Method for an advanced neural 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, for identifying and visually imaging 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 surgical techniques and equipment over recent decades, surgeries continue to be associated with an unacceptable number of iatrogenic injuries. Advanced surgical techniques, such as minimally invasive robotic surgery, appear to have, in some cases, actually increased the risk of certain injuries. Among these injuries, iatrogenic damage to nerves and other neural tissues, such as the dura mater, is among the worst, exposing patients to both short- and long-term risks of severe motor and sensory impairments. These injuries are also alarmingly common, 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 injuries to avoid unintentional nerve damage or to repair it intraoperatively during surgical procedures requires accurate identification and careful dissection of nerves and neural tissues, both of which present challenges when using standard visualization techniques. Consequently, the ability to accurately identify sensory and motor nerves, as well as the dura mater, during surgical procedures is crucial for injury prevention. Summary of the Invention [Problem to be solved by the invention]

[0004] Clear and reliable visualization of peripheral nerves and the dura mater, distinguishing and contrasting them from surrounding normal, non-neural, 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 surgeon's experience and training. Iatrogenic injury to peripheral motor and sensory nerves, as well as central nervous tissue such as the dura mater, causes disability that reduces patients' quality of life and places a considerable burden on the healthcare system. However, despite a surgeon's extensive academic and practical training and years of experience, iatrogenic nerve injury can occur because anatomical variations or the presence of pathology interfere with 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 mater. 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 interpreting the radiological image and visualizing human tissue with white light during surgery, which further increases the probability of error.

[0006] Fluorescence imaging, coupled with specialized fluorescent dyes / probes equipped with antibodies that indiscriminately attach to nerves, has proven successful in preclinical and clinical studies, helping surgeons identify peripheral nerves and / or the dura mater during surgery. However, labeling target tissues by administering or applying exogenous fluorescent substances, such as fluorescent agents, dyes, fluorescent markers, or fluorescent tissue probes, to patients, such as for labeling peripheral nerves, presents challenges. While most fluorescent tissue probes and 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). While several fluorescent dyes have been approved for clinical use, most require lengthy preparation, are expensive, require limited doses to mitigate toxicity, have short in vivo half-lives, can cause severe or fatal allergic reactions, and require precise timing of administration. Despite the potential for unpredictable side effects mentioned above, unless a fluorescent marker or dye is highly specific for neural tissue, it can actually cover peripheral nerves by enhancing the surrounding non-neural tissue, making visualization of peripheral nerves and / or the dura mater even more difficult. Nonspecific or competitive binding of exogenous fluorescent substances to neural tissue and / or surrounding non-neural tissues can result in low signal-to-background ratios and / or limited dynamic ranges when attempting to detect the tissue of interest. Furthermore, differences in fluorescence observed between tissues after administration of a fluorescent dye or marker may be the result of differences in tissue perfusion rather than differential uptake by different tissue types. Arteries perfusing peripheral nerves are significantly smaller than arteries perfusing other anatomical structures, which can accentuate differences in fluorescence resulting from perfusion differences.

[0007] In response to at least the above-mentioned problems, the 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, there is a need for improved visual imaging of tissues, particularly peripheral nerves and dura mater, without the need for fluorescent dyes, fluorescent tissue probes, or other fluorescent markers to increase the visual contrast between the nerves / dura mater and the non-nerve tissues surrounding the nerves / dura mater. This necessary visual contrast would allow for clear intraoperative visualization of the nerves / dura mater 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 are 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 range in the near-ultraviolet range to illuminate a tissue region of interest including healthy neural tissue and healthy non-neural tissue. The excitation light is 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 response to illumination with the excitation light. The healthy non-neural tissue, in response to illumination with the excitation light, avoids emitting any autofluorescent light in the second wavelength range or intrinsically autofluoresces and emits second autofluorescent light in the second wavelength range at a second intensity 50% lower than the first intensity.

[0011] The method includes irradiating a tissue region of interest, including healthy neural tissue and healthy non-neural tissue, with excitation light in a first wavelength range in the near-ultraviolet range. The method also includes capturing, with a camera, image data of endogenous autofluorescence light emitted from the healthy neural tissue at a first intensity in a second wavelength range in the visible light range. The method also includes capturing, with the camera, image data of optical signals received from the healthy non-neural tissue simultaneously with capturing the image data of the endogenous autofluorescence light emitted from the healthy neural tissue at a first intensity in the second wavelength range, wherein the healthy non-neural tissue, in response to being illuminated with the excitation light, at least one of: intrinsically autofluorescing and avoiding emitting any autofluorescence light in the second wavelength range; or intrinsically autofluorescing and emitting 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 interest and a second image of the healthy non-neural tissue in the tissue region of interest. The method includes displaying the first image and the second image on a display device, where the first image is contrasted with (differentiated from) 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 numerals refer to identical or functionally similar elements throughout the different drawings, are incorporated into and form a part of this specification, together with the following detailed description of the invention, and serve to further illustrate various embodiments and explain various principles and advantages all in accordance with the present disclosure. [Brief explanation 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. [Figure 2] FIG. 2 is a diagram of an exemplary interrogator suitable for use in the tissue imaging system of FIG. [Figure 3] FIG. 3 is a cross-sectional side view of the exemplary interrogator of FIG. 2 shown in an exemplary examination 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. [Figure 5] FIG. 5 is a perspective view of an exemplary control device 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 using 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 tissue 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 a diagram of some components of a first exemplary tissue imaging system, according to various embodiments. [Figure 13] FIG. 13 is a diagram of some 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 a 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 INVENTION

[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. Accordingly, specific structural and functional details described herein are intended, but not limited, to serve solely as a basis for the claims and as a representative basis for directing those skilled in the art to variously use the disclosed inventive subject matter in almost any proprietary structural and functional detail. Furthermore, the terms and phrases used herein are intended to provide understandable descriptions, but not to be limiting. Furthermore, unless otherwise specifically stated or clearly understood from the context of use, terms used herein will be described as singular and / or plural of the term.

[0015] introduction The ability to accurately identify nerves / dura mater and thereby safely separate them must be considered a high priority for surgeons. Furthermore, if nerves / dura mater are damaged during a procedure, detecting and repairing them is critically important. Most, if not all, serious structural tissue disruption and nerve / dura mater injuries occur in the surgical environment. Surgeons' knowledge of complex anatomical structures and the use of standard visual aids is often insufficient to avoid such injuries, regardless of their level of expertise. Nerve axon / dura mater injuries, including traction and partial or complete transection, are serious common complications associated with various surgical procedures. Such surgical procedures include, but are not limited to, brain and spine surgery, colon resection, thyroidectomy, parathyroidectomy, parotidectomy, coronary artery bypass graft (CABG), inguinal hernia repair, open-heart surgery, and breast cancer surgery, affecting up to 20% of patients. Although many iatrogenic neurological disorders resulting from surgical injuries improve with conservative treatment and physical therapy, some disorders 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, endogenous tissue autofluorescence offers the distinct advantage of providing real-time imaging without requiring invasive techniques or exposing patients to potentially unsafe compounds. Furthermore, the fluorescent dyes and fluorescent tissue probes utilized in most studies conducted to date regarding nerve identification are often difficult to obtain. They all rely 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 within the human body during surgical procedures and to develop corresponding techniques that utilize autofluorescence in the operating room in order 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 nervous 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 nervous tissue (any nerve / peripheral nerve / dura mater) by an integrated tissue imaging system in an apparatus configured for operating room use. According to various embodiments, the intrinsic autofluorescence of neural tissue is induced or elicited by the emission of an excitation electromagnetic signal (which may also be referred to as excitation light, excitation optical signal, etc.) and by the illumination of a tissue region of interest (under examination) to emit a fluorescent signal (which may also be referred to as fluorescent light, fluorescent optical 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 and bandpass optical filters that selectively transmit excitation light in the near ultraviolet (NUV) region, to significantly remove reflected light from the fluorescent light emitted into the neural tissue (and remove other possible interfering emitted electromagnetic signals), increases the perceived level of neural / dural autofluorescence, thereby increasing the visual contrast of the neural tissue from surrounding non-neural tissue.

