Source: http://www.google.es/patents/US9345428
Timestamp: 2018-01-19 22:00:46
Document Index: 392915290

Matched Legal Cases: ['Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60']

Patente US9345428 - Hyperspectral imaging of angiogenesis - Google Patentes
The invention is directed to methods and systems of hyperspectral and multispectral imaging of medical tissues. In particular, the invention is directed to new devices, tools and processes for the detection and evaluation of diseases and disorders such as, but not limited to diabetes and peripheral vascular...http://www.google.es/patents/US9345428?utm_source=gb-gplus-sharePatente US9345428 - Hyperspectral imaging of angiogenesis
Número de publicación US9345428 B2
Número de solicitud US 13/678,513
También publicado como US8548570, US20070249913, US20130137949, US20140012135, US20140012140
Número de publicación 13678513, 678513, US 9345428 B2, US 9345428B2, US-B2-9345428, US9345428 B2, US9345428B2
Citas de patentes (56), Otras citas (49), Clasificaciones (13), Eventos legales (1)
Hyperspectral imaging of angiogenesis
US 9345428 B2
The invention is directed to methods and systems of hyperspectral and multispectral imaging of medical tissues. In particular, the invention is directed to new devices, tools and processes for the detection and evaluation of diseases and disorders such as, but not limited to diabetes and peripheral vascular disease and cancer, that incorporate hyperspectral or multispectral imaging.
one or more polarizers in optical communication with the first stage optic;
a diagnostic protocol module adapted to detect a particular characteristic of the in-vivo tissue; and
obtain a multispectrally or hyperspectrally resolved image based on the plurality of images, and
obtain a pseudo-color image of the region of interest based on the multispectrally or hyperspectrally resolved image, the pseudo-color image enhancing the visibility of the particular characteristic of the in vivo tissue present in the region of interest; wherein the pseudo-color image comprises:
(iii) a color intensity plane that represents reflectance of radiation having a spectral band contained within a region that is from about 450 nm to about 580 nm.
2. The multispectral or hyperspectral medical imaging system of claim 1, wherein the imaging system weighs less than 25 pounds.
3. The multispectral or hyperspectral medical imaging system of claim 1, wherein the plurality of LED lights is configured in a circular array about the first stage optic.
4. The multispectral or hyperspectral medical imaging system of claim 1, wherein at least one respective LED light in the plurality of LED lights is configured to emit radiation in the visible spectrum.
5. The multispectral or hyperspectral medical imaging system of claim 1, wherein at least one respective LED light in the plurality of LED lights is configured to emit radiation in the near-infrared spectrum.
6. The multispectral or hyperspectral medical imaging system of claim 4, wherein at least one respective LED light in the plurality of LED lights is configured to emit radiation in the near-infrared spectrum.
7. The multispectral or hyperspectral medical imaging system of claim 1, comprising a first radiation filter placed in front of a respective LED light in the plurality of LED lights and a second matching radiation filter placed in optical communication with the imaging sensor.
8. The multispectral or hyperspectral medical imaging system of claim 1, wherein a first polarizer in the one or more polarizers is placed in front of a respective LED light in the plurality of LED lights and a second polarizer in the one or more polarizers is placed in optical communication with the first stage optic.
9. The multispectral or hyperspectral medical imaging system of claim 1, wherein the imaging sensor is configured to detect radiation in the visible spectrum.
10. The multispectral or hyperspectral medical imaging system of claim 1, wherein the imaging sensor is configured to detect radiation in the near-infrared spectrum.
11. The multispectral or hyperspectral medical imaging system of claim 9, wherein the imaging sensor is further configured to detect radiation in the near-infrared spectrum.
12. The multispectral or hyperspectral medical imaging system of claim 1, wherein the diagnostic processor is further configured to provide an output to a video display.
13. The multispectral or hyperspectral medical imaging system of claim 1, further comprising a communication interface in electrical communication with the diagnostic processor.
