阅读说明：本技术 利用光谱成像对微血管功能障碍的评估 (assessment of microvascular dysfunction using spectral imaging ) 是由 W·S·克鲁本三世 A·彼得罗帕奥利 P·M·特恩 于 2018-02-06 设计创作，主要内容包括：一种用于量化患者体内微血管功能的方法,包括稳定该患者的测试部分以进行分析。使用第一光谱成像技术测量微血管血流参数。使用第二光谱成像技术测量微血管储备参数。使用第三光谱成像技术测量组织呼吸参数。使用第四光谱成像技术测量微血管通透性参数。该方法进一步包括使用被配置为生成对应于患者体内微血管功能的汇总微血管参数的处理器,将微血管血流参数、微血管储备参数、组织呼吸参数,以及微血管通透性参数一起处理。(A method for quantifying microvascular function in a patient comprising stabilizing a test portion of the patient for analysis. A microvascular blood flow parameter is measured using a first spectral imaging technique. A microvascular reserve parameter is measured using a second spectral imaging technique. Tissue breathing parameters are measured using a third spectral imaging technique. The microvascular permeability parameter is measured using a fourth spectral imaging technique. The method further includes processing the microvascular blood flow parameter, the microvascular reserve parameter, the tissue respiration parameter, and the microvascular permeability parameter together using a processor configured to generate an aggregate microvascular parameter corresponding to microvascular function in the patient.)

1. A method of quantifying microvascular function in a patient, said method comprising:

Stabilizing the test portion of the patient for analysis;

Measuring a microvascular blood flow parameter of the test portion using a first spectral imaging technique;

Measuring a microvascular reserve parameter of the test portion using a second spectral imaging technique;

Measuring tissue respiration parameters of the test portion using a third spectral imaging technique;

Measuring a microvascular permeability parameter of said test portion using a fourth spectral imaging technique; and

Processing the microvascular blood flow parameter, the microvascular reserve parameter, the tissue respiration parameter, and the microvascular permeability parameter together using a processor configured to generate an aggregate microvascular parameter corresponding to the microvascular function in the patient.

2. The method of claim 1, wherein the first spectral imaging technique, the second spectral imaging technique, the third spectral imaging technique, and the fourth spectral imaging technique each comprise microscopic spectral imaging, endoscopic spectral imaging, camera spectral imaging, or a combination thereof.

3. the method of claim 1 or 2, wherein the test portion to be stabilized comprises an arm, leg, neck, head, shoulder, stomach, hand, thigh, calf, heel, foot, toe, knee, finger, elbow, chest, neck, penis, breast, face, earlobe, lip, cheek, or combinations thereof.

4. The method of any one of claims 1-3, wherein the microvascular blood flow parameter, the microvascular reserve parameter, the tissue respiration parameter and the microvascular permeability parameter are each measured at the outer surface of the epidermis, dermis, subcutaneous tissue, buccal mucosa, blephar inferior region, suprapalpebral region, auricle, and/or any internal organ during surgery, laparoscopy or endoscopy.

5. The method of any one of claims 1-4, wherein the first spectral imaging technique comprises a line-scan spectroscopic speckle technique.

6. The method of any of claims 1-5, wherein the first spectral imaging technique uses wavelengths from about 400nm to about 1500 nm.

7. A method according to any of claims 1-6, wherein the second spectral imaging technique is configured to observe capillary responses to ischemic stimuli in which blood supply is at least temporarily altered or shut off.

8. The method of any of claims 1-7, wherein the second spectral imaging technique uses a first wavelength from about 530nm to about 580nm, and a second wavelength from about 440nm to about 460 nm.

9. The method of any one of claims 1-8, wherein the third spectral imaging technique includes pulse oximetry for imaging hemoglobin (Hb) and oxygenated hemoglobin (HbO2) molecules.

10. The method of any of claims 1-9, wherein the third spectral imaging technique uses a first wavelength from about 530nm to about 580nm, and a second wavelength from about 440nm to about 460 nm.

11. The method of any one of claims 1-10, wherein the fourth spectral imaging technique is configured to image water (H2O) permeating multiple vessel walls.

12. The method of any of claims 1-11, wherein the fourth spectral imaging technique uses one or more wavebands including 2900nm, 1950nm, 1450nm, 1200nm, 900nm, 820nm, and 730 nm.

13. A method of quantifying microvascular function in a patient, said method comprising:

Measuring two or more microvascular parameters selected from the group consisting of a microvascular blood flow parameter, a microvascular reserve parameter, a tissue respiration parameter and a microvascular permeability parameter; and

Processing the two or more microvascular parameters using a processor (240) configured to generate aggregated microvascular parameters corresponding to the microvascular function in the patient;

Wherein the two or more microvascular parameters are measured using a spectral imaging technique comprising microscopic spectral imaging, endoscopic spectral imaging, camera spectral imaging or a combination thereof.

14. The method of claim 13, wherein the two or more microvascular system parameters are measured at the outer surface of the epidermis, dermis, subcutaneous tissue, buccal mucosa, infrapalpebral region, suprapalpebral region, auricle, and/or any internal organ during surgery, laparoscopy or endoscopy.

15. The method of claim 13 or 14, wherein the microvascular blood flow parameter is quantified with a line-scanning spectroscopic speckle technique using wavelengths from about 530nm to about 580 nm.

16. The method according to any one of claims 13-15, wherein the microvascular reserve parameter is quantified using the spectroscopic imaging technique by observing a capillary response to an ischemic stimulus in which blood supply is at least temporarily altered or shut off; and is

Wherein the spectral imaging technique uses a first wavelength from about 530nm to about 580nm and a second wavelength from about 440nm to about 460 nm.

