Method for advanced nervous tissue imaging system

Abstract

To provide a nervous tissue imaging system that does not require fluorescent dyes, fluorescent tissue probes or other fluorescent markers to increase visual contrast between the nerve / dura mater and non-nervous tissue surrounding the nerve / dura mater.SOLUTION: The system includes a housing containing an excitation light source, optically coupled with a source optical train, where the excitation light source emits excitation light in a first wavelength range, which can be in a near ultraviolet light range, to illuminate a tissue region of interest including healthy nervous tissue and healthy non-nervous tissue. The excitation light is in the first wavelength range that causes the healthy nervous tissue, in response to being illuminated with the excitation light, to endogenously autofluoresce and emit first autofluorescence light at a first luminance in a second wavelength range. The healthy non-nervous tissue, in response to being illuminated with the excitation light, either avoids emitting any autofluorescence light in the second wavelength range, or endogenously autofluoresces and emits second autofluorescence light in the second wavelength range at a second luminance that is lower than 50%of the first luminance.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is based on and claims priority to prior art U.S. Provisional Patent Application No. 63 / 050,018, filed July 9, 2020, prior art U.S. Provisional Patent Application No. 63 / 087,568, filed October 5, 2020, and prior art PCT patent application No. PCT / US2020 / 054457, filed October 6, 2020, the entire disclosures of which are hereby incorporated by reference in their entireties.

[0002] The present disclosure relates generally to systems, devices, and methods for tissue imaging. More particularly, the disclosed tissue imaging systems and associated methods are suitable for use with tissue under examination, including both neural and non-neural healthy tissue (e.g., non-cancerous and non-pathological tissue), whether in vivo or ex vivo, to identify and visually image neural tissue versus non-neural healthy tissue based on the autofluorescence of the neural tissue upon excitation with electromagnetic radiation. [Background technology]

[0003] Despite major advances in a vast number of surgical techniques and devices over the last few decades, there continues to be an unacceptable number of surgeries associated with iatrogenic injuries. Advanced surgical techniques, such as minimally invasive robotic surgery, appear to have actually increased the risk of certain injuries in some cases. Among these injuries, iatrogenic injuries to nerves and other neural tissues, such as the dura, are among the worst, exposing patients to both short-term and long-term risks of severe motor and sensory impairments. These injuries are also alarming because of their prevalence, with cases documented in up to 20% of patients undergoing certain common procedures, such as thyroidectomy, parotidectomy, breast and colon cancer resection, prostatectomy, and inguinal hernia repair. Recognizing the injury requires accurate identification and careful dissection of nerves and neural tissues to avoid unintentional nerve injury or to repair it intraoperatively during the surgical procedure, both of which are challenging measures when using standard visualization techniques. As a result, the ability to accurately identify sensory and motor nerves, as well as the dura, during the surgical procedure is crucial to prevent injury. Summary of the Invention [Problem to be solved by the invention]

[0004] Clear and reliable visualization of peripheral nerves and the dura mater as distinct / contrasting with surrounding normal non-nerve healthy tissue (e.g., non-cancerous and non-pathological tissue) is highly desirable when performing surgery in many areas of the human body. Current nerve-sparing techniques have success rates that depend on the type of surgery, the disease process being treated, and the experience and training of the surgeon. Iatrogenic damage to peripheral motor and sensory nerves, as well as central nervous tissue such as the dura mater, causes disabilities that result in reduced quality of life for patients and creates a substantial burden on the health care system. However, despite a surgeon's extensive academic and practical training and years of experience, iatrogenic nerve damage can occur because the presence of anatomical variations or pathologies prevents recognition of critical anatomical structures. Measures to improve recognition of peripheral nerves within the surgical field could prevent many such injuries.

[0005] Instruments such as electrical stimulators have an unknown level of accuracy and cannot identify sensory nerves or the dura. The use of imaging instruments such as computed tomography (CT) and magnetic resonance imaging (MRI) as intraoperative guides is problematic because there is a time lag between the interpretation of the radiological image and the visualization of human tissue with white light during surgery which further increases the probability of error.

[0006] Fluorescence imaging, in conjunction with probes equipped with antibodies that indiscriminately attach to specific fluorescent dyes / nerves, has proven successful in preclinical and clinical studies to help surgeons identify peripheral nerves and / or dura mater during surgery. However, labeling tissues of interest by administering or applying exogenous fluorescent substances, such as fluorescent agents, fluorescent dyes, fluorescent markers, or fluorescent tissue probes, to patients, such as to label peripheral nerves, is problematic. Although most fluorescent tissue probes and fluorescent dyes have been shown to be safe and effective, their long-term effects after nerve attachment are unpredictable, and as a result, they are not generally approved by the U.S. Food and Drug Administration ("FDA"). Although some fluorescent dyes are approved for clinical use, most require long preparation times, are expensive, must be used in limited doses to mitigate toxicity, have short half-lives in vivo, can cause severe or fatal allergic reactions, and require precise timing of administration. Despite the potential for unpredictable side effects mentioned above, unless the fluorescent marker or dye is highly specific to nerve tissue, it may actually cover the peripheral nerves even by improving the surrounding non-nerve tissue, making the visualization of the peripheral nerves and / or dura even more difficult. Non-specific or competitive binding of exogenous fluorescent substances to nerve tissue and / or surrounding non-nerve tissue may result in low signal-to-background ratios and / or limited dynamic range when attempting to detect the tissue of interest. Furthermore, after administration of the fluorescent dye or fluorescent marker, the observed differences in fluorescence between tissues may be the result of differences in tissue perfusion rather than differences in uptake by different tissue types. The arteries that perfuse peripheral nerves are very small compared to the arteries that perfuse other anatomical structures, which may accentuate the differences in fluorescence resulting from perfusion differences.

[0007] In response to at least the problems discussed above, administration or application of exogenous fluorescent substances, such as fluorescent agents, fluorescent dyes, fluorescent markers, and fluorescent tissue probes, to label tissues of interest, such as for intraoperative identification of peripheral nerves and / or the dura, produces inconsistent and unreliable results.

[0008] Due to these and other problems, a need exists for improved visual imaging of tissues, particularly peripheral nerves and dura, without the need for fluorescent dyes, fluorescent tissue probes, or other fluorescent markers to increase the visual contrast between the nerve / dura and the non-nerve tissue surrounding the nerve / dura. This necessary visual contrast would allow clear intraoperative visualization of the nerve / dura while simultaneously eliminating the increased patient risks associated with, for example, administering chemical markers or dyes to the patient.

[0009] Therefore, a need exists to overcome the problems of the prior art discussed above. [Means for solving the problem]

[0010] A neural tissue imaging system and method therefor is disclosed. The system includes a housing containing an excitation light source optically coupled to a light source array, the excitation light source emitting excitation light in a first wavelength region in the near ultraviolet range to illuminate a tissue region of a subject including healthy neural tissue and healthy non-neural tissue. The excitation light is in a first wavelength region that causes the healthy neural tissue to intrinsically autofluoresce and emit first autofluorescent light at a first intensity in a second wavelength region in response to being illuminated with the excitation light. The healthy non-neural tissue avoids emitting any autofluorescent light in the second wavelength region in response to being illuminated with the excitation light, or intrinsically autofluoresces and emits second autofluorescent light in the second wavelength region at a second intensity 50% lower than the first intensity.

[0011] The method includes emitting excitation light in a first wavelength range in the near-ultraviolet range to a tissue region of the target including healthy neural tissue and healthy non-neural tissue. The method captures with a camera image data of intrinsic autofluorescence light emitted from the healthy neural tissue at a first intensity in a second wavelength range in the visible light range. The method captures with the camera image data of optical signals received from the healthy non-neural tissue simultaneously with the capture of the image data of the intrinsic autofluorescence light emitted from the healthy neural tissue at a first intensity in the second wavelength range, the healthy non-neural tissue at least one of intrinsically autofluorescing and avoiding emitting any autofluorescence light in the second wavelength range in response to being illuminated with the excitation light, or intrinsically autofluorescing and emitting a second autofluorescence light in the second wavelength range at a second intensity 50% lower than the first intensity. The method forms a first image of the healthy neural tissue in the tissue region of the target and a second image of the healthy non-neural tissue in the tissue region of the target. The method includes displaying the first image and the second image on a display device, where the first image is contrasted (differentiated) with the second image to identify the location of neural tissue and the location of non-neural tissue within the tissue region of interest.

[0012] The accompanying drawings, in which like reference characters refer to identical or functionally similar elements throughout the separate drawings, and which, together with the following detailed description of the invention, are incorporated in and form a part of this specification, serve to further illustrate various embodiments and explain various principles and advantages all in accordance with the present disclosure. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a diagram of an example tissue imaging system, according to various embodiments of the present invention. [Diagram 2] FIG. 2 is a diagram of an exemplary interrogator suitable for use in the tissue imaging system of FIG. [Diagram 3] FIG. 3 is a cross-sectional side view of the exemplary interrogator of FIG. 2 shown in an exemplary interrogation of target tissue containing neural tissue surrounded by non-neural tissue. [Figure 4]FIG. 4 is a block diagram illustrating an example of a tissue imaging system, according to various embodiments. [Diagram 5] FIG. 5 is a perspective view of an exemplary controller suitable for use in a tissue imaging system, according to various embodiments. [Figure 6] FIG. 6 is a diagram of an exemplary tissue imaging system mounted on a medical cart. [Figure 7] 7A and 7B are screen display diagrams of an exemplary user interface of a settings menu for an exemplary tissue imaging system. [Figure 8] FIG. 8 is a diagram of an exemplary video display of a tissue imaging system, according to various embodiments. [Figure 9] FIG. 9 is a flow diagram illustrating a method of use of an exemplary tissue imaging system, according to various embodiments. [Figure 10] FIG. 10 is a diagram of the electromagnetic spectrum, including the ultraviolet spectrum, the visible spectrum, and the infrared spectrum, showing several wavelength bands of interest, according to various embodiments. [Figure 11] FIG. 11 is a diagram of an exemplary tissue region of a subject including neural and non-neural tissue, showing exemplary electromagnetic signals of different wavelengths including signals radiated onto and reflected from the tissue region of the subject, and showing an excitation signal radiated onto neural tissue in the tissue region of the subject and an intrinsic autofluorescence signal emitted from the neural tissue in response to the excitation signal radiated onto the neural tissue. [Figure 12] FIG. 12 is an illustration of several components of a first exemplary tissue imaging system, according to various embodiments. [Figure 13] FIG. 13 is a diagram of certain components of a second exemplary tissue imaging system, according to various embodiments. [Figure 14] FIG. 14 is a table showing filter parameters suitable for use in two exemplary embodiments of the tissue imaging system. [Figure 15] 15 and 16 are two views of camera components suitable for use in various embodiments of the tissue imaging system. [Figure 16] Same as above. [Figure 17] 17 and 18 are block diagrams illustrating exemplary components of a tissue imaging system, according to various embodiments. [Figure 18] Same as above. [Figure 19] 19 and 20 are two exemplary images corresponding to a surgical field showing the surgical field as it would appear under ambient light illumination and alternatively showing the surgical field as it would appear with a tissue imaging system according to various embodiments of the present invention. [Figure 20] Same as above. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Where necessary, detailed embodiments are disclosed herein, but it is understood that the disclosed embodiments are merely examples and that the devices, systems and methods described herein can be embodied in various forms. Thus, the specific structural and functional details described herein are not intended to be limiting, but are intended only as a basis for the claims, and as a representative basis for teaching those skilled in the art to variously use the disclosed inventive subject matter in almost any proprietary structure and function. Furthermore, the terms and phrases used herein are intended to provide an understandable description, but not to be limiting. Furthermore, unless otherwise specifically stated or clearly understood from the context of use, the terms used herein are described as the singular and / or plural of the term.

[0015] introduction The ability to accurately identify the nerves / dura and thereby safely separate them must be considered a high priority for the surgeon. Furthermore, it is critically important to detect and repair the nerves / dura if they are damaged during the procedure. Most, if not all, significant structural tissue destruction and nerve / dura injuries occur in the surgical environment. The surgeon's knowledge of the complex anatomical structures and the use of standard visual aids is often insufficient to avoid such injuries, regardless of the surgeon's level of expertise. Nerve axon / dura injuries, including traction and partial or complete transection, are significant common complications associated with various surgical procedures. Such surgical procedures include, but are not limited to, brain, spine surgery, colectomy, thyroidectomy, parathyroidectomy, parotidectomy, coronary artery bypass graft (CABG), inguinal hernia repair, open heart surgery, and breast cancer surgery, which affect up to 20% of patients. Although many iatrogenic neurological disorders resulting from surgical injuries improve with conservative and physical therapy, some conditions result in long-term or permanent disability.

[0016] Despite the potential value of using various fluorescent dyes, fluorescent markers, and fluorescent tissue probes to image nerves, tissue-intrinsic autofluorescence has the distinct advantage of providing real-time imaging without the need for invasive techniques or exposing patients to potentially unsafe compounds. Furthermore, the fluorescent dyes and fluorescent tissue probes utilized in most of the studies conducted to date on nerve identification are often difficult to procure. They all depend on blood flow to the area, which can be damaged by local disease (thrombus) or systemic disease (atheroma).

