WO2022010519A1 - Tissue imaging system - Google Patents

Tissue imaging system Download PDF

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Publication number
WO2022010519A1
WO2022010519A1 PCT/US2020/054457 US2020054457W WO2022010519A1 WO 2022010519 A1 WO2022010519 A1 WO 2022010519A1 US 2020054457 W US2020054457 W US 2020054457W WO 2022010519 A1 WO2022010519 A1 WO 2022010519A1
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WO
WIPO (PCT)
Prior art keywords
tissue
peripheral nerve
excitation light
light
imaging system
Prior art date
Application number
PCT/US2020/054457
Other languages
French (fr)
Inventor
Fernando DIP
Raul J. ROSENTHAL
Original Assignee
Axon Imaging, Llc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Axon Imaging, Llc filed Critical Axon Imaging, Llc
Priority to PCT/US2021/041113 priority Critical patent/WO2022011276A1/en
Priority to AU2021305238A priority patent/AU2021305238A1/en
Priority to EP21837678.8A priority patent/EP4179297A1/en
Priority to KR1020237004393A priority patent/KR20230035378A/en
Priority to JP2023501356A priority patent/JP2023533061A/en
Priority to CA3185419A priority patent/CA3185419A1/en
Publication of WO2022010519A1 publication Critical patent/WO2022010519A1/en
Priority to US17/678,668 priority patent/US11839361B2/en
Priority to US18/467,006 priority patent/US20240000301A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/40Detecting, measuring or recording for evaluating the nervous system
    • A61B5/4029Detecting, measuring or recording for evaluating the nervous system for evaluating the peripheral nervous systems
    • A61B5/4041Evaluating nerves condition
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/645Specially adapted constructive features of fluorimeters
    • G01N21/6456Spatial resolved fluorescence measurements; Imaging
    • G01N21/6458Fluorescence microscopy
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6486Measuring fluorescence of biological material, e.g. DNA, RNA, cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/04Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances
    • A61B1/043Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances for fluorescence imaging
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/313Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor for introducing through surgical openings, e.g. laparoscopes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/20Surgical microscopes characterised by non-optical aspects

Definitions

  • the disclosures herein relate to systems and devices for tissue imaging.
  • the disclosed invention relates to aa visual imaging system for intraoperative identification of peripheral nerves by use of excitation electromagnetic radiation-induced fluorescence, strictly without the use of dyes, markers, or probes.
  • iatrogenic injuries to nerves are among the most catastrophic, placing patients at risk for both short and long-term motor and sensory deficits. They also are disturbingly common, documented in up to twenty percent (20%) of patients undergoing certain common procedures like thyroidectomies, parotidectomies, resection of breast and colon cancers, prostatectomies, and inguinal hernia repairs. Avoiding unintentional nerve damage during operative procedures requires that nerves be identified accurately and dissected carefully, both challenging undertakings when standard visualization techniques are used. Consequently, the ability to accurately identify sensory and motor nerves during surgical procedures is crucial to prevent nerve injury.
  • Fluorescent imaging techniques in conjunction with special dyes, have proven successful in preclinical and clinical studies at helping surgeons identify peripheral nerves intraoperatively.
  • fluorescent dyes, markers, or probes to label peripheral nerves is problematic.
  • Most probes and dyes have not been shown to be safe and effective; consequently, they generally are not approved by the United States Food and Drug Administration (“FDA”).
  • FDA United States Food and Drug Administration
  • a few dyes have been approved for clinical use, but most require extensive preparation times, are costly, must be used in limited doses to mitigate toxicity, have short half-lives en vivo , may cause serious or even fatal allergic reactions, and require precise timing of administration.
  • markers or dyes are not highly specific for neural tissue, they can actually obscure a peripheral nerve by also enhancing surrounding non-neural tissue, making peripheral nerve visualization even more difficult. Additionally, observed differences in fluorescence between tissues following parenteral administration of a dye or marker may be the result of differences in tissue perfusion rather than differential uptake by different tissue types. Arteries perfusing peripheral nerves are very small compared with those perfusing other anatomic structures, which may accentuate differences in fluorescence arising from differential perfusion. [0007] For at least the foregoing issues, the use of dyes, markers, and probes for intraoperative identification of nerves gives inconsistent and unreliable results.
  • a tissue imaging system is described herein.
  • Embodiments of the tissue imaging system generates a visual image, either optically or digitally, wherein visualization of a target tissue structure, such as a peripheral nerve, is enhanced by generating autofluorescense of the peripheral nerve in response to illumination with an excitation light.
  • Autofluorescense distinguishes the peripheral nerve from surrounding adipose, muscle, and connective tissue. These surrounding tissues fluoresce (if at all) at an intensity substantially less than that of the target peripheral nerve.
  • Else of excitation light in the near-ultraviolet (NUV) wavelength range between about 300 nm and about 400 nm is particularly effective.
  • Emitted light emanating from the nerve in response to the excitation light is of a different wavelength than the excitation light, given that the nerve- emitted light is of a lower energy (higher wavelength) than the excitation light. Consequently, a filter interposed between the surgical field and a camera device or objective lens removes excitation and other ambient light reflected from the illuminated tissue, thus further enhancing contrast between the peripheral nerve and surrounding tissue, when viewed by the surgeon on a monitor screen or through an eyepiece lens.
  • a peripheral nerve visual imaging system comprising a housing configured for intraoperative use in a sterile environment, the housing containing a source optical train configured to direct an excitation light onto a tissue containing a peripheral nerve, wherein the excitation light illuminates the tissue and the peripheral nerve, and a receiving optical train configured to receive an emitted light from the peripheral nerve, wherein the emitted light is generated by the peripheral nerve in response to illumination of the peripheral nerve with the excitation light in the absence of a marker, a probe, or a dye; an excitation light source optically coupled to the source optical train; and a camera optically coupled to the receiving optical train and configured to generate a visual signal in response to the emitted light.
  • the peripheral nerve visual imaging system has a plurality of cameras.
  • the peripheral nerve visual imaging system further comprises a controller operatively coupled to the excitation light source and the camera, having a software residing on a memory; a processor that executes the software; a user interface operatively coupled to the processor; a visual display operatively coupled to the processor; and a power source, wherein the power source is medical-grade compliant.
  • a controller operatively coupled to the excitation light source and the camera, having a software residing on a memory; a processor that executes the software; a user interface operatively coupled to the processor; a visual display operatively coupled to the processor; and a power source, wherein the power source is medical-grade compliant.
  • an image display is operatively coupled to the processor.
  • the excitation light comprises a range of wavelengths between about 300 nanometers and about 400 nanometers.
  • the source optical train comprises an excitation filter optically interposed between the excitation light source and the tissue containing the peripheral nerve.
  • the receiving optical train comprises a detection filter optically interposed between the tissue containing the peripheral nerve and the detector, wherein the detection filter is configured not to transmit at least a portion of excitation light reflected by the tissue and the peripheral nerve.
  • the detection filter is configured to transmit at least a portion of the emitted light having a wavelength different from the excitation light to the camera.
  • the detection filter is a bandpass filter configured to transmit light having a range of wavelengths between about 400 nanometers to about 600 nanometers.
  • a tissue visual imaging device comprising a housing configured for intraoperative use in a sterile environment, the housing containing a receiving optical train configured to receive an emitted light from a tissue, wherein the emitted light is generated by the tissue in response to illumination of the tissue with an excitation light in the absence of a marker, a probe, or a dye.
  • the tissue visual imaging device also comprises an excitation light source configured to illuminate the tissue with the excitation light.
  • a user directly visualizes the emitted light through the receiving optical train.
  • a camera is optically coupled to the receiving optical train, wherein the receiving optical train is optically positioned between the tissue and the camera.
  • a controller is operatively coupled to the camera.
  • an image display is operatively coupled to the camera.
  • the housing comprises a user input device mounted thereon.
  • the tissue comprises a peripheral nerve. In some embodiments, the tissue comprises a spinal dura.
  • a method for intraoperative detection of a peripheral nerve comprising positioning a probe, the probe having a receiving optical train configured to obtain data used to form a visual image, proximate to a tissue containing a peripheral nerve; illuminating the tissue with an excitation light comprising a first wavelength, in the absence of a dye, a marker, or a probe, causing the tissue to generate an emitted light comprising a second wavelength in response to illumination with the excitation light of the first wavelength; detecting the emitted light from the tissue in the absence of a dye, marker, or a probe; and forming a visual image of a peripheral nerve distinguished from the tissue.
  • the method further comprises a step filtering the emitted light.
  • FIG. 1 is an illustration of an embodiment of a tissue imaging system
  • FIG. 2 is an illustration of an embodiment of an interrogation unit of a tissue imaging system
  • FIG. 3 is a cutaway-side view illustration of an embodiment of an interrogation unit of a tissue imaging system examining a tissue containing a peripheral nerve;
  • FIG. 4 is a partial schematic diagram of a tissue imaging system
  • FIG. 5 is an illustration of an embodiment of a controller for a tissue imaging system
  • FIG. 6 is an illustration of a tissue imaging system mounted on a medical cart
  • FIGs. 7A-7B are illustrations of an example user interface screen display of settings menus for a tissue imaging system
  • FIG. 8 is an example video display of a tissue imaging system
  • FIG. 9 is a diagram showing steps for a method of use of a tissue imaging system.
  • tissue autofluorescence has the distinct advantage of providing real-time imaging without the need for invasive techniques or patient exposure to potentially unsafe compounds. Moreover, the dyes and probes utilized in most of the research conducted thus far on nerve identification are often difficult to procure. [0032] The inventors believe they are the first to both study nerve autofluorescence in humans and develop corresponding technology leveraging autofluorescense in the operating room to prevent or reduce the risk or iatrogenic intraoperative nerve injury.
  • Embodiments of the disclosed invention allow for enhanced, real-time intraoperative visualization of peripheral nerves by causing and imaging nerve autofluorescence using different intensities and wavelengths of electromagnetic radiation coupled with different wavelength range-pass optical filters by an integrated system of devices configured for operating room use. Additionally, the inventors’ findings suggest that use of light wavelength filters, particularly optical filters that selectively transmit excitation light in the near-ultraviolet (NUV) range and bandpass optical filters to largely remove reflected light from nerve-emitted light increase perceived levels of nerve autofluorescence, thereby increasing visual contrast between nerves and surrounding tissue.
  • Embodiments of the disclosed invention are a means of altering the rate and severity of iatrogenic nerve in clinical surgical practice.
  • tissue imaging system is described herein.
  • the tissue imaging system is used specifically to enhance and facilitate intraoperative visualization of peripheral nerves by the operating surgeon.
  • tissue imaging system and “nerve imaging system” both mean a system comprised of devices and components utilized to enhance visualization of specific tissue structures, such as peripheral nerves, for example, from surrounding tissues. It is to be understood, however, that a nerve imaging system may, in some embodiments, be used to visualize non-neural structures or tissues.
  • a “medical device” is an instrument, apparatus, implement, machine, appliance, software, material, or other similar or related article intended to be used, alone or in combination for human beings for the specific medical purposes of diagnosis, prevention, monitoring, treatment or alleviation of disease.
  • a “peripheral nerve” is a motor, sensory, autonomic, or mixed- function nerve existing outside of the brain or spinal cord proper.
  • “peripheral nerve” includes cranial nerves outside of the dura enclosing the brain.
  • “Peripheral nerve” also includes mixed spinal nerves and spinal ganglia, whether outside of or enclosed by the spinal dura (thecal sac).
  • peripheral nerves include the facial nerve and its branches, the superior laryngeal nerve, the recurrent laryngeal nerve, the hypoglossal nerve, the spinal accessory nerve, nerve roots, nerve trunks, and nerve branches of the brachial plexus and the lumbar plexus, the long thoracic nerve, the medial and lateral pectoral nerves, sympathetic ganglia, pelvic sensory nerves, and many others.
  • spinal dura “dura,” or “thecal sac” is the thick, dense, fibrous membranous structure surrounding the spinal cord, dorsal and ventral spinal nerves, and dorsal spinal ganglia.
  • wavelength means a specific wavelength of an electromagnetic radiation, whether visible or invisible to the human eye, including near ultraviolet light, ultraviolet light, near-infrared light, or infrared light. “Wavelength” may represent a range of wavelengths. The range of wavelengths may discreet and continuous or may be discontinuous.
  • mitted light means electromagnetic radiation of a discrete wavelength or range of wavelengths emitted by a cell, a tissue, or an anatomic structure in response to illumination or irradiation with electromagnetic radiation of a different wavelength or range of wavelengths.
  • “Emitted light” originates solely from the cell, tissue, or anatomic structure and does not comprise reflected excitation light or light reflected from other sources of ambient light.