17. The method of any one of claims 13-16, wherein the tissue respiration parameter is quantified using the spectroscopic imaging technique by imaging hemoglobin (Hb) and oxygenated hemoglobin (O2Hb) molecules using pulse oximetry; and is

Wherein the spectral imaging technique uses a first wavelength from about 530nm to about 580nm and a second wavelength from about 440nm to about 460 nm.

18. the method of any one of claims 13-17, wherein the two or more microvascular parameters are measured by detecting carbon dioxide, oxygen, hemoglobin, carboxyhemoglobin, deoxyhemoglobin, methemoglobin, nitric oxide, or a combination thereof.

19. The method according to any one of claims 13-18, wherein the microvascular permeability parameter is quantified by imaging the permeation of water (H2O) through a plurality of blood vessel walls using a spectroscopic imaging technique; and is

wherein the spectral imaging technique uses one or more wavebands including 2900nm, 1950nm, 1450nm, 1200nm, 900nm, 820nm, and 730 nm.

20. the method of any one of claims 13-19, wherein the microvascular blood flow parameter is quantified with a line scanning spectroscopic speckle technique using wavelengths from about 400nm to about 1500 nm.

21. The method according to any one of claims 13-20, wherein the microvascular reserve parameter is quantified using the spectroscopic imaging technique by observing a capillary response to an ischemic stimulus in which blood supply is at least temporarily altered or shut off.

22. The method of any one of claims 13-21, wherein the microvascular reserve parameter is quantified using a wavelength from about 400nm to about 1500 nm.

23. The method according to any one of claims 13-22, wherein the microvascular reserve parameter is quantified using a first wavelength from about 530nm to about 580nm and a second wavelength from about 440nm to about 460 nm.

24. The method of any one of claims 13-23, wherein the tissue respiration parameter is quantified using the spectroscopic imaging technique by imaging hemoglobin (Hb) and oxygenated hemoglobin (O2Hb) molecules using pulse oximetry.

25. The method of any one of claims 13-24, wherein the tissue respiration parameter is quantified using a wavelength from about 400nm to about 1500 nm.

26. The method of any one of claims 13-25, wherein the tissue respiration parameter is quantified using a first wavelength from about 530nm to about 580nm and a second wavelength from about 440nm to about 460 nm.

27. the method of any one of claims 13-26, wherein the microvascular permeability parameter is quantified by imaging the permeation of water (H2O) through a plurality of blood vessel walls using a spectroscopic imaging technique.

28. The method of any one of claims 13-27, wherein the microvascular permeability parameter is quantified using a wavelength from about 400nm to about 1500 nm.

29. The method according to any one of claims 13-28, wherein the microvascular permeability parameter is quantified using one or more wavebands comprising 2900nm, 1950nm, 1450nm, 1200nm, 900nm, 820nm and 730 nm.

30. The method of any one of claims 13-29, wherein the two or more microvascular parameters are measured by detecting carbon dioxide, oxygen, hemoglobin, carboxyhemoglobin, deoxyhemoglobin, methemoglobin, nitric oxide, or a combination thereof.

31. The method according to any one of claims 13-30, further comprising:

Stabilizing a test portion of a patient for analysis, wherein the test portion to be stabilized comprises an arm, leg, neck, head, shoulder, stomach, hand, thigh, calf, heel, foot, toe, knee, finger, elbow, chest, neck, penis, breast, face, earlobe, lip, cheek, or a combination thereof.

32. An apparatus for quantifying microvascular function comprising:

A spectral imaging device configured to measure two or more microvascular parameters selected from the group consisting of: a microvascular blood flow parameter;

a microvascular reserve parameter;

A tissue breathing parameter;

A microvascular permeability parameter; and

A processor (240) configured to generate an aggregate microvascular parameter from the two or more microvascular parameters.

Technical Field

The present disclosure relates generally to spectral imaging of microvessels. More specifically, embodiments described herein relate to quantifying microvascular dysfunction in a patient using a number of parameters.

Technical Field

Effective and accurate quantification of microvascular function (MVF) addresses the clinical needs of various medical professionals, including surgical, diagnostic and prophylactic applications. Ensuring and maintaining proper microvascular function is critical to the health of essentially every tissue in the human body. One exemplary life-threatening condition that may be better treated or prevented by measuring microvascular function in a patient is sepsis.

sepsis is systemic inflammation due to complications resulting from infection. Sepsis is one of the most common and expensive causes of hospitalization in the united states, with 28-50% of septic patients dying. Since sepsis affects people over 65 years disproportionately, effective treatment is an increasing substantial clinical need. Sepsis is one reason for such a large problem because it is difficult to diagnose, quantify, and monitor. The main cause of morbidity and mortality in septic patients is organ failure. The vasculature circulates chemicals that trigger inflammation and these chemicals are activated primarily in the microvasculature, the site of chemical delivery. Therefore, microvascular dysfunction caused by the inflammatory response of sepsis greatly contributes to organ failure. By capturing relevant information about the patient's microvascular health, clinicians may be more appropriate to more effectively quantify and monitor a patient's sepsis.

Current methods for quantifying microvascular function in a patient typically include a variety of techniques such as, for example, pulse oximetry capillary refill rate, buccal mucosa microvascular imaging, and forearm laser doppler blood flow meter. While these various techniques are suitable for acquiring limited data, the methods currently used generally do not provide an overall assessment of microvascular function.