[0017] The inventors believe that they are the first items to study the intrinsic autofluorescence of nerves / peripheral nerves / dura mater in the human body during surgical procedures and develop corresponding techniques to exploit the autofluorescence in the operating room to prevent or reduce the risk and further recognize and repair iatrogenic intraoperative nerve / peripheral nerve / dura mater damage. Various embodiments of the disclosed invention allow for improved real-time intraoperative visualization of nerve tissue, which may include any type of nerve / peripheral nerve / dura mater, by using electromagnetic radiation of different intensities and wavelengths combined with pass optical filters of different wavelength ranges to generate and image the intrinsic autofluorescence of nerve tissue (any nerve / peripheral nerve / dura mater) by an integrated tissue imaging system of an apparatus configured for operating room applications. According to various embodiments, the intrinsic autofluorescence of the nervous tissue is induced or elicited by the emission of an excitation electromagnetic signal (which may also be referred to as excitation light, excitation light signal, etc.) and by illumination of the tissue region of interest (under examination) to generate a fluorescent signal (which may also be referred to as fluorescent light, fluorescent light signal, etc.) without the use of any fluorescent markers, fluorescent tissue probes, or fluorescent dyes. Furthermore, the inventors' findings suggest that the use of optical wavelength filters, particularly optical filters that selectively transmit excitation light in the near ultraviolet (NUV) range and bandpass optical filters, to substantially remove reflected light from the fluorescent light emitted into the nervous tissue (as well as remove other possible interfering emitted electromagnetic signals), increases the perceived level of nerve / dura autofluorescence, thereby increasing the visual contrast of the nervous tissue from the surrounding non-nerve tissue.

[0018] Various embodiments of the disclosed invention are a means of altering the rate and severity of iatrogenic neural tissue damage in clinical surgical practice.

[0019] Described herein is a system for imaging tissue. In some embodiments, the tissue imaging system is used specifically to improve and facilitate intraoperative visualization of nerves / peripheral nerves / dura mater by the surgeon.

[0020] As used herein, the terms "tissue imaging system," "nerve tissue imaging system," and "nerve / dural imaging system" are intended to mean a system of devices and components utilized to improve visualization of specific tissue structures, such as, for example, peripheral nerves / dura from surrounding healthy, non-pathological or non-cancerous tissue. However, it is understood that a nerve / dural imaging system may be used in some embodiments to visualize non-nerve structures or tissues.

[0021] As used herein, the term "medical device" means an instrument, apparatus, implement, machine, appliance, software, material, or other similar or related article intended for human use, alone or in combination, for a specific medical purpose of diagnosing, preventing, monitoring, treating, or mitigating disease.

[0022] The term "peripheral nerves" as used herein are motor, sensory, autonomic, or mixed function nerves that exist outside the brain or spinal cord proper. For purposes of this disclosure, "peripheral nerves" include cranial nerves outside the dura mater surrounding the brain. "Peripheral nerves" also include mixed spinal nerves and spinal ganglia, whether outside or surrounded by the spinal dura mater (dural sac). Some non-limiting examples of "peripheral nerves" include the facial nerve and its branches, superior laryngeal nerve, recurrent laryngeal nerve, hypoglossal nerve, spinal accessory nerve, nerve roots, nerve trunks, branches of the brachial and lumbar plexuses, long thoracic nerve, medial and lateral pectoral nerves, sympathetic ganglia, sensory nerves of the pelvis, and many others. As used herein, the term "spinal dura mater", "dura", "duramadre", or "dural sac" is a thick, dense, fibrous, membranous structure that surrounds the spinal cord, the anterior and posterior spinal nerves, and the posterior spinal ganglia. As used herein, the term "wavelength" refers to a particular wavelength of electromagnetic radiation, whether visible or invisible to the human eye, including near ultraviolet, ultraviolet, near infrared, or infrared. "Wavelength" may refer to a range of wavelengths. A range of wavelengths may be discrete portions and may be continuous or discontinuous.

[0023] As used herein, the term "emitted light" refers to electromagnetic radiation of a distinct portion or range of wavelengths emitted by a cell, tissue, or anatomical structure in response to illumination with electromagnetic radiation of a different wavelength or range of wavelengths. "Emitted light" originates solely from the cell, tissue, or anatomical structure and does not include light reflected from a source of reflected excitation light or ambient light. "Emitted light" results from the intrinsic properties of atoms, molecules, or the particular arrangement of atoms and molecules that form the cell, tissue, or anatomical structure.

[0024] As used herein, the term "excitation light" refers to electromagnetic radiation used to irradiate a cell, tissue, or anatomical structure to cause the cell, tissue, or anatomical structure to produce emitted light of a wavelength or range of wavelengths different from that of the excitation light.

[0025] As used herein, the term "low-pass filter," which may also be referred to as a "long-pass filter," refers to a low-pass (long-pass) wavelength optical filter, including a digital filter that passes electromagnetic radiation having wavelengths longer than a selected cutoff wavelength. A "low-pass filter" ("long-pass filter") may include a single optical filter element or multiple optical filter elements configured to pass electromagnetic radiation having wavelengths longer than a selected cutoff wavelength.

[0026] Accordingly, as used herein, the term "high pass filter," which may also be referred to as a "short pass filter," refers to a high (short pass) wavelength optical filter, including a digital filter that passes electromagnetic radiation having wavelengths shorter than a selected cutoff wavelength. A "high pass filter" ("short pass filter") may include a single optical filter element or multiple optical filter elements configured to pass electromagnetic radiation having wavelengths shorter than a selected cutoff wavelength.

[0027] As used herein, the term "bandpass filter" refers to a bandpass 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 "bandpass filter" may include a single optical filter element or multiple optical filter elements configured to pass electromagnetic radiation having a range of wavelengths within the selected range of wavelengths.

[0028] As used herein, the term "reflected light" refers to excitation light and / or other illuminating light, such as ambient light, white light, etc., that is reflected from tissue, surfaces, etc. and then passed to a receiving train. "Reflected light" is not "emitted light" as in "emitted light" which is separately defined herein.

[0029] The term "nerve tissue" as used herein is intended to mean tissue including one or more of the tissues of the central nervous system including nerves, peripheral nerves, dura mater, and nerves.

[0030] The term "healthy neural tissue" as used herein is intended to mean neural tissue, as defined herein, that is non-cancerous and non-pathological tissue.

[0031] The term "non-neural tissue" as used herein is intended to mean any living tissue, whether human or animal, that is not neural tissue, as defined herein.

[0032] The term "healthy non-neural tissue" as used herein is intended to mean non-neural tissue, as defined herein, that is non-cancerous and non-pathological tissue.

[0033] Overview of an Exemplary Tissue Imaging System The exemplary tissue imaging system may be used by medical personnel in a clinical environment, such as, for example, a hospital, an ambulatory surgery center, etc. In some embodiments, a surgeon or health care practitioner may use the tissue imaging system in combination with additional imaging devices, such as ultrasound, fluoroscopy, or other conventional imaging devices. The tissue imager may operate alone or be used with other such imaging devices, and in some embodiments may be used to help the surgeon distinguish neural tissue from other anatomical structures and surrounding non-nerve tissue, reducing the risk of damage to neural tissue, such as nerves / peripheral nerves / dura mater, etc. In some embodiments, the tissue imager is structurally adapted for use integrated with surgical microscopes, rigid or flexible endoscopes, 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 where integration of the medical device with the tissue imaging system is advantageous or desirable.

[0034] No fluorescent markers, fluorescent tissue probes, or fluorescent dyes are used in the nervous tissue. The tissue imaging system creates a visual image of the target tissue, such as the peripheral nerve / dura mater, by causing the target tissue to fluoresce in response to illumination with light, whether visible outside the visible light range. The tissue fluorescence occurs without the use of auxiliary chemical or pharmacological compositions, such as fluorescent dyes, fluorescent markers, fluorescent tissue probes, whether applied topically or administered (orally or parenterally). Typically, nervous tissue, such as the peripheral nerve, inherently fluoresces upon illumination with excitation light differently than surrounding healthy non-nerve tissue, e.g., normal / non-pathological / non-cancerous tissue, depending on the wavelength and intensity of the excitation light, the light filtering means, and the image processing techniques. The system utilizes contrasting levels of fluorescence to distinguish the nervous tissue, such as the peripheral nerve / dura mater, from the surrounding non-nerve tissue, and in particular, from healthy non-nerve tissue.

[0035] An important aspect of such tissue imaging systems includes a means for illuminating a tissue layer, such as a surgical field, with at least an excitation light and, optionally, an illumination light. According to various embodiments, the target tissue region of interest includes nerve tissue, such as nerves / peripheral nerves / dura mater, that intrinsically autofluoresces in response to the incident excitation light, different from the autofluorescence (if any) of adjacent and / or surrounding background non-nerve tissue in the tissue region of interest, and different from the reflected light, if any, for the tissue region of interest, with a higher intensity (brightness) in the wavelength range of the visible light range. A camera (which may also be referred to herein as a "dendrite camera"), or similar sensor / detector, receives the fluorescent light emitted into the tissue and possibly the reflected light from the tissue region of interest, and the optical signals are processed, such as to create a visual image of the tissue region of interest for display. The visual image includes a first image 802 of healthy neural tissue highlighted with a tissue imaging system, such as in white or other color (see, e.g., image 802 in FIG. 8 ), and a second image 804 of healthy non-neural tissue adjacent and / or surrounding the first image of neural tissue within the tissue region of interest (see, e.g., image 804 in FIG. 8 , which is a significantly darker image in contrast to the highlighted image 802 in FIG. 8 ). This visual image of the tissue region of interest includes the first image and the second image, such as for display on a display screen, and the contrast imaging between the first and second images indicates the location of the healthy neural tissue relative to the adjacent and / or surrounding healthy non-neural tissue. This visual image can provide important information to assist, for example, a surgeon in performing a surgical procedure on a patient.

[0036] In summary, an exemplary neural tissue imaging system may include a housing configured for use in a sterile environment, the housing containing an excitation light source optically coupled to a light source array configured to selectively controllably emit excitation light in a first wavelength range in the near-ultraviolet range from the excitation light source coupled through the light source array to illuminate a tissue region of a target including healthy neural tissue and healthy non-neural tissue, the excitation light source designed and configured to emit excitation light in a first wavelength range that causes the healthy neural tissue to intrinsically autofluoresce and emit first autofluorescent light at a first intensity in a second wavelength range in the visible light range in response to being illuminated by the excitation light, and further, the healthy non-neural tissue to at least one of intrinsically autofluoresce and avoid emitting any autofluorescent light in the second wavelength range, or intrinsically autofluoresce and emit second autofluorescent light in the second wavelength range at a second intensity (intensity) that is less than 50% of the first intensity in response to being illuminated by the excitation light. Control electronics electrically coupled to the excitation light source controls the excitation light source. A controller / processor is operably coupled to the control electronics and to the excitation light source and configured to selectively control at least one operating parameter of the excitation light source to control the excitation light from the excitation light source.

[0037] The tissue imaging system may include additional elements as described herein below.

[0038] The excitation light illuminating the tissue layer includes a wavelength or a range of wavelengths or intervals spanning a range of wavelengths (collectively referred to herein as "wavelengths") that produce an intrinsic effect on the biochemical structure of the tissue, such as nervous tissue. This intrinsic effect causes the tissue (e.g., nervous tissue) to emit fluorescent light at a specific range of wavelengths that is different (typically longer wavelengths) relative to the range of wavelengths (typically shorter wavelengths) of the excitation light. The tissue imaging system captures the wavelengths of light emitted from the nervous tissue in response to an intrinsic autofluorescence effect or other intrinsic property of the nervous tissue that is induced or elicited by the illumination of the nervous tissue with excitation light.

[0039] Some embodiments of the tissue imaging system include a software package residing on the data processor and memory. The software package moves an excitation light source through the data processor to emit light at a specific wavelength or range of wavelengths into the patient's body or body. In response to the emitted excitation light, the tissue emits light at a specific wavelength or range of wavelengths. The wavelength and intensity of the emitted light is specific to the specific tissue type and structure. Nerve tissues, such as nerves / peripheral nerves / dura mater, including nerve tissue, more particularly emit light (e.g., autofluoresce) at a unique and specific wavelength or range of wavelengths (hereinafter "emitted light") when stimulated or excited. Such emitted light may be due to fluorescence emission ("fluorescent light"), other phenomena, or fluorescence emission in combination with other phenomena. A tissue imaging system, such as a nerve / dura imaging system, receives light from an illuminated tissue (tissue region of interest) and, in some embodiments, filters the light with a detection filter to identify at least the emitted light on healthy nerve tissue, such as the nerve / dura, as opposed to the emitted light or reflected light on adjacent and / or surrounding healthy non-nerve tissue, and generate a corresponding data signal. The data signal, which represents an image of the nerve tissue, such as the nerve / dura, of the emitted light, as contrasted with a background image of the emitted light or reflected light on adjacent and / or surrounding healthy non-nerve tissue, is transmitted to an image display device for visualization by a user. Full details of the tissue imaging system are provided in the disclosure document and in several figures herein.

[0040] Discussion of Examples of Tissue Imaging Systems and Associated Component Apparatus FIG. 1 is a diagram of an example of a tissue imaging system 100, according to various embodiments. FIG. 1 illustrates the tissue-imaging system 100. The tissue imaging system 100 is a nerve tissue imaging system configured, in some embodiments, for intraoperative imaging of peripheral nerves. The system 100 includes various component devices for generating and transporting excitation light to illuminate a tissue region of interest believed to contain nerves / peripheral nerves / dura mater. In some embodiments, the system 100 includes various components for generating illumination light (e.g., white light or "near" white light) that may illuminate relevant structures and tissues within the tissue region of interest.