  • “Emitted light” arises as a consequence of an intrinsic property of the atoms, molecules, or a particular arrangement of atoms and molecules forming the cell, the tissue, or the anatomic structure.
  • excitation light means electromagnetic radiation used to illuminate or irradiate a cell, a tissue, or an anatomic structure to cause the cell, the tissue, or the anatomic structure to generate an emitted light comprising a different wavelength or range of wavelengths than the excitation light.
  • a “low-pass filter” means a low-pass wavelength optical filter, including a digital filter, that passes electromagnetic radiation having a wavelength longer than a selected cutoff wavelength.
  • a “low-pass filter” may comprise a single optical filter element or a plurality of optical filter elements configured to allow passage of electromagnetic radiation having a wavelength longer than the selected cutoff wavelength.
  • a “high-pass filter” means a high-pass wavelength optical filter, including a digital filter, that passes electromagnetic radiation having a wavelength shorter than a selected cutoff wavelength.
  • a “high-pass filter” may comprise a single optical filter element or a plurality of optical filter elements configured to allow passage of electromagnetic radiation having a wavelength shorter than the selected cutoff wavelength.
  • a “band-pass filter” means a band-pass wavelength optical filter, including a digital filter, that passes electromagnetic radiation having a range of wavelengths within a selected discrete range of wavelengths between a first wavelength and a second wavelength longer than the first wavelength.
  • a “band-pass filter” may comprise a single optical filter element or a plurality of optical filter elements configured to allow passage of electromagnetic radiation having a range of wavelengths within the selected range of wavelengths.
  • reflected light means excitation light and ambient light passing into a receiving optical train after being reflected from a tissue, a surface, or the like. “Reflected light” is not “emitted light” as “emitted light” is defined herein.
  • the tissue imaging system can be used by healthcare professionals in a clinical setting, for example, a hospital, an ambulatory surgical center, and the like.
  • a surgeon or healthcare practitioner may use the tissue imaging system in combination with additional imaging devices, such as ultrasound, fluoroscopy, or other conventional imaging devices.
  • additional imaging devices such as ultrasound, fluoroscopy, or other conventional imaging devices.
  • the tissue imaging device standing alone or used with such other imaging devices, may be used, in some embodiments, to help a surgeon distinguish peripheral nerves from other anatomical structures and surrounding tissue, decreasing the risk of injury to a peripheral nerve.
  • the tissue imaging device is structurally adapted for use integrated with an operating microscope, a rigid or flexible endoscope, laparoscopes, thoracoscopes, and related devices; end-effector instruments such as instruments used in minimally invasive surgical procedures throughout the body, surgical instruments used during traditional “open” procedures, or other medical devices with which integration of the medical device with a tissue imaging system is advantageous or desirable.
  • the tissue imaging system creates a visual image of a target tissue, such as a peripheral nerve, by causing the tissue to fluorescence in response to illumination with light, whether visible outside the range of visible light.
  • Tissue fluorescence occurs without use of adjunctive chemical or pharmacologic compositions, such as dyes, markers, probes, or the like, whether applied topically or administered (orally or parenterally).
  • adjunctive chemical or pharmacologic compositions such as dyes, markers, probes, or the like, whether applied topically or administered (orally or parenterally).
  • peripheral nerves fluoresce intrinsically upon illumination with excitation light differently than surrounding tissues, depending on the wavelength and intensity of the excitation light, light filtering means, and image processing techniques. The system exploits contrasting levels of fluorescence to distinguish peripheral nerves from surrounding tissue.
  • tissue imaging system include a means for illuminating a tissue bed, such as a surgical field, with an excitation light.
  • a target tissue such as tissue forming a peripheral nerve, autofluoresces in response to the incident excitation light at an intensity different from autofluorescence (if any) of the surrounding or background tissue.
  • a camera or similar detector receives the tissue-emitted fluorescent light, which is processed to create a visual image for display.
  • the tissue imaging system may include additional elements as discussed herein below.
  • the excitation light illuminating the tissue bed comprises a wavelength or a range of wavelengths, or intervals over a range of wavelengths (collectively referred to herein as “wavelength(s)” that cause an intrinsic effect of the biochemical structure of the tissue, such as nerve tissue.
  • This intrinsic effect causes the tissue to emit light at a particular wavelength or in a particular wavelength region that is different from the wavelength(s) of the excitation light.
  • the tissue imaging system captures the wavelength or wavelengths of light emitted from the tissue in response to the tissue’s intrinsic properties.
  • Some embodiments of the tissue imaging system comprise a data processor and a software package residing on a memory.
  • the software package directs an excitation light source via the data processor to emit light onto or into a patient’s body at a particular wavelength or range of wavelengths.
  • tissues emit light at a particular wavelength or in a particular wavelength region.
  • the wavelength and intensity of the emitted light is intrinsic to the particular tissue type and structure. More specifically, a peripheral nerve comprising nerve tissue, when stimulated or excited, emits an intrinsic and particular wavelength of range of wavelengths of light (hereinafter, “emitted light”). Such emitted light may be due to fluorescence, other phenomenon, or fluorescence in combination with other phenomenon.
  • the tissue imaging system such as a nerve imaging system, receives light from the illuminated tissue and, in some embodiments, filters it with a detection filter to identify at least a nerve-emitted light to generate a data signal.
  • the data signal representing an image of the nerve-emitted light is transmitted to an image display for visualization by the user.
  • FIG. 1 is an illustration of an embodiment of a tissue imaging system 100.
  • FIG. 1 shows a tissue-imaging system 100.
  • Tissue imaging system 100 in some embodiments, is a nerve tissue imaging system configured for intraoperative imaging of peripheral nerves.
  • System 100 comprises various component devices for generating an excitation light and directing this to illuminate a tissue thought to contain a peripheral nerve. In response to illumination of a tissue containing a peripheral nerve with excitation light, at least two different types of light are created: (1) reflected light, which is excitation light reflected by the tissue and the peripheral nerve; and (2) emitted light, which is light emitted by nerve or other tissue via fluorescence or other intrinsic property in response to energy received by the excitation light.
  • an interrogation unit 120 generates the excitation light and receives reflected and emitted light for imaging processing. This is discussed further herein below.
  • System 100 also includes a controller 140 housing components such as a processor and a user interface, in some embodiments.
  • elements of system 100 are electrically and communicatively coupled to one another by cables, such as a first cable 126 and a second cable 151.
  • a power source 152 is electrically coupled to controller 140.
  • FIG. 1 also shows an image display 150, whereupon a user of system 100 may visualize an image of the tissue being examined to determine the location of a peripheral nerve.
  • first cable 125 communicatively and electrically couples interrogation device 120 with controller 140 and a second cable 151 communicatively and electrically couples image display 150 to controller 140.
  • interrogation device 120 is “free-standing,” having an internal power source and a wireless communication means of exchanging instructions and data with controller 140.
  • image display 150 in some embodiments, comprises an internal or other separate power source and wireless communication means.
  • Examples of an internal power source include a battery.
  • the battery may be any battery suitable for use in a medical device, including a battery that is non-rechargeable and disposable, or a rechargeable battery.
  • Some examples of medically suitable, non- rechargeable batteries include an alkaline battery, a lithium battery, a solid-state battery, and the like.
  • the battery is a rechargeable battery, such as a nickel- cadmium batter, I nickel metal hydride battery, a nickel zinc battery, a lithium ion battery or other suitable rechargeable batter.
  • Embodiments of system 100 not comprising first cable 126 have a wireless communication means communicatively coupling interrogation unit 120 to controller 140.
  • Some embodiments of system 100 not comprising second cable 151 have a wireless communication means communicatively coupling image display 150 with controller 140.
  • Non-limiting examples of wireless communication means suitable for use in by various components of system 100 include transmitters and receivers using various wireless technologies well known in the art, including Bluetooth and WiFi wireless technology platforms.
  • FIG. 2 is an illustration of an embodiment of interrogation unit 120 of tissue imaging system 100 and FIG. 3 is a side view of an embodiment of interrogation unit 120 of tissue imaging system 100.
  • interrogation unit 120 comprises a housing 121 configured to house electronic, optical, and related elements configured to provide tissue illumination and collection of light from the illuminated tissue.
  • Housing 121 is formed from a medical grade material and configured for use in a sterile surgical environment.
  • housing 121 is configured for gas sterilization, such as using ethylene oxide, ozone, or other gases suitable for sterilizing sensitive electronic medical equipment that would be destroyed by heat-based sterilization systems and techniques.
  • housing 121 is not configured for sterilization but is used with a sterile disposable sac or equipment-condom is used that covers and at least partially encloses housing 121 wherein interrogation unit 120 may be used in a sterile operating- room environment.
  • Elements contained within or coupled to housing 121 include, in some embodiments, an excitation light source 102, a source optical train 116, a receiving optical train 117, a camera 122, and a handle 125.
  • first cable 126 electrically, communicatively, or electrically and communicatively couples interrogation unit 120 to controller 140.
  • Housing 121 may also contain additional elements, for example, mounting or fixation means, electronics, cooling means, thermal insulation, and the like, according to a particular embodiment or embodiments of interrogation unit 120.
  • interrogation unit 120 is arranged and configured as shown in FIGs. 2 and 3.
  • Handle 125 is coupled to housing 131 separate or generally opposite from a distal end 127, such that elements of source optical train 115 and receiving optical train 117 are not obscured from radiating and receiving light.
  • Handle 125 in some embodiments, is a unitary body with housing 121.
  • First cable 126 enters interrogation unit 120 a handle 125, in some embodiments, to keep first cable 126 out of a line-of-sight between a distal end 127 and the tissue being illuminated and visualized.
  • source optical train 116 and receiving optical train 117 are arranged alongside one another within housing 121 in a configuration similar to that shown by FIG. 3.
  • source optical train 117 is a plurality of source optical trains configured in an array or pattern, such as the circular pattern of eight (8) source optical trains 117 around a perimeter of distal end 127 shown by FIG. 2.
  • tissue 104 may be more brightly and evenly illuminated with excitation light 110. Bright and uniform illumination may reduce light shadowing effects allowing enhanced visualization of tissue 104 by system 100.
  • Other and any number of arrangements, patterns, or arrays comprising any number of source optical trains 117 are considered to be within the scope of this disclosure.
  • Excitation light source 102 is located within housing 121, in some embodiments. In some alternate embodiments, excitation light source 102 resides in a location remote from interrogation unit 120, and excitation light 110 is transmitted to interrogation unit 120 through a light transmission means, such as fiberoptic bundle, for example.
  • a remote excitation light source 102 may be a “free-standing” device, or may be housed within or coupled to a console such as those used in robotically assisted or computer-assisted surgery, a medical device cart, or the like.
  • the light transmission means may be unitary with first cable 126 or may be mechanically and optically coupled between excitation light source 102 and interrogation unit 120 as a separate elongate cable-like structure, for example.
  • Excitation light source 102 generates excitation light comprising a broad band of wavelengths or light confined to a narrower wavelength range.
  • excitation light source 102 is a narrow-wavelength range source such as a light-emitting diode (LED) or a laser.
  • excitation light source 102 comprises a wide wavelength-range “white” light source, such as a halogen (xenon) lamp, a 450-Watt xenon lamp, a tungsten-halogen lamp, or a mercury arc lamp, for example.
  • Excitation light source 102 emits excitation light 110 which passes from source optical train 116 of interrogation unit 120 to illuminate a tissue 104.
  • Excitation light source 102 is configured to emit excitation light 110 at a particular wavelength to stimulate or excite tissue 104 through an effect intrinsic to the tissue; for example, a fluorescent effect. Because the effect is intrinsic i.e., of the essential nature or constitution of the tissue and originating wholly from within the tissue, fluorescent (or other) dyes, markers, probes, and the like are not necessary for operation of system 100.
  • the generated wavelength of excitation light 110 by excitation light source 102 maximizes the difference between intrinsic fluorescent effects of the peripheral nerve and the surrounding tissue, in some embodiments. In a visual image, this difference between fluorescent effects is represented by contrast between a peripheral nerve and surrounding tissue, whereunder system 100 enhances visualization of a peripheral nerve, or other target tissue, for a user, such as a surgeon.
  • the wavelength of excitation light 110 is a range between about 300 nanometers (nm) and about 400 nm. In some embodiments, the wavelength of excitation light 110 is between about 360 nm and about 390 nm. In some embodiments, the wavelength of excitation light 110 is a range of wavelengths between about 455 nm and about 510 nm. In some embodiments, the wavelength of excitation light 110 is about 485 nm.
  • Source optical train 116 directs excitation light 110 from interrogation unit 120; i.e., to illuminate tissue.
