HYPERSPECTRAL IMAGING SYSTEMS AND RELATED METHODS

Abstract

Systems and methods for analyzing sublingual microcirculation perfusion and identifying particular nerve tracts. In exemplary embodiments, a digital micro-mirror device is configured to direct a reflected light to a subject area and a controller is configured to alter a parameter of the reflected light.

Claims

1. A system for identifying a nerve tract, the system comprising: a light source; a digital micro-mirror device; an optical detector; an analyzer; a controller coupled to the digital micro-mirror device; and a stimulator configured to provide a stimulus to a nerve tract, wherein: the light source is configured to emit light to the digital micro-mirror device; the digital micro-mirror device is configured to direct a reflected light to a subject area; the controller is configured to alter a parameter of the reflected light; the optical detector is configured to detect a response light from the subject area; and the analyzer is configured to analyze the response light and generate an image of the subject area wherein the nerve tract is distinguished from an area surrounding the nerve tract.

2. The system of claim 1 wherein the analyzer is configured to generate an image of the subject area wherein the nerve tract is a different color than the area surrounding the nerve tract.

3. The system of claim 1 wherein the stimulator is configured as a flashing light.

4. The system of claim 1 wherein the stimulator is a component of eyewear configured to be worn by a subject.

5. The system of claim 1 wherein the controller is configured to alter the parameter of the reflected light at least once per second.

6. The system of claim 1 wherein the controller is configured to alter the parameter of the reflected light at least twice per second.

7. The system of claim 1 wherein the controller is configured to alter the parameter of the reflected light at least three times per second.

8. The system of claim 1 wherein the analyzer comprises a computer-readable medium configured to analyze the response light and generate an image of the subject area.

9. A method for identifying a nerve tract, the method comprising: providing a stimulus to a nerve tract; directing light to a digital micro-mirror device; directing a reflected light from the digital micro-mirror device to a subject area; dynamically controlling the reflected light from micro-mirror device to the subject area; detecting a response light from the subject area; and analyzing the response light from the subject area and generating an image of the subject area wherein the nerve tract is distinguished from an area surrounding the nerve tract.

10. The method of claim 9 wherein dynamically controlling the reflected light from the micro-mirror device to the subject area comprises altering a parameter of the reflected light at least once per second.

11. The method of claim 9 wherein dynamically controlling the reflected light from the micro-mirror device to the subject area comprises altering a parameter of the reflected light at least twice per second.

12. The method of claim 9 wherein dynamically controlling the reflected light from the micro-mirror device to the subject area comprises altering a parameter of the reflected light at least three times per second.

13. The method of claim 10 wherein the parameter comprises the wavelength of the reflected light.

14. The method of claim 10 wherein the parameter comprises the location of the reflected light.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The following drawings form part of the present specification and are included to further demonstrate certain aspects of exemplary embodiments of the present invention.

[0028] FIG. 1 is a schematic diagram illustrating a system according to a first exemplary embodiment.

[0029] FIG. 2 is an image generated by the embodiment according to FIG. 1.

[0030] FIG. 3 is a diagram of an anatomical area analyzed by the embodiment according to FIG. 1.

[0031] FIG. 4 is a spectrum of response light generated by the embodiment according to FIG. 1.

[0032] FIG. 5 is an image of nerve bundles generated by the embodiment according to FIG. 1.

[0033] FIG. 6 is an image of ion channels generated by the embodiment according to FIG.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0034] Various features and advantageous details are explained more fully with reference to the non-limiting embodiments that are illustrated in the accompanying drawings and detailed in the following description. Descriptions of well-known starting materials, processing techniques, components, and equipment are omitted so as not to unnecessarily obscure the invention in detail. It should be understood, however, that the detailed description and the specific examples, while indicating embodiments of the invention, are given by way of illustration only, and not by way of limitation. Various substitutions, modifications, additions, and/or rearrangements within the spirit and/or scope of the underlying inventive concept will become apparent to those skilled in the art from this disclosure.

[0035] In the following description, numerous specific details are provided, such as examples of material selections, dimensions, etc., to provide a thorough understanding of the present embodiments. One skilled in the relevant art will recognize, however, that the invention may be practiced without one or more of the specific details, or with other methods, components, materials, and so forth. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring aspects of the invention.

