (alternative the probe) for acquiring the LSCI images of the illuminated target of interest, receiving the acquired LSCI images from the detector, and processing the acquired LSCI images to obtain speckle contrast images for the intraoperative assessment of parathyroid gland viability.
  • a controller alternative computer configured to control operations of the imaging head (alternative the probe) for acquiring the LSCI images of the illuminated target of interest, receiving the acquired LSCI images from the detector, and processing the acquired LSCI images to obtain speckle contrast images for the intraoperative assessment of parathyroid gland viability.
  • a perfused parathyroid gland has low speckle contrast
  • a devascularized parathyroid gland has high speckle contrast.
  • the computer that controls the instrument (home-built machine with six 3.7 GHz cores - Intel OEM Core ⁇ 7-8700K) and a single mode 785 nm diode laser with 80 mW power output (Innovative Photonics Solutions, Monmouth Junction, NJ), guided through electronics and optical fiber respectively.
  • system may also include a display for displaying the speckle contrast images of the parathyroid gland in real-time.
  • the handheld LSCI device can be combined with another lab-built device for detecting parathyroid gland using fluorescence, and marketed to endocrine surgeons.
  • the handheld LSCI system can very feasibly be combined with near-infrared autofluorescence detection, which is used for intraoperative parathyroid identification.
  • the result of such a combination would provide surgeons with a single tool to both identify parathyroid glands and assess their vascularity during operations. This has the potential to improve patient outcomes after surgery.
  • Extending the PTEye's capabilities to include parathyroid vascularity assessment could involve attaching a fiber bundle to the already existing probe and a camera and lenses to image the output of the fiber bundle as described above.
  • the laser source used in the PTEye for autofluorescence detection could also be used for laser speckle contrast imaging.
  • the handheld LSCI device/probe according to the invention allows for a more compact final product capable of assisting surgeons in first identifying parathyroid glands, and then assessing their viability.
  • the invention relates a method for intraoperative assessment of parathyroid gland viability of a living subject for guidance in a surgery.
  • FIG. 7 shows schematically a flowchart for intraoperative assessment of parathyroid gland viability of a living subject according to one embodiment of the invention.
  • the method includes providing a beam of light onto a tissue surface of a parathyroid gland of a patient to illuminate the tissue surface; acquiring images of the illuminated tissue surface, where each of the acquired images comprises a speckle pattern; and processing the acquired images to obtain speckle contrast images for the intraoperative assessment of parathyroid gland viability.
  • speckle contrast images a perfused parathyroid gland has low speckle contrast, and a devascularized parathyroid gland has high speckle contrast.
  • said processing the acquired images of the parathyroid gland by the controller is performed with calculating a plurality of speckle contrasts from the acquired images of the parathyroid gland.
  • said calculating plurality of speckle contrasts comprises defining a window with a number of pixels over which a speckle contrast is to be calculated; moving the window across the acquired image of the speckle pattern; and at each location, calculating the speckle contrast as a standard deviation of pixel intensity values a s within the window divided by a mean intensity value (/) as follows: where the resultant speckle contrast image has values that range from 0 to 1, with values closer to 0 representing regions of greater motion (perfusion) and 1 representing regions with no motion.
  • said processing the acquired LSCI images comprises an LSCI threshold mechanism for frame selection that gets rid of the frames that contain excessive motion and thus realizes assessment of the viability of the target parathyroid intraoperatively.
  • a frame selection code is applied to selection frames with tolerable motion.
  • a machine learning algorithm is applied to reduce the motion artifact have on the LSCI taken by the system.
  • the algorithm developed to automatically threshold for motion artifact that is introduced into the captured frame A universal mean of the contrast value over the each frame is threshold with a calculated number based on the taken video and threshold applied. Any frame that is below the threshold means that there exist excessive amount of motion artifact that will confound with the blood flow information and thus will be discarded out of the video; in contrary, frames that are above the threshold means that the frame was taken in relative stillness and the motion artifact that was introduced during the exposure time is tolerable by the laser speckle contrast image and thus should be preserved and used as indicator of whether the parathyroid is well vascularized.