Disclosure of Invention

according to one embodiment, a method of quantifying microvascular function in a patient is provided. The method of quantifying microvascular function in a patient comprises stabilizing a test portion of the patient for analysis, measuring a microvascular blood flow parameter of the test portion using a first spectral imaging technique, measuring a microvascular reserve parameter of the test portion using a second spectral imaging technique, measuring a tissue respiration parameter of the test portion using a third spectral imaging technique, and measuring a microvascular permeability parameter of the test portion using a fourth spectral imaging technique. The method of quantifying microvascular function in a patient further comprises processing together a microvascular blood flow parameter, a microvascular reserve parameter, a tissue respiration parameter, and a microvascular permeability parameter using a processor configured to generate an aggregate microvascular parameter corresponding to microvascular function in the patient.

According to another embodiment, a method of quantifying microvascular function in a patient is provided. The method of quantifying microvascular function in a patient comprises measuring two or more microvascular parameters selected from the group consisting of a microvascular blood flow parameter, a microvascular reserve parameter, a tissue respiration parameter and a microvascular permeability parameter, and processing the two or more microvascular parameters using a processor configured to generate an aggregate microvascular parameter corresponding to microvascular function in the patient. The two or more microvascular parameters are measured using spectral imaging techniques including microscopic spectral imaging, endoscopic spectral imaging, camera spectral imaging or combinations thereof.

According to yet another embodiment, an apparatus for quantifying microvascular function is provided. The apparatus for quantifying microvascular function comprises a spectral imaging device configured to measure two or more microvascular parameters selected from the group consisting of a microvascular blood flow parameter, a microvascular reserve parameter, a tissue respiration parameter and a microvascular permeability parameter, and a processor configured to generate an aggregate microvascular parameter from the two or more microvascular parameters.

According to yet another embodiment, a method of quantifying microvascular blood flow in a patient's buccal mucosa or tongue includes stabilizing a test portion of the patient for analysis, positioning a coherent light source and a spectral imaging system in a transmission geometry relative to the test portion, and measuring a microvascular blood flow parameter of the test portion using the spectral imaging system. The test portion includes lips, cheeks, tongue, or a combination thereof.

The present disclosure extends to a method of quantifying microvascular function in a patient, the method comprising: stabilizing the test portion of the patient for analysis; and measuring the microvascular blood flow parameter of the test portion using a spectral imaging technique.

The present disclosure extends to a method of quantifying microvascular function in a patient, the method comprising: stabilizing the test portion of the patient for analysis; and measuring a microvascular reserve parameter of the test portion using a spectral imaging technique.

The present disclosure extends to a method of quantifying microvascular function in a patient, the method comprising: stabilizing the test portion of the patient for analysis; tissue breathing parameters of the test portion are measured using spectral imaging techniques.

The present disclosure extends to a method of quantifying microvascular function in a patient, the method comprising: stabilizing the test portion of the patient for analysis; and measuring the microvascular permeability parameter of the test portion using a spectral imaging technique.

The present disclosure extends to a method of quantifying microvascular function in a patient, the method comprising: stabilizing the test portion of the patient for analysis; measuring a microvascular blood flow parameter of the test portion using a first spectral imaging technique; measuring a microvascular reserve parameter of the test portion using a second spectral imaging technique; measuring tissue respiration parameters of the test portion using a third spectral imaging technique; measuring the microvascular permeability parameter of the test portion using a fourth spectral imaging technique; and processing together the microvascular blood flow parameter, the microvascular reserve parameter, the tissue respiration parameter, and the microvascular permeability parameter using a processor configured to generate an aggregate microvascular parameter corresponding to microvascular function in the patient.

The present disclosure extends to a method of quantifying microvascular function in a patient, the method comprising: measuring two or more microvascular parameters selected from the group consisting of a microvascular blood flow parameter, a microvascular reserve parameter, a tissue respiration parameter and a microvascular permeability parameter; and processing the two or more microvascular parameters using a controller configured to generate aggregated microvascular parameters corresponding to microvascular function in the patient; wherein the two or more microvascular parameters are measured using spectral imaging techniques including microscopic spectral imaging, endoscopic spectral imaging, camera spectral imaging or combinations thereof.

The following detailed description will describe additional features and advantages that will be in part apparent to those skilled in the art from that description or may be learned by practice of the embodiments described herein, including the detailed description, claims, and drawings.

It is to be understood that both the foregoing general description and the following detailed description are exemplary and are intended to provide an overview or framework for understanding the nature and character of the claims. The various drawings are included to provide a further understanding, and are incorporated in and constitute a part of this specification. The drawings illustrate one or more embodiments and, together with the description, serve to explain the principles and operations of the embodiments.

Drawings

FIG. 1 is a schematic flow chart diagram illustrating a method for quantifying microvascular function in a patient according to one embodiment;

FIG. 2 is a schematic representation of a hyperspectral camera that may be used in the method;

FIG. 3 is a schematic block/flow diagram illustrating an interface between a user, a test section and a device according to one embodiment;

FIG. 4 is an exemplary representation of microvascular circulation;

FIG. 5 is a series of images taken in reflectance mode using hyperspectral cameras with different spectral bands, according to an example;

FIG. 6 is a perspective view of a mouth imaged in a transmissive mode using a hyperspectral camera, according to an embodiment; and

Fig. 7 is a schematic flow chart diagram illustrating a method for quantifying microvascular function in a patient according to another embodiment.