[0041] In response to illuminating a tissue region of the target, containing nerves / peripheral nerves / dura mater therein, with excitation light, at least two different types of light (electromagnetic radiation signals) are generated: (1) reflected light, which may include excitation light reflected by non-nerve tissue and nervous tissue (e.g., nerves / peripheral nerves / dura mater) within the tissue region of the target, and (2) emitted light, which is light (electromagnetic radiation signals) emitted by nervous tissue (e.g., nerves / peripheral nerves / dura mater) or possibly other non-nerve tissue due to fluorescence emission or other intrinsic properties in response to radiant energy received by the excitation light illuminating the tissue region of the target.

[0042] In response to illuminating a tissue region of the target, containing nerves / peripheral nerves / dura mater therein, with illuminating light, at least two different types of light (electromagnetic radiation signals) are generated: (1) reflected illuminating light that is reflected by neural and non-neural tissues within the tissue region of the target, and (2) possible emitted light that is light (electromagnetic radiation signals) emitted by non-neural tissues due to fluorescence or other inherent properties in response to radiant energy received by the illuminating light illuminating the tissue region of the target.

[0043] In some embodiments, the interrogator 120 (see also, e.g., Figures 2 and 3) generates excitation light and receives reflected and emitted light for imaging. In some embodiments, the interrogator 120 may generate illumination light in addition to or instead of excitation light and receive reflected light (and possibly emitted light) for imaging. Examples of this system and process are described in more detail further below.

[0044] System 100 also includes a controller 140 that, in some embodiments, houses components such as a processor 142 (see, e.g., FIG. 4) and a user interface 146. In some embodiments, the elements of system 100 are electrically and communicatively coupled to each other by cables, such as first cable 126 and second cable 151, as in the example shown in FIG. 1. In some embodiments, a power source 152 is electrically coupled to controller 140.

[0045] 1 also shows an image display 150 so that a user of system 100 may visualize an image of the examined tissue region (tissue region of interest) that may indicate, by contrast imaging, the location of healthy neural tissue versus adjacent and / or surrounding healthy non-neural tissue 804. See, for example, FIG. 8 showing an image display displaying a formed image (highlighted in white or other color in FIG. 8) of healthy neural tissue 802 contrasted with adjacent and / or surrounding healthy non-neural tissue 804 (a much darker image contrasted with highlighted image 802 in FIG. 8).

[0046] The depiction of the various devices forming the system 100 shown in FIG. 1 is by way of example only, and additional configurations of the interrogation device 120, the controller 140, and the visual display device 150 are within the scope of these disclosures and teachings described herein. For example, in some embodiments, as shown in FIG. 1, a first cable 125 communicatively electrically couples the interrogation device 120 to the controller 140, and a second cable 151 communicatively electrically couples the visual display device 150 to the controller 140. This is by way of illustrative example only and is not intended to be limiting. In some embodiments, the interrogation device 120 is "freestanding" and has an internal power source and wireless communication means for wirelessly exchanging instructions and data with the controller 140. Similarly, the visual display device 150 in some embodiments includes an internal or other separate power source and wireless communication means capable of wirelessly communicating image data and other information with the controller 140.

[0047] Examples of internal power sources include batteries. The batteries can be any battery suitable for use in a medical device, including non-rechargeable disposable batteries, or rechargeable batteries. Some examples of non-rechargeable batteries suitable for medical use include alkaline batteries, lithium batteries, solid state batteries, etc. In some embodiments, the battery is a rechargeable battery, such as a NiCad battery, a NiMH battery, a Ni-Zinc battery, a Li-ion battery, or other suitable rechargeable energy storage device.

[0048] Embodiments of the system 100 that do not include the first cable 126 may include wireless communication means that wirelessly communicatively couple the interrogator 120 to the controller 140. Some embodiments of the system 100 that do not include the second cable 151 may include wireless communication means that wirelessly communicatively couple the visual display device 150 to the controller 140.

[0049] Non-limiting examples of wireless communication means suitable for use by the various components of system 100 include transmitters and receivers using various known wireless technologies, including, for example, Bluetooth and WiFi wireless technology platforms.

[0050] FIG. 2 is a diagram of an embodiment of the interrogator 120 of the tissue imaging system 100. FIG. 3 is a side view of an embodiment of the interrogator 120 of the tissue imaging system 100. As in the embodiment shown in FIGS. 2 and 3, the interrogator 120 comprises a housing 121 configured to house electronic, optical, and related elements configured in some other embodiments to provide tissue illumination and collection of light from the illuminated tissue region of interest. The housing 121 is formed from medical grade materials and configured for use in a sterile surgical environment. In some embodiments, the housing 121 is configured for gas sterilization, such as using ethylene oxide, ozone, or other gases suitable for sterilizing sensitive electronic medical equipment that may be destroyed by heat-based sterilization systems and techniques. In some embodiments, the housing 121 is not configured for sterilization, but uses a protective coating of the device that covers and at least partially encapsulates the housing 121 such that the interrogator 120 may be used in a sterile disposable bag or in a sterile operating room environment. Elements contained within and coupled to the housing 121, in some embodiments, include the excitation light source 102, the illumination light source 103, the light source array 116, the light receiving array 117, the camera 122 (see FIG. 4), and the handle 125. In some embodiments, a first cable 126 electrically, communicatively, or electrically and communicatively couples the interrogator 120 to the controller 140. The housing 121 may also contain additional elements, such as mounting or fastening means, electronics, cooling means, insulation, etc., according to a particular embodiment or various embodiments of the interrogator 120.

[0051] In some embodiments, the interrogator 120 is arranged and configured as shown in Figures 2 and 3. The handle 125 is coupled to the housing 121 spaced from or generally opposite the distal end 127 so that the elements of the light source array 116 and the light receiving array 117 are not hidden from the emitted and received light. The handle 125 is unitary with the housing 121 in some embodiments. The first cable 126 enters the interrogator 120 via the handle 125 in some embodiments to keep the first cable 126 out of the line of sight between the distal end 127 and the tissue area of ​​interest to be illuminated and visualized. In some embodiments, the light source array 116 and the light receiving array 117 are arranged next to each other within the housing 121 in a configuration similar to that shown in Figure 3. The depiction of the light source array 116 and the light receiving array 117 within the housing 121 in Figure 3 is by way of illustration and is provided by way of example, and other configurations of the light source array 116 and the light receiving array 117 are within the scope of the disclosure herein.

[0052] For example, in some embodiments of the system 100, the light source array 117 is a plurality of light source arrays arranged in an array or pattern, such as the circular pattern of eight light source arrays 117 around the circumference of the distal end 127 shown in FIG. 2. In this and other embodiments including an array of light source arrays 117, the target tissue region 104 may be more brightly and evenly illuminated with the excitation light 110. Brighter and more even illumination may reduce light shadowing effects that may allow for improved visualization of the target tissue region 104 by the system 100. Other and any number of arrangements, patterns, or arrays including any number of light source arrays 117 are contemplated as being within the scope of the present disclosure, without limitation.

[0053] The excitation light source 102 (see FIG. 4 ) is disposed within the housing 121 in some embodiments. Optionally, in certain embodiments, the illumination light source 103 (see FIG. 4 ) is disposed within the housing 121. In some embodiments, the illumination light source 103 comprises a source of “white” light (or nearly white light) in a wide electromagnetic radiation signal wavelength-range, such as, for example, a halogen (xenon) lamp, a 450 watt xenon lamp, a tungsten-halogen lamp, a mercury arc lamp, etc. In certain embodiments, the illumination light emitted from the illumination light source 103 may be coupled through one or more optical filters to “tune” the “white” light (or nearly white light) illumination signal to a range of wavelengths designed not to interfere with detection of emitted light 112 resulting solely from fluorescent effects or other inherent properties of neural tissue within the tissue region 104 of interest. According to various embodiments of system 100, all or a portion of reflected light 114 (which is mostly derived from the illumination light emitted by illumination source 103), emitted light 112, and, if applicable, non-emitted ambient light, are collected by a light receiving array 117 of interrogator 120.

[0054] In some alternative embodiments, the excitation light source 102 (see FIG. 4) is located at a location remote from the interrogator 120, and the excitation light 110 is transmitted to the interrogator 120 by light transmission means, such as, for example, a fiber optic bundle. The 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 robotic or computer assisted surgery, medical device carts, etc. The light transmission means may be integral to the first cable 126, or may be mechanically, optically coupled between the excitation light source 102 and the interrogator 120, for example, as a separate elongated cable-like structure.

[0055] The excitation light source 102 generates excitation light that may include wavelengths of a broadband electromagnetic radiation signal, or alternatively, excitation light that is limited to a narrower wavelength range of the electromagnetic radiation signal. For example, in some embodiments, the excitation light source 102 may include a narrow wavelength range light source, such as a light emitting diode (LED) or a laser. In some embodiments, the excitation light source 102 includes a source of "white" light (or near white light) in the broad electromagnetic radiation signal wavelength-range, such as, for example, a halogen (xenon) lamp, a 450 watt xenon lamp, a tungsten-halogen lamp, a mercury arc lamp, or the like.

[0056] The excitation light source 102 emits excitation light 110 (electromagnetic radiation signal) that passes from the light source array 116 of the interrogator 120 to illuminate (radiate) the target tissue region 104. The excitation light source 102 is configured to emit the excitation light 110 at a particular wavelength to stimulate or excite neural tissue within the target tissue region 104, for example, due to an effect that is specific to neural tissue of an intrinsic autofluorescence effect. Because the effect is specific, i.e., an intrinsic property or composition of the tissue, and originates entirely within neural tissue, no fluorescent (or other) dyes, fluorescent markers, fluorescent tissue probes, etc. are necessary or used in the operation of the tissue imaging system 100.

[0057] The excitation light 110 at a wavelength generated by the excitation light source 102, which may be optically coupled through an optical filter, in some embodiments maximizes the difference between the inherent intrinsic fluorescence effects of healthy neural tissue and surrounding healthy non-neural tissue. In a visual image display device, for example, a noticeable difference in the images is observable on the display screen between a highlighted image (e.g., see 802 in FIG. 8 ) corresponding to the intrinsic fluorescence effects of neural tissue in the tissue region of interest and a darker unhighlighted image (e.g., see 804 in FIG. 8 ) corresponding to the absence (or minimal presence) of fluorescence effects and reduced reflected light from adjacent and / or surrounding non-neural tissue in the tissue region of interest. A very noticeable difference between the two images on the display screen, such as a highlighted image corresponding to the intrinsic autofluorescence effects of neural tissue visually contrasted with a darker unhighlighted image corresponding to the absence (or minimal presence) of fluorescence effects and reduced reflected light from adjacent and / or surrounding non-neural tissue, improves the visualization of the neural tissue in the tissue region of interest (under examination) versus the neural tissue adjacent to or surrounding the neural tissue. This contrasted visualization of nervous and non-nervous tissues within a tissue region of interest can provide important information to aid, for example, a surgeon in performing a surgical procedure on a patient. For a striking example of this contrast, in accordance with various alternative embodiments, compare the image of the surgical field of FIG. 19 with the image of the surgical field shown in FIG. 20. In FIG. 19, under ambient white light conditions, it is very difficult to distinguish the presence of nervous tissue 1902 relative to the non-nervous tissue adjacent and / or surrounding the nervous tissue. In FIG. 20, using an exemplary embodiment of tissue imaging system 100, a formed highlighted image of nervous tissue 2002 is clearly observable against a darker background image of the non-nervous tissue adjacent and / or surrounding the nervous tissue 2002.

[0058] In some exemplary embodiments, the wavelength of the excitation light 110 is in the range of about 365 nanometers (nm) to about 400 nm. In some exemplary embodiments, the wavelength of the excitation light 110 is in the wavelength range of about 382 nm to about 392 nm. In some exemplary embodiments, the wavelength of the excitation light 110 may be in the wavelength range of about 455 nm to about 510 nm. In some exemplary embodiments, the wavelength of the excitation light 110 may be about 485 nm.

[0059] The light source array 116, i.e., moves the excitation light 110 from the interrogator 120 to illuminate the tissue region of interest. The light source array 116 may be proximate or adjacent to the excitation light source 102. In some embodiments, the light source array 116 comprises a single optical lens or multiple optical lenses to appropriately focus or disperse and move the excitation light 110 for illumination of the tissue region of interest 104. In some embodiments, the excitation light source 102 directly illuminates the tissue region of interest 104 with the excitation light 110, and the interrogator 120 does not include the light source array 116. In some embodiments, the light source array 116 is contained within the excitation light source 102 that is separate from the interrogator 120. In some embodiments, the light source array 116 includes a fiber optic bundle, as described herein. According to embodiments, the light source array 116 may include any combination including, without limitation, one or more of an optical lens, multiple optical lenses, or a fiber optic bundle.