14. The multispectral or hyperspectral medical imaging system of claim 1, wherein each respective spectral band in the plurality of spectral bands used by the diagnostic protocol module has a bandwidth of less than 20 nm.
15. The multispectral or hyperspectral medical imaging system of claim 1, wherein the diagnostic processor is further configured to:
divide the multispectrally or hyperspectrally resolved image of the region of interest into a plurality of radial segments; and
compare the particular characteristic of the in vivo tissue at a first respective radial segment in the plurality of radial segments to the particular characteristic of the in vivo tissue at a second respective radial segment in the plurality of radial segments.
16. The multispectral or hyperspectral medical imaging system of claim 15, wherein the comparison of the particular characteristic of the in vivo tissue at the first radial segment to the particular characteristic of the in vivo tissue at the second radial segment is used to evaluate at least one of wound healing, tissue regeneration, angiogenesis, vasculogenesis, arteriogenesis, infection, inflammation, microvascular disease, and changes in the tissue associated with therapy.
17. The multispectral or hyperspectral medical imaging system of claim 1, wherein the diagnostic processor is further configured to:
compare the particular characteristic of the in vivo tissue at a respective radial segment in the plurality of radial segments in a multispectrally or hyperspectrally resolved image of the region of interest acquired at a first point in time to the particular characteristic of the in vivo tissue at the same respective radial segment in the plurality of radial segments in a multispectrally or hyperspectrally resolved image of the region of interest acquired at a second point in time.
18. The multispectral or hyperspectral medical imaging system of claim 17, wherein the comparison of the particular characteristic of the in vivo tissue at the first point in time to the particular characteristic of the in vivo tissue at the second point in time is used to evaluate at least one of wound healing, tissue regeneration, angiogenesis, vasculogenesis, arteriogenesis, infection, inflammation, microvascular disease, and changes in the tissue associated with therapy.
19. The multispectral or hyperspectral medical imaging system of claim 17, wherein the comparison of the particular characteristic of the in vivo tissue at the first point in time to the particular characteristic of the in vivo tissue at the second point in time is used to evaluate the result of hyperbaric therapy delivered to assist in the healing of foot ulceration.
The present application is a continuation of U.S. patent application Ser. No. 11/692,131, filed Mar. 27, 2007, which issued as U.S. Pat. No. 8,548,570, and which claims priority to U.S. Provisional Application No. 60/785,977, filed Mar. 27, 2006, and is a continuation in part of U.S. patent application Ser. No. 11/689,783, filed Mar. 22, 2007, which issued as U.S. Pat. No. 8,224,425, and which claims priority to U.S. Provisional Patent Application No. 60/784,476, filed Mar. 22, 2006, and is a continuation in part of U.S. patent application Ser. No. 11/396,941, filed Apr. 4, 2006, which issued as U.S. Pat. No. 8,374,682, and which claims priority to U.S. Provisional Application No. 60/667,677, filed Apr. 4, 2005, and U.S. Provisional Application No. 60/785,977, filed Mar. 27, 2006. The present application is also a continuation in part to U.S. patent application Ser. No. 11/288,410, filed Nov. 29, 2005, which issued as U.S. Pat. No. 8,320,996, and which claims priority to U.S. Provisional Application No. 60/631,135, filed Nov. 29, 2004, U.S. Provisional Application No. 60/667,678, filed on Apr. 4, 2005, and U.S. Provisional Application No. 60/732,146, filed Nov. 2, 2005. All of these provisional applications, non-provisional applications, and patents are hereby incorporated by reference.
The invention is directed to methods and systems of hyperspectral and multispectral imaging of biological and medical tissues. In particular, the invention is directed to new devices, tools and processes for the detection and evaluation of diseases and disorders such as diabetes and peripheral vascular disease that are amenable to diagnosis using hyperspectral/multispectral imaging.