Detailed Description

The methods and corresponding devices herein use spectral imaging to image the microvasculature of a patient to obtain information about the local and global microvascular health of the patient. As understood in the art, the overall microvascular system health of a patient as described herein is correlated with prognosis of sepsis, however many other additional clinical applications for this technology are possible, for example in surgical, diagnostic and prophylactic applications. In some embodiments, the use of the method and apparatus is to provide a clinician with critical information about the health of a patient's microvasculature to better diagnose, treat, manage, and detect problems with current, suspected, or past sepsis. In some embodiments, quantification of microvascular function in a patient is measured as an aggregate microvascular parameter derived using a combination of two or more metrics: microvascular blood flow, microvascular reserve, tissue respiration and microvascular permeability. Current analysis techniques analyze and provide data for only one of these four metrics. The method associated with processing images acquired using spectroscopic techniques is a core principle disclosed herein. While modifications to pulse oximetry devices may provide illegal information about microvascular stores, and lateral flow dark field imaging devices may be able to provide information about permeability, none of these currently available devices combine microvascular blood flow, microvascular stores, tissue respiration, and microvascular permeability metrics to provide a global measure of a patient's overall microvascular health.

By using spectral imaging techniques to generate images of the microvasculature, these images will prove relevant and may find clinical acceptance, as the images and relevant data will be more familiar than pure spectral data. Methods known in the art generally fail to produce quantifiable data for multiple measures of microvascular dysfunction as disclosed herein.

Reference will now be made in detail to the present preferred embodiments, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.

Referring now to fig. 1, according to a first embodiment, a method 100 is disclosed for quantifying microvascular function in a patient, such as a human. The method 100 of quantifying microvascular function in a patient includes stabilizing a test portion of the patient for analysis at step 104. At step 108, a microvascular blood flow parameter of the test portion is measured using a first spectral imaging technique. At step 112, a measurement of a microvascular reserve parameter of the test portion is made using a second spectral imaging technique. At step 116, tissue respiration parameters of the test portion are measured using a third spectral imaging technique. At step 120, a fourth spectral imaging technique is used to measure the microvascular permeability parameter of the test portion. The method 100 of quantifying microvascular function in a patient further comprises processing a microvascular blood flow parameter, a microvascular reserve parameter, a tissue respiration parameter, and a microvascular permeability parameter together in step 124 using a controller configured to generate an aggregate microvascular parameter corresponding to microvascular function in the patient.

each of the first, second, third, and fourth spectral imaging techniques may be performed bedside, and may use one or more hyperspectral imaging cameras in conjunction with various wavelength bands to image and quantify, respectively, a microvascular blood flow parameter, a microvascular reserve parameter, a tissue respiration parameter, and a microvascular permeability parameter. The hyperspectral camera may include a wavelength dispersive element and a detection element. The wavelength dispersive element receives light and separates or disperses the light according to wavelength. The wavelength dispersive element may comprise optics such as prisms, lenses and mirrors. The wavelength dispersive element may be a spectrometer. The spectrometer may be an Offner spectrometer. The Offner spectrometer is a particularly compact spectrometer that enables the hyperspectral imaging system of the invention to be miniaturized. An example of an Offner spectrometer is described in U.S. patent No.7,697,137, the disclosure of which is hereby incorporated by reference in its entirety. The wavelength dispersive element may direct light to the detection element. The detection element may detect the wavelength, intensity, polarization, or other characteristic of the light dispersed by the wavelength dispersive element. The detection element may be a photodetector, a CCD device, a diode array, a focal plane array, a CMOS device, or other types of image detectors known in the art for sensing electromagnetic radiation reflected within a wavelength range associated with a physical object in a real world scene.

Each of the microvascular blood flow parameters, microvascular reserve parameters, tissue respiration parameters and microvascular permeability parameters may be measured by detecting one or more compounds in the blood, tissue, cells, extracellular fluid and/or arterial/capillary walls. For example, in some embodiments, the detected compounds may include carbon dioxide (CO2), oxygen (O2), hemoglobin, oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin, methemoglobin, nitric oxide, and/or other compounds known in the art that may be found in vivo using spectroscopic measurements. In addition, each of the microvascular blood flow parameter, the microvascular reserve parameter, the tissue respiration parameter, and the microvascular permeability parameter can be measured by monitoring the difference (Δ) or rate of change (kinetics) of the one or more detectable compounds described above using a combination of occlusion and reperfusion. By occluding and then re-perfusing the vascular system, the measured changes and/or kinetics of the detectable compound associated with the corresponding vascular parameter may provide a variety of useful information to the caregiver.

FIG. 2 shows a hyperspectral camera including a monolithic Offner spectrometer and a detector. The hyperspectral camera 140 includes a monolithic Offner spectrometer 148 within an optical enclosure 158. The hyperspectral camera 140 includes a slit 152 and a detector 154 attached to an optics housing 158. In the illustrated configuration, the monolithic Offner spectrometer 148 is a one-to-one optical relay made from a single piece of transmissive material 144 that includes an entrance surface 156, a first mirror 160 (formed when a reflective coating 178 is applied to the surface of the transmissive material 144 as illustrated), a diffraction grating 164 (formed when a reflective coating 178 is applied to the surface of the transmissive material 144 as illustrated), a second mirror 168 (formed when a reflective coating 178 is applied to the surface of the transmissive material 144 as illustrated), and an exit surface 172.

When the slit 152 receives the light beam 182 from a remote object (not shown) and directs the light beam 182 to the monolithic Offner spectrometer 148, the hyperspectral camera 140 operates to produce an image of the remote object over a continuous range of narrow spectral bands. The monolithic Offner spectrometer 148 diffracts the optical beam 182 and forwards the diffracted optical beam 186 to the detector 154. In particular, the slit 152 directs the light beam 182 to the entrance surface 156. The first mirror 160 receives the light beam 182 transmitted through the incident surface 156 and reflects the light beam 182 toward the diffraction grating 164. The diffraction grating 164 receives and diffracts the light beam 182 and reflects the diffracted light beam 186 to the second mirror 168. The second mirror 168 receives the diffracted beam 186 and reflects the diffracted beam 186 to the exit surface 172. The detector 154 processes the diffracted beam 186 received from the exit surface 172.