[0060] In some embodiments, the light source array 116 includes an excitation filter 111 configured to narrow, limit, band pass, or "tune" the wavelength of the excitation light 110 to an optimal range to produce minimal or zero fluorescence emission of the surrounding healthy non-neural tissue, while causing healthy neural tissue to produce emitted light (fluorescent light) 111, which may be in a narrow, limit, band pass range of wavelengths due to intrinsic autofluorescence effects. In particular, any minimal fluorescence emission of the surrounding healthy non-neural tissue will emit other light outside of the narrow, limit, band pass range of wavelengths of the emitted light 111 from the neural tissue. In some embodiments, by using one or more optical filters optically coupled to the light source array and one or more illumination sources, any illumination light (such as from the illumination light source 103 shown in FIG. 4 ) and therefore any reflected light from the target tissue region 104 may be rejected or substantially reduced from the narrow, limit, band pass range of wavelengths of the emitted light 111 from the neural tissue. Further, by using one or more optical filters optically coupled to the light receiving train and the light detection device (e.g., an imaging camera device), any excitation light 110 may be rejected or substantially reduced from the narrow, limited, band-passed range of wavelengths of emitted light 111 from neural tissue, while in certain embodiments, allowing the illumination light reflected from the tissue region of interest to pass. Additionally, any minimal fluorescence effects of non-neural tissue (from the emitted illumination light and, if applicable, from the emitted excitation light) may emit light substantially outside of the narrow, limited, band-passed range of wavelengths of emitted light 111 from neural tissue, and may be rejected or substantially reduced from the narrow, limited, band-passed range of wavelengths of emitted light 111 from neural tissue. As discussed above, the addition of one or more filters, whether coupled to the light source train or to the light receiving train, may improve contrast of the emitted light 111 from neural tissue compared to any light from non-neural tissue in the tissue region of interest.

[0061] Excitation filter 111 is particularly useful in embodiments where excitation light source 102 is a broadband white light source, such as a halogen or mercury arc source, as opposed to excitation light 110 from a narrower band source, such as certain LED or laser excitation light sources. Thus, in some embodiments, excitation filter 111 is a bandpass filter.

[0062] In some embodiments, the excitation filter 111 may be a low-pass (long-pass) filter. In some embodiments, the excitation filter 111 is a high-pass (short-pass) filter. In some embodiments, the excitation filter 111 is a bandpass filter of about 382 nm to about 392 nm. In some embodiments, the excitation filter 111 includes a high-pass (short-pass) filter of about 300 nm. In some embodiments, the excitation filter 111 includes a low-pass (long-pass) filter of about 400 nm. In some embodiments, the excitation filter 111 is a bandpass filter of about 300 to about 400 nm. In some embodiments, the excitation filter 111 is a bandpass filter of about 320 to about 380 nm. In some embodiments, the excitation filter 111 is a bandpass filter of about 325 nm to about 375 nm. In some embodiments, the excitation filter 111 includes a low-pass (long-pass) filter of about 350 nm. In some embodiments, the excitation filter 111 includes a low-pass (long-pass) filter of about 300 nm, and in some embodiments, the excitation filter 111 includes a high-pass (short-pass) filter of about 400 nm.

[0063] It should be noted that Fig. 15 and Fig. 16 show various exemplary embodiments of a camera imager or dendritic camera device. The camera 1500 comprises a light receiving train including a camera housing and a lens 1502 as shown in Fig. 15, and possibly one or more optical filters 1502 with or adjacent to the lens in certain embodiments. Fig. 16 shows an example of a tissue imager 1600, which may also be referred to as a dendritic camera. The tissue imager 1600 is manageable by its handle 1606. The tissue imager 1600 comprises a ring portion, which in this example includes multiple light sources and possibly one or more sensor / detector / camera devices. The lens / filter 1604 is located in a central region of the ring portion and is a component of the light source train that combines one or more excitation light signals and / or one or more illumination light signals from one or more light sources in the tissue imager 1600. The light signals are moved through the lens / filter 1604 to selectively emit the light signals to the tissue region of interest.

[0064] 17 and 18 show exemplary components of a tissue imaging system, according to various embodiments. An exemplary camera imager 1700, which may also be referred to as a dendritic camera device, is shown in FIG. 17. The exemplary camera imager 1700 is operable by a user. The device 1700 is connectable to a computing system 1800, shown in FIG. 18, via an Ethernet network link 1702. The camera imager 1700 includes various components such as illumination optics including at least one light source 1706 with control electronics. A light source array 1704 is also shown to couple light signals from at least one light source 1706 through one or more lenses and filters. A camera block 1708 includes a computer interface that connects camera electronic input and output signals through an Ethernet connecting cable to the computing system 1800. The camera 1708 also includes a receiver array including one or more detection filters and / or lenses 1710. The computing system 1800 includes an information handling system 1812, which may include one or more processors, memory, storage devices, power circuits, and data communication interfaces.

[0065] A touch panel display device 1810 is shown as a component of computing system 1800. The touch panel display device 1810 provides an output user interface device and an input user interface device for communicating with a user of computing system 1800. Computing system 1800 also includes a computing networking interface that is communicatively coupleable to an external network that can be used to communicate information and control signals between computing system 1800 and another computing device communicatively coupled to the network.

[0066] Continuing with the discussion of the exemplary tissue imaging system 100, and with particular reference to FIG. 3, the target tissue region 104, in response to being illuminated with excitation light 110, again transfers light to the interrogator 120. This transferred light includes reflected light 114, possibly including a reflected component of the excitation light 110 from the target tissue region. Healthy neural tissue within the target tissue region 104 has inherent fluorescent properties when illuminated with excitation light 110, creating emitted light 112. The emitted light 112 is derived solely from the fluorescent emission or other inherent properties of a portion of the target tissue region 104 (e.g., healthy neural tissue). All or a portion of the reflected light 114, emitted light 112, and non-emitted ambient or other illumination light from the illumination source 103 are collected by a receiver array 117 of the interrogator 120 in some embodiments of the system 100.

[0067] FIG. 11 shows examples of various types of light that may be irradiated onto a tissue region of interest, including neural tissue 1102 and non-neural tissue 1104 adjacent to or surrounding the neural tissue 1102. Excitation light 1110 is emitted from a light source, such as within tissue imaging system 100. The excitation light 1110 is designed in the system to specifically induce or elicit an intrinsic autofluorescence effect of the neural tissue 1102. This effect may be due to biological and / or chemical factors within the neural tissue, such as due to its composition and other unique properties of the neural tissue. For example, neural tissue may be characterized by a high content of lipids and proteins. Neural tissue does not contain significant amounts of sugars. Complex lipids (e.g., phospholipids and sphingophospholipids) and unesterified cholesterol may be the most abundant lipids. Proteins, including protein crystals, may be autofluorescent when excited with ultraviolet (UV) light of a particular wavelength. The unique properties of neural tissue that may be autofluorescent when excited with ultraviolet light of a particular wavelength may differ significantly from other non-neural tissues within a patient's body. The inventors have observed that, under certain illumination conditions, tissue regions of a subject containing healthy neural tissue and healthy non-neural tissue can emit high intensity intrinsic autofluorescent light 1111 from the neural tissue 1102 in response to illumination of the neural tissue 1102 with excitation light in a particular range of wavelengths. One such wavelength range of excitation light is believed to be in the range of about 382 nm to about 392 nm. The neural tissue is believed to intrinsically autofluoresce in response to illumination with excitation light 1110 including wavelengths in the aforementioned range. The wavelength of the intrinsic autofluorescent light 1111 that is believed to be most bright is in the range of about 433 nm to about 450 nm. The excitation light 1110 illuminating the non-neural tissue 1104 is reflected as reflected light from the non-neural tissue 1104 in the same wavelength range as the excitation light 1110 (about 382 nm to about 392 nm). Any irradiated light to the target tissue region, which may include wavelengths in a broader region 1008 (see FIG. 10 ) or a narrower region 1010, will be mostly reflected from the target tissue region, including from both healthy neural tissue 1102 and healthy non-neural tissue 1104.In certain embodiments that use illumination light in a broader wavelength range (nearly white light) 1008 to improve detection of the intrinsic autofluorescence light 1111, one or more optical filters (including notch filters) can couple illumination light from the light source into the light source array while substantially eliminating the wavelength range 1006 that is characteristic of the intrinsic autofluorescence light 1111 emitted from neural tissue 1102. This "notch" filtering of the illumination light can reduce possible interference from reflected illumination light while detecting the wavelengths of the intrinsic autofluorescence light 1111.

[0068] According to various embodiments, the light receiving array 117 includes a single optical lens or multiple optical lenses and is configured to focus and move light, including the emitted light 112, to the camera 122 (see FIG. 4). In some embodiments, the light receiving array 117 includes a single focusing lens. In some embodiments, the light receiving array 117 includes multiple (in any number, combination, and arrangement) focusing lenses and possibly diverging lenses configured to at least focus the emitted light 112 to the camera 122. Some embodiments of the system 100 do not include a light receiving array 117 where the camera 122 is a "chip on a stick" image-sensor charge-coupled device ("CCD") camera. Some embodiments of the light receiving array 117 may include a detection filter but no lens.

[0069] In some embodiments, the light receiving train 117 includes a detection filter, as shown in FIG. 3. In some embodiments, the detection filter is an optical filter that removes reflected light 114 and ambient light having wavelengths outside the range of the detection filter. However, in some embodiments, the light receiving train 117 does not include a detection filter. The detection filter allows only light of a desired wavelength (e.g., a wavelength corresponding to neural tissue emitted light in response to an intrinsic autofluorescence effect induced or elicited by illumination with excitation light) to pass through the detection filter and to the camera 122 (see FIG. 4). In some embodiments of the system 100, the light-filtering function of the detection filter is performed digitally by an image processing software package present in the data processor or information processing system. The appropriate detection filter may depend on other aspects of the system 100, particularly the wavelength of the emitted light 112, which in turn depends on the intrinsic properties of the neural tissue, such as the spinal cord dura or dura mater, that is targeted for visualization. In addition to configuring the detection filter to allow passage of wavelengths corresponding to emitted light 112, such as emitted light to neural tissue, the detection filter 124 may also be configured to allow passage of wavelengths of emitted light 112 that allow visualization of non-neural tissue adjacent to or surrounding peripheral nerves, where adjacent or surrounding non-neural tissue emits light at a specific wavelength or specific wavelength range different from the wavelength of the excitation light and different from the emitted light 112, such as neural tissue emission light. Nervous tissue inherently produces a higher intensity emitted light 112 than many non-neural tissues in response to the same intensity (luminosity) and wavelength of excitation light 110. Thus, light emitted from non-neural tissue adjacent to or surrounding neural tissue, such as fat or muscle tissue, has a significantly lower intensity than light emitted from neural tissue. Although the surrounding non-neural tissue may still be visualized, the neural tissue may be easily visually distinguished from the surrounding non-neural tissue, such as those shown in FIG. 8 and FIG. 20.

[0070] In some embodiments, the detection filter is a bandpass filter that allows preferential passage of fluorescent light 1006 (see FIG. 10) including wavelengths in the range of about 433 nm to about 450 nm, which corresponds to the range of excitation light 1004 with wavelengths in the range of about 382 nm to about 392 nm. In some embodiments, the detection filter is a bandpass filter with a range of about 450 nm to about 575 nm. In some embodiments, the detection filter 124 is a bandpass filter having a range of about 480 nm to about 500 nm. In some embodiments, the detection filter is a bandpass filter with a range of about 450 nm to about 575 nm. In some embodiments, the detection filter is a bandpass filter with a range of about 425 nm to about 525 nm. In some embodiments, the detection filter is a bandpass filter with a range of about 440 nm to about 570 nm. In some embodiments, the detection filter is a low-pass (long-pass) filter with a range longer than about 400 nm. In some embodiments, the detection filter includes a low pass filter having a region greater than about 425 nm, hi some embodiments, the detection filter is a low pass filter having a region greater than about 450 nm.

[0071] In some embodiments, the detection filter comprises a high-pass (short-pass) filter having a wavelength range shorter than about 600 nm. In some embodiments, the detection filter comprises a high-pass (short-pass) filter having a wavelength range shorter than about 575 nm. In some embodiments, the detection filter comprises a high-pass (short-pass) filter having a wavelength range shorter than about 550 nm. In some embodiments, the detection filter comprises a high-pass (short-pass) filter having a wavelength range shorter than about 510 nm.

[0072] The camera 122 receives light from a light receiving array 117 in some embodiments.

[0073] In some embodiments, the camera 122 is configured to communicate digital information representing the collected light from the light receiving array 117 to a processor, which digitally processes the information to create a visual image that is displayed on a digital screen or monitor. The camera 122 is an image sensor / detector in some embodiments. Thus, in some embodiments, the camera 122 is a digital camera module configured to couple to the processor. The camera 122 is, in some embodiments, a monochromatic or polychromatic digital camera. 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, the camera 122 is an optical camera with an eyepiece for direct visualization of a non-digital visual image. Camera 122, with or without receiver array 117, in some embodiments may be optically coupled to visualization devices other than interrogator 120, such as a surgical microscope / lapascope, thoracoscope, arthroscope, bronchoscope, ureteroscope, etc., for flexible fiber optic endoscopes.