[0036] FIG. 1 illustrates one embodiment of a system 100 for conducting hyperspectral imaging. In this exemplary embodiment, system 100 comprises a light source 110, a filter 130, a digital micromirror device (DMD) 150, optical detector 170 and controller 190. In the exemplary embodiment shown, DMD 150 can be provided by Texas Instruments DLP division. In this embodiment, DMD 150 is coupled to controller 190 via electrical coupling 155, and detector 170 is coupled to controller via electrical coupling 175. Electrical couplings 155 and 175 may comprise wireless or wired couplings, including fiber optic couplings.

[0037] A general overview of the operation of system 100 will be presented initially, followed by a more detailed description of specific embodiments. During operation, system 100 can be used to identify or analyze certain conditions or components based on the light reflected or fluoresced from (or absorbed by) the subject. For example, light source 110 can direct light 120 through filter 130 to DMD 150, which is controlled by controller 190 to direct reflected light 140 to a subject area 160. As used herein, the term light will be used to refer to electromagnetic radiation. Response light 180 is reflected and/or fluoresced from subject area 160 and is detected by optical detector 170, which communicates to an analyzer 192 data relating to response light 180. This data can then be deconvolved relative to the direct reflected light 140 to analyze subject area 160.

[0038] In specific embodiments, controller 190 comprises several individual components including, for example, a mirror controller 191 to control DMD 150. Controller 190 may also comprise analyzer 192 to deconvolve or analyze the data received from optical detector 170. In certain embodiments, controller 190 may used to control DMD 150 so that DMD 150 directs reflected light 140 to provide a dynamic stimulus to subject area 160. In particular embodiments, parameters of reflected light 140, including for example, frequency, intensity, and location, can be altered in rapid succession (e.g., multiple times per second) and the response from subject area 160 can be analyzed via changes in response light 180. In this manner, multiple variables can be determined in sub-second periods permitting their analysis in a real-time algorithm. Such real-time algorithms may be executed in an index algorithm 194 to consolidate these multiple variables into an index of fewer dimensions. Particular embodiments illuminate tissue with reflected light and analyze response light for wavelengths between 380 and 1600 nm simultaneously, generating an entire spectral signature.

[0039] In specific embodiments, system 100 may be used to detect changes in mucosal microcirculatory perfusion, including for example, conditions associated with sepsis. In the circulatory shock and inflammation associated with sepsis, microcirculation is disturbed secondary to coagulation leading to microvascular thrombosis, adhesion of leukocytes to the vasculature, and the decreased deformability of red blood cells (RBCs). These factors can lead to microcirculatory shunting, cellular distress, and organ failure.

[0040] Previous hyperspectral imaging systems have used a liquid crystal tunable filter (LCTF), capable of only about one image every 30 seconds. However, exemplary embodiments of system 100 are capable of generating images every 300 ms. Although specific exemplary embodiments will be described in detail, it is understood that variations may be implemented in other exemplary embodiments of the present disclosure.

[0041] In one exemplary embodiment, light source 110 directs broadband light 120 that is diffracted through a slit filter 130. The light passing through slit filter 130 is reflected from DMD 150, and optically directed to subject area 160. By individually controlling the state of each mirror of DMD 150, the subject area 160 is illuminated with a programmed selection of wavelengths of reflected light 140. Optical detector 170 can then measure the spectrum of response light 180 reflected from subject area 160. The programmed spectrum of light 140 may simply be a single bandpasssimilar to the liquid crystal tunable filer (LCTF) outputor a more complex combination of wavelengths that cannot be duplicated by the LCTF, including for example, ultraviolet (UV) through near-infrared (NIR).

[0042] The use of mirrors incorporated into DMD 150, rather than liquid crystals allows reflected light 140 to be manipulated faster and over a broader wavelength range. System 100 further allows a user to program controller 190 to provide a predetermined complex spectra or color mixtures of reflected light 140 reflected from DMD 150.

[0043] Numerous changes occur in the sublingual microvasculature during medical conditions, including for example, systemic inflammatory response syndrome (SIRS) or sepsis. Of these, several factors can be assessed by the system 100. For example, decreases in perfusion will result in poorer oxygenation of the tissue, poorer CO.sub.2 clearance, and local acidosis. As a result of disseminated intravascular coagulation (DIC), a potential step in the sequence of SIRS or sepsis, fibrin can form in the microvasculature. The presence of fibrin indicates a pathologic condition. Further, red blood cells (RBCs) can become static or sluggish since they are not able to deform to the diameter of the capillary and the available capillary diameter decreases with the thrombin formation.