Still referring to fig. 2, transmissive material 144 is selected to have high transparency over the range of wavelengths obtained from the scene during imaging. The wavelengths of interest may include near infrared wavelengths, visible wavelengths, and/or ultraviolet wavelengths. Suitable materials for transmissive material 144 include plastics, dielectrics, and gases (e.g., air, nitrogen, argon, etc.). When a gas is used, first mirror 160, second mirror 168, and reflective coating 178 are affixed to optical housing 158 by posts or other mounts.

The detector 154 is selected to have a wavelength (color) sensitivity based on the type of transmissive material 144 used to fabricate the monolithic Offner spectrometer 148. For example, if the monolithic Offner spectrometer 148 is made of plastic (e.g., Polymethylmethacrylate (PMMA), polystyrene, polycarbonate), then the diffraction wavelength range will be primarily in visible light and the detector 154 may be a Complementary Metal Oxide Semiconductor (CMOS) camera 154. If the monolithic Offner spectrometer 148 is made of an infrared transmissive material, the detector 154 would be an IR detector, such as a mercury cadmium telluride (HgCdTe), indium antimonide (InSb) or lead sulfide (PbS) based detector.

the hyperspectral camera 140 may further include additional optics for receiving or directing the light beam 182 and/or the diffracted light beam 186 to or from different directions, allowing for flexible positioning of the slit 152 and/or the detector 154 relative to the optical housing 158. The hyperspectral imaging system may also include a battery module (not shown). The battery module may include a rechargeable battery and may be removably coupled to the hyperspectral camera, the mobile display device, or other modules of the hyperspectral imaging system. Battery power may also be provided by a battery contained within the mobile display device. The hyperspectral imaging system may also be adapted to receive power from an external battery.

referring now to FIG. 3, the hyperspectral imaging system 200 includes an illumination source 220, the illumination source 220 generating light that contacts the test portion 212 and is then transmitted or directed to the hyperspectral camera 140 and/or the scanning optics module 228. The hyperspectral camera 140 may include a controller 232 to process image data obtained from the patient. The image data may include spectral data, wavelength data, polarization data, intensity data, and/or position data. The controller 232 may receive image data from the test portion 212 or detection element via the processor 240 and transform or otherwise manipulate the image data into the aggregated microvascular parameters specified by the user 204. The user 204 may use the user interface 208 to select various specifications of the various hyperspectral cameras 140 and scanning optics modules 228, such as wavelengths used by the first, second, third, and fourth spectral imaging techniques. The data processing may include converting the image data into any of several visual forms known in the art, and may include shading, or other visual effects intended to represent the position, depth, composition, motion, or other characteristics of objects in the scene. In some embodiments, the data processing performed by processor 240 may include converting the image data into a corresponding microvascular blood flow parameter, microvascular reserve parameter, tissue respiration parameter or microvascular permeability parameter.

In particular, the image data may be used to map and/or measure the concentration of the component of interest, which may then be used to calculate the required parameters. A microvascular blood flow parameter is a measure of blood flow through a vessel or tissue. As described in more detail below, microvascular blood flow parameters may be calculated by measuring the change in spectral intensity speckle variation. The microvascular reserve parameter is a calculated quantity, which is an indicator of relative microcirculation perfusion reserve, calculated according to the equation MVR (%) [ 1- (q35/q45) ] 100 by using the ratio of average baseline perfusion (q35) to perfusion achievable at 45 ° (q 45). Perfusion is the process of fluid passage through the circulatory system to the organ or tissue, specifically, the delivery of blood to the capillary bed. As described below, the microvascular reserve parameter may be calculated based on the observed rate of response to ischemic stimulation. The tissue breathing parameter is a measure of the gas exchange that occurs between blood and tissue. As described below with respect to fig. 4, tissue breathing parameters may be calculated based on the concentrations of oxyhemoglobin and deoxyhemoglobin determined based on the image data. The microvascular permeability parameter is a measure of the ability of the vessel wall to allow small molecules (including drugs, nutrients, water, ions, etc.) or even whole cells (such as lymphocytes) to flow into and out of the vessel. The microvascular permeability parameter may be calculated based on a mapping of water movement after occlusion.

in additional embodiments, the data processing performed by controller 232 and/or processor 240 may include a transformation of the respective microvascular blood flow parameters, microvascular reserve parameters, tissue respiration parameters and/or microvascular permeability parameters to generate an aggregate microvascular parameter and/or an aggregate microvascular image.

The data received and/or processed by the hyperspectral camera may be transmitted to a mobile display device for further processing and/or display. Data transfer may be through a data interface, such as a data link or USB connection. The hyperspectral camera 140 may also include a memory 236. The memory 236 may be used to store image data. The image data may be unprocessed or processed image data. The image data stored in the hyperspectral camera may be downloaded to an external computer for processing. The image data stored in the hyperspectral camera may be processed offline.

The hyperspectral imaging system 200 may include a scanning optical module 228. The scanning optics module 228 may include movable optics for scanning a scene. The movable optics may acquire image data from slices of the scene and may be systematically repositioned or reconfigured to sample the scene continuously on a slice-by-slice basis. The slice image data acquired by the scanning optics may be directed to the hyperspectral camera 140 for acquisition and processing. The scanning optics module 228 may include rotatable optical elements, such as rotatable mirrors or lenses. The scanning optics module 228 may be removably coupled to the hyperspectral camera 140, the mobile display device, or a rechargeable battery module.