  • a user needs to start the laser for speckle illumination and the camera for image streaming; aim the camera at the target parathyroid at a distance that the camera can be in focus, which one can either use computer for focus check or just via a display connected to the computer with human eyes; an automated program runs and checks for the optimum exposure time for laser speckle contrast imaging; with the optimum exposure time determined, the camera starts to acquire a speckle video.
  • the computer processes the raw video to a laser speckle contrasting video.
  • Another program is ran to determine a threshold of the contrast value. The threshold is then applied to the laser speckle contrast video that only frames that are held rather stationary remain.
  • a screen that connects to the computer displays the selected frames. Subsequently, about 10 successive selected frames are averaged for their area of interest's average contrast value and finally, a value for the parathyroid speckle contrast is obtained and fitted to a logistic regression model to determine the likelihood of devascularization. Thus it acts as an aiding tool for the surgeons to determine the vascularity/ viability of the parathyroids or other organs.
  • FIG. 8A-8B show phantom data according to embodiments of the invention.
  • this is one embody of color hue that blue indicate motion of the object in the image and yellow represent static of that.
  • the color choice does not affect the result of laser speckle contrast imaging.
  • the lower the value of the pixel (contrast value) corresponds to the faster in motion and vice versa.
  • the contrast value can be converted into the speed of the flow (blood flow in this case).
  • the LSCI can be converted into a speed map.
  • this invention uses laser speckle imaging to provide a real-time non- invasive means to inform the surgeons whether or not a parathyroid gland is still being perfused and is therefore viable.
  • the invented apparatus or device acquires and processes images of the parathyroid gland.
  • the device comprises a 785 nm wavelength laser and a near-infrared camera with a zoom lens, positioned above the surgical filed via an articulated arm.
  • the laser light is diffused onto the tissue surface and images are acquired by the camera. Images are acquired using a program developed on commercially available software, and processed to produce speckle contrast image through the lab-developed dynamic link library file written in C++.
  • the imaging system for assessment of a tissue of a living subject comprises a light source for emitting a beam of light; a light delivery member coupled to the light source for delivering and directing the beam of light onto a tissue surface of the living subject to illuminate the tissue surface; a light collection member configured to collect light from the illuminated tissue surface responsive to the illumination; a detector coupled to the collection member for acquiring images of the light from the illuminated tissue surface, wherein each of the acquired images comprises a speckle pattern; and a controller arranged to operate the detector to acquire the images of the light from the illuminated tissue surface, receive the acquired images from the detector, and process the acquired images to obtain speckle contrast images for the intraoperative assessment oftissue viability.
  • the intraoperative assessment may also include, but is not limited to, evaluating perfusion/b!ood flow of the tissue
  • the tissue is a parathyroid gland, a pancreas gland, or an adrenal gland.
  • the light source comprises an infrared laser.
  • the light source comprises a diode laser emitting the beam of light at a wavelength of about 785 nm. It should be noted that other wavelengths can also be used to practice the invention.
  • the light delivery member comprises at least one optical fiber optically coupled to the light source for delivering the beam of light emitted from the light source.
  • a diffuser placed at a distal end of the at least one optical fiber for diffusing the beam of light onto the tissue surface.
  • the distal end of the at least one optical fiber is the end that operably close to the target of interest.
  • the diffuser is a hollow center diffuser.
  • a beam shaper is placed at a distal end of the illumination channel for focusing or collimating or directing the beam of light onto the tissue surface.
  • the beam shaper comprises a biconvex lens.
  • the beam shaper comprises a ball lens.
  • the light delivery member further comprises a linear polarizer placed at the front of the diffuser.
  • the collection member comprises one or more optical fibers, including a fiber bundle.
  • the collection member further comprises a rod lens placed on a distal end of the one or more optical fibers to optimize the collection of light and image formation at a predetermined working distance.
  • the distal end of the one or more optical fibers is the end that operably close to the target of interest.
  • the collection member further comprises a polarizer placed on a distal end of the one or more optical fibers for reduction of spectral reflection.
  • the system further comprises at least one lens placed in an optical path between the collection member and the detector for collecting and focusing light from the one or more optical fibers onto the detector.
  • the detector comprises at least one camera.
  • a high-speed camera is deployed for motion error control.