[0074] One non-limiting example of a camera 1206 optically coupled to a visualization device, such as a flexible endoscope 1208, according to various embodiments, is shown in FIG. 12. The tissue imaging system can be used to inspect a tissue region of interest (tissue under inspection) 1202 within a generally enclosed cavity within a patient's body. The light box device 1204 optically couples selectable light signals from one or more light sources 1220, 1222 to an optical concentrator 1224, which, according to this embodiment, couples light emitted from the selected one or more light sources 1220, 1222 through a fiber optic cable (fiber optic light guide) 1210, which guides the emitted light, for example, to a rigid or flexible endoscopic device 1208. The rigid or flexible endoscopic device 1208 further includes an optical waveguide, which guides the emitted light, for example, to a generally enclosed cavity within the patient's body, thereby illuminating the tissue region of interest 1202 with excitation light. The tissue region of interest 1202 may include neural tissue adjacent to or surrounded by non-neural tissue. The neural tissue and non-neural tissue may include healthy neural tissue and healthy non-neural tissue, respectively. According to this embodiment, excitation light (e.g., in the near-ultraviolet wavelength region of about 382 nm to about 392 nm, which may be "tuned" by selection of bandpass optical filter Filter 1 in the first light source 1220) may be selectively emitted from the first light source 1220 in one or more light sources 1220, 1222 under processor control in response to computer instructions operating in an information processing system 1812 (see FIG. 18). According to this embodiment, FIG. 10 illustrates a wavelength region for excitation light 1004 within the electromagnetic spectrum 1002. Each of the optical filters Filter 1, Filter 2, and Filter 3 shown in FIG. 12 may include one or more optical filters that may be used to "tune" the design of the wavelength region for the optical signal. The source optical filters, Filter 1 and Filter 2, "condition" the optical signals emitted from each source 1220,122.

[0075] The sensor / detector / camera optical filter, Filter 3, "conditions" the optical signal received by the sensor / detector / camera 1206 in the tissue imaging system.

[0076] According to this embodiment, illumination light (e.g., in the visible wavelength range of about 400 nm to about 760 nm that can be "tuned" in second light source 1222 by selection of bandpass optical filter Filter 2) can be selectively emitted from second light source 1222 under processor control in response to computer instructions operating in information processing system 1812 (see FIG. 18). According to this embodiment, FIG. 10 shows the wavelength range length for this nearly "white" illumination light 1008 within the electromagnetic spectrum 1002.

[0077] In certain embodiments, the illumination light may be emitted in an alternative narrower range of wavelengths (e.g., in the visible light wavelength range of about 470 nm to about 760 nm wavelengths that may be "tuned" by selection of bandpass optical filter Filter 1 in second light source 1222), shown in FIG. 10 as illumination light 1010. This alternative illumination light 1010 may act to effectively illuminate anatomical structures and tissues within target tissue region 1202 with a nearly "white" illumination light 1010, while substantially avoiding interference with any fluorescent light (e.g., in the wavelength range of about 433 nm to about 450 nm) emitted from neural tissue within target tissue region 1202. In this example, FIG. 10 illustrates a wavelength range within the electromagnetic spectrum 1002 for fluorescent light 1006 that may be emitted from neural tissue in response to illumination of the neural tissue with excitation light 1004. In certain embodiments where the illumination light is in a broader wavelength range for substantially "white" illumination light 1008, it is apparent from Figure 10 that this broader wavelength range for illumination light 1008 overlaps with the wavelength range for fluorescent light 1006. To avoid interference of the substantially "white" illumination light 1008 with detection of the fluorescent light 1006 that may be emitted from neural tissue, the illumination light filter (filter 1) may include a notch filter that removes the wavelengths of fluorescent light 1006 from the substantially "white" illumination light 1008 emitted from the second light source 1222 and used to illuminate the tissue region 1202 of interest.

[0078] The first light source 1220, according to this embodiment, includes an LED light enclosure and one or more LEDs therein that emit excitation light in the near UV range. According to this embodiment, an optical filter (Filter 2) optically couples and "conditions" the emitted band wavelength range excitation light from the LED light enclosure of the first light source 1220 to a fiber optic light concentrator lens 1224. The light source array, in this embodiment, includes the first light source 1220, the concentrator lens 1224, one or more optical fibers 1210, and outputs from the light guide within the endoscope 1208, thereby guiding the excitation light to illuminate the target tissue region 1202. The processor can control the brightness level of the excitation light emitted out of the first light source 1220, in addition to selectively switching the first light source on or off.

[0079] The second light source 1222, according to this embodiment, includes an LED light enclosure and one or more LEDs therein that emit illumination light, which in this embodiment includes "white" (or nearly white) light. According to this embodiment, an optical filter (Filter 1) optically couples and "conditions" the band wavelength region illumination light from the LED light enclosure of the second light source 1222 to a fiber optic light concentrator lens 1224. The light source array, in this embodiment, includes the second light source 1222, the concentrator lens 1224, one or more optical fibers 1210, and an output from a light guide within the endoscope 1208, thereby guiding the illumination light to illuminate the target tissue region 1202. In addition to selectively switching the second light source on or off, the processor can control the brightness level of the illumination light emitted out from the second light source 1222.

[0080] In this example, the optical signal, whether it includes emitted light (fluorescent light) and / or reflected light from the tissue region of interest 1202, is guided by one or more optical waveguides in the flexible endoscope 1208 to a fiber optic cable (fiber optic optical waveguide) 1211, and thereby to a filter, Filter 3, a lens, and into the camera 1206. The optical receiver train, in this example, includes one or more optical waveguides in the flexible endoscope 1208, the fiber optic cable 1211, a filter, Filter 3, and a lens, which couple the optical signal into the camera 1206. FIG. 14 shows a table of two exemplary embodiments illustrating the filter selection options for Filters 1-3, as shown in FIG. 12 and as described above.

[0081] 1-4, in some embodiments, the interrogator 120 comprises multiple cameras 122, with each camera 122 of the multiple cameras 122 optically coupled to one of the corresponding multiple light rows 117. Various embodiments including two or more cameras 122 may be useful for capturing optical signals and displaying a stereoscopic visual image of the tissue region 104 of interest.

[0082] 4 is a partial schematic diagram of tissue imaging system 100 showing the digital data path in some embodiments. According to this example, processor 142 includes a data processor, such as a microprocessor, for processing digital input from and delivering data and instructions to various input / output devices, including, in some embodiments, excitation light source 102, illumination light source 103, camera 122, user interface 146, memory 145, video recorder 160, and image display device 150. Processor 142 receives digital input from camera 122, user interface 146, and memory 145. Depending on the embodiment of system 100, a variety of suitable processors may be used as processor 142, including microprocessors of medical computers, such as those currently used in existing medical imaging and computer-aided imaging applications. In some embodiments, processor 142 is a number of microprocessors that perform 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 through, user interface management, wireless communication, and other specific functions.

[0083] The processor 142 executes a software package 144 resident on the memory 145 and operating on the processor 142. In some embodiments, the software package 144 is configured to perform preferential visualization of a first tissue within a tissue region of interest, such as neural tissue, versus a second tissue, such as non-neural tissue, which may include, for example, adipose tissue, muscle tissue, connective tissue, and the like.

[0084] The processor 142 , in some embodiments, is configured to deliver instructions to the camera 122 regarding power supply, aperture size, etc., and to receive image data from the camera 122 .

[0085] Memory 145 is a data storage device. Memory 145 may, in some embodiments, be configured as a writeable memory or a combination of writeable and read-only memory.

[0086] The visual image data signals from the processor 142 are received by the image display 150. The image display 150 displays a visual image, such as peripheral nerves over background tissue, to a surgeon or other user of the system 100. Depending on the embodiment of the tissue imaging system 100, the image display 150 may be a standard video monitor, a high definition video monitor such as those used during minimally invasive surgical procedures, or a computer monitor. The display 150 may be a light emitting diode (LED) display, including, without limitation, any medical display device such as an organic LED (OLED), liquid crystal display (LCD), plasma display, quantum dot display (QLED), or other visual image display devices currently used or to be developed in the future.

[0087] Recording and archiving of visual image data may be useful, such as for medical records, teaching and instruction, and other uses. Accordingly, some embodiments of system 100 include a video recorder 160. Video recorder 160 may receive visual image data from processor 142 and output visual image data to image display device 150. Standard digital or analog (video tape) devices may include video recorder 160 in accordance with embodiments of system 100.

[0088] The user interface 146 is a means by which a user of the tissue imaging system 100 interacts with and controls functions, including exchanging information and commands, as well as adjusting settings of the various components and elements of the system 100. Some non-limiting examples of these functions include turning on or off power to the system 100 or any of its individual components, changing the intensity (luminosity) of the excitation light 110 emitted from the excitation light source 102, and changing the wavelength of the excitation light 110 by engaging an optical or digital filter, or by changing the light source, i.e., white light vs. filtered (bandpass or otherwise) of the excitation light 110, etc. Changing the bandpass wavelength of a digital filter is, in some embodiments, changed or adjusted via the user interface 146. The user interface 146 may include analog buttons or switches, digital input switches, digital touch screens, toggle switches, whether digital or analog, joysticks, wheels, or any combination thereof.

[0089] In some embodiments, the user interface 146 includes multiple user interfaces.

[0090] As a non-limiting example embodiment in which user interface 146 is multiple user interfaces, system 100 may include a combination of (i) a graphical user interface present on controller 140, (ii) a button or other switch located on housing 121 of interrogator 120, (iii) a floor-based foot-actuated toggle or other switch for changing tissue illumination (i.e., excitation light 110) between white light and filtered light, or the like. FIG. 5 is a diagram 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. Additionally, connection interface 147 is shown. Connection interface 147 may be a high-definition multimedia interface (HDMI), a set of input / output connectors for external recording devices, a universal serial bus (USB), or the like. In some embodiments, including the embodiment shown in FIG. 5, controller 140 includes multiple connection interfaces 147.

[0091] The connection interface 147 may increase the functionality of the system 100, for example, a USB interface may allow images to be stored on a USB storage medium and / or integrated into a medical HIPAA recorder. The controller 140 includes or is electrically coupled to a medical compatible power source 152. In some embodiments, the controller 140 includes one or more wireless connection interfaces 147, such as a Bluetooth or WiFi wireless interface, communicatively coupled to one or more components (any combination) forming the tissue imaging system 100, which may include, but may not be limited to, the excitation light source 102, the illumination light source 103, the light source array 116, the light receiving array 117, the camera 122, the image display 150, and the video recorder 160.

[0092] 6 is a diagram of tissue imaging system 100 mounted on a medical cart 164. Medical cart 164 is optionally used to integrate, mount, transport, and house one or more components of system 100, such as, for example, controller 140, excitation light source 102, video recorder 160, image display device 150, and any associated accessories. In some embodiments, more than one medical cart 164 can be used to mount, transport, and / or house components of system 100. For example, in some embodiments, excitation light source 102 and illumination light source 103 are mounted on one medical cart 164, while the controller, along with other components, is mounted on a second medical cart 164.

[0093] 7A is a front view of an embodiment of a user interface 146 including a screen display showing an example of a main menu for tissue imaging system 100. The main menu may be displayed by user interface 146, in some embodiments, as a screen located on controller 140 or as a screen located on interrogator 120. The main menu provides information to a user and allows the user to provide inputs to control, configure, or adjust elements of system 100, as described herein. For example, the main menu provides the user with information regarding exposure settings, sensitivity settings, memory status, access to sub-menus and controls for digital video storage, etc. Additional functionality of this illustrated embodiment includes commands to take a picture, start a video recording, send to a video screen showing a visual image of the surgical field, or set controller 140 to a standby mode.

[0094] 7B is a front view of an embodiment of user interface 146 showing an exemplary settings menu for system 100. This exemplary display, in some embodiments, provides a user with options to select the language of the menus displayed by user interface 146, adjust the illumination level settings of excitation light source 102, adjust the camera sensitivity settings, and provide instructions for copying pictures and images to a USB or other digital storage device.

[0095] 8 is an example of an image display 150 showing an image of nervous tissue 802 and an image of non-nerve tissue adjacent to or surrounding the nervous tissue 802 in the surgical field. The setting status indicator is also displayed as an inset in the tissue image display of the surgical field.

[0096] 9 is a flow diagram illustrating exemplary process steps for a method of using a tissue imaging system. The method begins at step 202. In some embodiments, the method includes positioning steps 208 and 210, an illuminating step 220, a receiving step 222, a detecting step 230, a visual image forming step 240, and a display image step. In some embodiments, the detecting step 230 further includes a filtering step.

[0097] Positioning steps 208 and 210, in some embodiments, include positioning an interrogator, a probe with a light receiving array configured to acquire data used to form a visual image in proximity to a tissue region of the subject containing healthy neural tissue adjacent to or surrounded by healthy non-neural tissue. In some embodiments, the tissue region of the subject includes a surgical wound. In some embodiments, the tissue region of the subject includes a surgical wound bed containing the spinal cord, anterior and posterior spinal nerves, and a portion of the spinal dura, such as a portion of the dural sac containing the dorsal spinal ganglion. In some embodiments, the visual image formed, step 240, includes an image of healthy neural tissue 802, such as nerves, peripheral nerves, and / or dura, visually contrasted with adjacent and / or surrounding healthy non-neural tissue 804 (a much darker image contrasted with the highlighted image 802 in FIG. 8).

[0098] The illuminating step 220, in some embodiments, includes illuminating the tissue with excitation light comprising a first wavelength in the absence of a dye, marker, or probe, causing emitted light comprising a second wavelength to be produced in response to illumination with the excitation light of the first wavelength. In some embodiments, the first wavelength is in a wavelength range. In some embodiments, the wavelength range is in the near ultraviolet range. In some embodiments, the wavelength range is from about 300 nanometers (nm) to about 400 nm. In some embodiments, the wavelength of the excitation light is about 370 nm. In some embodiments, the wavelength of the excitation light is in the wavelength range of about 455 nm to about 510 nm. In some embodiments, the wavelength of the excitation light is about 485 nm. In some embodiments, the excitation light originates from an interrogator.