  • Source optical train 116 may be proximate to or contiguous with excitation light source 102.
  • source optical train 116 comprises an optical lens, or a plurality of optical lenses to appropriately focus or disperse and direct excitation light 110 for illumination of tissue 104.
  • excitation light source 102 illuminates tissue 104 directly with excitation light 110 and interrogation unit 120 does not comprise source optical train 116.
  • source optical train 116 is contained within excitation light source 102 separate from interrogation unit 120.
  • source optical train 116 comprises a fiberoptic bundle as discussed herein. According to the embodiment, source optical train 116 may comprise any combination including one or more of an optical lenses, a plurality of optical lenses, or a fiberoptic bundle, without limitation.
  • source optical train 116 comprises an excitation filter 111 configured to narrow, constrict, or “tune” the wavelength of excitation light 110 to a range optimal for causing the peripheral nerve, or other target structure or tissue type, to produce emitted light 111 and causing minimal or no fluorescence of the surrounding tissue.
  • Excitation filter 111 is particularly useful for embodiments wherein excitation light source 102 is a broad-band white light source, such as a halogen or mercury-arc source, versus excitation light 110 from a more narrow-band source, such as certain LED or laser excitation light sources. Accordingly, in some embodiments, excitation filter 111 is a bandpass filter. In some embodiments, excitation filter 111 is a low-pass filter.
  • excitation filter 111 is a high-pass filter. In some embodiments, excitation filter 111 is an about 300 nm high-pass filter. In some embodiments, excitation filter 111 is an about 400 nm low-pass filter. In some embodiments, excitation filter 111 is an about 300 to an about 400 nm bandpass filter. In some embodiments, excitation filter 111 is an about 320 to an about 380 nm bandpass filter. In some embodiments, excitation filter 111 is an about 325 nm to an about 375 nm bandpass filter. In some embodiments, excitation filter 111 is an about 350 nm low-pass filter. In some embodiments, excitation filter 111 is an about 300 nm low-pass filter. In some embodiments, excitation filter 111 is an about 400 nm high-pass filter.
  • tissue 104 illuminated with excitation light 110 directs light back to interrogation unit 120.
  • This directed light includes a reflected light 114, including the tissue-reflected component of excitation light 110. If tissue 104 has intrinsic fluorescent properties when illuminated with excitation light 110, tissue 104 produces an emitted light 112. Emitted light 112 originates solely through fluorescence or other intrinsic property of a portion of tissue 104. All or a portion of reflected light 114, emitted light 112, and non-emitted ambient light are collected by receiving optical train 117 of interrogation unit 120, in some embodiments of system 100.
  • Receiving optical train 117 comprises an optical lens or a plurality of optical lenses and is configured to focus and direct light comprising emitted light 112 onto a camera 122.
  • receiving optical train 117 comprises a single focusing lens.
  • receiving optical train 117 comprises a plurality of any number, combination, and arrangement of focusing lenses and dispersing lenses configured to focus at least emitted light 112 onto camera 122.
  • Some embodiments of system 100 do not comprise receiving optical train 117, wherein camera 122 is a “chip on a stick” image-sensor charge coupled device (“CCD”) camera.
  • Some embodiments of receiving optical train 117 comprise a detection filter 124 but do not comprise a lens.
  • receiving optical train 117 comprises detection filter 124, as shown in FIG. 3.
  • detection filter 124 is an optical filter that filters out reflected light 114 and ambient light having wavelengths outside of the range of filter 124. In some embodiments, however, receiving optical train 117 does not comprise detection filter 124.
  • Detection filter 124 may allow only desired wavelengths of light (e.g., wavelengths the correspond to the nerve-emitted light) to pass through detection filter 124 to a camera 122.
  • the light filtering function of detection filter 124 is performed digitally by an image processing software package residing on a data processor.
  • the appropriate detection filter 124 can depend on other aspects of system 100, particularly with respect to the wavelength of emitted light 112 which, in turn, depends on the intrinsic properties of the peripheral nerve or other tissue, such as spinal dura, targeted for visualization.
  • detection filter 124 may also be configured to allow wavelengths of emitted light 112 to pass that enable visualization of tissue surrounding a peripheral nerve, wherein the surrounding tissue emits light at a particular wavelength or in a particular wavelength range that is different from the wavelength(s) of the excitation light.
  • Peripheral nerves intrinsically form emitted light 112 of a higher intensity than many non-nerve tissues in response to the same intensity (luminosity) and wavelength of excitation light 110. For this reason, light emitted from tissue surrounding a peripheral nerve, such as adipose or muscle tissue, will have a significantly lower intensity that light emitted from the peripheral nerve. The surrounding tissue can still be visualized, but the peripheral nerve is visually distinguished from the surrounding tissue.
  • detection filter 124 is a bandpass filter that preferentially allows light to pass comprising wavelengths in a range of about 400 nm to about 600 nm consistent with a range of emitted light 112 surrounding a wavelength of about 488 nm. In some embodiments, detection filter 124 is a bandpass filter with a range of about 450 nm to about 575 nm. In some embodiments, detection filter 124 is a bandpass filter with a range of about 480 nm to a range of about 500 nm. In some embodiments, detection filter 124 is a bandpass filter with a range of about 450 nm to about 575 nm.
  • detection filter 124 is a bandpass filter with a range of about 425 nm to about 525 nm. In some embodiments, detection filter 124 is a bandpass filter with a range of about 440 nm to about 570 nm.
  • detection filter 124 is a high-pass filter with a range of longer than about 400 nm. In some embodiments, detection filter 124 is a high-pass filter with a range of longer than about 425 nm. In some embodiments, detection filter 124 is a high-pass filter with a range of longer than about 450 nm.
  • detection filter 124 is a low-pass filter with a range of shorter than about 600 nm. In some embodiments, detection filter 124 is a low-pass filter with a range of shorter than about 575 nm. In some embodiments, detection filter 124 is a low-pass filter with a range of shorter than about 550 nm. In some embodiments, detection filter 124 is a low-pass filter with a range of shorter than about 510 nm.
  • Camera 122 receives light from receiving optical train 117, in some embodiments.
  • camera 122 is configured to communicate digital information representing light collected from receiving optical train 117 to a processor, wherein the processor digitally processes the information to generate a visual image displayed on a digital screen or monitor.
  • Camera 122 in some embodiments, is an image sensor. Accordingly, in some embodiments, camera 122 is a digital camera module configured to couple to a processor.
  • Camera 122 is a monochromatic or polychromatic digital camera, in some embodiments.
  • One non-limiting example of a suitable camera 122 is the VM- 010-KSP09.A0 digital camera module (PHYTEC Messtechnik GmbH, Mainz, Germany).
  • camera 122 is an optical camera having an eyepiece for direct visualization of a non-digital visual image.
  • Camera 122 with or without receiving optical train 117, can be optically coupled to visualization devices other than interrogation unit 120, such as an operating microscope/ laparoscope, thoracoscope, arthroscope, bronchoscope, ureteroscope, or the like; for a flexible fiberoptic endoscope, in some embodiments.
  • interrogation unit 120 comprises a plurality of cameras 122, each camera 122 of the plurality of cameras 122 optically coupled to one receiving optical train 117 of a corresponding plurality of optical trains 117.
  • Embodiments comprising more than one camera 122 may be useful to from a stereoscopic visual image of tissue 104.
  • FIG. 4 is a partial schematic diagram of a tissue visualization system 100 showing digital data paths in some embodiments.
  • a processor 142 comprises a data processor, such as a microprocessor, for processing digital inputs and delivering data and instruction so output devices, including excitation light source 102, camera 122, a user interface 146, a memory 145, a video recorder 160, and a visual display 150, in some embodiments.
  • Processor 142 receives digital inputs from camera 122, user interface 146, and a memory 145.
  • various suitable processors may be used as processor 142, including a medical-grade computer microprocessor such as currently used in existing medical imaging and computer-assisted imaging applications.
  • processor 142 is a plurality of microprocessors executing functions related to specific tasks, such as digital image processing and/or image enhancement, digital recording and memory management, excitation light source management, digital optical filtering of emitted and reflected light passing, user interface management, wireless communications, and other specific functions, in some embodiments.
  • Processor 142 executes a software package 144 residing on memory 145 and running on processor 142.
  • software package 144 is configured to conduct preferential visualization of a first tissue, such as a peripheral nerve, compared to a second tissue, such as adipose tissue, muscle tissue, connective tissue, and the like.
  • Processor 142 is configured to deliver instructions related to power delivery, aperture size, and the like to camera 122 and to receive image data from camera 122, in some embodiments.
  • Memory 145 is a data storage device. Memory 145 may be configured as a writable memory or a combination of a writable memory and a read-only memory, in some embodiments.
  • Visual image data signals from processor 142 are received by visual display 150.
  • Visual display 150 displays a visual image, such as a peripheral nerve on background tissue, to a surgeon or other user of system 100.
  • visual display 150 may be a standard video monitor, a high-resolution video monitor such as used during minimally invasive surgical procedures, or a computer monitor.
  • Display 150 may be a light emitting diode (LED) display, including an organic LED (OLED), a liquid crystal display (LCD) a plasma display, a quantum dot display (QLED), or any medical-grade of other visual image display such as is currently used or shall be developed at a future time, without limitation.
  • LED light emitting diode
  • OLED organic LED
  • LCD liquid crystal display
  • QLED quantum dot display
  • Video recorder 160 receives visual image data from processor 142 and may output visual image data to visual display 150.
  • a standard digital or analog (video tape) device may comprise video recorder 160, according to the embodiment of system 100.
  • User interface 146 is a means wherein a user of system 100 interacts with and controls functions, including information exchange and instructions, and settings adjustments of various components and elements of system 100. Some non-limiting examples of these functions include initiating or terminating power delivery to system 100 or any of its individual components, varying the intensity (luminosity) of excitation light 110 emitted from excitation light source 102; varying the wavelength of excitation light 110 through engaging optical or digital filters or by changing light sources, i.e., white light versus filtered (band-pass or other) of excitation light 110, and the like. Varying the pass-wavelength of a digital filter is varied, changed, or adjusted via user interface 146, in some embodiments. User interface 146 may comprise analog buttons or switches, digital input switches, a digital touchscreen, toggle switches, joysticks, wheels, whether digital or analog, or any combination thereof.
  • user interface 146 comprises a plurality of user interfaces.
  • system 100 may comprise a combination of (i) a graphical user interface residing on controller 140; (ii) button or other switches disposed on housing 121 of interrogation unit 120; (iii) a floor-based foot-activated toggle or other switch to change tissue illumination (i.e., excitation light 110) between white light and filtered light; and the like, in some embodiments.
  • FIG. 5 is a graphic illustration of an embodiment of a controller for tissue imaging system 100.
  • controller 140 having processor 142, memory 145, and user interface 146. Also shown is a connection interface 147.
  • Connection interface 147 may be a high-definition multimedia interface (HDMI), a set of external recording device input-output connectors, a universal serial bus (USB), and the like.
  • controller 140 comprises a plurality of connection interfaces 147.
  • Connection interface(s) 147 may increase the functionality of system 100, for example, wherein the USB interface enables images to be stored on a USB storage medium and/or integrated with a medical -grade fflPAA recording device.
  • Controller 140 comprises or is electrically coupled to a medical grade- compliant power source 152.
  • controller 140 comprises one or more wireless connection interface(s) 147, such as Bluetooth or WiFi wireless interface, for example, communicatively coupled to one, more than one, or any combination and number of components forming system 100 which may include but are not limited to excitation light source 102, source optical train 116, receiving optical train 117, camera 122, image display 150, and video recorder 160.
  • wireless connection interface(s) 147 such as Bluetooth or WiFi wireless interface
  • FIG. 6 is an illustration of tissue imaging system 100 mounted on a medical cart 164.
  • Medical cart 164 is, optionally, used to aggregate, mount, transport, and store one or more components of system 100, such as controller 140, excitation light source 102, video recorder 160, image display 150, and any related accessories, for example.
  • more than one medical cart 164 is used to mount, transport, and/or store components of system 100.
  • excitation light source 102 is mounted on one medical cart 164 and controller, along with other components, is mounted on a second medical cart 164.
  • FIG. 7A is a front view of an embodiment of user interface 146 comprising a screen display showing an example of a main menu for tissue imaging system 100.
  • Main menu may be displayed by user interface 146 as a screen located on controller 140 or a screen located on interrogation unit 120, in some embodiments.
  • Main menu provides information to the user and permits the user to provide input controlling, setting, or adjusting elements of system 100, as discussed herein.