  • a camera that is capable of capturing moving images with exposures of less than 1/20 second or frame rates in excess of 20 fps is deployed for motion error control.
  • the at least one camera comprises an infrared camera or a near- infrared camera.
  • the at least one camera comprises a charge-coupled device (CCD) camera or a complementary metal oxide semiconductor (CMOS) camera.
  • CCD charge-coupled device
  • CMOS complementary metal oxide semiconductor
  • the system further comprises a display for displaying the speckle contrast images of the tissue in real-time.
  • a perfused parathyroid gland has low speckle contrast
  • a devascularized parathyroid gland has high speckle contrast
  • the imaging system for assessment of a tissue of a living subject, comprising a light source for emitting a beam of light to illuminate the tissue; and an imaging head positioned over the tissue for acquiring laser speckle contrast imaging (LSCI) images of light from the illuminated tissue responsive to the illumination.
  • LSCI laser speckle contrast imaging
  • the light source comprises an infrared laser.
  • the imaging head comprises: an illumination channel coupled to the light source for delivering and directing the beam of light onto the tissue surface to illuminate the tissue surface; and an imaging channel positioned in relationship to the illumination channel for acquiring images of the light from the illuminated tissue surface, wherein each of the acquired images comprises a speckle pattern.
  • the light source is placed in the illumination channel.
  • the illumination channel comprises a diffuser placed at a distal end of the illumination channel for diffusing the beam of light onto the tissue surface.
  • the distal end of the illumination channel is the end that operably close to the tissue.
  • the illumination channel comprises a beam shaper placed at a distal end of the at least one optical fiber for focusing or collimating or directing the beam of light onto the tissue surface.
  • the beam shaper comprises a ball lens.
  • the illumination channel further comprises a linear polarizer placed at the front of the optic.
  • the imaging channel comprises at least one camera.
  • the at least one camera comprises a CCD camera or a CMOS camera.
  • the imaging channel further comprises a polarizer placed the front of the at least one camera for reduction of spectral reflection.
  • the imaging channel is 1.5 mm in diameter.
  • the system further comprises a controller configured to control operations of the imaging head for acquiring the LSCI images of the illuminated tissue, receiving the acquired LSCI images from the at least one camera, and processing the acquired LSCI images to obtain speckle contrast images for the intraoperative assessment of tissue viability.
  • the method for assessment of a tissue of a living subject comprising: directing a beam of light onto the tissue surface to illuminate the tissue surface; acquiring laser speckle contrast imaging (LSCI) images of light from the illuminated tissue responsive to the illumination; and processing the acquired LSCI images for the intraoperative assessment of tissue viability.
  • LSCI laser speckle contrast imaging
  • said processing the acquired images comprises calculating a plurality of speckle contrasts from the acquired images of the tissue.
  • said calculating plurality of speckle contrasts comprises: defining a window with a number of pixels over which a speckle contrast is to be calculated; moving the window across the acquired image of the speckle pattern; and at each location, calculating the speckle contrast as a standard deviation of pixel intensity values a s within the window divided by a mean intensity value (/) as follows: wherein the resultant speckle contrast image has values that range from 0 to 1, with values closer to 0 representing regions of greater motion (perfusion) and 1 representing regions with no motion.
  • said processing the acquired images comprises an LSCI threshold mechanism for frame selection that removes frames that contain excessive motion, thereby realizing the viability assessment of the target of interest intraoperatively.
  • a frame selection code is applied to selection frames with tolerable motion. In some embodiments, a frame selection code is applied to selection frames with tolerable motion.
  • a universal threshold is applied to all frames. The threshold take the mean of all pixels of individual frames and filter out the frames with lower mean contrast value, as lower contrast value of the whole image is an indication that the frame is blurred out (contains excessive motion).
  • a universal mean of the contrast value over each frame is threshold with a calculated number based on the acquired video and threshold applied, such that when a frame is below the threshold, there exists excessive amount of motion artifact that confounds with the blood flow information in the frame; and when a frame are above the threshold, the frame is acquired in relative stillness and the motion artifact that is introduced during the exposure time is tolerable by the LSCI.
  • said processing the acquired images comprises discarding a frame out of the video when the frame is below the threshold, and preserving a frame when the frame is above the threshold and using the preserved frame an indicator of whether the target of interest is well vascularized.