Still referring to FIG. 3, the illumination source 220, the hyperspectral camera 140, and the scanning optics module 228 together represent at least one spectral imaging technique 216. In some embodiments, two, three, four, or more spectral imaging techniques and their associated components may be coupled to the processor 240 to generate an aggregate microvascular parameter and/or an aggregate microvascular image.

The method of quantifying a microvascular blood flow parameter, a microvascular reserve parameter, a tissue respiration parameter, and a microvascular permeability parameter together using the hyper-spectral imaging system 200, and combining these parameters using the processor 240 to provide/generate an aggregate microvascular parameter and/or an aggregate microvascular image may be performed using a variety of different techniques. In some embodiments, the aggregate microvascular parameter may be one or more values corresponding to the overall or overall microvascular health of the patient. In other embodiments, the aggregate microvascular image may be an image corresponding to the patient's overall or overall microvascular health, for example, a heat map or other averaged image that brings corresponding microvascular blood flow parameters, microvascular reserve parameters, tissue respiration parameters and/or microvascular permeability parameters or data into the calculation of the image.

A microvascular blood flow parameter may be measured using a first spectral imaging technique. In some embodiments, the first spectral imaging technique may be a line scan spectral speckle technique. The line scan spectroscopic speckle technique is performed by stabilizing a test portion of a patient for analysis, and then using the hyperspectral camera 140 to image and capture data of the test portion. In some embodiments, a full spectrum scan of the test portion may be used. From data captured from the image using the hyperspectral camera 140, a column in the image is selected, either automatically or manually by the user 204, wherein the selected column contains a vessel of interest. Additional line scans at selected locations can be performed while keeping the test portion stable to measure and calculate blood flow at selected pixel groups by observing changes in spectral intensity speckle variations. Microvascular blood flow parameters may be measured using wavelengths between about 400nm to about 3000nm, about 400nm to about 1500nm, about 400nm to about 800nm, or about 530nm to about 580 nm. Both Diffuse Correlation Spectroscopy (DCS) and Diffuse Optical Spectroscopy (DOS) monitor speckle changes to examine arterial occlusion and vascular occlusion responses to establish microvascular blood flow parameters. In some embodiments, microvascular blood flow is quantified using a line-scan spectral speckle technique by scanning the entire area of the test portion and selecting the column in the image that contains the vessel of interest, and performing a line scan at that location while the tissue is held steady, and calculating the flow at the selected pixel set by observing the change in spectral intensity speckle variation. In other embodiments, the first spectral imaging technique may be a spectral technique including diffuse correlation spectroscopy, diffuse optical spectroscopy, or a combination thereof to detect arterial occlusion and vascular occlusion responses to calculate DCS/DOS flow values.

A microvascular reserve parameter may be measured using a second spectral imaging technique. In some embodiments, the second spectral imaging technique may observe capillary responses to ischemic stimuli in which blood supply is at least temporarily altered or shut off. By spectrally monitoring the rate of response to ischemic stimuli, the ratio of hemoglobin present before and after occlusion can be determined. By releasing the ischemic stimulus during the spectral scan, the test portion of the scan can be monitored during and after the release of the ischemic stimulus. The microvascular reserve parameter may be measured using a wavelength between about 400nm to about 1500nm, about 400nm to about 800nm, about 530nm to about 580nm, or about 440nm to about 460 nm.

Tissue breathing parameters may be measured using a third spectral imaging technique. In some embodiments, the third spectral imaging technique may use spectral classification such as pulse oximetry to image tissue respiratory molecules such as hemoglobin (Hb) and oxyhemoglobin (HbO 2). Referring to fig. 4, a representative perfusion region 260 where tissue respiration can be measured is shown, where tissue oxygenation is mapped as a function of position along the blood vessel. In some embodiments, sepsis is heterogeneous in its nature throughout the body, particularly its effects on the microvasculature. Therefore, it would be advantageous and possibly different from other techniques to be able to image and quantify large areas of interest. Tissue breathing parameters may be measured using wavelengths between about 400nm and about 1500nm, between about 400nm and about 800nm, between about 530nm and about 580nm, or between about 440nm and about 460 nm.

The microvascular permeability parameter may be measured using a fourth spectral imaging technique. In some embodiments, the fourth spectral imaging technique may image how water (H2O) permeates through multiple vessel walls of the microvasculature. By monitoring the water movement after application of the occlusion by spectroscopy, one can gauge the time required for the water level to return to normal. According to the Enhanced Permeability and Retention (EPR) effect, if the microvasculature leaks, it will take longer for water to leave the occlusion area. The microvascular permeability parameter may be measured using wavelengths between about 800nm to about 2 m. Hyperspectral imaging can also monitor wavelength bands of about 820nm and about 730 nm. Additional intensity bands at 2900nm, 1950nm and 1450nm can be monitored by hyperspectral imaging; a middle band of about 1200nm and about 900 nm; and weak bands at about 820nm and 730 nm.

referring to fig. 5, three different spectral keys (a-C) are used to show a patient occluding large blood vessels in the forearm. The a image uses white light, the B image uses VNIR (visible-near infrared) light, and the C image also uses VNIR light. As shown on the occluded forearm, hyperspectral imaging system 200 (fig. 3) may be used in reflectance mode to generate one or more of a microvascular blood flow parameter, a microvascular reserve parameter, a tissue respiration parameter, and a microvascular permeability parameter.

referring to FIG. 6, an oral imaging embodiment is shown in which transmittance may be measured by the hyperspectral imaging system 200 as shown in FIG. 3. In some embodiments, a hyperspectral imaging system 200 is employed, although it is contemplated that in other embodiments a multispectral imaging system may be used. Thus, any suitable imaging system may be selected as long as it is capable of detecting the particular compound to be imaged on the field of view, including but not limited to H2O, oxyhemoglobin, deoxyhemoglobin, and the like. The image of the patient's open mouth 600 depicts the general location 602 (black ring) to be imaged, as well as the location of the illumination source 220 and the hyper-spectral camera 140. Although in the embodiment depicted in FIG. 6, a hyperspectral camera 140 is shown, it is contemplated that in other embodiments, a scanning optical module 228 or other imaging system detector may be used in addition to the hyperspectral camera 140 or as an alternative to the hyperspectral camera 140.