[0018] Various embodiments of the disclosed invention are a means of altering the rate and severity of iatrogenic nerve 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 refer to a system of devices and components utilized to improve visualization of specific tissue structures, such as peripheral nerves / dural tissue, from surrounding healthy, non-pathological, or non-cancerous tissue. However, it is understood that a nerve / dural imaging system may, in some embodiments, be used to visualize non-nerve structures or tissues.

[0021] As used herein, the term "medical device" means an instrument, apparatus, implement, machine, instrument, 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] As used herein, the term "peripheral nerve" refers to a motor, sensory, autonomic, or mixed-function nerve that resides outside the brain or spinal cord proper. For purposes of this disclosure, "peripheral nerve" includes cranial nerves outside the dura mater surrounding the brain. "Peripheral nerve" also includes mixed spinal nerves and spinal ganglia, whether outside or surrounded by the spinal dura mater (dural sac). Some non-limiting examples of "peripheral nerve" 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 terms "spinal dura mater," "dura," "duramadre," or "dural sac" refer to the 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 specific 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 wavelength range. A wavelength range may be discrete and may be continuous or discontinuous.

[0023] As used herein, the term "emitted light" refers to electromagnetic radiation of a distinct wavelength or range of wavelengths emitted by a cell, tissue, or anatomical structure in response to irradiation 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 the source of reflected excitation light or ambient light. "Emitted light" results from the intrinsic properties of atoms, molecules, or the specific arrangement of atoms and molecules that form the cell, tissue, or anatomical structure.

[0024] As used herein, the term "excitation light" means 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," sometimes 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-pass (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 that is 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 passes to a receiving train. "Reflected light" is not "emitted light" as in "emitted light," which is separately defined herein.

[0029] As used herein, the term "nerve tissue" 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] As used herein, the term "healthy nervous tissue" is intended to mean nervous tissue, as defined herein, that is non-cancerous and non-pathological tissue.

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

[0032] As used herein, the term "healthy non-neural tissue" 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 clinical settings, such as hospitals, ambulatory surgery centers, etc. In some embodiments, a surgeon or healthcare practitioner may use the tissue imaging system in combination with additional imaging devices, such as ultrasound, fluoroscopy, or other conventional imaging devices. The tissue imaging device operates alone or with other such imaging devices and, in some embodiments, may be used to help the surgeon distinguish nervous tissue from other anatomical structures and surrounding non-nerve tissue, reducing the risk of damage to nervous tissue, such as nerves, peripheral nerves, dura mater, etc. In some embodiments, the tissue imaging device 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 a tissue imaging system is advantageous or desirable.

[0034] No fluorescent markers, fluorescent tissue probes, or fluorescent dyes are used in nervous tissue. The tissue imaging system creates a visual image of a target tissue, such as a 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, or fluorescent tissue probes, whether applied topically or administered (orally or parenterally). Typically, nervous tissue, such as peripheral nerves, inherently fluoresces upon illumination with excitation light differently from surrounding healthy non-nerve tissue, e.g., normal / non-pathological / non-cancerous tissue, depending on the wavelength and intensity of the excitation light, light filtering means, and image processing techniques. The system utilizes contrasting levels of fluorescence to distinguish nervous tissue, such as peripheral nerves / dura mater, from surrounding non-nerve tissue, particularly 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 nervous tissue, such as nerves / peripheral nerves / dura mater, that intrinsically autofluoresces in response to incident excitation light at a higher intensity (brightness) within the wavelength range of the visible light range, distinct from the autofluorescence (if any) of adjacent and / or surrounding background non-neural tissue within the tissue region of interest and distinct from the reflected light, if any, for the tissue region of interest. 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, if possible, 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 nervous tissue highlighted by the tissue imaging system, such as in white or another color (see, e.g., image 802 in FIG. 8 ), and a second image 804 of healthy non-nerve tissue adjacent to and / or surrounding the first image of nervous tissue within the tissue region of interest (see, e.g., image 804 in FIG. 8 , which is a significantly darker image contrasted with 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 between the first and second images indicates the location of the healthy nervous tissue relative to the adjacent and / or surrounding healthy non-nerve 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 control and 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 interest 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 (intensity) in a second wavelength range in the visible light range in response to illumination by the excitation light, and further, the healthy non-neural tissue, in response to illumination by the excitation light, 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. 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 described herein below.

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

[0039] Some embodiments of the tissue imaging system include a data processor and a software package residing on the memory. The software package moves an excitation light source via the data processor to emit light at a specific wavelength or range of wavelengths at or within the patient's 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 are specific to the specific tissue type and structure. More specifically, nerve tissue, such as nerves / peripheral nerves / dura mater, including nerve tissue, emits light at a specific and specific wavelength or range of wavelengths (hereinafter "emitted light") when stimulated or excited (e.g., autofluorescence). Such emitted light can be due to fluorescence ("fluorescent light"), other phenomena, or fluorescence 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 light emitted from at least healthy neural tissue, such as the nerve / dura, as compared to light emitted from or reflected by adjacent and / or surrounding healthy non-neural tissue, and generate a corresponding data signal. The data signal, representing an image of the neural tissue, e.g., the nerve / dura, as emitted light, as compared to a background image of light emitted from or reflected by adjacent and / or surrounding healthy non-neural tissue, is transmitted to an image display device for visualization by a user. Full details of tissue imaging systems 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 tissue imaging system 100, according to various embodiments. FIG. 1 illustrates tissue-imaging system 100, which, in some embodiments, is a nerve-tissue imaging system configured for intraoperative imaging of peripheral nerves. 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, system 100 includes various components for generating illumination light (e.g., white light or "near" white light) that can illuminate relevant structures and tissues within the tissue region of interest.

[0041] In response to illuminating a tissue region of interest, 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-nervous tissue and nervous tissue (e.g., nerves / peripheral nerves / dura mater) within the tissue region of interest; 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-nervous tissue due to fluorescence or other intrinsic properties in response to radiant energy received by the excitation light illuminating the tissue region of interest.