  • the main menu provides the user with information regarding an illumination setting, a sensitivity setting, status of memory for digital video storage, access to sub-menus and controls, and the like. Additional functionality of this illustrated embodiment includes a command to capture a photograph, initiate a video recording, transfer to a video screen showing a visual image of the operative field, or setting controller 140 to a standby mode.
  • FIG. 7B is a front view of an embodiment of user interface 146 showing an example settings menu of system 100.
  • This example display provides the user with options to select a language for menus displayed by user interface 146, adjust an illumination level setting of excitation light source 102, adjust a camera sensitivity setting, and provide an instruction to copy photos and video to a USB or other digital storage device, in some embodiments.
  • FIG. 8 is an example of image display 150 showing a peripheral nerve within a surgical field with a settings status indicator also displayed as an inset within the surgical field display.
  • FIG. 9 is a diagram showing steps for a method 200 of using of a tissue imaging system.
  • Method 200 comprises a positioning step 210, an illuminating step 220, a detecting step 230, and a forming step 240.
  • method 200 further comprises a filtering step 235.
  • Positioning step 210 comprises positioning an interrogation unit, the probe having a receiving optical train, configured to obtain data used to form a visual image proximate to a tissue containing a peripheral nerve.
  • the tissue is a surgical wound containing a peripheral nerve.
  • the tissue is a surgical wound bed containing a portion of a spinal dura, such as a portion of the thecal sac containing the spinal cord, anterior and posterior spinal nerves, the dorsal spinal ganglia and .
  • the visual image comprises a peripheral nerve.
  • the visual image comprises spinal dura.
  • Illuminating step 220 comprises illuminating the tissue with an excitation light comprising a first wavelength, in the absence of a day, a marker, or a probe, causing the tissue to generate an emitted light comprising a second wavelength in response to illumination with the excitation light of the first wavelength.
  • the first wavelength is a range of wavelengths.
  • the range of wavelengths is in the near-ultraviolet range.
  • the range of wavelengths is between about 300 nanometers (nm) and about 400 nm.
  • the wavelength of excitation light is about 370 nm.
  • the wavelength of the excitation light is a range of wavelengths between about 455 nm and about 510 nm. In some embodiments, the wavelength of the excitation light is about 485 nm. In some embodiments, the excitation light emanates from the interrogation unit.
  • Detecting step 230 comprises detecting the emitted light from the tissue in the absence of a dye, a marker, or a probe.
  • a receiving optical train collects emitted light from the tissue, excitation light reflected from the tissue, and ambient light for filtering and processing.
  • Filtering step 235 comprises filtering the emitted light. Filtering step 235 removes at least a portion of the reflected excitation light and at least a portion of the ambient light while preferentially allowing passage of a substantially larger portion of the emitted light. In some embodiments, filtering step 235 is performed by an optical filter. In some embodiments, the optical filter is comprised by a receiving optical train. In some embodiments, filtering step 235 comprises digital filtering of received light by a processor, such as a processor comprised by a controller and running a software package stored on a memory. In some embodiments, the digitally filtered light is received by a receiving optical train.
  • Forming step 240 comprises forming a visual image of a peripheral nerve distinguished from the tissue.
  • the visual image is formed, in some embodiments by processing of light received by an interrogation unit comprising a camera.
  • the light is digitally processed by the camera.
  • the light is digitally processed by a controller.
  • the light is not digitally processed and the visual image is an optical image viewed through a lens.
  • the lens is comprised by a receiving optical train.
  • Case 1 A 35-year-old woman presented with a painless, slowly-growing nodule in the left lateral face that, on palpation, felt soft and non-moveable, was non-tender, and measured 3cm in maximum diameter. The patient’s neurological examination was entirely normal, including no evidence of facial paralysis. Ultrasound revealed a solid hypoechoic nodule in the left parotid gland. Fine needle aspiration (FNA) was performed, which revealed a benign pleomorphic adenoma.
  • FNA Fine needle aspiration
  • Case 2 A 55-year-old woman presented with a painless, slowly-growing nodule in the left lateral face that, upon palpation, felt firm and rubbery, was non-tender, and measured 2.5cm in maximum diameter.
  • the patient As with the previous case, the patient’s neurological examination was normal, ultrasound revealed a solid hypoechoic nodule in the left parotid gland, and FNA revealed a benign pleomorphic adenoma.
  • Case 3 A 43-year-old woman presented with a painless, slowly-growing nodule in the right lateral, lower face, in the area of the lower pole of the parotid gland. On palpation, the nodule felt firm and non-mobile, was non-tender, and measured 4cm in maximum diameter. On CT scan, the lesion was well defined and well-encapsulated. Fine needle aspiration revealed both myoepithelial and mesenchymal components consistent with a pleomorphic adenoma.
  • a total parotidectomy was performed in each of cases 1-3, described above, using a tissue imaging system for enhanced intra-operative visualization of the facial nerve and its branches.
  • An Avelino-Gutierrez incision was used for each patient.
  • a superficial cervical-fascial flap was created between the superficial musculoaponeurotic system layer and the parotid fascia until the anterior border of the parotid gland was visible.
  • the facial nerve trunk was identified, and dissection of the facial nerve branches was performed using the tissue imaging system to permit visualization of the surgical field under near-ultraviolet (NUV) light.
  • NUV near-ultraviolet
  • Case 4 A 45-year-old female patient was referred to our clinic with a 1.1cm subcutaneous nodule laterally positioned on the right side of the neck. Physical examination revealed a firm, painless nodule in the area of the right lobe of the thyroid, which moved up and down when the patient swallowed. On ultrasound, a solid 11 c 20mm nodule was visualized that was irregular in shape, with numerous small calcifications and an unclear border. Serum thyroglobulin was elevated. On FNA, papillary thyroid carcinoma diagnosed, after which further imaging revealed disseminated metastases consistent with Bethesda stage IV. Surgical removal of the thyroid and central and lateral neck dissection were performed.
  • Case 5 A previously healthy 88-year-old male was referred for severe low back pain that limited his walking to roughly 500 meters before he had to rest. His baseline examination revealed vibrant tenderness in the low back over the L4 spinous process, but no neurological deficits. Both CT and MRI revealed tumor infiltration into and resultant destruction of the 4 th lumbar vertebra, along with soft tissue infiltration into the epidural space. A transpedicular percutaneous biopsy was performed that revealed non- Hodgkin’s B-cell lymphoma. After discussing various options, a decision was made to perform two-stage spinal surgery prior to initiating chemotherapy: the first stage to decompress the spinal canal; the second stage to reconstruct and stabilize the lumbar spine.
  • Case 6 During a difficult delivery, a baby suffered a right brachial plexus injury. At six months of age, she was brought into the clinic by her parents exhibiting both shoulder and elbow flexion palsy, and was scheduled for surgical reconstruction using a sural nerve graft harvested from the contralateral lower limb to replace the affected part of the brachial plexus and the suprascapular nerve. Under NUV light, the contralateral sural nerve, and the ipsilateral brachial plexus, phrenic nerve and suprascapular nerve all were easily visualized throughout their course in the surgical field. The surgery proceeded without complication, and the child is currently in rehabilitation. [0101] A tissue imaging system has been described herein.
  • the system produces a visual image, either optically or digitally, of a surgical field, wherein visualization of a target tissue structure, such as a peripheral nerve or spinal dura, is enhanced by autofluorescense or other intrinsic property of the peripheral nerve or spinal dura in response to illumination with excitation light. Filtering of the excitation light, emitted light, reflected light, or a combination thereof enhances the visual image by further distinguishing the target tissue structure from surrounding adipose, muscle, or connective tissue.
  • Use of excitation light in the NUV wavelength range between about 300 nm and about 400 nm is particularly effective.

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Abstract

A tissue imaging system (100) facilitates enhanced intraoperative visualization of peripheral nerves (105). The system of devices (100) and methods (200) is capable, among other things, of emitting excitation light (110, 220) onto or into tissues (104) of a patient at a wavelength or band of wavelengths that stimulate light emission intrinsic properties (fluorescence) of peripheral nerves in the absence of dyes, markers, or probes. Embodiments of the tissue imaging system filter (124, 235) light received from tissues (112, 114) in the operative field to identify and distinguish nerve-emitted light (112) and display (240) an enhanced visual image of a peripheral nerve onto a display (150), such as a video monitor. The tissue imaging system (100) can be adapted to various platforms, including surgical microscopes, fiberoptic endoscopic devices, laparoscopes, thoracoscopes, and arthroscopes; and related devices used during traditional open surgery.

Description

TISSUE IMAGING SYSTEM
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application No. 63/050018 filed on July 9, 2020 and U.S. Provisional Application No. 63/087568 filed on October 5, 2020, each of which are included entirely herein by reference.
BACKGROUND OF THE INVENTION
Technical Field
[0002] The disclosures herein relate to systems and devices for tissue imaging.
Specifically, the disclosed invention relates to aa visual imaging system for intraoperative identification of peripheral nerves by use of excitation electromagnetic radiation-induced fluorescence, strictly without the use of dyes, markers, or probes.
State of the Art
[0003] Despite numerous major advancements in surgical techniques and equipment over recent decades, surgery continues to be linked to an unacceptably high number of iatrogenic injuries. In some instances, advanced surgical techniques, like minimally- invasive and robotic surgery, appear to have actually increased the risk of certain injuries. Among these injuries, iatrogenic injuries to nerves are among the most catastrophic, placing patients at risk for both short and long-term motor and sensory deficits. They also are disturbingly common, documented in up to twenty percent (20%) of patients undergoing certain common procedures like thyroidectomies, parotidectomies, resection of breast and colon cancers, prostatectomies, and inguinal hernia repairs. Avoiding unintentional nerve damage during operative procedures requires that nerves be identified accurately and dissected carefully, both challenging undertakings when standard visualization techniques are used. Consequently, the ability to accurately identify sensory and motor nerves during surgical procedures is crucial to prevent nerve injury.
[0004] Clear and reliable visualization of peripheral nerves is highly desirable when performing operations in many areas of the body. Current nerve-sparing techniques have a rate of success that is dependent upon the type of operation, the disease process being treated, and the surgeon’s experience and training. Iatrogenic injury to peripheral motor and sensory nerves causes impairment resulting reduced quality of life for patients and creates significant burdens to the healthcare system. Despite surgeons’ extensive academic and practical training, and irrespective of years of experience, however, iatrogenic nerve damage may also occur because anatomical variations and the presence of pathology can hamper recognition of critical anatomical structures. A means to enhance recognition of peripheral nerves within the surgical field could prevent many such injuries.
[0005] Tools like electrical stimulation devices possess an unknown level of accuracy and cannot identify sensory nerves. The use of imaging tools like computed tomography (CT) and magnetic resonance imaging (MRI) as intraoperative guides is problematic because of time latency between image interpretation and surgery increases the probability of inaccuracies.
[0006] Fluorescent imaging techniques, in conjunction with special dyes, have proven successful in preclinical and clinical studies at helping surgeons identify peripheral nerves intraoperatively. However, the of fluorescent dyes, markers, or probes to label peripheral nerves is problematic. Most probes and dyes have not been shown to be safe and effective; consequently, they generally are not approved by the United States Food and Drug Administration (“FDA”). A few dyes have been approved for clinical use, but most require extensive preparation times, are costly, must be used in limited doses to mitigate toxicity, have short half-lives en vivo , may cause serious or even fatal allergic reactions, and require precise timing of administration. If markers or dyes are not highly specific for neural tissue, they can actually obscure a peripheral nerve by also enhancing surrounding non-neural tissue, making peripheral nerve visualization even more difficult. Additionally, observed differences in fluorescence between tissues following parenteral administration of a dye or marker may be the result of differences in tissue perfusion rather than differential uptake by different tissue types. Arteries perfusing peripheral nerves are very small compared with those perfusing other anatomic structures, which may accentuate differences in fluorescence arising from differential perfusion. [0007] For at least the foregoing issues, the use of dyes, markers, and probes for intraoperative identification of nerves gives inconsistent and unreliable results.
[0008] Because of these and other problems, there is a need for improved visual imaging of tissue; particularly, peripheral nerves, that does not require dyes, tissue probes, or other markers to increase visual contrast between the nerve and tissue surrounding the nerve. This would allow for clear intraoperative visualization of nerves while simultaneously eliminating increased patient risk associated with the administration of chemical markers or dyes.
[0009] Accordingly, what is needed is a device and method for intraoperative imaging of peripheral nerves in the absence of dyes, markers, or probes to enhance visualization of peripheral nerves and mitigate against iatrogenic injury during surgery.