[0099] The detection step 230, in some embodiments, includes moving the emitted light away from the tissue in the absence of dyes, markers, or probes. In some embodiments, a receiving train collects the emitted light from the tissue, the excitation light reflected from the tissue, and the ambient light for filtering and processing.

[0100] The filtering step 235, in some embodiments, includes filtering the emitted light, which removes at least a portion of the reflected excitation light and at least a portion of the ambient light, while preferentially passing a substantially larger portion of the emitted light.

[0101] In some embodiments, the filtering step 230 is performed by an optical filter. In some embodiments, the optical filter is included by the light receiving train. In some embodiments, the filtering step 230 includes digital filtering of the received light by a processor, such as a processor operating a software package included by the controller and stored in a memory. In some embodiments, the digitally filtered light is received by the light receiving train.

[0102] Forming step 240, in some embodiments, includes forming a visual image of nervous tissue, such as a peripheral nerve, that contrasts and is differentiated from images of non-nerve tissue adjacent and / or surrounding the nervous tissue. The visual image is formed (240) by processing light received by an interrogator that in some embodiments includes 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 included with the light receiving train. The method ends at step 252.

[0103] Alternative Exemplary Embodiments of a Tissue Imaging System FIG. 13 illustrates an exemplary embodiment of a tissue imaging system that selectively performs imaging of neural tissue versus imaging of non-neural tissue using near-ultraviolet illumination and can alternatively or simultaneously perform imaging of a target tissue region 1302 using infrared (IR) light. The inventors have realized that perfusion of neural tissue tends to be significantly lower than perfusion of non-neural tissue. By selectively illuminating the target tissue region with an infrared signal from an infrared source 1304 and detecting the infrared signal emitted from the target tissue region 1302, a generated image of the neural tissue in the target tissue region 1302 can be visually contrasted with a generated image of the non-neural tissue in the target tissue region 1302. The generated image of the neural tissue is typically a darker image (lower brightness) relative to the generated image of the non-neural tissue (higher brightness). The two images can be visually contrasted with each other, such as on a display screen, to identify the location of the neural tissue relative to the location of the non-neural tissue in the target tissue region 1302.

[0104] Near-UV source 1304 may include one or more optical filters 1306 to couple excitation light to a light receiving train that, according to this example, includes detection filter 1322, lens 1324, and guide light to camera 1320. This set of components for the near-UV excitation light and, if applicable, detection of intrinsic autofluorescence light from neural tissue versus detection of light from non-neural tissue has a similar description as already described above with respect to various exemplary embodiments of the tissue imaging system.

[0105] The infrared source 1308 may include one or more infrared LEDs and one or more optical filters 1310 for coupling infrared light to the tissue region of interest and from there to couple the infrared signal to the receiver train and camera 1320. Detection of infrared light may be selectively performed either alternatively or simultaneously with detection of intrinsic autofluorescence light from neural tissue versus detection of light from non-neural tissue, if applicable, according to various embodiments. The two sets of images, images from infrared detection and images from intrinsic autofluorescence light detection from neural tissue, may be processed from the camera by a processing system that overlays the images and displays the overlaid image that most likely indicates the location of healthy neural tissue and healthy non-neural tissue within the tissue region of interest 1302.

[0106] Improved tissue imaging to distinguish neural tissue from non-neural tissue by adding temperature detection of different tissues The tip of the endoscopic probe coupled to the camera may include a temperature sensor (e.g., one or more infrared detectors) capable of detecting different temperatures of different tissues within the tissue region of interest. Nervous tissue may often be cooler than non-nervous tissue because nervous tissue does not contain (or is not perfused with) blood, as do the veins, arteries, and muscles in non-nervous tissue. Vascularized tissue glows different colors such that nerves and dura are distinguishable from adjacent and / or surrounding non-nervous tissue structures due to the temperature difference between the nervous and non-nervous tissues. The intrinsic temperatures of various tissues within the tissue region of interest can be measured using an endoscopic probe equipped with temperature sensors (e.g., using one or more temperature sensors strategically positioned around the exterior surface of the endoscopic probe tip). Thermal potential differences are measured across the tissue region of interest and a temperature map can be created that highlights the major temperature transitions between adjacent non-nervous tissue structures and the nervous tissue. Nervous tissue can be further contrasted from adjacent or surrounding non-neural tissue using tissue imaging by detecting the intrinsic autofluorescence of the nervous tissue contrasted against optical signals received from the non-neural tissue in the tissue region of interest. The processing system can then combine (e.g., overlay) the intrinsic autofluorescence image with temperature maps of various tissues in the tissue region of interest. This can form a composite image of the tissue region of interest in which a first composite image of the nervous tissue can be contrasted with a second composite image of the non-neural tissue. This combination of thermal mapping and intrinsic autofluorescence imaging over the same tissue region of interest can increase the sensitivity and specificity in the detection process used by the processing system to better distinguish between nervous and non-neural tissues in the tissue region of interest. This combined detection process improves the identification of nervous tissue versus the identification of non-neural tissue for tissue imaging systems.

[0107] Use of impedance and polarization analysis Nerves have a basal emission of energy when excited by white light that is detectable by the human eye on a display device. Different polarized waves are generated that, when illuminated in the near ultraviolet, can then be detected by special sensors that convert the moving polarized waves into noise or vibrations that alert the surgeon to the proximity of nerve tissue before the human eye can visualize the nerve tissue on the display device.

[0108] This detection can be combined with one or more of the thermal mapping and intrinsic autofluorescence imaging detection steps described above to improve sensitivity and specificity within the detection steps used by the processing system to better distinguish between neural and non-neural tissue within the tissue region of interest.

[0109] Using impedance and polarization from non-contact electrical stimulation combined with analysis to alter intrinsic autofluorescence optical signals Nerves can be induced to generate a traveling polarized wave (e.g., a traveling pulsed electrical signal) that travels along the axons of the neural tissue in response to a pulsed / changing electric field generated in proximity to the neural tissue. The pulsed / changing electric field can be generated in a variety of different ways. In one embodiment, a drive coil can be positioned near the tip of an endoscopic probe coupled to a camera. An oscillating electrical signal applied to the drive coil can generate a pulsed / changing electric field in proximity to the neural tissue. This traveling pulsed electrical signal travels along the axons of the neural tissue and can be detected by an electronic pickup sensor, or other electrical signal detection circuitry, without even physical contact with the neural tissue. Non-neural tissue does not respond (with a traveling polarized wave) to the pulsed / changing electric field.

[0110] It is expected that the polarized wave traveling along the axon will also temporarily modify the intrinsic autofluorescence effect of the nervous tissue with the wavefront of the traveling polarized wave. The intrinsic autofluorescence effect modified (at one point in the axon) with the traveling wavefront will be temporarily different from the intrinsic autofluorescence effect along the remainder of the axon. Neural tissue (with a polarized wavefront traveling along the axon of the nervous tissue) will exhibit a changing wavelength (and possibly a changing intensity) of the intrinsic autofluorescence light signal emitted from the nervous tissue with a wavefront that is different from the intrinsic autofluorescence light signal emitted from the nervous tissue at other parts of the axon. That is, the autofluorescence light signal emitted from the nervous tissue will temporarily change its wavelength and possibly change its intensity following a polarized wavefront traveling along the axon of the nervous tissue.

[0111] This change in the autofluorescence light signal can be correlated to the pulsating / changing electric field signal that drives the polarized light wavefront traveling along the axon. Furthermore, detection of this pulsating (changing) autofluorescence light signal can be captured by a camera in a series of sequential images of the tissue region of interest. The series of sequential images can be analyzed in real-time or near real-time by a processing system using image processing. From the analysis, the processing system can create an overview map of the path of the axon proximate to the moving wavefront of the polarized light. This map of the path of the neural tissue (along the axon) can show separate images of the neural tissue and non-neural tissue. These images alert the surgeon to the location of the neural and non-neural tissue within the tissue region of interest.

[0112] This detection of the varying autofluorescence light signal to map the location of the axons of the neural tissue can be combined with one or more of the thermal mapping and intrinsic autofluorescence imaging detection processes described above to improve the sensitivity and specificity in the detection process used by the processing system to better distinguish between neural and non-neural tissue within the tissue region of interest. The surgeon will be guided to the location of the neural and non-neural tissue within the tissue region of interest by reference to the images of the neural tissue and non-neural tissue adjacent to or surrounding the neural tissue. EXAMPLES

[0113] The above description of various embodiments of the invention is illustrated in part by the examples listed below.

[0114] Example 1 - Head and neck tumors Case 1: A 35-year-old woman presented with a painless, slowly growing nodule on the left lateral side that felt soft and immobile on palpation; the nodule was non-tender and measured 3 cm in maximum diameter. The patient's neurological examination was completely normal with no signs of facial paralysis. Ultrasound revealed a firm, hypoechoic nodule within the left parotid gland. Fine needle aspiration (FNA) was performed and revealed a benign pleomorphic adenoma.

[0115] Case 2: A 55-year-old woman presented with a painless, slowly growing nodule on the left lateral side that felt firm and springy on palpation; the nodule was nontender and measured 2.5 cm in maximum diameter. As in the previous case, the patient's neurological exam was normal, and ultrasound revealed a firm, hypoechoic nodule in the left parotid gland, and FNA revealed a benign pleomorphic adenoma.

[0116] Case 3: A 43-year-old woman presented with a painless, slowly enlarging nodule on the underside of the right lateral surface in the region of the inferior pole of the parotid gland. On palpation, the nodule felt firm, immobile, nontender, and measured 4 cm in maximum diameter. CT scan showed the lesion to be well defined and well encapsulated. Fine-needle aspiration revealed both myoepithelial and mesenchymal components, consistent with pleomorphic adenoma.

[0117] Total parotidectomy was performed in each of cases 1-3 above, using a tissue imaging system for improved intraoperative visualization of the facial nerve and its branches. The Avelino-Gutierrez incision was used in each patient. A superficial cervical fascial flap was created between the superficial musculoaponeurotic system layer and the parotid fascia until the anterior edge of the parotid gland was visible. At this point, the facial nerve trunk was identified and the facial nerve branches were dissected using a tissue imaging system to allow visualization of the surgical field under near ultraviolet (NUV) light. Under NUV light, the cervical facial and ascending branches and the length of these branches were brightly autofluorescent and therefore clearly identified. In all three patients, parotidectomy was completed and drainage tubes were placed without intraoperative complications, and both immediate postoperative and postoperative neurological examinations were normal. All three patients were discharged home on postoperative day 1 and remained free of complications or neurological deficits at the time of their final visit.

[0118] Example 2 - Thyroid Cancer Case 4: A 45-year-old woman was seen in our clinic with a symptom of a 1.1 cm subcutaneous nodule located on the right lateral side of the neck. Physical examination revealed a firm, painless nodule in the right lobe region of the thyroid gland that moved up and down when the patient swallowed. Ultrasound visualized a firm 11 x 20 mm nodule with multiple small calcifications and an indistinct border, heterogeneous shape. Serum thyroglobulin was elevated. FNA diagnosed papillary thyroid carcinoma, and further imaging subsequently showed disseminated metastases, consistent with Bethesda stage IV. The thyroid gland was surgically removed and the middle and lateral neck sections were dissected. During the surgical resection, both the laryngeal and hypoglossal recurrent nerves were brightly autofluorescent under NUV light and easily avoided. During the neck dissection, all nerves within the surgical field were again clearly identified throughout their course under NUV, and this degree of visualization was clearly of higher quality than that achieved under white light. .

[0119] Example 3 - Neurosurgery Case 5: A previously healthy 88-year-old male presented with severe lower back pain with a walking distance limit of approximately 500 meters without rest. His baseline examination revealed severe lower back tenderness over the L4 spinous process, but no neurological deficits. Both CT and MRI showed tumor invasion and resulting destruction of the L4 vertebra, along with soft tissue invasion into the epidural space. A percutaneous biopsy of the pedicle was performed, which showed non-Hodgkin's B-cell lymphoma. After considering various options, it was decided to perform a two-stage spinal surgery, with a first stage to decompress the spinal canal and a second stage to reconstruct and stabilize the lumbar spine, before initiating chemotherapy.

[0120] The surgery was performed under general anesthesia using a mini-open retroperitoneal approach with the patient in a right lateral decubitus position. The procedure was then performed in a 360° (ventro-dorsal) fashion, including instrumentation and posterior percutaneous instrumentation followed from L2 to the sacrum. For the second step involving the resection of the L4 vertebral body, the disc and tumor tissue of both L3-4 and L4-5 located ventrally in the spinal canal were resected after reconstruction of the anterior column using a titanium mesh prosthesis. A left anterolateral approach was adopted. The patient did not suffer any intraoperative or postoperative complications other than wound discomfort and had no postoperative pain. The patient was discharged on the third day after the second surgery and started chemotherapy within one week. The patient became fully ambulatory and pain-free.

[0121] Case 6: An infant suffered a right brachial plexus injury during a difficult birth. A six-month-old female infant, accompanied by her parents, was seen at our clinic with symptoms of flexion paresis at both the shoulder and elbow and was scheduled for reconstructive surgery using a sural nerve graft harvested from the contralateral lower leg to restore the affected brachial plexus and suprascapular nerve. The contralateral sural nerve, ipsilateral brachial plexus, phrenic nerve, and suprascapular nerve were all easily visualized throughout the surgical field under NUV light. The surgery proceeded without complications and the infant is currently undergoing rehabilitation.