[0042] In response to illuminating a target tissue region 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 nervous and non-nerve tissue within the target tissue region, and (2) possible emitted light that is light (electromagnetic radiation signals) emitted by non-nerve tissue due to fluorescence or other inherent properties in response to radiant energy received by the illuminating light illuminating the target tissue region.

[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 further described in more detail below.

[0044] System 100 also includes, in some embodiments, a controller 140 that houses components such as a processor 142 (see, e.g., FIG. 4 ) and a user interface 146. In some embodiments, as in the example shown in FIG. 1 , the elements of system 100 are electrically and communicatively coupled to each other by cables, such as first cable 126 and second cable 151. 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 can visualize an image of the examined tissue region (the examined tissue region) that may, through contrast imaging, indicate the location of healthy nervous tissue in contrast to adjacent and / or surrounding healthy non-nerve tissue. See, for example, FIG. 8, which shows an image display displaying a formed image of healthy nervous tissue 802 (highlighted in white or another color in FIG. 8) in contrast to adjacent and / or surrounding healthy non-nerve tissue 804 (a much darker image that contrasts with the highlighted image 802 in FIG. 8).

[0046] The depiction of the various devices forming system 100 shown in FIG. 1 is by way of example only, and additional configurations of interrogation device 120, controller 140, and 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 , first cable 125 communicatively and electrically couples interrogation device 120 to controller 140, and second cable 151 communicatively and electrically couples visual display device 150 to controller 140. This is an illustrative example only and is not intended to be limiting. In some embodiments, interrogation device 120 is “freestanding” and has an internal power source and wireless communication means for wirelessly exchanging instructions and data with controller 140. Similarly, visual display device 150, in some embodiments, includes an internal or other separate power source and wireless communication means for wirelessly communicating image data and other information with 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 nickel-cadmium battery, nickel-metal hydride battery, nickel-zinc battery, lithium-ion battery, or other suitable rechargeable energy storage device.

[0048] Embodiments of system 100 that do not include first cable 126 may have wireless communication means that wirelessly communicatively couples interrogator 120 to controller 140. Some embodiments of system 100 that do not include second cable 151 may have wireless communication means that wirelessly communicatively couples visual display 150 to 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 an interrogator 120 of tissue imaging system 100. FIG. 3 is a side view of an embodiment of an interrogator 120 of tissue imaging system 100. As in the embodiment shown in FIGS. 2 and 3, interrogator 120, in some other embodiments, comprises a housing 121 configured to house electronic, optical, and related elements configured to provide tissue illumination and collection of light from the irradiated tissue region of interest. Housing 121 is formed from medical-grade materials and configured for use in a sterile surgical environment. In some embodiments, housing 121 is configured for gas sterilization, such as using ethylene oxide, ozone, or other gases suitable for sterilizing sensitive electronic medical equipment that may be destroyed by heat-based sterilization systems and techniques. In some embodiments, housing 121 is not configured for sterilization, but uses a protective coating that covers and at least partially encapsulates housing 121, allowing interrogator 120 to be used in a sterile disposable bag or in a sterile operating room environment. Elements contained within and coupled to housing 121, in some embodiments, include excitation light source 102, illumination light source 103, light source array 116, light receiving array 117, camera 122 (see FIG. 4), and handle 125. In some embodiments, first cable 126 electrically, communicatively, or electrically and communicatively couples interrogator 120 to controller 140. 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 interrogator 120.

[0051] In some embodiments, the interrogator 120 is arranged and configured as shown in FIGS. 2 and 3. The handle 125 is coupled to the housing 121 spaced apart 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, in some embodiments, unitary with the housing 121. The first cable 126, in some embodiments, enters the interrogator 120 via the handle 125 to maintain the first cable 126 out of the line of sight between the distal end 127 and the target tissue region to be illuminated and visualized. In some embodiments, the light source array 116 and the light receiving array 117 are arranged alongside each other within the housing 121 in a configuration similar to that shown in FIG. 3. The depiction of the light source array 116 and the light receiving array 117 within the housing 121 in FIG. 3 is for illustration and is provided by way of example; other configurations of the light source array 116 and the light receiving array 117 are within the scope of this disclosure.

[0052] For example, in some embodiments of system 100, 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 distal end 127 shown in FIG. 2. In this and other embodiments including an array of light source arrays 117, target tissue region 104 may be more brightly and evenly illuminated with excitation light 110. Brighter, more even illumination may reduce light shadowing effects, which may improve visualization of target tissue region 104 by system 100. Other and any number of arrangements, patterns, or arrays including any number of light source arrays 117 are considered within the scope of the present disclosure, without limitation.

[0053] In some embodiments, excitation light source 102 (see FIG. 4 ) is disposed within housing 121. Optionally, in certain embodiments, illumination light source 103 (see FIG. 4 ) is disposed within housing 121. In some embodiments, illumination light source 103 comprises a source of “white” light (or nearly white light) in a broad electromagnetic radiation signal wavelength-range, such as, for example, a halogen (xenon) lamp, a 450-watt xenon lamp, a tungsten-halogen lamp, or a mercury arc lamp. In certain embodiments, the illumination light emitted from 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 fluorescence effects or other intrinsic properties of neural tissue within 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 light source 103), emitted light 112, and, if applicable, non-emitted ambient light, are collected by light receiving array 117 of interrogator 120.

[0054] In some alternative embodiments, the excitation light source 102 (see FIG. 4) is located remotely 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 "freestanding" 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 with the first cable 126, or may be mechanically and 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 the 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 a wide wavelength range of the electromagnetic radiation signal, such as, for example, a halogen (xenon) lamp, a 450 watt xenon lamp, a tungsten-halogen lamp, or a mercury arc lamp.

[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 excitation light 110 at a particular wavelength to stimulate or excite neural tissue within the target tissue region 104 due to, for example, the inherent autofluorescence effect of neural tissue. Because the effect is inherent, i.e., an intrinsic property or composition of the tissue, and originates entirely within neural tissue, fluorescent (or other) dyes, fluorescent markers, fluorescent tissue probes, etc. are not required or used in the operation of the tissue imaging system 100.