Diabetes afflicts an estimated 194 million people worldwide, affecting 7.9% of Americans (over 21 million people) and 7.8% of Europeans. Between 85% and 95% of all diabetics suffer from. Type 2 diabetes, although nearly 5 million people worldwide suffer from Type 1 diabetes, affecting an estimated 1.27 million people in Europe and another 1.04 million people in the United States1. Both Type 1 and Type 2 diabetic patients are at higher risk for a wide array of complications including heart disease, kidney disease (e.g. nephropathy), ocular diseases (e.g. glaucoma), and neuropathy and nerve damages to name a few2. The feet of diabetic patients are at risk for a wide array of complications, which are discussed below. Problems with the foot that affect the ambulatory nature of the patient are not only important from the standpoint of physical risk, but also convey an emotional risk as well, as these problems disrupt the fundamental independence of the patient by limiting his or her ability to walk.
Peripheral arterial disease (PAD) affects primarily people older than 55. There are currently 59.3 million Americans older than 55, and over 12 million of them have symptomatic peripheral vascular disease. It is estimated that only 20% of all patients with PAD have been diagnosed at this time. This represents a dramatically underpenetrated market. Although pharmacologic treatments for PAD have traditionally been poor, 2.1 million nevertheless receive pharmacologic treatment for the symptoms of PAD, and current diagnostic tests are not considered to be very sensitive indicators of disease progression or response to therapy. Additionally, 443,000 patients undergo vascular procedures such as peripheral arterial bypass surgery (100,000) or peripheral angioplasty (343,000) annually and are candidates for pre and post surgical testing. One difficulty in diagnosing PAD is that in the general population, only about 10%© of persons with PAD experience classic symptoms of intermittent claudication. About 40% of patients do not complain of leg pain, while the remaining 50% have leg symptoms which differ from, classic claudication.
Diabetic feet are at risk for a wide range of pathologies, including microcirculatory changes, peripheral vascular disease, ulceration, infection, deep tissue destruction and metabolic complications. The development of an ulcer in the diabetic foot is commonly a result of a break in the barrier between the dermis of the skin and the subcutaneous fat that cushions the foot during ambulation. This, in turn, can lead to increased pressure on the dermis, resulting in tissue ischemia and eventual death, and ultimately result in an ulcer.4 There are a number of factors that weigh heavily in the process of ulceration5—affecting different aspects of the foot—that lead to a combination of effects that greatly increase the risk of ulceration:6
The present invention overcomes the problems and disadvantages associated with current strategies, techniques, instrumentation and designs, and provides new tools and methods for detecting tissue at risk of developing into an ulcer, for detecting problems with diabetic foot disease, for assessing general tissue damage and metabolic state, and for evaluating the potential for wounds to heal.
One embodiment of the invention is directed to a medical instrument comprising a first stage optic responsive to illumination of tissue, a spectral separator, one or more polarizers, an imaging sensor, a diagnostic processor, a filter control interface, a general purpose operating module to assess the state of tissue in diabetic subjects following a set of instructions, and a calibrator. Preferably, the instrument further comprises a second stage optic responsive to illumination of tissue. Preferably, the set of instructions comprises preprocessing hyperspectral information, building a visual image, defining a region, of interest in tissue, converting the visual image into units of optical density by taking a negative logarithm of each decimal base, decomposing a spectra for each pixel into several independent components, determining three planes for an RGB pseudo-color image, determining a sharpness factor plane, converting the RGB pseudo-color image to a hue-saturation-value/intensity image having a plane, adjusting the hue-saturation-value/intensity image plane with the sharpness factor plane, converting the hue-saturation-value/intensity image back to the RGB pseudo-color image, removing outliers beyond a standard deviation and stretching image between 0 and 1, displaying the region of interest in pseudo-colors; and characterizing a metabolic state of the tissue of interest.
Preferably, defining the color intensity plane as apparent concentration of one or a mathematical combination of oxygenated Hb, deoxygenated Hb, and total Hb, oxygen saturation, defining the color intensity plane as reflectance in blue-green-orange region, adjusting the hue saturation comprises adjusting a color resolution of the pseudo-color image according to quality of apparent concentration of one or a mathematical combination of oxygenated Rb, deoxygenated Hb, and total Hb, oxygen saturation, adjusting the hue saturation further comprises one or a combination of reducing resolution of hue and saturation color planes by binning the image, resizing the image, and smoothing the image through filtering higher frequency components out, and further interpolating the smoothed color planes on a grid of higher resolution intensity plane.