  • a machine learning algorithm is applied to reduce motion artifact on the acquired LSCI images.
  • methods such as Pixel2pixel could be used to reconstruct the image with motion removed.
  • Pix2Pix GAN is a conditional GAN (cGAN). Unlike vanilla GAN which uses only real data and noise to learn and generate images, cGAN uses real data, noise as well as labels to generate images. In essence, the generator learns the mapping from the real data as well as the noise. However, this is just one machine learning method to reduce the motion artifact. It should be noted that other machine learning methods can also be utilized to practice the invention.
  • the method further comprises displaying the speckle contrast images of the parathyroid gland in real-time.
  • Yet another aspect of the invention provides a non -transitory computer readable storage medium/memory that stores computer executable instructions or program codes.
  • the computer executable instructions or program codes enable a computer or a similar computing apparatus to complete various operations of the above-disclosed method for processing LSCI images for intraoperative guidance in a surgery.
  • the storage medium/memory may include, but is not limited to, high-speed random access medium/memory such as DRAM, SRAM, DDR RAM or other random access solid state memory devices, and non-volatile memory such as one or more magnetic disk storage devices, optical disk storage devices, flash memory devices, or other non volatile solid state storage devices.

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Abstract

La présente invention concerne un système d'imagerie pour l'évaluation de la viabilité d'un tissu d'un sujet vivant qui comprend une source de lumière pour émettre un faisceau de lumière ; un élément de distribution de lumière couplé à la source de lumière pour distribuer le faisceau de lumière sur une surface de tissu du sujet vivant pour éclairer la surface de tissu ; un élément de collecte de lumière configuré pour collecter la lumière provenant de la surface de tissu éclairée en réponse à l'éclairage ; un détecteur couplé à l'élément de collecte pour acquérir des images de la lumière provenant de la surface de tissu éclairée ; et un dispositif de commande agencé pour actionner le détecteur pour acquérir les images de la lumière provenant de la surface de tissu éclairée, recevoir les images acquises depuis le détecteur et traiter les images acquises pour l'évaluation peropératoire de la viabilité tissulaire.
PCT/US2022/036633 2021-07-09 2022-07-11 Système d'imagerie de contraste à granularité laser et ses applications WO2023283479A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090118622A1 (en) * 2007-11-06 2009-05-07 The Regents Of The University Of California APPARATUS AND METHOD FOR WIDEFIELD FUNCTIONAL IMAGING (WiFI) USING INTEGRATED STRUCTURED ILLUMINATION AND LASER SPECKLE IMAGING
US20110013002A1 (en) * 2007-07-06 2011-01-20 Oliver Bendix Thompson Laser Speckle Imaging Systems and Methods
US20140316284A1 (en) * 2011-09-26 2014-10-23 The Johns Hopkins University Anisotropic processing of laser speckle images
US20170105623A1 (en) * 2008-07-30 2017-04-20 Vanderbilt University Intra-operative use of fluorescence spectroscopy and applications of same
US20190328309A1 (en) * 2016-12-27 2019-10-31 Vanderbilt University Methods and apparatus for intraoperative assessment of parathyroid gland vascularity using laser speckle contrast imaging and applications of same

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110013002A1 (en) * 2007-07-06 2011-01-20 Oliver Bendix Thompson Laser Speckle Imaging Systems and Methods
US20090118622A1 (en) * 2007-11-06 2009-05-07 The Regents Of The University Of California APPARATUS AND METHOD FOR WIDEFIELD FUNCTIONAL IMAGING (WiFI) USING INTEGRATED STRUCTURED ILLUMINATION AND LASER SPECKLE IMAGING
US20170105623A1 (en) * 2008-07-30 2017-04-20 Vanderbilt University Intra-operative use of fluorescence spectroscopy and applications of same
US20140316284A1 (en) * 2011-09-26 2014-10-23 The Johns Hopkins University Anisotropic processing of laser speckle images
US20190328309A1 (en) * 2016-12-27 2019-10-31 Vanderbilt University Methods and apparatus for intraoperative assessment of parathyroid gland vascularity using laser speckle contrast imaging and applications of same

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