[0057] In some embodiments, excitation light 110 at a wavelength generated by excitation light source 102, which may be optically coupled through an optical filter, 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 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 within the tissue region of interest and a darker, non-highlighted 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 within the tissue region of interest. A highly noticeable difference between 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, non-highlighted image corresponding to the absence (or minimal presence) of fluorescence effects and reduced reflected light from adjacent and / or surrounding non-neural tissue, improves visualization of the neural tissue in contrast to the neural tissue adjacent to or surrounding the neural tissue within the tissue region of interest (under examination). This contrasting visualization of nervous and non-nervous tissue within a tissue region of interest can provide important information to assist, for example, a surgeon in performing a surgical procedure on a patient. For a striking example of this contrast, compare the image of the surgical field of view in FIG. 19 with the image of the surgical field of view shown in FIG. 20 , according to various alternative embodiments. In FIG. 19 , under ambient white light conditions, it is very difficult to distinguish the presence of nervous tissue 1902 from the non-nervous tissue adjacent to and / or surrounding the nervous tissue. In FIG. 20 , using an exemplary embodiment of tissue imaging system 100, a highlighted image of nervous tissue 2002 is clearly observable against a darker background image of the non-nervous tissue adjacent to and / or surrounding 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 target tissue region. The light source array 116 may be proximate to 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, split, and move the excitation light 110 for illumination of the target tissue region 104. In some embodiments, the excitation light source 102 directly illuminates the target tissue region 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, separate from the interrogator 120. In some embodiments, the light source array 116 comprises 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 from surrounding healthy non-neuronal tissue, while causing healthy neural tissue to produce emitted light (fluorescent light) 111, which may be in a narrow, limit, band-passed range of wavelengths due to intrinsic autofluorescence effects. In particular, any minimal fluorescence emission from surrounding healthy non-neuronal tissue will emit other light outside the narrow, limit, band-passed range of wavelengths of the emitted light 111 from the neural tissue. In some embodiments, 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 illumination light source 103 shown in FIG. 4 ) and, accordingly, any reflected light from the target tissue region 104, can be rejected or significantly reduced from the narrow, limit, band-passed range of wavelengths of the emitted light 111 from the neural tissue. Additionally, by using one or more optical filters optically coupled to the light receiving array and the light detection device (e.g., an imaging camera device), any excitation light 110 may be rejected or significantly 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 significantly 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 array or the light receiving array, may improve the 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 pumped sources. Thus, in some embodiments, excitation filter 111 is a bandpass filter.

[0062] In some embodiments, excitation filter 111 can be a low-pass (long-pass) filter. In some embodiments, excitation filter 111 is a high-pass (short-pass) filter. In some embodiments, excitation filter 111 is a bandpass filter from about 382 nm to about 392 nm. In some embodiments, excitation filter 111 includes a high-pass (short-pass) filter of about 300 nm. In some embodiments, excitation filter 111 includes a low-pass (long-pass) filter of about 400 nm. In some embodiments, excitation filter 111 is a bandpass filter from about 300 to about 400 nm. In some embodiments, excitation filter 111 is a bandpass filter from about 320 to about 380 nm. In some embodiments, excitation filter 111 is a bandpass filter from about 325 nm to about 375 nm. In some embodiments, 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 FIGS. 15 and 16 illustrate various exemplary embodiments of a camera imager or dendrite camera device. The camera 1500, as shown in FIG. 15, comprises a camera housing and a light receiving train including a lens 1502, possibly including one or more optical filters 1502 with or adjacent to the lens in certain embodiments. FIG. 16 illustrates an example of a tissue imager 1600, which may also be referred to as a dendrite camera. The tissue imager 1600 is manageable by its handle 1606. The tissue imager 1600, in this example, comprises a ring portion containing multiple light sources and possibly one or more sensors / detectors / camera devices. The lens / filter 1604 is located within a central region of the ring portion and is a component of a 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 within the tissue imager 1600. The light signals are moved through the lens / filter 1604 to selectively emit the light signals to a tissue region of interest.

[0064] 17 and 18 illustrate exemplary components of a tissue imaging system, according to various embodiments. An exemplary camera imager 1700, also referred to as a dendrite camera device, is shown in FIG. 17. This exemplary camera imager 1700 is user-operable. 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 coupling an optical signal from the at least one light source 1706 through one or more lenses and filters. A camera block 1708 includes a computer interface that couples camera electronic input and output signals via an Ethernet cable to the computing system 1800. The camera 1708 also includes a receiver array that includes one or more detection filters and / or lenses 1710. The computing system 1800 includes an information processing 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, which 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, which possibly includes 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, producing emitted light 112. The emitted light 112 originates 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 light receiving array 117 of the interrogator 120 in some embodiments of the system 100.

[0067] FIG. 11 shows examples of various types of light that can be applied to 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 the 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 inherent 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 specific wavelengths. The unique properties of neural tissue, which may be autofluorescent when excited with ultraviolet light of specific wavelengths, may differ significantly from other non-neural tissues within a patient's body. The inventors have observed that, under certain lighting conditions, a tissue region of a subject containing healthy neural tissue and healthy non-neural tissue can emit highly intense endogenous 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. Nervous tissue is believed to intrinsically autofluoresce in response to illumination with excitation light 1110 comprising wavelengths in the aforementioned range. The wavelength of the endogenous autofluorescent light 1111 that is believed to be most intense 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 (about 382 nm to about 392 nm) as the excitation light 1110. 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 within 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 filtering out 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, light receiving train 117 includes a single optical lens or multiple optical lenses and is configured to focus and transfer light, including emitted light 112, to camera 122 (see FIG. 4 ). In some embodiments, light receiving train 117 includes a single focusing lens. In some embodiments, light receiving train 117 includes multiple (any number, combination, and arrangement) focusing lenses and possibly diverging lenses configured to at least focus emitted light 112 to camera 122. Some embodiments of system 100 do not include light receiving train 117 where camera 122 is a “chip-on-a-stick” image-sensor charge-coupled device (“CCD”) camera. Some embodiments of light receiving train 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 detection filter's range. 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 on 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 residing in a 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 unique properties of the neural tissue, such as the spinal cord dura or dura mater, targeted for visualization. In addition to configuring the detection filter to pass wavelengths corresponding to emitted light 112, such as emitted light for neural tissue, the detection filter 124 may also be configured to pass wavelengths of emitted light 112, allowing 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 wavelength range different from the wavelength of the excitation light and different from the emitted light 112, such as neural tissue emission. Nervous tissue inherently produces 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. While the surrounding non-neural tissue may still be visualized, the neural tissue may be easily visually distinguished from surrounding non-neural tissue, such as that shown in FIGS. 8 and 20 .

[0070] In some embodiments, the detection filter is a bandpass filter that preferentially allows passage of fluorescent light 1006 (see FIG. 10 ), including wavelengths in the range of about 433 nm to about 450 nm, which coincides with the wavelength range of excitation light 1004, which is 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, detection filter 124 is a bandpass filter with 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 comprises a low-pass (long-pass) filter having a region greater than about 425 nm, hi some embodiments, the detection filter is a low-pass (long-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] Camera 122 receives light from light receiving array 117 in some embodiments.

[0073] In some embodiments, camera 122 is configured to communicate digital information representing the collected light from 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. Camera 122, in some embodiments, is an image sensor / detector. Thus, in some embodiments, camera 122 is a digital camera module configured to couple to the processor. Camera 122, in some embodiments, is 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, 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, may in some embodiments be optically coupled to visualization devices other than interrogator 120, such as a surgical microscope / laparoscope, 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 examine a target tissue region (tissue under examination) 1202 within a substantially enclosed cavity within a patient's body. The light box device 1204, according to this example, optically couples selectable light signals from one or more light sources 1220, 1222 to an optical concentrator 1224, which 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 substantially enclosed cavity within the patient's body, thereby illuminating the target tissue region 1202 with excitation light. The tissue region 1202 of interest 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 range from about 382 nm to about 392 nm, which may be "tuned" by selection of bandpass optical filter Filter 1 in first light source 1220) may be selectively emitted from first light source 1220 in one or more light sources 1220, 1222 under processor control in response to computer instructions executed by information processing system 1812 (see FIG. 18 ). According to this embodiment, FIG. 10 illustrates a wavelength range for excitation light 1004 within electromagnetic spectrum 1002. Each of optical filters Filter 1, Filter 2, and Filter 3 shown in FIG. 12 may include one or more optical filters that can be used to "tune" the design of the wavelength range for the optical signal. The source optical filters, Filter 1 and Filter 2, "condition" the optical signals emitted from each light 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, which 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 running 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., the visible light wavelength range from about 470 nm to about 760 nm, which 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 the anatomical structures and tissues within target tissue region 1202 with nearly "white" illumination light 1010, while substantially avoiding interference with any fluorescent light (e.g., the wavelength range from 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 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 the detection of fluorescent light 1006, which 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-ultraviolet range. According to this embodiment, an optical filter (Filter 2) optically couples and "conditions" the emitted band-wavelength 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 an output from a light guide within the endoscope 1208, thereby guiding the excitation light to illuminate the target tissue region 1202. In addition to selectively switching the first light source on or off, the processor can control the brightness level of the excitation light emitted from the first light source 1220.