In particular, in the embodiment depicted in fig. 6, the hyper-spectral camera 140 is located within the open mouth 600 of the patient while the illumination source 220 is located outside the mouth 600, with the location to be imaged 602 located between the illumination source 220 and the hyper-spectral camera 140, such that the illumination source 220 and the hyper-spectral camera 140 are positioned in a transmission geometry relative to the location to be imaged 602. As used herein, "transmission geometry" refers to an arrangement in which the location to be imaged 602 is oriented 180 ° from the hyper-spectral camera 140 and the illumination source 220, where the location to be imaged 602 is located between the hyper-spectral camera 140 and the illumination source 220. However, in some embodiments, the illumination source 220 may be located within the open mouth 600 while the hyperspectral camera 140 is located outside the mouth 600, with the location to be imaged 602 located between the illumination source 220 and the hyperspectral camera 140. While various embodiments herein contemplate that the illumination source 220 and the hyperspectral camera 140 are positioned in a transmissive geometry, it is also contemplated that in some particular embodiments a reflective geometry may be utilized. As used herein, "reflective geometry" refers to an arrangement in which the location to be imaged 602 is positioned parallel to the hyperspectral camera 140, or at some angle between 0 and 180, and the illumination source 220 directs light onto the location to be imaged 602 at a predetermined angle. In the reflective geometry, the hyperspectral camera 140 and the illumination source 220 are located on the same side of the location to be imaged 602. However, it is believed that a more significant tissue penetration depth can be achieved using the transmission geometry.

In fig. 6, the location to be imaged 602 is a portion of the patient's cheek 604, but other regions of the mouth may be selected. For example, the location to be imaged may include the lips, tongue, cheeks, or a combination thereof. Without being bound by theory, it is believed that measuring microvascular function using the buccal mucosa or tongue as the site 602 to be imaged may reduce temperature fluctuations as compared to using another site covered by skin (such as those sites described in more detail herein). In addition, it is believed that the microvasculature may be more easily exposed in the tongue due to the lack of skin. Thus, it is believed that such embodiments may result in an increase in signal-to-noise ratio, as well as a reduction in the variability of the measurements. However, it is contemplated that other locations may be employed, including but not limited to earlobes, fingers, toes, or the penis, breast or skin portion folded upon itself.

The illumination source 220 may be a coherent light source, such as a laser beam, or it may be an incoherent light source, such as a conventional light source, including but not limited to a filament, fluorescent tube, or Light Emitting Diode (LED) source. In some embodiments, the illumination source 220 to be used is selected based at least in part on the type of spectrum to be employed. In one particular embodiment, the illumination source 220 is a coherent light source and the spectral imaging technique employs a hyperspectral imaging technique, a line-scan spectral speckle technique, or a diffuse optical spectroscopy technique, as described in more detail herein. The illumination source 220 may use wavelengths from about 400nm to about 3000nm or from about 400nm to about 1500 nm. The particular wavelength of the illumination source 220 may vary depending at least in part on the parameter(s) to be measured.

in some embodiments, the vasculature of the site to be imaged 602 may be occluded by designing clamping mechanisms on both sides of the site. For example, the cheek 604 may be occluded using a ring clamp by placing one ring on the outside of the cheek 604 (near the illumination source 200) and one ring on the inside of the cheek 604 (near the hyper-spectral camera 140). To occlude the vasculature, the jaws may be closed to apply pressure to the cheeks 604 via the ring.

In practice, the illumination source 200 transmits light through the location to be imaged 602 and the hyperspectral camera 140 images the test portion and captures data, as described above and in more detail below. In various embodiments, the hyperspectral camera 140 may acquire images and data corresponding to microvascular blood flow of the patient within the location 602 to be imaged. However, it is contemplated that in other embodiments, as described above and below, other metrics such as microvascular permeability, tissue respiration, or microvascular reserve may be quantified.

Image stabilization and replication may help quantify these four metrics, so a repeatable graphic may need to be drawn or marked within the field of view of the hyperspectral camera to ensure that the images are identical. For example, when the images are aligned, the two images may be subtracted or correlated with a better degree of certainty. In some embodiments, the first, second, third, and fourth spectral imaging techniques each include microscopic spectral imaging, endoscopic spectral imaging, camera spectral imaging, or a combination thereof.