[0122] A tissue imaging system is described herein. The tissue imaging system creates a visual image, either optically or digitally, such as a surgical field, and visualization of a target tissue region of the subject may include a formed highlighted image of neural tissue within the tissue region of the subject, such as a peripheral nerve or spinal dura, that is improved by the intrinsic autofluorescence or other inherent properties of the neural tissue, such as a peripheral nerve or spinal dura, in response to illumination with excitation light. The generated visual image includes a formed highlighted image of the neural tissue and a formed darker image of non-neural tissue adjacent to and / or surrounding the neural tissue. Filtering of the excitation light, emitted light, reflected light, or a combination thereof improves the visual image by further distinguishing the target tissue structure from surrounding fat, muscle, or connective tissue. The use of excitation light in the NUV wavelength region of about 300 nm to about 400 nm is particularly effective.

[0123] Prophetic exemplary applications for tissue imaging systems, such as thyroidectomy, as described above. Once the thyroidectomy is started, the thyroid lobes are exposed and the superior pedicles are ligated, the parathyroid glands are identified. The recurrent laryngeal nerve, close to the parathyroid glands, needs to be made clear with continued transection. The laryngeal nerve is at risk of injury. The surgeon's assistant positions the dendritic camera approximately 20 cm from the surgical field, which illuminates the nerve (healthy nerve tissue) and acquires autofluorescence images of its entire trajectory.

[0124] Guided by the autofluorescence from the nerve contrasted with light emitted or reflected by healthy non-nerve tissue adjacent to and / or surrounding healthy nerve tissue, the surgeon dissects and separates the return nerve from surrounding structures.

[0125] The dendritic camera is capable of distinguishing nerves from adjacent normal structures (healthy non-neural tissue) by means of illumination with light of a particular excitation wavelength range. The excitation light may be generated and emitted using one or more optical filters incorporated with a light source within the imaging system. At the same time, the processor, operating in response to the software, is capable of analyzing the different images formed from the light signals received from the tissue region of interest, blocking or significantly reducing the intensity of light signals that are not fluorescent light emitted from neural tissue, and increasing the resolution of structures (neural tissue) that glow with fluorescent light of a particular wavelength, e.g., light signals emitted from neural tissue, e.g., from nerves.

[0126] Robotic Prostatectomy A 30° lens that is part of the robotic platform is used for bladder neck dissection. The anterior bladder neck is divided to assess the location of the ureteral orifices and the presence of the middle lobe, followed by division of the posterior bladder neck. The vas deferens and seminal vesicles are then identified. The ducts are divided and the seminal vesicles are dissected in a non-cauterizing manner to avoid possible damage to the neurovascular bundle. The posterior layer of Denonvilliers fascia is divided to allow identification of perirectal adipose tissue, which acts as a guide between the prostate and the rectum. To optimize nerve sparing, the surgeon switches between white light and near-ultraviolet light using a dendritic camera (e.g., using a dendritic adapter attached to the rigid endoscope of the robotic arm), which allows the surgeon to see an image of healthy nerve tissue in the tissue area of ​​interest and distinguish healthy nerve tissue from normal healthy non-nerve tissue. Utilizing a dual mode combining white light and NUV light, the lateral prostatic fascia is incised on each side to allow the surgeon to visualize the neurovascular bundle (nerve tissue) from the normal non-nerve tissue adjacent to and / or surrounding the nerve tissue and drop posterolaterally to perform a bilateral nerve-sparing procedure.

[0127] The neurovascular bundle, which is visible and distinguishable from healthy non-neural tissue, is released distally to the level of the urethra and apex of the prostate when using NUV light. At this point, the only remaining attachments of the prostate were the dorsal venous plexus (DVC) and the urethra. The DVC and urethra are then divided, freed of the prostate, and the specimen is placed into a 10 mm end-cap bag.

[0128] Laparoscopic Nissen fundoplication The surgeon can visualize the upper abdomen after laparoscopic evaluation of the abdominal cavity and insufflation with carbon dioxide. To identify the gastroesophageal junction and avoid damage to the vagus nerve that could result in severe gastroparesis, the surgeon utilizes a dendritic camera with NUV light to identify the anterior and posterior vagus nerves and distinguish them from other normal healthy non-nervated soft tissue and vascular structures. This measure becomes even more important when the surgeon re-operates the area and the tissues are glued together by scar tissue. Here, the camera with NUV light can identify and track the nerves, preventing their severing.

[0129] Laparoscopic / Open Inguinal Hernia Repair When operating in the patient's groin with an open technique, the surgeon dissects the cord structures with white light to identify the hernia sac. The surgeon holds an open dendritic camera in his hand, which can be attached to a special arm (e.g., using a dendritic adapter attached to a rigid endoscope) and can switch from white light to NUV light using the dendritic camera, to identify the ilioinguinal nerve (nerve tissue) as well as the pudendal branch of the genitofemoral nerve while dissecting the cord, to prevent them from being transected by the surgeon or being included in the implanted mesh. Both can result in sensory loss or long-term incapacitating groin pain. The dendritic camera using the adapter is attached to the laparoscope, which, when operating with a laparoscope, projects onto a display monitor and allows the surgeon to visualize the image of the same structures in the tissue area of ​​interest, thereby preventing those nerve tissues from being damaged or blocked by the mesh.

[0130] Open / Laparoscopic / Robotic Pelvic Surgery When operating within the pelvic region (e.g., in colorectal surgery, gynecological or urological procedures), either openly by using a handheld Dendritic Camera device, or laparoscopically by using a Dendritic Camera with an adapter attached to an endoscope, or robotically by attaching the Dendritic Camera adapter to a robotic arm, the surgeon can dissect and remove anatomical structures utilizing the Dendritic Camera's NUV light, which identifies and protects nerves (nerve tissue) by distinguishing it from normal healthy non-nerve tissue adjacent to and / or surrounding it.

[0131] Open heart and open / thoracoscopic pulmonary surgery Phrenic nerve injury after cardiac surgery has a variable incidence depending on the care it requires. Final studies have shown that this complication is associated with cold-induced injury during cardioplegia planning and, if possible, mechanical damage during internal mammary artery harvesting. Outcomes are also variable and depend greatly on the patient's underlying condition, especially with regard to pulmonary function. Patient responses can range from asymptomatic radiological abnormalities to severe pulmonary insufficiency requiring prolonged mechanical ventilation and other associated morbidity and even mortality. The surgeon uses either a handheld open dendritic camera attached to a special arm or a thoracoscopic dendritic camera with an adapter attached to the thoracoscope to visualize the phrenic nerve (nerve tissue) and protect it from being transected when harvesting the mammary artery and / or opening the pericardium (which is adjacent to and / or surrounds the nerve tissue).

[0132] Upper and lower limb surgery When performing vascular, neurosurgical, plastic and / or orthopedic procedures, surgeons make large incisions in the skin to assess the anatomical compartments in order to perform the final procedure. During this procedure, the surgeon must distinguish between nerves (nerve tissue) and normal muscle and vascular structures (non-nerve tissue adjacent to and / or surrounding the nerve tissue). Holding the Dendritic Camera in a special arm or held by an assistant, the surgeon can illuminate with the NUV light emitted by the Dendritic Camera to identify the nerves (nerve tissue) and distinguish them from the normal surrounding soft tissue and vascular structures (non-nerve tissue adjacent to and / or surrounding the nerve tissue).

[0133] Neurosurgical Procedures Using a dendritic camera with a universal adapter attached to the microscope, the interaction between the images provided by the NUV camera and the real-time images captured by the microscope allows the surgeon to address separately the healthy non-nervous tissue and / or the neural structures (healthy neural tissue) involved or surrounded by neoplastic processes such as meningiomas, metastases, neurofibromatosis, etc. The NUV dendritic camera visualization of images of healthy neural tissue contrasted with adjacent and / or surrounding healthy non-nervous tissue, in combination with temperature and flow detectors, gives the surgeon the possibility to access sensory areas such as the cavernous sinuses and remove the invading processes, without restrictions, and with minimal healthy tissue destruction, evacuation.

[0134] Skull base surgery Protrusions into the skull base that invade or disrupt the dura are difficult to resect. Using the NUV dendritic camera, awareness of the dura (nerve tissue) facilitates dissection and resection, and even allows the surgeon to resect "within healthy boundaries" (non-nerve tissue adjacent to and / or surrounding healthy neural tissue), as in general surgery.

[0135] Spinal Surgery The use of the Dendritic Camera allows the surgeon to identify the dura (healthy neural tissue) by imaging the neural tissue in contrast to adjacent and / or surrounding healthy non-neural tissue, which provides the greatest likelihood for procedural success when using the Dendritic Camera within spine surgery.

[0136] Percutaneous discectomy The use of a dendritic camera with an adapter to an endoscope provides the surgeon with immediate tissue imaging feedback of the location of the nerve root (healthy nerve tissue) as opposed to the location of adjacent and / or surrounding healthy non-nerve tissue (by indirectly knowing the dural covering of the nerve), when approaching the spine with an endoscope, thus allowing unambiguous dissection from the surrounding ligamentum flavum and disc or bone material.

[0137] Thoracoscopic sympathectomy NUV imaging using a dendritic camera (e.g., using a dendritic adapter attached to a rigid endoscope) immediately shows the surgeon the location of the sympathetic chain and its collateral fibers (nerve tissue) as contrasted with the location of adjacent and / or surrounding healthy non-nerve tissue. This precise location of the nervous and non-nerve tissue is critical when performing a sympathectomy for hyperhidrosis.

[0138] Thoracoscopic discectomy The use of NUV illumination and a dendritic camera within the thoracic cavity (e.g., using a dendritic adapter attached to a rigid endoscope) gives the surgeon important information about the location of the sympathetic fibers (nerve tissue) versus the location of adjacent and / or surrounding healthy non-nerve tissue before entering the spinal canal and dura after opening the canal so that the spinal cord can be successfully decompressed.

[0139] Non-limiting Examples The present invention may be implemented as a system, method, and / or computer program product at any possible level of technical detail of integration. The computer program product may include a computer-readable storage medium having computer-readable program instructions thereon for causing a processor to perform aspects of the present invention.

[0140] A computer readable storage medium may be a contact-type device capable of holding and storing instructions for use by an instruction execution device. A computer readable storage medium may be, for example, but not limited to, an electronic storage device, a magnetic storage device, an optical storage device, an electromagnetic storage device, a semiconductor storage device, or any suitable combination of the above. A non-exhaustive list of more specific examples of computer readable storage media includes the following: portable floppy disks, hard disks, random access memory (RAM), read only memory (ROM), electrically erasable ROM (EPROM or flash memory), static RAM (SRAM), portable compact disk read only memory (CD-ROM), digital versatile disk (DVD), Memory Stick®, floppy disk, mechanical coding devices such as punch cards or ridge structures in grooves having instructions recorded thereon, and any suitable combination of the above. As used herein, a computer readable storage medium is not to be construed as a transitory signal per se, such as an electric wave or other propagable electromagnetic wave, an electromagnetic wave propagated through a waveguide or other transmission medium (e.g., light pulses passing through a fiber optic cable), or an electrical signal transmitted through an electrical wire.

[0141] The computer readable program instructions described herein can be downloaded from the computer readable storage medium to a respective computing / processing device or to an external computer or storage device via a network, for example, the Internet, a local area network, a wide area network, and / or a wireless network. The network can include copper transmission cables, optical fiber for transmission, wireless transmission, routers, firewalls, switches, gateway computers, and / or edge servers.

[0142] A network adapter card or network interface in each computing / processing device receives computer readable program instructions from the network and forwards the computer readable program instructions for recording in a computer readable storage medium in the respective computing / processing device.

[0143] The computer readable program instructions for carrying out the steps of the present invention may be either source code or object code written in any combination of one or more programming languages, including assembler instructions, Instruction Set Architecture (ISA) instructions, machine instructions, machine dependent instructions, microcode, firmware instructions, state setting data, configuration data for integrated circuits, or object oriented programming languages ​​such as Smalltalk, C++, and procedural programming languages ​​such as the "C" programming language or similar programming languages. The computer readable program instructions may be executed completely on the user's computer, partially on the user's computer as a stand-alone software package, partially on the user's computer, partially on a remote computer, or completely on a remote computer or server. In the latter case, the remote computer may be connected to the user's computer by any type of network, including a local area network (LAN) or wide area network (WAN), or may be connected to an external computer (e.g., by the Internet using an Internet Service Provider). In some embodiments, electronic circuitry including, for example, a programmable logic circuit, a field programmable gate array (FPGA), or a programmable logic array (PLA) may execute computer readable program instructions using state information of the computer readable program instructions to personalize the electronic circuitry to perform aspects of the invention.

[0144] Aspects of the present invention are described herein with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the invention. It will be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer readable program instructions.

[0145] These computer-readable program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to create a machine such that the instructions, executed by the processor of the computer or other programmable data processing apparatus, perform the functions / acts identified in the block(s) of the flowcharts and / or block diagrams. These computer-readable program instructions may also be stored in a computer-readable storage medium capable of directing a computer, programmable data processing apparatus, and / or other apparatus to function in a particular manner, such that the computer-readable storage medium having instructions stored therein comprises an article of manufacture including instructions that implement aspects of the functions / acts identified in the block(s) of the flowcharts and / or block diagrams.