[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 comprises "white" (or nearly white) light. According to this embodiment, an optical filter (Filter 1) optically couples and "conditions" the band wavelength range 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 comprising emitted light (fluorescent light) and / or reflected light from the tissue region of interest 1202, is guided by one or more optical waveguides within flexible endoscope 1208 to fiber optic cable (fiber optic light guide) 1211, thence to filter Filter 3, a lens, and into camera 1206. The optical receiver train, in this example, includes one or more optical waveguides within flexible endoscope 1208, fiber optic cable 1211, filter Filter 3, and a lens, which couple the optical signal into camera 1206. Figure 14 shows a table of two exemplary embodiments illustrating filter selection options for Filters 1-3, as shown in Figure 12 and as described above.

[0081] 1-4, in some embodiments, the interrogator 120 comprises multiple cameras 122, each of which is optically coupled to one of the light receiving rows 117 of a corresponding plurality of 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] FIG. 4 is a partial schematic diagram of tissue imaging system 100 illustrating 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, various suitable processors can 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 plurality 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 passing emitted and reflected light, user interface management, wireless communication, and other specific functions.

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

[0084] The processor 142 is configured, in some embodiments, 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 that, in some embodiments, may be configured as writable memory or a combination of writable and read-only memory.

[0086] The visual image data signals from processor 142 are received by image display 150, which displays a visual image, such as a peripheral nerve over background tissue, to a surgeon or other user of system 100. Depending on the embodiment of tissue imaging system 100, 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. 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 device currently in use or to be developed in the future.

[0087] Recording and archiving of visual image data may be useful for purposes such as 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 the visual image data to image display device 150. Standard digital or analog (video tape) devices may comprise video recorder 160 according to 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, and adjusting settings of the various components and elements of the system 100. Some non-limiting examples of these functions include turning power on or off 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 versus filtered (bandpass or otherwise), such as the excitation light 110. 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, a digital touchscreen, a toggle switch, whether digital or analog, a joystick, a wheel, 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, in some embodiments, 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 an external recording device, 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] Connection interface 147 may increase the functionality of 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 recording device. Controller 140 includes or is electrically coupled to a medical-grade power source 152. In some embodiments, controller 140 includes one or more wireless connection interfaces 147, such as a Bluetooth or WiFi wireless interface, that are communicatively coupled to one or more components (in any combination) forming tissue imaging system 100, including, but not limited to, excitation light source 102, illumination light source 103, light source array 116, light receiving array 117, camera 122, image display 150, and 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, two or more medical carts 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 the 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 may provide the user with information regarding illumination settings, sensitivity settings, memory status, access to submenus and controls for digital video storage, etc. Additional functionality of this illustrated embodiment includes commands to take a photograph, start video recording, send to a video screen showing a visual image of the surgical field, or place controller 140 in 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 setting for excitation light source 102, adjust the camera sensitivity setting, and provide instructions for copying photos and images to a USB or other digital storage device.

[0095] 8 is an example of an image display device 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 within the tissue image display device of the surgical field.

[0096] 9 is a flow chart 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 interest containing healthy neural tissue adjacent to or surrounded by healthy non-neural tissue. In some embodiments, the tissue region of interest includes a surgical wound. In some embodiments, the tissue region of interest 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 in 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 irradiating step 220, in some embodiments, includes irradiating the tissue with excitation light comprising a first wavelength in the absence of a dye, marker, or probe, such that emitted light comprising a second wavelength is 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 from 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 detecting step 230, in some embodiments, includes transferring emitted light from the tissue in the absence of dyes, markers, or probes. In some embodiments, a receiving train collects emitted light from the tissue, excitation light reflected from the tissue, and 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, 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, filtering step 230 includes digital filtering of the received light by a processor, such as a processor included by the controller and operating a software package stored in 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, contrasted and differentiated from images of non-nerve tissue adjacent to and / or surrounding the nervous tissue. The visual image is formed 240 by processing light received by an interrogator, which 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 in 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 nervous tissue versus non-neural tissue using near-ultraviolet illumination and, alternatively, or simultaneously, can also perform imaging of a target tissue region 1302 using infrared (IR) light. The inventors have recognized that perfusion of nervous tissue tends to be significantly lower than perfusion of non-neural tissue. By selectively illuminating the target tissue region 1302 with an infrared signal from an infrared source 1304 and detecting the infrared signal emitted from the target tissue region 1302, an image formed of nervous tissue within the target tissue region 1302 can be visually contrasted with an image formed of non-neural tissue within the target tissue region 1302. The image formed of nervous tissue is typically a darker image (lower brightness) relative to the image formed of 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 nervous tissue relative to the location of non-neural tissue within the target tissue region 1302.

[0104] Near-UV light 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 near-UV excitation light and, if applicable, detection of intrinsic autofluorescence light from neural tissue versus detection of light from non-neural tissue has similar descriptions 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 into the tissue region of interest and from there, coupling the infrared signal to a light receiving array and camera 1320. The detection of infrared light can be selectively performed either alternatively to or simultaneously with the detection of intrinsic autofluorescence light from neural tissue versus the detection of light from non-neural tissue, if applicable, according to various embodiments. The two sets of images, one from infrared detection from neural tissue and one from intrinsic autofluorescence light detection, can 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 can include a temperature sensor (e.g., one or more infrared detectors) capable of detecting the different temperatures of different tissues within the tissue region of interest. Nervous tissue can 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 within non-nervous tissue. Vascularized tissue glows different colors due to the temperature difference between nervous and non-nervous tissue, such that nerves and dura mater are distinguishable from adjacent and / or surrounding non-nervous tissue structures. 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 can be measured across the tissue region of interest, and a temperature map can be created. This map 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 compared to optical signals received from non-neural tissue within the tissue region of interest. The processing system can then combine (e.g., overlay) the intrinsic autofluorescence image with temperature maps of various tissues within 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 within the detection process used by the processing system to better distinguish between nervous and non-neural tissue within 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 radiation 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 a display device.

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

[0109] Utilizing Impedance and Polarization from Non-Contact Electrical Stimulation Combined with Analysis to Alter Intrinsic Autofluorescence Optical Signals In response to a pulsating / changing electric field generated in proximity to the neural tissue, the 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. The pulsating / 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 pulsating / 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 pulsating / changing electric field.