BRIEF SUMMARY OF THE INVENTION
[0010] A tissue imaging system is described herein. Embodiments of the tissue imaging system generates a visual image, either optically or digitally, wherein visualization of a target tissue structure, such as a peripheral nerve, is enhanced by generating autofluorescense of the peripheral nerve in response to illumination with an excitation light. Autofluorescense distinguishes the peripheral nerve from surrounding adipose, muscle, and connective tissue. These surrounding tissues fluoresce (if at all) at an intensity substantially less than that of the target peripheral nerve. Else of excitation light in the near-ultraviolet (NUV) wavelength range between about 300 nm and about 400 nm is particularly effective. Emitted light emanating from the nerve in response to the excitation light is of a different wavelength than the excitation light, given that the nerve- emitted light is of a lower energy (higher wavelength) than the excitation light. Consequently, a filter interposed between the surgical field and a camera device or objective lens removes excitation and other ambient light reflected from the illuminated tissue, thus further enhancing contrast between the peripheral nerve and surrounding tissue, when viewed by the surgeon on a monitor screen or through an eyepiece lens.
[0011] Disclosed is a peripheral nerve visual imaging system comprising a housing configured for intraoperative use in a sterile environment, the housing containing a source optical train configured to direct an excitation light onto a tissue containing a peripheral nerve, wherein the excitation light illuminates the tissue and the peripheral nerve, and a receiving optical train configured to receive an emitted light from the peripheral nerve, wherein the emitted light is generated by the peripheral nerve in response to illumination of the peripheral nerve with the excitation light in the absence of a marker, a probe, or a dye; an excitation light source optically coupled to the source optical train; and a camera optically coupled to the receiving optical train and configured to generate a visual signal in response to the emitted light. In some embodiments, the peripheral nerve visual imaging system has a plurality of cameras.
[0012] In some embodiments, the peripheral nerve visual imaging system further comprises a controller operatively coupled to the excitation light source and the camera, having a software residing on a memory; a processor that executes the software; a user interface operatively coupled to the processor; a visual display operatively coupled to the processor; and a power source, wherein the power source is medical-grade compliant. In some embodiments, an image display is operatively coupled to the processor.
[0013] In some embodiments, the excitation light comprises a range of wavelengths between about 300 nanometers and about 400 nanometers. In some embodiments, the source optical train comprises an excitation filter optically interposed between the excitation light source and the tissue containing the peripheral nerve.
[0014] In some embodiments, the receiving optical train comprises a detection filter optically interposed between the tissue containing the peripheral nerve and the detector, wherein the detection filter is configured not to transmit at least a portion of excitation light reflected by the tissue and the peripheral nerve. In some embodiments, the detection filter is configured to transmit at least a portion of the emitted light having a wavelength different from the excitation light to the camera. In some embodiments, the detection filter is a bandpass filter configured to transmit light having a range of wavelengths between about 400 nanometers to about 600 nanometers.
[0015] Also disclosed is a tissue visual imaging device comprising a housing configured for intraoperative use in a sterile environment, the housing containing a receiving optical train configured to receive an emitted light from a tissue, wherein the emitted light is generated by the tissue in response to illumination of the tissue with an excitation light in the absence of a marker, a probe, or a dye.
[0016] In some embodiments, the tissue visual imaging device also comprises an excitation light source configured to illuminate the tissue with the excitation light. In some embodiments, a user directly visualizes the emitted light through the receiving optical train. In some embodiments, a camera is optically coupled to the receiving optical train, wherein the receiving optical train is optically positioned between the tissue and the camera. In some embodiments, a controller is operatively coupled to the camera. In some embodiments, an image display is operatively coupled to the camera. In some embodiments, the housing comprises a user input device mounted thereon.
[0017] In some embodiments, the tissue comprises a peripheral nerve. In some embodiments, the tissue comprises a spinal dura.
[0018] Disclosed is a method for intraoperative detection of a peripheral nerve by steps comprising positioning a probe, the probe having a receiving optical train configured to obtain data used to form a visual image, proximate to a tissue containing a peripheral nerve; illuminating the tissue with an excitation light comprising a first wavelength, in the absence of a dye, a marker, or a probe, causing the tissue to generate an emitted light comprising a second wavelength in response to illumination with the excitation light of the first wavelength; detecting the emitted light from the tissue in the absence of a dye, marker, or a probe; and forming a visual image of a peripheral nerve distinguished from the tissue.
[0019] In some embodiments, the method further comprises a step filtering the emitted light.
[0020] The foregoing and other features and advantages of the invention will be apparent to those of ordinary skill in the art from the following more particular description of the invention and the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] FIG. 1 is an illustration of an embodiment of a tissue imaging system;
[0022] FIG. 2 is an illustration of an embodiment of an interrogation unit of a tissue imaging system; [0023] FIG. 3 is a cutaway-side view illustration of an embodiment of an interrogation unit of a tissue imaging system examining a tissue containing a peripheral nerve;
[0024] FIG. 4 is a partial schematic diagram of a tissue imaging system;
[0025] FIG. 5 is an illustration of an embodiment of a controller for a tissue imaging system;
[0026] FIG. 6 is an illustration of a tissue imaging system mounted on a medical cart;
[0027] FIGs. 7A-7B are illustrations of an example user interface screen display of settings menus for a tissue imaging system;
[0028] FIG. 8 is an example video display of a tissue imaging system; and
[0029] FIG. 9 is a diagram showing steps for a method of use of a tissue imaging system.
DETAILED DESCRIPTION
[0030] The ability to identify nerves accurately and, thereby, dissect them safely must be considered a high priority of surgeons. Most, if not all, critical, structural tissue disruption and nerve injury occurs in the operative setting. A surgeon’s knowledge of complex anatomical structures and use of standard visual aids is often insufficient to avoid such injuries, regardless of the surgeon’s level of expertise. Nerve axonal injury, including traction and partial or complete transection, is a significant, common complication associated with a variety of surgical procedures, including colonic resections, thyroidectomies, parathyroidectomies, parotidectomies, groin hernia repairs, and breast cancer surgery, affecting up to 20% of patients. Although the majority of iatrogenic neuropathies that result from operative injury resolve with conservative management and physiotherapy, some cause prolonged or permanent impairment.
[0031] Despite the potential value of using various fluorescent dyes, markers, and probes to image nerves, tissue autofluorescence has the distinct advantage of providing real-time imaging without the need for invasive techniques or patient exposure to potentially unsafe compounds. Moreover, the dyes and probes utilized in most of the research conducted thus far on nerve identification are often difficult to procure. [0032] The inventors believe they are the first to both study nerve autofluorescence in humans and develop corresponding technology leveraging autofluorescense in the operating room to prevent or reduce the risk or iatrogenic intraoperative nerve injury. Embodiments of the disclosed invention allow for enhanced, real-time intraoperative visualization of peripheral nerves by causing and imaging nerve autofluorescence using different intensities and wavelengths of electromagnetic radiation coupled with different wavelength range-pass optical filters by an integrated system of devices configured for operating room use. Additionally, the inventors’ findings suggest that use of light wavelength filters, particularly optical filters that selectively transmit excitation light in the near-ultraviolet (NUV) range and bandpass optical filters to largely remove reflected light from nerve-emitted light increase perceived levels of nerve autofluorescence, thereby increasing visual contrast between nerves and surrounding tissue. Embodiments of the disclosed invention are a means of altering the rate and severity of iatrogenic nerve in clinical surgical practice.
[0033] A system for imaging tissue is described herein. In some embodiments, the tissue imaging system is used specifically to enhance and facilitate intraoperative visualization of peripheral nerves by the operating surgeon.
[0034] As used herein, “tissue imaging system” and “nerve imaging system” both mean a system comprised of devices and components utilized to enhance visualization of specific tissue structures, such as peripheral nerves, for example, from surrounding tissues. It is to be understood, however, that a nerve imaging system may, in some embodiments, be used to visualize non-neural structures or tissues.
[0035] As used herein, a “medical device” is an instrument, apparatus, implement, machine, appliance, software, material, or other similar or related article intended to be used, alone or in combination for human beings for the specific medical purposes of diagnosis, prevention, monitoring, treatment or alleviation of disease.
[0036] As used herein, a “peripheral nerve” is a motor, sensory, autonomic, or mixed- function nerve existing outside of the brain or spinal cord proper. For the purposes of this disclosure, “peripheral nerve” includes cranial nerves outside of the dura enclosing the brain. “Peripheral nerve” also includes mixed spinal nerves and spinal ganglia, whether outside of or enclosed by the spinal dura (thecal sac). Some non-limiting examples of “peripheral nerves” include the facial nerve and its branches, the superior laryngeal nerve, the recurrent laryngeal nerve, the hypoglossal nerve, the spinal accessory nerve, nerve roots, nerve trunks, and nerve branches of the brachial plexus and the lumbar plexus, the long thoracic nerve, the medial and lateral pectoral nerves, sympathetic ganglia, pelvic sensory nerves, and many others.
[0037] As used herein, “spinal dura” “dura,” or “thecal sac” is the thick, dense, fibrous membranous structure surrounding the spinal cord, dorsal and ventral spinal nerves, and dorsal spinal ganglia.
[0038] As used herein, “wavelength, “ or “wavelengths” means a specific wavelength of an electromagnetic radiation, whether visible or invisible to the human eye, including near ultraviolet light, ultraviolet light, near-infrared light, or infrared light. “Wavelength” may represent a range of wavelengths. The range of wavelengths may discreet and continuous or may be discontinuous.
[0039] As used herein, “emitted light” means electromagnetic radiation of a discrete wavelength or range of wavelengths emitted by a cell, a tissue, or an anatomic structure in response to illumination or irradiation with electromagnetic radiation of a different wavelength or range of wavelengths. “Emitted light” originates solely from the cell, tissue, or anatomic structure and does not comprise reflected excitation light or light reflected from other sources of ambient light. “Emitted light” arises as a consequence of an intrinsic property of the atoms, molecules, or a particular arrangement of atoms and molecules forming the cell, the tissue, or the anatomic structure.
[0040] As used herein, “excitation light” means electromagnetic radiation used to illuminate or irradiate a cell, a tissue, or an anatomic structure to cause the cell, the tissue, or the anatomic structure to generate an emitted light comprising a different wavelength or range of wavelengths than the excitation light.
[0041] As used herein, a “low-pass filter” means a low-pass wavelength optical filter, including a digital filter, that passes electromagnetic radiation having a wavelength longer than a selected cutoff wavelength. A “low-pass filter” may comprise a single optical filter element or a plurality of optical filter elements configured to allow passage of electromagnetic radiation having a wavelength longer than the selected cutoff wavelength. Correspondingly, a “high-pass filter” means a high-pass wavelength optical filter, including a digital filter, that passes electromagnetic radiation having a wavelength shorter than a selected cutoff wavelength. A “high-pass filter” may comprise a single optical filter element or a plurality of optical filter elements configured to allow passage of electromagnetic radiation having a wavelength shorter than the selected cutoff wavelength.
[0042] Also used herein, a “band-pass filter” means a band-pass wavelength optical filter, including a digital filter, that passes electromagnetic radiation having a range of wavelengths within a selected discrete range of wavelengths between a first wavelength and a second wavelength longer than the first wavelength. A “band-pass filter” may comprise a single optical filter element or a plurality of optical filter elements configured to allow passage of electromagnetic radiation having a range of wavelengths within the selected range of wavelengths.
[0043] As used herein, “reflected light” means excitation light and ambient light passing into a receiving optical train after being reflected from a tissue, a surface, or the like. “Reflected light” is not “emitted light” as “emitted light” is defined herein.
[0044] The tissue imaging system can be used by healthcare professionals in a clinical setting, for example, a hospital, an ambulatory surgical center, and the like. In some embodiments, a surgeon or healthcare practitioner may use the tissue imaging system in combination with additional imaging devices, such as ultrasound, fluoroscopy, or other conventional imaging devices. The tissue imaging device, standing alone or used with such other imaging devices, may be used, in some embodiments, to help a surgeon distinguish peripheral nerves from other anatomical structures and surrounding tissue, decreasing the risk of injury to a peripheral nerve. In some embodiments, the tissue imaging device is structurally adapted for use integrated with an operating microscope, a rigid or flexible endoscope, laparoscopes, thoracoscopes, and related devices; end-effector instruments such as instruments used in minimally invasive surgical procedures throughout the body, surgical instruments used during traditional “open” procedures, or other medical devices with which integration of the medical device with a tissue imaging system is advantageous or desirable.
[0045] No markers, probes, or dyes are used. The tissue imaging system creates a visual image of a target tissue, such as a peripheral nerve, by causing the tissue to fluorescence in response to illumination with light, whether visible outside the range of visible light. Tissue fluorescence occurs without use of adjunctive chemical or pharmacologic compositions, such as dyes, markers, probes, or the like, whether applied topically or administered (orally or parenterally). Typically, peripheral nerves fluoresce intrinsically upon illumination with excitation light differently than surrounding tissues, depending on the wavelength and intensity of the excitation light, light filtering means, and image processing techniques. The system exploits contrasting levels of fluorescence to distinguish peripheral nerves from surrounding tissue.