[0146] The computer readable program instructions may also be loaded into a computer, other programmable data processing device, or other device to create a series of operational steps executed by the computer, other programmable device, or other device, such that the instructions executed by the computer, other programmable device, or other device perform the functions / acts identified in the block(s) of the flowcharts and / or block diagrams.

[0147] The flowcharts and block diagrams in the drawings illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to various embodiments of the present invention. In this regard, each block in the flowcharts or block diagrams may represent a module, segment, or portion of instructions that includes one or more executable instructions for performing a particular logical function. In some alternative implementations, the functions described in the blocks may occur out of the order described in the figures. For example, two blocks shown in succession may in fact be executed substantially simultaneously, or the blocks may sometimes be executed in the reverse order, depending on the functionality involved. It is also noted that each block of the block diagrams and / or flowchart diagrams, and combinations of blocks in the block diagrams and / or flowchart diagrams, may be executed by a dedicated hardware-based system that performs a particular function or function or executes a combination of dedicated hardware and computer instructions.

[0148] Although this specification may describe components and functions implemented in embodiments with respect to particular standards and protocols, the present invention is not limited to such standards and protocols. Each such standard represents a state-of-the-art example. Such standards are sometimes superseded by faster or more efficient equivalents having essentially the same functionality.

[0149] The example diagrams described herein are intended to provide a general understanding of the structures of the various embodiments, and are not intended to serve as a complete description of all elements and features of devices and systems that may utilize the structures described herein. Many other embodiments will become apparent to those skilled in the art upon reviewing the above description. Other embodiments are available and derivable therefrom, such that structural and logical substitutions and modifications are possible without departing from the scope of the present invention. The drawings are also for representational purposes only and may not be drawn to scale. Certain proportions thereof may be exaggerated, while others may be minimized. The specification and drawings are therefore to be regarded in an illustrative sense, rather than a limiting sense.

[0150] Although specific embodiments are illustrated and described herein, it should be understood that any arrangement contemplated to achieve the same purpose may be substituted for the specific embodiment shown. The examples herein are intended to cover any and all adaptations or variations of the various embodiments. Combinations of the above embodiments, as well as other embodiments not specifically described herein, are contemplated herein.

[0151] The Abstract is provided with the understanding that it is not intended to be used to interpret or limit the scope or meaning of the claims. Moreover, in the above Detailed Description, various features are grouped together in a single exemplary embodiment for the purpose of streamlining the disclosure. This method of disclosure is not to be interpreted as reflecting an intention that the claimed embodiments require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed embodiment. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as separately claimed subject matter.

[0152] Although a single processor is illustrated for the information processing system, information processing systems with multiple central processing units (CPUs) or processors can be used equally effectively. Various embodiments of the present invention can further incorporate interfaces, each including a separate, fully programmed microprocessor used to offload processing from the processor. Additionally, various embodiments can include an input user interface, and / or an output user interface. Examples of input user interfaces can include, but are not limited to, for example, a mouse, a keyboard, a keypad, a touchpad, or a microphone for receiving spoken commands and input data, and the like. Examples of output user interfaces can include, but are not limited to, for example, a display device, a light, a lamp, a touch-type output device, or a speaker for outputting audible signals and / or audio responses to received spoken commands and input data.

[0153] The operating system contained within the main memory for the processing system may be any suitable multitasking and / or multiprocessing operating system, including, but not limited to, any of the following: Linux, UNIX, Windows, and Windows server-based operating systems. Various embodiments of the present invention may use any other suitable operating system. Various embodiments of the present invention utilize an architecture, such as an object-oriented framework mechanism, in which instructions of the operating system components are executable on any processor located within the information processing system. Various embodiments of the present invention may be adapted to function with any data communication connection, including, but not limited to, modern analog and / or digital technologies, via wired, wireless, short-range wireless, wide-range wireless, optical, fiber optic, satellite, or future networking mechanisms.

[0154] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a," "an," and "the" are intended to include the plural meaning unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising," when used herein, specify the presence of the stated features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof. The term "another," as used herein, is defined as at least a second or more. The terms "including" and "having," as used herein, are defined as comprising (i.e., open-ended phrases). The term "coupled," as used herein, is defined as connected, although not necessarily directly, and not necessarily mechanically. "Communicatively coupled" refers to coupling components such that they can communicate with each other, for example, by wires, wireless or other communication medium. The terms "communicatively coupled" or "communicatively coupled" include, but are not limited to, communicating electronic control signals that may cause one element to move or control another element. The term "configured to" describes hardware, software or a combination of hardware and software that is set up, arranged, assembled, made of, configured, designed or has any combination of these characteristics to perform a particular function. The term "adapted to" describes hardware, software or a combination of hardware and software that is capable of housing, making, or suitable to perform a particular function.

[0155] The terms "controller," "computer," "processor," "server," "client," "computer system," "computing system," "personal computing system," "processing system," or "information processing system" describe an example of a suitably configured processing system adapted to carry out one or more embodiments of the present disclosure. Any suitably configured processing system may be similarly used with the embodiments of the present disclosure, including, but not limited to, personal computers, laptop personal computers (laptop PCs), tablet computers, smart phones, mobile phones, wireless communication devices, handheld terminals, workstations, and the like. A processing system may include one or more processing systems or processors. A processing system may be realized in a centralized manner within one processing system, or in a distributed manner where different elements are distributed across several interconnected processing systems. The corresponding structures, materials, acts, and equivalents of all means or steps and functional elements within the scope of the following claims are intended to include any structures, materials, or acts for performing the functions in combination with other claimed elements as specifically recited in the claims.

[0156] The description of this application has been presented for purposes of illustration and description, but is not intended to be exhaustive or to limit the invention to the disclosed form. Many modifications and variations will be apparent to those skilled in the art without departing from the scope of the invention. The present embodiment has been selected and described in order to best explain the principles and practical applications of the invention and to enable others skilled in the art to understand the invention for various embodiments with various modifications as appropriate for the specific use envisioned.

Claims

1. 1. A method for a neural tissue imaging system, comprising: selectively switching on an excitation light source; optically coupling excitation light from the excitation light source into a light source optics and optically filtering the excitation light to pass only excitation light signals within a first wavelength range of 365 nm to 400 nm; uniformly illuminating a tissue region of the target with the excitation light emitted from the light source optics such that healthy neural tissue within the tissue region of the target intrinsically autofluoresces and emits first autofluorescent light at a first intensity in a second wavelength range of 433 nm to 450 nm in response to being illuminated with the excitation light; selectively illuminating the illumination light sources; optically coupling illumination light from the illumination light source into a second array of light sources and optically filtering the illumination light to pass only illumination light signals with wavelengths outside of the first wavelength region and outside of the second wavelength region, thereby emitting visible illumination light from the second array of light sources, and directing the visible illumination light emitted from the second array of light sources to illuminate a tissue region of interest within a surgical field of a patient's body; receiving, by a receiving array, an optical signal comprising the first autofluorescent light emitted from healthy neural tissue within a tissue region of interest; optically filtering the received optical signal to pass only the optical signal at wavelengths in the second wavelength range; and optically coupling the optically filtered received optical signal to a camera device.

2. 2. The method of claim 1, further comprising the step of capturing image data of the optically filtered received optical signal, the image data including the first autofluorescence light emitted from healthy neural tissue and received by the light receiving train, by the camera device.

3. 3. The method of claim 2, further comprising displaying, on a display screen in real time, an image showing healthy neural tissue versus healthy non-neural tissue surrounding the healthy neural tissue in a tissue region of interest within the surgical field of the patient's body based on the captured image data.

4. performing image processing of the image data captured by the camera device; overlaying the first image of autofluorescent light emitted from healthy neural tissue with images of surrounding healthy non-neural tissue within the tissue region of interest to create a composite image of the tissue region of interest; 3. The method of claim 2, further comprising the step of displaying in real time on a display screen a composite image showing healthy nerve tissue contrasted with surrounding healthy non-nerve tissue in a tissue region of interest within the surgical field of the patient's body.

5. The method of claim 1 , wherein the first wavelength range is from 382 nm to 392 nm.

6. 1. A method for a neural tissue imaging system, comprising: selectively switching on an excitation light source; optically coupling excitation light from the excitation light source into a light source optics and optically filtering the excitation light to pass only excitation light signals within a first wavelength range of 365 nm to 400 nm; directing the excitation light emitted from the light source optics to uniformly illuminate a tissue region of a target, thereby causing healthy neural tissue within the tissue region of a target to intrinsically autofluoresce and emit a first autofluorescent light at a first intensity in a second wavelength range of 433 nm to 450 nm in response to being illuminated with the excitation light; receiving, by a receiving array, an optical signal comprising the first autofluorescent light emitted from healthy neural tissue in a tissue region of interest; optically filtering the received optical signal to pass only the optical signals having wavelengths within the second wavelength region; and optically coupling the optically filtered received optical signal to a camera device.

7. 7. The method of claim 6, further comprising the step of capturing image data of the optically filtered received optical signal including the first autofluorescent light emitted from the healthy neural tissue and received by the light receiving train with the camera device.

8. 10. The method of claim 7, further comprising displaying, on a display screen in real time, an image showing healthy neural tissue versus healthy non-neural tissue surrounding the healthy neural tissue in a tissue region of interest within the surgical field of the patient's body based on the captured image data.

9. performing image processing of the image data captured by the camera device; overlaying the first image of autofluorescent light emitted from healthy neural tissue with an image of surrounding healthy non-neural tissue to create a composite image of the tissue region of interest; 10. The method of claim 7, further comprising displaying in real time on a display screen a composite image showing healthy neural tissue versus surrounding healthy non-neural tissue within a tissue region of interest within the surgical field of the patient's body.

10. The method of claim 6, wherein the first wavelength range is from 382 nm to 392 nm.

11. 1. A method for a neural tissue imaging system, comprising: selectively switching on an excitation light source; optically coupling excitation light from the excitation light source into a light source optics and optically filtering the excitation light to pass only excitation light signals within a first wavelength range of 365 nm to 400 nm; uniformly illuminating a tissue region of the target with the excitation light emitted from the light source optics such that healthy neural tissue within the tissue region of the target intrinsically autofluoresces and emits first autofluorescent light at a first intensity in a second wavelength range of 433 nm to 450 nm in response to being illuminated with the excitation light; selectively illuminating an illumination source; optically coupling illumination light from the illumination source into a second light source optics and optically filtering the illumination light to pass only illumination light signals having wavelengths longer than the second wavelength range, thereby emitting visible illumination light from the second light source optics, and directing the visible illumination light emitted from the second light source optics to illuminate a tissue region of interest within a surgical field of a patient's body; selectively switching off the illumination source; receiving, with the illumination light source turned off, an optical signal including the first autofluorescent light emitted from healthy neural tissue in a target tissue region by a receiving optical system; optically filtering the received optical signal to pass only the optical signal having a wavelength in the second wavelength range; and optically coupling the optically filtered received optical signal to a camera device.

12. 12. The method of claim 11, further comprising the step of capturing image data of the optically filtered received optical signal, the image data including the first autofluorescent light emitted from healthy neural tissue and received by a receiver array, by the camera device.

13. 13. The method of claim 12, further comprising displaying, on a display screen in real time, an image showing healthy neural tissue versus healthy non-neural tissue surrounding the healthy neural tissue in a tissue region of interest within a surgical field of a patient's body based on the captured image data.

14. performing image processing of the image data captured by the camera device; overlaying the first image of autofluorescent light emitted from healthy neural tissue with images of surrounding healthy non-neural tissue within the tissue region of interest to create a composite image of the tissue region of interest; 13. The method of claim 12, further comprising displaying in real time on a display screen a composite image showing healthy neural tissue versus surrounding healthy non-neural tissue within a tissue region of interest within the surgical field of the patient's body.

15. The method of claim 11, wherein the first wavelength range is from 382 nm to 392 nm.

16. 1. A method for a neural tissue imaging system, comprising: selectively switching on an excitation light source; optically coupling excitation light from the excitation light source into a light source optics and optically filtering the excitation light to pass only excitation light signals within a first wavelength range of 365 nm to 400 nm; uniformly illuminating a tissue region of the target with the excitation light emitted from the light source optics such that healthy neural tissue within the tissue region of the target intrinsically autofluoresces and emits first autofluorescent light at a first intensity in a second wavelength range of 433 nm to 450 nm in response to being illuminated with the excitation light; selectively illuminating the illumination light sources; optically coupling illumination light from the illumination light source into a second array of light sources and optically filtering the illumination light to pass only illumination light signals with wavelengths outside of the first wavelength region and outside of the second wavelength region, thereby emitting substantially white visible illumination light from the second array of light sources, and directing the substantially white visible illumination light emitted from the second array of light sources to illuminate a tissue region of interest within a surgical field of a patient's body; receiving, by a receiver array, the optical signal comprising the first autofluorescent light emitted from healthy neural tissue within a tissue region of interest; optically filtering the received optical signal to pass only the optical signal at wavelengths in the second wavelength range; and optically coupling the optically filtered received optical signal to a camera device; capturing image data of the optically filtered received optical signal with a camera device, the image data including the first autofluorescent light emitted from healthy neural tissue and received by the light receiving array; performing image processing of the image data captured by the camera device; overlaying the first image of autofluorescent light emitted from healthy neural tissue with images of surrounding healthy non-neural tissue within the tissue region of interest to create a composite image of the tissue region of interest; and displaying in real time on a display screen a composite image showing healthy nerve tissue contrasted with surrounding healthy non-nerve tissue in a tissue region of interest within a surgical field of the patient's body.

Images