[0110] It is expected that polarized light waves traveling along the axon will also temporarily modify the intrinsic autofluorescence effect of the neural tissue with the wavefront of the traveling polarized light waves. An intrinsic autofluorescence effect modified by a traveling wavefront (at one point within the axon) will be temporarily different from the intrinsic autofluorescence effect along the remainder of the axon. Neural tissue (with a polarized light wavefront traveling along the axon of the neural tissue) will exhibit a varying wavelength (and, possibly, varying intensity) of intrinsic autofluorescence light signals emitted from the neural tissue with a wavefront that is different from the intrinsic autofluorescence light signals emitted from the neural tissue at other parts of the axon. That is, the autofluorescence light signals emitted from the neural tissue will temporarily change their wavelength and, possibly, their intensity following a polarized light wavefront traveling along the axon of the neural 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 a summary map of the path of the axon in proximity to the traveling 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 varying autofluorescence light signals to map the location of axons in neural tissue can be combined with one or more of the thermal mapping and intrinsic autofluorescence imaging detection processes described above to improve sensitivity and specificity in the detection processes 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 neural and non-neural tissue within the tissue region of interest by reference to images of the neural tissue and non-neural tissue adjacent to or surrounding the neural tissue. [Example]

[0113] The above description of various embodiments of the present 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 enlarging nodule on the left lateral side that felt soft and immobile on palpation. The nodule was nontender 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, revealing a benign pleomorphic adenoma.

[0115] Case 2: A 55-year-old woman presented with a painless, gradually enlarging nodule on the left lateral side that felt firm and elastic on palpation. The nodule was nontender and measured 2.5 cm in maximum diameter. As in the previous case, the patient's neurological examination was normal, and ultrasound revealed a firm, hypoechoic nodule in the left parotid gland. 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 aspect of the parotid gland in the region of the inferior pole. 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 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 border of the parotid gland was visible. At this point, the facial nerve trunk was identified, and the facial nerve branches were transected using a tissue imaging system to allow visualization of the surgical field under near-ultraviolet (NUV) light. Under NUV light, the cervicofacial and ascending branches and their lengths were brightly autofluorescent and therefore clearly identified. In all three patients, parotidectomy was completed, drainage tubes were placed without intraoperative complications, and both immediate and postoperative neurological examinations were normal. All three patients were discharged home on the postoperative day 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 presented to our clinic with a 1.1 cm subcutaneous nodule located on the right lateral side of her neck. Physical examination revealed a firm, painless nodule in the right lobe region of the thyroid gland, which moved up and down during swallowing. Ultrasound revealed an 11 x 20 mm firm nodule with multiple small calcifications, an unclear border, and an irregular shape. Serum thyroglobulin was elevated. FNA revealed a diagnosis of papillary thyroid carcinoma, and subsequent imaging revealed disseminated metastases consistent with Bethesda stage IV disease. The thyroid gland was surgically removed, and the central 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; this level of visualization was clearly higher quality than that achieved under white light. .

[0119] Example 3 - Neurosurgery Case 5: A previously healthy 88-year-old man 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 scans demonstrated tumor invasion of the fourth lumbar vertebra and resulting destruction, along with soft tissue infiltration into the epidural space. A percutaneous biopsy of the pedicle was performed, revealing non-Hodgkin's B-cell lymphoma. After considering various options, a two-stage spinal surgery was decided upon, consisting of 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 ministomy retroperitoneal approach with the patient in the right lateral decubitus position. The procedure was performed in a 360° (ventrodorsal and ventral) manner, including instrumentation and posterior percutaneous instrumentation from L2 to the sacrum. For the second step, involving resection of the L4 vertebral body, the disc and tumor tissue from both L3-4 and L4-5 vertebrae located ventrally within the spinal canal were removed after reconstruction of the anterior column using a titanium mesh prosthesis. A left-sided anterolateral approach was used. The patient experienced no intraoperative or postoperative complications other than wound discomfort and no postoperative pain. The patient was discharged three days after the second surgery and began 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 labor. The six-month-old female infant, accompanied by her parents, presented to 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 limb 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] Tissue imaging systems are described herein. The tissue imaging systems generate visual images, either optically or digitally, of a surgical field or the like, and visualization of a target tissue region of interest may include a generated highlighted image of neural tissue within the tissue region of interest, such as a peripheral nerve or spinal dura mater, that is enhanced by the intrinsic autofluorescence or other inherent properties of the neural tissue, such as a peripheral nerve or spinal dura mater, in response to illumination with excitation light. The generated visual image includes a generated highlighted image of the neural tissue and a generated 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 further distinguishes the target tissue structure from surrounding fat, muscle, or connective tissue, improving the visual image. The use of excitation light in the NUV wavelength range 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 initiated, 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, must be revealed with continued transection. The laryngeal nerve is at risk of injury. The surgeon's assistant positions a 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] The surgeon dissects and separates the recurrent nerve from surrounding structures, guided by the autofluorescence from the nerve contrasted with light emitted or reflected by healthy non-nerve tissue adjacent to and / or surrounding the healthy nerve tissue.

[0125] Dendrite cameras can distinguish nerves from adjacent normal structures (healthy non-neural tissue) by illuminating them with light in a specific excitation wavelength range. The excitation light can be generated and emitted using one or more optical filters integrated with a light source within the imaging system. Simultaneously, a processor, operating in response to software, can analyze the different images formed from the optical signals received from the tissue region of interest and block or significantly reduce the intensity of optical signals that are not fluorescent light emitted from neural tissue, thereby increasing the resolution of structures (e.g., nerves) that glow with fluorescent light of a specific wavelength, such as the optical signals emitted by neural tissue.

[0126] Robotic prostatectomy A 30° deflection lens, 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 potential damage to the neurovascular bundle. The posterior layer of Denonvilliers' fascia is divided to allow identification of perirectal adipose tissue, which serves as a guide between the prostate and the rectum. To optimize nerve sparing, the surgeon utilizes a dendritic camera (e.g., using a dendritic adapter attached to the rigid endoscope on the robotic arm) that switches between white light and near-ultraviolet light, allowing the surgeon to view images of healthy nerve tissue within the tissue region 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, visible and distinguishable from healthy non-neural tissue, is released distally to the level of the urethra and prostate apex using NUV light. At this point, the only remaining attachments of the prostate are the dorsal venous plexus (DVC) and urethra. The DVC and urethra are then divided, freeing the prostate, and the specimen is placed in a 10 mm end-cap bag.

[0128] Laparoscopic Nissen fundoplication After assessing the abdominal cavity laparoscopically and insufflating with carbon dioxide, the surgeon can visualize the upper abdomen. To identify the gastroesophageal junction and avoid damage to the vagus nerve, which can result in severe gastroparesis, the surgeon utilizes a near-ultraviolet (NUV) dendritic camera to identify the anterior and posterior vagus nerves and distinguish them from other normal, healthy, non-nervated soft tissues and vascular structures. This tool becomes even more important if the surgeon re-manipulates this area and tissues are glued together with scar tissue. Here, the NUV camera can identify and track the nerve, preventing its severance.