[0044] Tissue pCO.sub.2 levels can be detected by variable absorption of near infrared (NIR) wavelengths of reflected light 140. Oxyhemoglobin can be detected with variable absorption of red and NIR wavelengths of reflected light 140. When exposed to reflected light 140, fibrin will fluoresce at certain frequencies, which can also be detected by optical detector 170.

[0045] In this embodiment, system 100 images each of these attributes in succession by varying the illuminating spectra of reflected light 140 for each factor. In certain embodiments, system 100 can then collect the reflected or fluoresced response light 180 and analyzer 192 can calculate variables including pO.sub.2, pCO.sub.2, and fibrin content, combining them into an index algorithm 194 calculated by software incorporated in controller 190. This index can be trended to track the progression of sepsis, for example. A fuzzy inference system (FIS) is one means of generating such an algorithm. Using weighting factors, time sequence relationships, and relative changes in values, an index is determinable. A decrease in pO.sub.2 followed by an increase in pCO.sub.2 in the presence of fibrin would constitute an exemplary embodiment.

[0046] As shown in FIG. 2, system 100 can be used to display a visual image of changes in sublingual microcirculation perfusion. In image 210 to the left generated by system 100, a rubber band 201 has been placed around far left digit 205 to constrict blood flow. As indicated in graph 230 on the right, the percent of oxyhemoglobin is measured at approximately 50 percent (based on the color of digit 205). In image 220 to the right generated by system 100, the constriction has been removed and the blood flow to the digit increased. As indicated by graph 230, the percent of oxyhemoglobin has increased to approximately 80 percent due to the hyperfusion following the release of pressure. While visible light will eventually indicate a paling of the skin when blood flow is restricted, system 100 can indicate changes in blood flow much sooner and with greater sensitivity than would be visible with exposure of the skin to visible light. The image shown in FIG. 2 is merely one example of the type system 100 is capable of generating. Other images, for example, may comprise an index that includes the pO.sub.2, pCO.sub.2, and fibrin content, as previously discussed.

[0047] In another exemplary embodiment, system 100 can be used to detect relatively static RBCs in the sublingual microcirculation to provide an indication of DIC and progressing sepsis. In this embodiment, providing an excitation spectrum of reflected light 140 near 400 nm will cause RBCs to fluoresce response light 180. With the high frame rate available with system 100, sequential images captured by optical detector 170 can be compared to estimate the velocity of the RBCs. Under normal conditions, capillary blood velocity is approximately 900 m/sec. With a relatively even distribution of RBCs in the plasma, a frame rate of 300 ms will give the appearance of threads of RBCs within the vasculature. In pathophysiologic conditions, portions of the capillary have essentially zero flow resulting in isolated clumps of RBCs, which would be clearly distinguishable from the thread-like appearance of normal movement.

[0048] As described herein, system 100 provides a non-contacting means of assessing sublingual perfusion and DIC, which can overcome one important shortcoming of the existing OPS and SDF technologies. Further, this will allow straightforward calculations in near real-time of pO.sub.2, pCO.sub.2, and fibrin content rather than post-processing assessment of, for instance, capillary density by counting the vessels crossing arbitrary lines in a field of view. Furthermore, reliance on a combination of variables that are present in the condition is more reliable than a univariate system. System 100 can generate multiple measurements by altering the illuminating spectrum on successive sweeps of the field of view.

[0049] In certain embodiments, system can also provide a visual display of subject area 160 encoded with the physiologic information, in addition to providing a summary calculation. While the index is calculated and displayed, each element of the index can also be available for quality assurance and user acceptance.

[0050] In another exemplary embodiment, system 100 can be configured to identify specific anatomical features, including for example, nerve bundles or tracts. For example, in a specific embodiment, system 100 can be configured to identify primary optic or cochlear nerve tracts that are myelinated. The general principles of operation in this embodiment are similar to those of the previously described embodiment used for the detection of SIRS or sepsis. For example, light source 160 directs light 120 through filter 130 to DMD 150, which is controlled by controller 190. DMD 150 directs reflected light 140 to subject area 160, which reflects and/or fluoresces response light 180 that is detected by optical detector 170. The light detected by optical detector 170 can then be analyzed by controller 190 (e.g. via specific software incorporated in controller 190) to identify specific nerve tracts.