[0046] Significant aspects of such a tissue imaging system include a means for illuminating a tissue bed, such as a surgical field, with an excitation light. A target tissue, such as tissue forming a peripheral nerve, autofluoresces in response to the incident excitation light at an intensity different from autofluorescence (if any) of the surrounding or background tissue. A camera or similar detector receives the tissue-emitted fluorescent light, which is processed to create a visual image for display. The tissue imaging system may include additional elements as discussed herein below.
[0047] The excitation light illuminating the tissue bed comprises a wavelength or a range of wavelengths, or intervals over a range of wavelengths (collectively referred to herein as “wavelength(s)” that cause an intrinsic effect of the biochemical structure of the tissue, such as nerve tissue. This intrinsic effect causes the tissue to emit light at a particular wavelength or in a particular wavelength region that is different from the wavelength(s) of the excitation light. The tissue imaging system captures the wavelength or wavelengths of light emitted from the tissue in response to the tissue’s intrinsic properties.
[0048] Some embodiments of the tissue imaging system comprise a data processor and a software package residing on a memory. The software package directs an excitation light source via the data processor to emit light onto or into a patient’s body at a particular wavelength or range of wavelengths. In response to the emitted light, tissues emit light at a particular wavelength or in a particular wavelength region. The wavelength and intensity of the emitted light is intrinsic to the particular tissue type and structure. More specifically, a peripheral nerve comprising nerve tissue, when stimulated or excited, emits an intrinsic and particular wavelength of range of wavelengths of light (hereinafter, “emitted light”). Such emitted light may be due to fluorescence, other phenomenon, or fluorescence in combination with other phenomenon. The tissue imaging system, such as a nerve imaging system, receives light from the illuminated tissue and, in some embodiments, filters it with a detection filter to identify at least a nerve-emitted light to generate a data signal. The data signal representing an image of the nerve-emitted light is transmitted to an image display for visualization by the user.
[0049] Full details of a tissue imaging system are provided by the written disclosures and several drawing figures herein.
[0050] FIG. 1 is an illustration of an embodiment of a tissue imaging system 100. FIG. 1 shows a tissue-imaging system 100. Tissue imaging system 100, in some embodiments, is a nerve tissue imaging system configured for intraoperative imaging of peripheral nerves. System 100 comprises various component devices for generating an excitation light and directing this to illuminate a tissue thought to contain a peripheral nerve. In response to illumination of a tissue containing a peripheral nerve with excitation light, at least two different types of light are created: (1) reflected light, which is excitation light reflected by the tissue and the peripheral nerve; and (2) emitted light, which is light emitted by nerve or other tissue via fluorescence or other intrinsic property in response to energy received by the excitation light. In some embodiments, an interrogation unit 120 generates the excitation light and receives reflected and emitted light for imaging processing. This is discussed further herein below.
[0051] System 100 also includes a controller 140 housing components such as a processor and a user interface, in some embodiments. In some embodiments, as in the example shown in FIG. 1, elements of system 100 are electrically and communicatively coupled to one another by cables, such as a first cable 126 and a second cable 151. In some embodiments, a power source 152 is electrically coupled to controller 140. FIG. 1 also shows an image display 150, whereupon a user of system 100 may visualize an image of the tissue being examined to determine the location of a peripheral nerve.
[0052] The depiction of various devices forming system 100 shown by FIG. 1 is by way of example only; additional configurations of interrogation device 120, controller 140, and image display 150 are within the scope of these disclosures and the teachings found herein. For example, in some embodiments and as shown in FIG. 1, first cable 125 communicatively and electrically couples interrogation device 120 with controller 140 and a second cable 151 communicatively and electrically couples image display 150 to controller 140. This is not meant to be limiting. In some embodiments interrogation device 120 is “free-standing,” having an internal power source and a wireless communication means of exchanging instructions and data with controller 140. Similarly, image display 150, in some embodiments, comprises an internal or other separate power source and wireless communication means.
[0053] Examples of an internal power source include a battery. The battery may be any battery suitable for use in a medical device, including a battery that is non-rechargeable and disposable, or a rechargeable battery. Some examples of medically suitable, non- rechargeable batteries include an alkaline battery, a lithium battery, a solid-state battery, and the like. In some embodiments, the battery is a rechargeable battery, such as a nickel- cadmium batter, I nickel metal hydride battery, a nickel zinc battery, a lithium ion battery or other suitable rechargeable batter.
[0054] Embodiments of system 100 not comprising first cable 126 have a wireless communication means communicatively coupling interrogation unit 120 to controller 140. Some embodiments of system 100 not comprising second cable 151 have a wireless communication means communicatively coupling image display 150 with controller 140.
[0055] Non-limiting examples of wireless communication means suitable for use in by various components of system 100 include transmitters and receivers using various wireless technologies well known in the art, including Bluetooth and WiFi wireless technology platforms.
[0056] FIG. 2 is an illustration of an embodiment of interrogation unit 120 of tissue imaging system 100 and FIG. 3 is a side view of an embodiment of interrogation unit 120 of tissue imaging system 100. As in the embodiments shown in FIGs. 2 and 3, and in some other embodiments, interrogation unit 120 comprises a housing 121 configured to house electronic, optical, and related elements configured to provide tissue illumination and collection of light from the illuminated tissue. Housing 121 is formed from a medical grade material and configured for use in a sterile surgical environment. In some embodiments, housing 121 is configured for gas sterilization, such as using ethylene oxide, ozone, or other gases suitable for sterilizing sensitive electronic medical equipment that would be destroyed by heat-based sterilization systems and techniques. In some embodiments, housing 121 is not configured for sterilization but is used with a sterile disposable sac or equipment-condom is used that covers and at least partially encloses housing 121 wherein interrogation unit 120 may be used in a sterile operating- room environment. Elements contained within or coupled to housing 121 include, in some embodiments, an excitation light source 102, a source optical train 116, a receiving optical train 117, a camera 122, and a handle 125. In some embodiments, first cable 126 electrically, communicatively, or electrically and communicatively couples interrogation unit 120 to controller 140. Housing 121 may also contain additional elements, for example, mounting or fixation means, electronics, cooling means, thermal insulation, and the like, according to a particular embodiment or embodiments of interrogation unit 120.
[0057] In some embodiments, interrogation unit 120 is arranged and configured as shown in FIGs. 2 and 3. Handle 125 is coupled to housing 131 separate or generally opposite from a distal end 127, such that elements of source optical train 115 and receiving optical train 117 are not obscured from radiating and receiving light. Handle 125, in some embodiments, is a unitary body with housing 121. First cable 126 enters interrogation unit 120 a handle 125, in some embodiments, to keep first cable 126 out of a line-of-sight between a distal end 127 and the tissue being illuminated and visualized. In some embodiments, source optical train 116 and receiving optical train 117 are arranged alongside one another within housing 121 in a configuration similar to that shown by FIG. 3. The depiction of source optical train 116 and receiving optical train 117 within housing 121 by FIG. 3 is diagrammatic and offered by example; other configurations of source optical train(s) 116 and receiving optical train(s) 117 are within the scope of the disclosures herein. [0058] For example, in some embodiments of system 100, source optical train 117 is a plurality of source optical trains configured in an array or pattern, such as the circular pattern of eight (8) source optical trains 117 around a perimeter of distal end 127 shown by FIG. 2. In this, and other embodiments comprising an array of source optical trains 117, tissue 104 may be more brightly and evenly illuminated with excitation light 110. Bright and uniform illumination may reduce light shadowing effects allowing enhanced visualization of tissue 104 by system 100. Other and any number of arrangements, patterns, or arrays comprising any number of source optical trains 117, without limitation, are considered to be within the scope of this disclosure.
[0059] Excitation light source 102 is located within housing 121, in some embodiments. In some alternate embodiments, excitation light source 102 resides in a location remote from interrogation unit 120, and excitation light 110 is transmitted to interrogation unit 120 through a light transmission means, such as fiberoptic bundle, for example. A remote excitation light source 102 may be a “free-standing” device, or may be housed within or coupled to a console such as those used in robotically assisted or computer-assisted surgery, a medical device cart, or the like. The light transmission means may be unitary with first cable 126 or may be mechanically and optically coupled between excitation light source 102 and interrogation unit 120 as a separate elongate cable-like structure, for example.
[0060] Excitation light source 102 generates excitation light comprising a broad band of wavelengths or light confined to a narrower wavelength range. For example, in some embodiments, excitation light source 102 is a narrow-wavelength range source such as a light-emitting diode (LED) or a laser. In some embodiments, excitation light source 102 comprises a wide wavelength-range “white” light source, such as a halogen (xenon) lamp, a 450-Watt xenon lamp, a tungsten-halogen lamp, or a mercury arc lamp, for example.
[0061] Excitation light source 102 emits excitation light 110 which passes from source optical train 116 of interrogation unit 120 to illuminate a tissue 104. Excitation light source 102 is configured to emit excitation light 110 at a particular wavelength to stimulate or excite tissue 104 through an effect intrinsic to the tissue; for example, a fluorescent effect. Because the effect is intrinsic i.e., of the essential nature or constitution of the tissue and originating wholly from within the tissue, fluorescent (or other) dyes, markers, probes, and the like are not necessary for operation of system 100.
[0062] The generated wavelength of excitation light 110 by excitation light source 102 maximizes the difference between intrinsic fluorescent effects of the peripheral nerve and the surrounding tissue, in some embodiments. In a visual image, this difference between fluorescent effects is represented by contrast between a peripheral nerve and surrounding tissue, whereunder system 100 enhances visualization of a peripheral nerve, or other target tissue, for a user, such as a surgeon. In some embodiments, the wavelength of excitation light 110 is a range between about 300 nanometers (nm) and about 400 nm. In some embodiments, the wavelength of excitation light 110 is between about 360 nm and about 390 nm. In some embodiments, the wavelength of excitation light 110 is a range of wavelengths between about 455 nm and about 510 nm. In some embodiments, the wavelength of excitation light 110 is about 485 nm.
[0063] Source optical train 116 directs excitation light 110 from interrogation unit 120; i.e., to illuminate tissue. Source optical train 116 may be proximate to or contiguous with excitation light source 102. In some embodiments, source optical train 116 comprises an optical lens, or a plurality of optical lenses to appropriately focus or disperse and direct excitation light 110 for illumination of tissue 104. In some embodiments, excitation light source 102 illuminates tissue 104 directly with excitation light 110 and interrogation unit 120 does not comprise source optical train 116. In some embodiments, source optical train 116 is contained within excitation light source 102 separate from interrogation unit 120. In some embodiments, source optical train 116 comprises a fiberoptic bundle as discussed herein. According to the embodiment, source optical train 116 may comprise any combination including one or more of an optical lenses, a plurality of optical lenses, or a fiberoptic bundle, without limitation.
[0064] In some embodiments, source optical train 116 comprises an excitation filter 111 configured to narrow, constrict, or “tune” the wavelength of excitation light 110 to a range optimal for causing the peripheral nerve, or other target structure or tissue type, to produce emitted light 111 and causing minimal or no fluorescence of the surrounding tissue. Excitation filter 111 is particularly useful for embodiments wherein excitation light source 102 is a broad-band white light source, such as a halogen or mercury-arc source, versus excitation light 110 from a more narrow-band source, such as certain LED or laser excitation light sources. Accordingly, in some embodiments, excitation filter 111 is a bandpass filter. In some embodiments, excitation filter 111 is a low-pass filter. In some embodiments, excitation filter 111 is a high-pass filter. In some embodiments, excitation filter 111 is an about 300 nm high-pass filter. In some embodiments, excitation filter 111 is an about 400 nm low-pass filter. In some embodiments, excitation filter 111 is an about 300 to an about 400 nm bandpass filter. In some embodiments, excitation filter 111 is an about 320 to an about 380 nm bandpass filter. In some embodiments, excitation filter 111 is an about 325 nm to an about 375 nm bandpass filter. In some embodiments, excitation filter 111 is an about 350 nm low-pass filter. In some embodiments, excitation filter 111 is an about 300 nm low-pass filter. In some embodiments, excitation filter 111 is an about 400 nm high-pass filter.