[0129] Laparoscopic / Open Inguinal Hernia Repair When operating within a patient's groin using an open technique, surgeons use white light to separate cord structures to identify hernia sacs. While separating cords, surgeons hold an open dendritic camera in their hands, which can be attached to a specialized 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, to prevent them from being transected by the surgeon or being included in the implanted mesh. Both can result in sensory impairment or long-term, disabling groin pain. When operated with a laparoscope, the dendritic camera using the adapter is attached to the laparoscope, projecting onto a display monitor that allows the surgeon to visualize the image of the same structures within 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), surgeons can use the Dendrite Camera's NUV light to identify and protect nerves (nerve tissue) by distinguishing it from normal, healthy, non-nerve tissue adjacent to and / or surrounding it, either openly using a handheld Dendrite Camera device, or laparoscopically using a Dendrite Camera with an adapter attached to an endoscope, or robotically by attaching the Dendrite Camera adapter to a robotic arm, to dissect and remove anatomical structures.

[0131] Open-heart and open / thoracoscopic lung surgery The incidence of phrenic nerve injury after cardiac surgery varies depending on the care required. Final studies have shown that this complication is associated with cold-induced injury during cardioplegia and, if possible, mechanical damage during internal mammary artery harvesting. Outcomes are also variable and depend largely on the patient's underlying condition, particularly with regard to pulmonary function. Patient responses can range from asymptomatic radiological abnormalities to severe pulmonary dysfunction requiring prolonged mechanical ventilation and other associated morbidity and even mortality. When harvesting mammary arteries and / or opening the pericardium (which is adjacent to and / or surrounds the nerve tissue), surgeons use either a handheld orifice dendritic camera attached to a specialized arm or a thoracoscopic dendritic camera with an adapter attached to a thoracoscope to visualize the phrenic nerve (nerve tissue) and protect it from transsection when harvesting mammary arteries.

[0132] Upper and lower limb surgery When performing vascular, neurosurgical, plastic, and / or orthopedic procedures, surgeons make large incisions in the skin to assess anatomical compartments in order to perform the final procedure. During this procedure, surgeons must distinguish between nerves (nerve tissue) and normal muscle and vascular structures (non-nerve tissue adjacent to and / or surrounding the nerve tissue). By holding the Dendrite Camera in a specialized arm or having an assistant hold it, the surgeon can illuminate the NUV light emitted by the Dendrite Camera to identify 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 dendrite camera with a universal adapter attached to a microscope, the interaction between the images provided by the NUV camera and the real-time images captured by the microscope allows the surgeon to individually address healthy non-neural tissue and / or neural structures (healthy neural tissue) involved or surrounded by neoplastic processes such as meningiomas, metastases, neurofibromatosis, etc. The NUV dendrite camera visualization of images of healthy neural tissue contrasted with adjacent and / or surrounding healthy non-neural tissue, in combination with temperature and flow detectors, gives the surgeon the possibility to access sensory areas such as the cavernous sinus and remove intruding processes, with no restrictions on evacuation with minimal disruption of healthy tissue.

[0134] Skull base surgery Protrusions into the skull base that invade or disrupt the dura mater are difficult to resect. Using the NUV Dendrite Camera, recognition of the dura mater (nerve tissue) facilitates dissection and resection, even allowing 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 Dendrite Camera allows the surgeon to identify the dura mater (healthy nerve tissue) by imaging the nerve tissue in contrast to adjacent and / or surrounding healthy non-nerve tissue, which provides the greatest chance for procedural success when using the Dendrite 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 recognizing the nerve's dural covering), when approaching the spine with an endoscope, thus allowing for unequivocal dissection from the surrounding ligamentum flavum and disc or bony material.

[0137] Thoracoscopic sympathectomy NUV imaging using a dendritic camera (e.g., using a dendritic adapter attached to a rigid endoscope) quickly shows the surgeon the location of the sympathetic chain and its collateral fibers (nerve tissue) in contrast to the location of adjacent and / or surrounding healthy non-nerve tissue. This precise location of the nerve and non-nerve tissue is crucial when performing 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 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, allowing the spinal cord to 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 is 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 disks, mechanical coding devices such as punch cards or raised structures in grooves having instructions recorded thereon, and any suitable combination of the above. As used herein, computer-readable storage medium does not construe ephemeral signals per se, such as radio waves or other propagating electromagnetic waves, electromagnetic waves propagated through a waveguide or other transmission medium (e.g., light pulses passing through a fiber optic cable), or electrical signals transmitted through electrical wires.

[0141] The computer-readable program instructions described herein can be downloaded from a computer-readable storage medium to a respective computing / processing device or to an external computer or external storage device over a network, for example, the Internet, a local area network, a wide area network, and / or a wireless network, which may 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 entirely 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 entirely 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 a 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 by utilizing state information of the computer readable program instructions to personalize the electronic circuitry to perform aspects of the present 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 make 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 flowchart and / or block diagram block(s). 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 containing instructions that implement aspects of the functions / acts identified in the flowchart and / or block diagram block(s).

[0146] The computer-readable program instructions may also be loaded into a computer, other programmable data processing device, or other device to execute a series of operational steps on the computer, other programmable device, or other device to create a computer-implemented process such that the instructions, executed on the computer, other programmable device, or other device, perform the function(s) / act(s) identified in the flowchart and / or block diagram block(s).

[0147] The flowcharts and block diagrams in the figures 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 a flowchart or block diagram 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 noted in the blocks may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, 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, can be implemented by dedicated hardware-based systems that perform specific functions or actions or execute 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 illustrations described herein are intended to provide a general understanding of the structure of 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. Accordingly, the specification and drawings are to be regarded in an illustrative sense, rather than a restrictive 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, and 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 foregoing 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 handling system, information handling 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, a mouse, keyboard, keypad, touchpad, or microphone for receiving spoken commands and input data. Examples of output user interfaces can include, but are not limited to, a display device, a light, a lamp, a touch-sensitive 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, 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 for 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, wide-area, 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 reference unless the context clearly dictates otherwise. It will be further understood that the terms "comprises" and / or "comprising," when used herein, specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not exclude 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 wire, 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, consisting of, configured, designed, or has any combination of these features to perform a particular function. The term "adapted to" describes hardware, software, or a combination of hardware and software that can accommodate, be made, or is 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 handling system” describe examples of suitably configured processing systems adapted to implement one or more embodiments of the present disclosure. Any suitably configured processing system may similarly be used with embodiments of the present disclosure, including, but not limited to, personal computers, laptop personal computers (laptop PCs), tablet computers, smartphones, mobile phones, wireless communication devices, handheld devices, workstations, etc. A processing system may include one or more processing systems or processors. A processing system may be implemented in a centralized fashion within one processing system or in a distributed fashion where different elements are distributed across several interconnected processing systems. Corresponding structure, material, acts, and equivalents of all means or steps and functional elements within the scope of the following claims are intended to include any structure, material, or acts for performing a function in combination with other claimed elements, as specifically recited in the claim.