[0051] As shown in FIG. 3, in one specific embodiment subject area 160 may be an area approximately 3 cm.sup.2 comprising an optic tract 161 with a length of approximately 30 mm (orbital portion) and a 3 mm diameter. Each nerve bundle contains about 1.2 million individual nerve fibers, providing sufficient volume for an adequate signal to noise ratio, as described further below.

[0052] In certain embodiments, during operation of system 100 action potentials can be generated on optic tract 161 by a periodic and repetitive stimulation provided by a stimulator 162. For example, optic tract 161 can be excited by applying stimulator 162, which may be configured as a flashing light incorporated into a goggle in certain embodiments. Exposure to such stimulation to receptors (e.g. the bulb of the eye 163) coupled to optic tract 161 can generate a response signal in optic tract 161, even if the subject is under anesthesia, as explained more fully below.

[0053] Under resting conditions, sodium pumps on the lipid bilayer of optic tract 161 actively move Na.sup.+ ions to the outside of optic tract 161 resulting in a resting potential of about 70 mV (inside relative to outside). During an action potential, voltage sensitive sodium channels are triggered to open in response to a stimulus. This can allow Na.sup.+ ions to migrate to the inside of the membrane in response to the concentration gradient. A refractory period then prohibits the stimulus from reactivating that segment, keeping the electrical signal moving unidirectionally on optic tract 161. This refractory period is also a result of a change in the protein configuration of the sodium channel.

[0054] With constant stimulation of optic tract 161 by stimulator 162, there will be at any given time a constant flux of open, closed, and refractory ion channels on optic tract 161 relative to other nerve tracts (e.g., cochlear given a lack of auditory stimulation). The signature of this mixture of open, closed, and refractory channels is identified by the appropriate spectral signature made possible by system 100. This can allow a user to differentiate the primary nerve bundles such as optic tract 161 from other nerve tracts.

[0055] A spectrum of response light 180 indicative of the myelin layer can be found by targeting both the lipids (e.g., glycolipid) and proteins (e.g., myelin basic protein) of the layer. One example of a spectrum of myelin basic protein is shown in FIG. 4. Protein conformation and subsequent quantification is known to be possible with UV-visible spectroscopy. Further enhancement of the signal to noise ratio may also be achieved by a principle component analysis of the spectrum signatures. While a single nerve fiber would not provide an adequately target size to analyze, the optic nerve bundle comprises over one million nerve fibers, greatly increasing the concentration of target proteins.

[0056] In certain embodiments, system 100 can generate a two dimensional image with the concentration of the target encoded on the physical image. The oxygenation of various digits is shown by way of example of this technique. The targeted nerve bundles are similarly encoded on a 2D image intraoperatively as shown in FIG. 5. The varying oxygenation levels can be indicated by different colors 501, 502 and 503 shown in FIG. 5. Models of ion channels are also shown in FIG. 6 and differentiated by colors 601, 602, 603, and 604.

[0057] Certain embodiments may also incorporate an injection of a material that would selectively bind to myelin. This could allow the myelin to be more readily detectable with spectroscopy. In addition, this technique may be useful for evaluating degeneration of myelin sheaths, as is the case with various neurological disorders such as multiple sclerosis, Guillain-Barre syndrome, and Charcot-Marie-Tooth disease. Hyperspectral imaging incorporated by system 100 may also be used for establishing a baseline intensity of myelin presence and allow for tracking of degenerating myelin either during progression of the disease or as an indicator of pending neuropathy.

[0058] The following references are incorporated by reference herein: [0059] U.S. Pat. No. 6,640,130 [0060] U.S. Pat. No. 6,770,484 [0061] U.S. Pat. No. 6,937,885 [0062] U.S. Patent Publication 2010/0056928 [0063] Detection and Analysis of the Intestinal Ischemia Using Visible and Invisible Hyperspectral Imaging, IEEE Transactions on Biomedical Engineering, Vol. 58, No. 8, August 2010. [0064] Imaging Hemoglobin Oxygen Saturation in Sickle Cell Disease Patients Using Noninvasive Visible Reflectance Hyperspectral Techniques: Effects of Nitric Oxide, Am J Physiol Heart Circ Physiol 285:H1183-9, 2003.