[0065] As shown by FIG. 3, tissue 104 illuminated with excitation light 110 directs light back to interrogation unit 120. This directed light includes a reflected light 114, including the tissue-reflected component of excitation light 110. If tissue 104 has intrinsic fluorescent properties when illuminated with excitation light 110, tissue 104 produces an emitted light 112. Emitted light 112 originates solely through fluorescence or other intrinsic property of a portion of tissue 104. All or a portion of reflected light 114, emitted light 112, and non-emitted ambient light are collected by receiving optical train 117 of interrogation unit 120, in some embodiments of system 100. Receiving optical train 117 comprises an optical lens or a plurality of optical lenses and is configured to focus and direct light comprising emitted light 112 onto a camera 122. In some embodiments, receiving optical train 117 comprises a single focusing lens. In some embodiments, receiving optical train 117 comprises a plurality of any number, combination, and arrangement of focusing lenses and dispersing lenses configured to focus at least emitted light 112 onto camera 122. Some embodiments of system 100 do not comprise receiving optical train 117, wherein camera 122 is a “chip on a stick” image-sensor charge coupled device (“CCD”) camera. Some embodiments of receiving optical train 117 comprise a detection filter 124 but do not comprise a lens.
[0066] In some embodiments, receiving optical train 117 comprises detection filter 124, as shown in FIG. 3. In some embodiments, detection filter 124 is an optical filter that filters out reflected light 114 and ambient light having wavelengths outside of the range of filter 124. In some embodiments, however, receiving optical train 117 does not comprise detection filter 124. Detection filter 124 may allow only desired wavelengths of light (e.g., wavelengths the correspond to the nerve-emitted light) to pass through detection filter 124 to a camera 122. In some embodiments of system 100, the light filtering function of detection filter 124 is performed digitally by an image processing software package residing on a data processor.
[0067] The appropriate detection filter 124 can depend on other aspects of system 100, particularly with respect to the wavelength of emitted light 112 which, in turn, depends on the intrinsic properties of the peripheral nerve or other tissue, such as spinal dura, targeted for visualization. In addition to configuring detection filter 124 to allow passage of wavelengths corresponding to emitted light 112, such as nerve-emitted light, detection filter 124 may also be configured to allow wavelengths of emitted light 112 to pass that enable visualization of tissue surrounding a peripheral nerve, wherein the surrounding tissue emits light at a particular wavelength or in a particular wavelength range that is different from the wavelength(s) of the excitation light. Peripheral nerves intrinsically form emitted light 112 of a higher intensity than many non-nerve tissues in response to the same intensity (luminosity) and wavelength of excitation light 110. For this reason, light emitted from tissue surrounding a peripheral nerve, such as adipose or muscle tissue, will have a significantly lower intensity that light emitted from the peripheral nerve. The surrounding tissue can still be visualized, but the peripheral nerve is visually distinguished from the surrounding tissue.
[0068] In some embodiments, detection filter 124 is a bandpass filter that preferentially allows light to pass comprising wavelengths in a range of about 400 nm to about 600 nm consistent with a range of emitted light 112 surrounding a wavelength of about 488 nm. In some embodiments, detection filter 124 is a bandpass filter with a range of about 450 nm to about 575 nm. In some embodiments, detection filter 124 is a bandpass filter with a range of about 480 nm to a range of about 500 nm. In some embodiments, detection filter 124 is a bandpass filter with a range of about 450 nm to about 575 nm. In some embodiments, detection filter 124 is a bandpass filter with a range of about 425 nm to about 525 nm. In some embodiments, detection filter 124 is a bandpass filter with a range of about 440 nm to about 570 nm.
[0069] In some embodiments, detection filter 124 is a high-pass filter with a range of longer than about 400 nm. In some embodiments, detection filter 124 is a high-pass filter with a range of longer than about 425 nm. In some embodiments, detection filter 124 is a high-pass filter with a range of longer than about 450 nm.
[0070] In some embodiments, detection filter 124 is a low-pass filter with a range of shorter than about 600 nm. In some embodiments, detection filter 124 is a low-pass filter with a range of shorter than about 575 nm. In some embodiments, detection filter 124 is a low-pass filter with a range of shorter than about 550 nm. In some embodiments, detection filter 124 is a low-pass filter with a range of shorter than about 510 nm.
[0071] Camera 122 receives light from receiving optical train 117, in some embodiments. In some embodiments, camera 122 is configured to communicate digital information representing light collected from receiving optical train 117 to a processor, wherein the processor digitally processes the information to generate a visual image displayed on a digital screen or monitor. Camera 122, in some embodiments, is an image sensor. Accordingly, in some embodiments, camera 122 is a digital camera module configured to couple to a processor. Camera 122 is a monochromatic or polychromatic digital camera, in some embodiments. One non-limiting example of a suitable camera 122 is the VM- 010-KSP09.A0 digital camera module (PHYTEC Messtechnik GmbH, Mainz, Germany). In some embodiments, camera 122 is an optical camera having an eyepiece for direct visualization of a non-digital visual image. Camera 122, with or without receiving optical train 117, can be optically coupled to visualization devices other than interrogation unit 120, such as an operating microscope/ laparoscope, thoracoscope, arthroscope, bronchoscope, ureteroscope, or the like; for a flexible fiberoptic endoscope, in some embodiments.
[0072] In some embodiments, interrogation unit 120 comprises a plurality of cameras 122, each camera 122 of the plurality of cameras 122 optically coupled to one receiving optical train 117 of a corresponding plurality of optical trains 117. Embodiments comprising more than one camera 122 may be useful to from a stereoscopic visual image of tissue 104.
[0073] FIG. 4 is a partial schematic diagram of a tissue visualization system 100 showing digital data paths in some embodiments. A processor 142 comprises a data processor, such as a microprocessor, for processing digital inputs and delivering data and instruction so output devices, including excitation light source 102, camera 122, a user interface 146, a memory 145, a video recorder 160, and a visual display 150, in some embodiments. Processor 142 receives digital inputs from camera 122, user interface 146, and a memory 145. Depending on the embodiment of system 100, various suitable processors may be used as processor 142, including a medical-grade computer microprocessor such as currently used in existing medical imaging and computer-assisted imaging applications. In some embodiments, processor 142 is a plurality of microprocessors executing functions related to specific tasks, such as digital image processing and/or image enhancement, digital recording and memory management, excitation light source management, digital optical filtering of emitted and reflected light passing, user interface management, wireless communications, and other specific functions, in some embodiments.
[0074] Processor 142 executes a software package 144 residing on memory 145 and running on processor 142. In some embodiments, software package 144 is configured to conduct preferential visualization of a first tissue, such as a peripheral nerve, compared to a second tissue, such as adipose tissue, muscle tissue, connective tissue, and the like.
[0075] Processor 142 is configured to deliver instructions related to power delivery, aperture size, and the like to camera 122 and to receive image data from camera 122, in some embodiments. [0076] Memory 145 is a data storage device. Memory 145 may be configured as a writable memory or a combination of a writable memory and a read-only memory, in some embodiments.
[0077] Visual image data signals from processor 142 are received by visual display 150. Visual display 150 displays a visual image, such as a peripheral nerve on background tissue, to a surgeon or other user of system 100. Depending on the embodiment of system 100, visual display 150 may be a standard video monitor, a high-resolution video monitor such as used during minimally invasive surgical procedures, or a computer monitor. Display 150 may be a light emitting diode (LED) display, including an organic LED (OLED), a liquid crystal display (LCD) a plasma display, a quantum dot display (QLED), or any medical-grade of other visual image display such as is currently used or shall be developed at a future time, without limitation.
[0078] Recordation and archiving of visual image data may be useful, such as for medical record keeping, teaching and instruction, and other uses. Accordingly, some embodiments of system 100 comprise a video recorder 160. Video recorder 160 receives visual image data from processor 142 and may output visual image data to visual display 150. A standard digital or analog (video tape) device may comprise video recorder 160, according to the embodiment of system 100.
[0079] User interface 146 is a means wherein a user of system 100 interacts with and controls functions, including information exchange and instructions, and settings adjustments of various components and elements of system 100. Some non-limiting examples of these functions include initiating or terminating power delivery to system 100 or any of its individual components, varying the intensity (luminosity) of excitation light 110 emitted from excitation light source 102; varying the wavelength of excitation light 110 through engaging optical or digital filters or by changing light sources, i.e., white light versus filtered (band-pass or other) of excitation light 110, and the like. Varying the pass-wavelength of a digital filter is varied, changed, or adjusted via user interface 146, in some embodiments. User interface 146 may comprise analog buttons or switches, digital input switches, a digital touchscreen, toggle switches, joysticks, wheels, whether digital or analog, or any combination thereof.
[0080] In some embodiments, user interface 146 comprises a plurality of user interfaces. As a non-limiting example embodiment wherein user interface 146 is a plurality of user interfaces, system 100 may comprise a combination of (i) a graphical user interface residing on controller 140; (ii) button or other switches disposed on housing 121 of interrogation unit 120; (iii) a floor-based foot-activated toggle or other switch to change tissue illumination (i.e., excitation light 110) between white light and filtered light; and the like, in some embodiments.
[0081] FIG. 5 is a graphic illustration of an embodiment of a controller for tissue imaging system 100. FIG 5 shows controller 140 having processor 142, memory 145, and user interface 146. Also shown is a connection interface 147. Connection interface 147 may be a high-definition multimedia interface (HDMI), a set of external recording device input-output connectors, a universal serial bus (USB), and the like. In some embodiments, including the embodiment shown in FIG. 5, controller 140 comprises a plurality of connection interfaces 147. Connection interface(s) 147 may increase the functionality of system 100, for example, wherein the USB interface enables images to be stored on a USB storage medium and/or integrated with a medical -grade fflPAA recording device. Controller 140 comprises or is electrically coupled to a medical grade- compliant power source 152. In some embodiments, controller 140 comprises one or more wireless connection interface(s) 147, such as Bluetooth or WiFi wireless interface, for example, communicatively coupled to one, more than one, or any combination and number of components forming system 100 which may include but are not limited to excitation light source 102, source optical train 116, receiving optical train 117, camera 122, image display 150, and video recorder 160.
[0082] FIG. 6 is an illustration of tissue imaging system 100 mounted on a medical cart 164. Medical cart 164 is, optionally, used to aggregate, mount, transport, and store one or more components of system 100, such as controller 140, excitation light source 102, video recorder 160, image display 150, and any related accessories, for example. In some embodiments, more than one medical cart 164 is used to mount, transport, and/or store components of system 100. For example, in some embodiments excitation light source 102 is mounted on one medical cart 164 and controller, along with other components, is mounted on a second medical cart 164.
[0083] FIG. 7A is a front view of an embodiment of user interface 146 comprising a screen display showing an example of a main menu for tissue imaging system 100. Main menu may be displayed by user interface 146 as a screen located on controller 140 or a screen located on interrogation unit 120, in some embodiments. Main menu provides information to the user and permits the user to provide input controlling, setting, or adjusting elements of system 100, as discussed herein. For example, the main menu provides the user with information regarding an illumination setting, a sensitivity setting, status of memory for digital video storage, access to sub-menus and controls, and the like. Additional functionality of this illustrated embodiment includes a command to capture a photograph, initiate a video recording, transfer to a video screen showing a visual image of the operative field, or setting controller 140 to a standby mode.
[0084] FIG. 7B is a front view of an embodiment of user interface 146 showing an example settings menu of system 100. This example display provides the user with options to select a language for menus displayed by user interface 146, adjust an illumination level setting of excitation light source 102, adjust a camera sensitivity setting, and provide an instruction to copy photos and video to a USB or other digital storage device, in some embodiments.
[0085] FIG. 8 is an example of image display 150 showing a peripheral nerve within a surgical field with a settings status indicator also displayed as an inset within the surgical field display.
[0086] FIG. 9 is a diagram showing steps for a method 200 of using of a tissue imaging system. Method 200, in some embodiments, comprises a positioning step 210, an illuminating step 220, a detecting step 230, and a forming step 240. In some embodiments, method 200 further comprises a filtering step 235. [0087] Positioning step 210, in some embodiments, comprises positioning an interrogation unit, the probe having a receiving optical train, configured to obtain data used to form a visual image proximate to a tissue containing a peripheral nerve. In some embodiments, the tissue is a surgical wound containing a peripheral nerve. In some embodiments, the tissue is a surgical wound bed containing a portion of a spinal dura, such as a portion of the thecal sac containing the spinal cord, anterior and posterior spinal nerves, the dorsal spinal ganglia and . In some embodiments, the visual image comprises a peripheral nerve. In some embodiments the visual image comprises spinal dura.