[0156] The description in 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 form disclosed. Many modifications and variations will be apparent to those skilled in the art without departing from the scope of the invention. The present embodiments have been chosen and described to best explain the principles and practical applications of the invention and to enable others skilled in the art to understand the invention in various embodiments with various modifications as suited to the particular uses envisioned.

Claims

1. 1. A method of operating a neural tissue imaging system, comprising: the neural tissue imaging system selectively switching on an excitation light source; the neural tissue imaging system optically coupling excitation light from the excitation light source into 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; the light source optical system uniformly radiating the excitation light to the outside; the neural tissue imaging system selectively illuminating an illumination source; the neural tissue imaging system optically coupling illumination light from the illumination light source to a second array of light sources and optically filtering the illumination light to pass only illumination light signals with wavelengths outside the first wavelength range and outside a second wavelength range of 433 nm to 450 nm, thereby externally emitting visible illumination light from the second array of light sources; an operation method including the steps of the nerve tissue imaging system receiving an optical signal from the outside using an optical receiver array, 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.

2. The operating method described in claim 1, further comprising a step in which the neural tissue imaging system captures image data of the received optical signal received by the light receiving array and optically filtered by the camera device.

3. The operating method described in claim 2, further comprising a step in which the neural tissue imaging system displays on a display screen an image showing, based on the captured image data, portions of the received optical signal in the second wavelength region where it is detected with high brightness in contrast to portions of the received optical signal in the second wavelength region where it is detected with low brightness.

4. The neural tissue imaging system performs image processing of the image data captured by the camera device; a step in which the nerve tissue imaging system creates an image by comparing an image of a portion where the received optical signal in the second wavelength region is detected at a high brightness with an image of a portion where the received optical signal in the second wavelength region is detected at a low brightness, the brightness of which is lower than that of the received optical signal in the second wavelength region detected at a high brightness; 3. The method of claim 2, further comprising the step of: displaying on a display screen a contrast image showing areas where the received optical signal in the second wavelength region is detected at high brightness compared to areas where the received optical signal in the second wavelength region is detected at low brightness.

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

6. 1. A method of operating a neural tissue imaging system, comprising: the neural tissue imaging system selectively switching on an excitation light source; the neural tissue imaging system optically coupling excitation light from the excitation light source into 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; the light source optical system uniformly radiating the excitation light to the outside; a receiving array of optical signals from the outside of the neural tissue imaging system; optically filtering the received optical signals to pass only optical signals having wavelengths within a second wavelength range of 433 nm to 450 nm; and optically coupling the optically filtered received optical signals to a camera device.

7. The operating method described in Claim 6, further comprising a step in which the camera device captures image data of the received optical signal received by the light receiving array and optically filtered.

8. The operating method described in Claim 7, further comprising a step in which the neural tissue imaging system displays on a display screen an image showing, based on the captured image data, portions of the received optical signal in the second wavelength region where it is detected with high brightness in contrast to portions of the received optical signal in the second wavelength region where it is detected with low brightness.

9. The neural tissue imaging system comprising: a step of performing image processing on the image data captured by the camera device; a step in which the nerve tissue imaging system creates an image by comparing an image of a portion where the received optical signal in the second wavelength region is detected at a high brightness with an image of a portion where the received optical signal in the second wavelength region is detected at a low brightness, the brightness of which is lower than that of the received optical signal in the second wavelength region detected at a high brightness; 8. The method of claim 7, further comprising the step of: displaying on a display screen a contrast image showing areas where the received optical signal in the second wavelength region is detected with high brightness in contrast to areas where the received optical signal in the second wavelength region is detected with low brightness.

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

11. 1. A method of operating a neural tissue imaging system, comprising: selectively switching on an excitation light source in the neural tissue imaging system; the neural tissue imaging system optically coupling excitation light from the excitation light source into 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; the light source optical system uniformly radiating the excitation light to the outside; the neural tissue imaging system selectively illuminating an illumination source; the neural tissue imaging system optically coupling illumination light from the illumination light source to a second light source optical system and optically filtering the illumination light to pass only illumination light signals with wavelengths longer than a second wavelength range of 433 nm to 450 nm, thereby emitting visible illumination light from the second light source optical system to the outside; the neural tissue imaging system selectively switching off the illumination source; an operating method including the steps of: receiving an optical signal from the outside using a light receiving optical system while the illumination light source is turned off, 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. The operating method described in claim 11, further comprising a step in which the camera device captures image data of the received optical signal received by an optical receiver array and optically filtered.

13. The operating method described in claim 12, further comprising a step in which the neural tissue imaging system displays on a display screen an image showing, based on the captured image data, portions of the received optical signal in the second wavelength region where it is detected with high brightness in contrast to portions of the received optical signal in the second wavelength region where it is detected with low brightness.

14. The neural tissue imaging system comprising: a step of performing image processing on the image data captured by the camera device; a step in which the nerve tissue imaging system creates an image by comparing an image of a portion where the received optical signal in the second wavelength region is detected at a high brightness with an image of a portion where the received optical signal in the second wavelength region is detected at a low brightness, the brightness of which is lower than that of the received optical signal in the second wavelength region detected at a high brightness; 13. The method of claim 12, further comprising the step of the nerve tissue imaging system displaying on a display screen a contrast image showing areas where the received optical signal in the second wavelength region is detected with high brightness in contrast to areas where the received optical signal in the second wavelength region is detected with low brightness.

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

16. 1. A method of operating a neural tissue imaging system, comprising: the neural tissue imaging system selectively switching on an excitation light source; the neural tissue imaging system optically coupling excitation light from the excitation light source into 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; the light source optical system uniformly radiating the excitation light to the outside; the neural tissue imaging system selectively illuminating an illumination source; the neural tissue imaging system optically coupling illumination light from the illumination light source to a second array of light sources and optically filtering the illumination light to pass only illumination light signals with wavelengths outside the first wavelength range and outside a second wavelength range of 433 nm to 450 nm, thereby externally emitting substantially white visible illumination light from the second array of light sources; receiving an optical signal from an external device via a light receiving array of the nerve tissue imaging 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; capturing, by the camera device, image data of the optically filtered received optical signals received by the optical receiver train; the neural tissue imaging system performing image processing of the image data captured by the camera device; a step in which the nerve tissue imaging system creates an image by comparing an image of a portion where the received optical signal in the second wavelength region is detected at a high brightness with an image of a portion where the received optical signal in the second wavelength region is detected at a low brightness, the brightness of which is lower than that of the received optical signal in the second wavelength region detected at a high brightness; and the nerve tissue imaging system displays on a display screen a contrast image showing areas where the received optical signal in the second wavelength region is detected at high brightness compared to areas where the received optical signal in the second wavelength region is detected at low brightness.

17. A method of operating a neural tissue imaging system, comprising: the neural tissue imaging system selectively switching on an excitation light source; the neural tissue imaging system optically coupling excitation light from the excitation light source into 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; the light source optical system uniformly radiating the excitation light to the outside; a receiving array of optical signals from the outside of the neural tissue imaging system; optically filtering the received optical signals to pass only optical signals having wavelengths within a second wavelength range of 425 nm to 510 nm; and optically coupling the optically filtered received optical signals to a camera device.

Images