There are many possible locations on a patient to image the microvasculature: through the skin of the endoscope, the cheek (buccal mucosa), the ear, under the eye, and any internal organs during surgery (laparoscopic or open). In addition, the method may provide a transillumination rather than a reflection-based system. In some embodiments, the test portion comprises an arm, leg, neck, head, shoulder, stomach, hand, thigh, calf, heel, foot, toe, knee, finger, elbow, chest, neck, penis, breast, face, or combinations thereof. In other embodiments, the microvascular blood flow parameter, microvascular reserve parameter, tissue respiration parameter, and microvascular permeability parameter are each measured at the outer surface of the epidermis, dermis, subcutaneous tissue, buccal mucosa, infrapalpebral region, suprapalpebral region, ear, and any internal organ during surgery, laparoscopy, or endoscopy.

referring now to fig. 7, a method 300 for quantifying microvascular function in a patient is disclosed, according to a second embodiment. The method 300 of quantifying microvascular function in a patient includes stabilizing a test portion of the patient for analysis at step 304. The method 300 additionally includes measuring two or more microvascular parameters selected from the group consisting of a microvascular blood flow parameter, a microvascular reserve parameter, a tissue respiration parameter and a microvascular permeability parameter in step 308 and processing the two or more microvascular parameters using a controller configured to generate an aggregate microvascular parameter corresponding to microvascular function in the patient in step 312. The two or more microvascular parameters are measured using spectral imaging techniques including microscopic spectral imaging, endoscopic spectral imaging, camera spectral imaging or combinations thereof.

It will be appreciated that the descriptions summarizing and teaching the previously discussed method for quantifying microvascular function in a patient (which may be used in any combination) are equally applicable to the second embodiment of the present invention, which, where applicable, further discloses a method for quantifying microvascular function in a patient.

as described herein, the method of quantifying a microvascular blood flow parameter, a microvascular reserve parameter, a tissue respiration parameter, and a microvascular permeability parameter using hyperspectral imaging system 200, and combining these parameters using processor 240 to provide/generate an aggregate microvascular parameter as shown in fig. 3 may be performed using a variety of different techniques.

according to a third embodiment, an apparatus for quantifying microvascular function is provided. An apparatus for quantifying microvascular function includes a first spectral imaging technique for measuring a microvascular blood flow parameter, a second spectral imaging technique for measuring a microvascular reserve parameter, a third spectral imaging technique for measuring a tissue respiration parameter, and a fourth spectral imaging technique for measuring a microvascular permeability parameter. The apparatus for quantifying microvascular function further comprises a processor configured to generate an aggregate microvascular parameter corresponding to microvascular function in the patient by processing together each of a microvascular blood flow parameter, a microvascular reserve parameter, a tissue respiration parameter, and a microvascular permeability parameter.

it will be appreciated that the description of the methods for quantifying microvascular function in a patient discussed earlier (which may be used in any combination) are equally applicable to the third embodiment of the present invention, which further discloses an apparatus for quantifying microvascular function where applicable.

Those of ordinary skill in the art will appreciate that the configuration of the devices and other components described are not limited to any particular material. Other exemplary embodiments of the devices disclosed herein may be formed from a variety of materials, unless otherwise specified herein.

As used herein, the term "and/or," when used in a list of two or more items, means that any one of the listed items can be used alone, or any combination of two or more of the listed items can be employed. For example, if a composition is described as comprising component A, B and/or C, the composition may comprise only a; only B; only C; a combination of A and B; a combination of A and C; a combination of B and C; or a combination of A, B and C.

For the purposes of this disclosure, the term "coupled" (in all its forms, coupled, etc.) generally means that two components are connected (electrically or mechanically) directly or indirectly to each other. Such a connection may be fixed in nature or movable in nature. Such joining may be achieved with the two components (electrically or mechanically) and any additional intermediate members being integrally formed with each other or with the two components as a single unitary body. Unless otherwise specified, such connections may be permanent in nature, or may be removable or releasable in nature.

It is also important to note that the construction and arrangement of the elements of the apparatus as shown in the exemplary embodiments is illustrative only. Although only a few embodiments of the present inventions have been described in detail in this disclosure, those skilled in the art who review this disclosure will readily appreciate that many modifications are possible (e.g., variations in sizes, dimensions, structures, shapes and proportions of the various elements, values of parameters, mounting arrangements, use of materials, colors, orientations, etc.) without materially departing from the novel teachings and advantages of the subject matter recited. For example, elements shown as integrally formed may be constructed of multiple parts or elements shown as multiple parts may be integrally formed, the operation of the interfaces may be reversed or otherwise varied, the length or width of the structures and/or members or connectors or other elements of the system may be varied, and the nature or number of adjustment positions provided between the elements may be varied. It should be noted that the elements and/or components of the system may be constructed from any of a variety of materials that provide sufficient strength or durability in any of a variety of colors, textures, and combinations. Accordingly, all such modifications are intended to be included within the scope of this invention. Other substitutions, modifications, changes and omissions may be made in the design, operating conditions and arrangement of the desired and other exemplary embodiments without departing from the spirit of the present inventions.

Unless explicitly stated otherwise, any method set forth herein is in no way to be construed as requiring that its steps be performed in a specific order. Thus, where a method claim does not substantially recite an order to be followed by its steps or it is not otherwise specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that any particular order be inferred.

It will be understood that any described process or steps within a described process may be combined with other disclosed processes or steps to form structures within the scope of the present apparatus. The exemplary structures and processes disclosed herein are for illustrative purposes and are not to be construed as limiting.

It should also be understood that variations and modifications can be made on the aforementioned structures and methods without departing from the concepts of the present apparatus, and further it should be understood that such concepts are intended to be covered by the following claims unless these claims by their language expressly state otherwise.

The above description should be considered that of the illustrated embodiments only. Modifications of the apparatus will occur to those skilled in the art and to those who make or use the apparatus. Therefore, it is to be understood that the embodiments shown in the drawings and described above are merely for illustrative purposes and are not intended to limit the scope of the apparatus, which is defined by the following claims as interpreted according to the principles of patent law, including the doctrine of equivalents.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the invention.