[0088] Illuminating step 220, in some embodiments, comprises illuminating the tissue with an excitation light comprising a first wavelength, in the absence of a day, a marker, or a probe, causing the tissue to generate an emitted light comprising a second wavelength in response to illumination with the excitation light of the first wavelength. In some embodiments, the first wavelength is a range of wavelengths. In some embodiments, the range of wavelengths is in the near-ultraviolet range. In some embodiments, the range of wavelengths is between about 300 nanometers (nm) and about 400 nm. In some embodiments, the wavelength of excitation light is about 370 nm. In some embodiments, the wavelength of the excitation light is a range of wavelengths between about 455 nm and about 510 nm. In some embodiments, the wavelength of the excitation light is about 485 nm. In some embodiments, the excitation light emanates from the interrogation unit.
[0089] Detecting step 230, in some embodiments, comprises detecting the emitted light from the tissue in the absence of a dye, a marker, or a probe. In some embodiments, a receiving optical train collects emitted light from the tissue, excitation light reflected from the tissue, and ambient light for filtering and processing.
[0090] Filtering step 235, in some embodiments, comprises filtering the emitted light. Filtering step 235 removes at least a portion of the reflected excitation light and at least a portion of the ambient light while preferentially allowing passage of a substantially larger portion of the emitted light. In some embodiments, filtering step 235 is performed by an optical filter. In some embodiments, the optical filter is comprised by a receiving optical train. In some embodiments, filtering step 235 comprises digital filtering of received light by a processor, such as a processor comprised by a controller and running a software package stored on a memory. In some embodiments, the digitally filtered light is received by a receiving optical train.
[0091] Forming step 240, in some embodiments, comprises forming a visual image of a peripheral nerve distinguished from the tissue. The visual image is formed, in some embodiments by processing of light received by an interrogation unit comprising a camera. In some embodiments, the light is digitally processed by the camera. In some embodiments, the light is digitally processed by a controller. In some embodiments, the light is not digitally processed and the visual image is an optical image viewed through a lens. In some embodiments, the lens is comprised by a receiving optical train.
EXAMPLES
[0092] The foregoing description of embodiments of the invention is demonstrated, in part, by the examples listed below.
Example 1-Head and neck tumors
[0093] Case 1: A 35-year-old woman presented with a painless, slowly-growing nodule in the left lateral face that, on palpation, felt soft and non-moveable, was non-tender, and measured 3cm in maximum diameter. The patient’s neurological examination was entirely normal, including no evidence of facial paralysis. Ultrasound revealed a solid hypoechoic nodule in the left parotid gland. Fine needle aspiration (FNA) was performed, which revealed a benign pleomorphic adenoma.
[0094] Case 2: A 55-year-old woman presented with a painless, slowly-growing nodule in the left lateral face that, upon palpation, felt firm and rubbery, was non-tender, and measured 2.5cm in maximum diameter. As with the previous case, the patient’s neurological examination was normal, ultrasound revealed a solid hypoechoic nodule in the left parotid gland, and FNA revealed a benign pleomorphic adenoma.
[0095] Case 3: A 43-year-old woman presented with a painless, slowly-growing nodule in the right lateral, lower face, in the area of the lower pole of the parotid gland. On palpation, the nodule felt firm and non-mobile, was non-tender, and measured 4cm in maximum diameter. On CT scan, the lesion was well defined and well-encapsulated. Fine needle aspiration revealed both myoepithelial and mesenchymal components consistent with a pleomorphic adenoma.
[0096] A total parotidectomy was performed in each of cases 1-3, described above, using a tissue imaging system for enhanced intra-operative visualization of the facial nerve and its branches. An Avelino-Gutierrez incision was used for each patient. A superficial cervical-fascial flap was created between the superficial musculoaponeurotic system layer and the parotid fascia until the anterior border of the parotid gland was visible. At this point, the facial nerve trunk was identified, and dissection of the facial nerve branches was performed using the tissue imaging system to permit visualization of the surgical field under near-ultraviolet (NUV) light. Under NUV light, the cervicofacial and temporofacial branches and lengths of these branches auto-fluoresced brightly and, hence, were clearly identified. In all three patients, the parotidectomy was completed and a drain placed without intra-operative complications, and both the immediate-post- operative and post-operative day #1 neurological examinations remained normal. All three patients were discharged to their homes on the first post-operative day and remained without complications or neurological deficits at the time of their final surgery clinic visit.
Example 2-Thyroid Carcinoma
[0097] Case 4: A 45-year-old female patient was referred to our clinic with a 1.1cm subcutaneous nodule laterally positioned on the right side of the neck. Physical examination revealed a firm, painless nodule in the area of the right lobe of the thyroid, which moved up and down when the patient swallowed. On ultrasound, a solid 11 c 20mm nodule was visualized that was irregular in shape, with numerous small calcifications and an unclear border. Serum thyroglobulin was elevated. On FNA, papillary thyroid carcinoma diagnosed, after which further imaging revealed disseminated metastases consistent with Bethesda stage IV. Surgical removal of the thyroid and central and lateral neck dissection were performed. During the former, both the recurrent laryngeal and hypoglossal nerve fluoresced brightly under NUV light and were easily avoided. During neck dissection, all nerves within the surgical field again were clearly identified throughout their course under NUV, and this degree of visualization was clearly superior to that achieved under white light. Example 3-Neurosurgery
[0098] Case 5: A previously healthy 88-year-old male was referred for severe low back pain that limited his walking to roughly 500 meters before he had to rest. His baseline examination revealed exquisite tenderness in the low back over the L4 spinous process, but no neurological deficits. Both CT and MRI revealed tumor infiltration into and resultant destruction of the 4th lumbar vertebra, along with soft tissue infiltration into the epidural space. A transpedicular percutaneous biopsy was performed that revealed non- Hodgkin’s B-cell lymphoma. After discussing various options, a decision was made to perform two-stage spinal surgery prior to initiating chemotherapy: the first stage to decompress the spinal canal; the second stage to reconstruct and stabilize the lumbar spine.
[0099] Surgery was performed under general anesthesia using a mini-open retroperitoneal approach with the patient placed in a right lateral decubitus position. The procedure then was performed in a 360° (ventro-dorsal) fashion, including instrumentation, and entailed posterior percutaneous instrumentation from L2 through to the sacrum. For the second step involving resection of the L4 vertebral body, both the L3-4 and L4-5 intervertebral discs and tumor tissue located ventrally in the spinal canal were resected followed by reconstruction of the anterior column using a titanium mesh prosthesis. A left-sided anterolateral approach was adopted. The patient experienced neither intra-operative nor post-operative complications and, other than wound discomfort, was pain free postoperatively. He left the hospital three days after the second surgery and started chemotherapy within one week. He remained fully ambulatory and pain free.
[0100] Case 6: During a difficult delivery, a baby suffered a right brachial plexus injury. At six months of age, she was brought into the clinic by her parents exhibiting both shoulder and elbow flexion palsy, and was scheduled for surgical reconstruction using a sural nerve graft harvested from the contralateral lower limb to replace the affected part of the brachial plexus and the suprascapular nerve. Under NUV light, the contralateral sural nerve, and the ipsilateral brachial plexus, phrenic nerve and suprascapular nerve all were easily visualized throughout their course in the surgical field. The surgery proceeded without complication, and the child is currently in rehabilitation. [0101] A tissue imaging system has been described herein. The system produces a visual image, either optically or digitally, of a surgical field, wherein visualization of a target tissue structure, such as a peripheral nerve or spinal dura, is enhanced by autofluorescense or other intrinsic property of the peripheral nerve or spinal dura in response to illumination with excitation light. Filtering of the excitation light, emitted light, reflected light, or a combination thereof enhances the visual image by further distinguishing the target tissue structure from surrounding adipose, muscle, or connective tissue. Use of excitation light in the NUV wavelength range between about 300 nm and about 400 nm is particularly effective.
[0102] The embodiments and examples set forth herein were presented in order to best explain the present invention and its practical application, and to thereby enable those of ordinary skill in the art to make and use the invention. However, those of ordinary skill in the art will recognize that the foregoing description and examples have been presented for the purpose of illustration and example only. The description as set forth is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible, in light of the teachings herein above.

Claims

CLAIMS What is claimed is:
1. A peripheral nerve visual imaging system comprising: a housing configured for intraoperative use in a sterile environment, the housing containing a source optical train configured to direct an excitation light onto a tissue containing a peripheral nerve, wherein the excitation light illuminates the tissue and the peripheral nerve, and a receiving optical train configured to receive an emitted light from the peripheral nerve, wherein the emitted light is generated by the peripheral nerve in response to illumination of the peripheral nerve with the excitation light in the absence of a marker, a probe, or a dye; an excitation light source optically coupled to the source optical train; and a camera optically coupled to the receiving optical train and configured to generate a visual signal in response to the emitted light.
2. The peripheral nerve visual imaging system of claim 1, further comprising a controller operatively coupled to the excitation light source and the camera, having: a software residing on a memory; a processor that executes the software; a user interface operatively coupled to the processor; a visual display operatively coupled to the processor; and a power source, wherein the power source is medical-grade compliant.
3. The peripheral nerve visual imaging system of claim 1, wherein the excitation light comprises a range of wavelengths between about 300 nanometers and about 400 nanometers.
4. The peripheral nerve visual imaging system of claim 1, wherein the source optical train comprises an excitation filter optically interposed between the excitation light source and the tissue containing the peripheral nerve.
5. The peripheral nerve visual imaging system of claim 1, wherein the receiving optical train comprises a detection filter optically interposed between the tissue containing the peripheral nerve and the detector, wherein the detection filter is configured not to transmit at least a portion of excitation light reflected by the tissue and the peripheral nerve.
6. The detection filter of claim 5, wherein the detection filter is configured to transmit at least a portion of the emitted light having a wavelength different from the excitation light to the camera.
7. The peripheral nerve visual imaging system of claim 1, having a plurality of cameras.
8. The peripheral nerve visual imaging system of claim 1, wherein the detection filter is a bandpass filter configured to transmit light having a range of wavelengths between about 400 nanometers to about 600 nanometers.
9. The peripheral nerve visual imaging system of claim 2, further comprising an image display operatively coupled to the processor.
10. A tissue visual imaging device comprising: a housing configured for intraoperative use in a sterile environment, the housing containing a receiving optical train configured to receive an emitted light from a tissue, wherein the emitted light is generated by the tissue in response to illumination of the tissue with an excitation light in the absence of a marker, a probe, or a dye.
11. The tissue visual imaging device of claim 10, comprising an excitation light source configured to illuminate the tissue with the excitation light.
12. The tissue visual imaging device of claim 10, wherein a user directly visualizes the emitted light through the receiving optical train.
13. The tissue visual imaging device of claim 10, comprising a camera optically coupled to the receiving optical train, wherein the receiving optical train is optically positioned between the tissue and the camera.
14. The tissue visual imaging device of claim 13, comprising a controller operatively coupled to the camera.
15. The tissue visual imaging device of claim 10, wherein the housing comprises a user input device mounted thereon.
16. The nerve imaging device of claim 13, comprising an image display operatively coupled to the camera.
17. The tissue visual imaging device of claim 10, wherein the tissue comprises a peripheral nerve.
18. The tissue visual imaging device of claim 10, wherein the tissue comprises spinal dura.
19. A method for intraoperative detection of a peripheral nerve by steps comprising: positioning a probe, the probe having a receiving optical train configured to obtain data used to form a visual image, proximate to a tissue containing a peripheral nerve; illuminating the tissue with an excitation light comprising a first wavelength, in the absence of a dye, a marker, or a probe, causing the tissue to generate an emitted light comprising a second wavelength in response to illumination with the excitation light of the first wavelength; detecting the emitted light from the tissue in the absence of a dye, marker, or a probe; forming a visual image of a peripheral nerve distinguished from the tissue.
20. The method of claim 15, further comprising a step filtering the emitted light.
PCT/US2020/054457 2020-07-09 2020-10-06 Tissue imaging system WO2022010519A1 (en)

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PCT/US2021/041113 WO2022011276A1 (en) 2020-07-09 2021-07-09 Advanced nervous tissue imaging system
AU2021305238A AU2021305238A1 (en) 2020-07-09 2021-07-09 Advanced nervous tissue imaging system
EP21837678.8A EP4179297A1 (en) 2020-07-09 2021-07-09 Advanced nervous tissue imaging system
KR1020237004393A KR20230035378A (en) 2020-07-09 2021-07-09 Advanced Neuronal Tissue Imaging System
JP2023501356A JP2023533061A (en) 2020-07-09 2021-07-09 Advanced nerve tissue imaging system
CA3185419A CA3185419A1 (en) 2020-07-09 2021-07-09 Advanced nervous tissue imaging system
US17/678,668 US11839361B2 (en) 2020-07-09 2022-02-23 Advanced nervous tissue imaging system
US18/467,006 US20240000301A1 (en) 2020-07-09 2023-09-14 Method for advanced nervous tissue imaging system

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