Another embodiment is directed to quantifying an increase in the vasculature around a wound, and can be used for comparisons to adjacent tissue. Embodiments of this invention can be used to quantify an increase in vasculature as the result of a proangiogenic agent. Proangiogenic agents include, but are not limited to, vascular endothelial growth factors (VEGF), epidermal growth factor (EGF), tumor necrosis factor (TNF-α), interleukin-1α, and substance P. Other embodiments quantify a decrease in vasculature as a result of an antiangiogenic agent. Antiangiogenic agents include, but are not limited to, angiostatin, interferon-α, metalloproteinase inhibitors, and other angiogenesis inhibitor drugs approved by the FDA. Other embodiments are used to quantify enhanced wound healing due to a proangiogenic agent. Preferably, enhanced wound healing is quantified due to a proangiogenic agent in diabetics. More preferably, embodiments are used to quantify enhanced wound healing in diabetic foot ulcers due to a proangiogenic agent. Other embodiments are used to quantify delayed cancer growth due to an antiangiogenic agent. Other embodiments are directed to quantifying a reduction in cancer size due to an antiangiogenic agent. Other embodiments are used to quantify a decrease in cancer growth due to an antiangiogenic agent. Other embodiments are used to quantify enhanced wound healing due to negative pressure wound therapy. Other embodiments are directed to quantifying enhanced wound healing due to hyperbaric therapy.
Another embodiment is directed to automatic image processing/target recognition to highlight regions, tissues, or issues of interest. Another embodiment is directed to projecting an image into the field of view of the operator of an apparatus of this invention in such a way as to provide further useful information than simply viewing the target tissue unaided would provide. Other embodiments of this invention are directed to viewing tissues with an MHSI (multispectral/hyperspectral imaging) device. Other embodiments are directed to determining the status of a wound in absolute terms, as well as with respect to other tissues. Other embodiments are directed to quantifying the physiologic states of tissue, or of tissue-like compounds.
FIG. 3: OxyHb and DeoxyHb HSV/I color chart. Schematic representation of the MHSI display (left) showing the interplay between the oxyHb and deoxyHb coefficients and describing some of the potential physiological consequences of values of the MHSI. In one embodiment, tissues determined to have high oxyhemoglobin and low deoxyhemoglobin levels (upper left-hand quadrant of FIG. 3) are displayed in a color located proximal to a first terminal color (e.g., purple) along a color scale and are faded. These tissues are provided high oxygen delivery and have low oxygen extraction. The oxygen delivery in these tissues exceeds the tissue oxygen demand. These are healthy tissues having the lowest risk for ulceration and the highest probability of healing. In one embodiment, tissues determined to have high oxyhemoglobin and high deoxyhemoglobin levels (upper right-hand quadrant of FIG. 3) are displayed in a color located proximal to a first terminal color (e.g., purple) along a color scale and are bright. These tissues are provided high oxygen delivery and have high oxygen extraction. The balance of oxygenated blood in these tissues reflects high perfusion and high metabolic rates. These tissues are at lower risk for ulceration and have a probable likelihood of healing. In one embodiment, tissues determined to have low oxyhemoglobin and high deoxyhemoglobin levels (lower right-hand quadrant of FIG. 3) are displayed in a color located proximal to a second terminal color (e.g., brown) along a color scale and are bright. These tissues are provided low oxygen delivery and have high oxygen extraction. The oxygen demand in these tissues exceeds the oxygen delivery. These tissues are at risk for ulceration. In one embodiment, tissues determined to have low oxyhemoglobin and low deoxyhemoglobin levels (lower left-hand quadrant of FIG. 3) are displayed in a color located proximal to a second terminal color (e.g., brown) along a color scale and are faded. These tissues are provided low oxygen delivery and have low oxygen extraction, indicating the lowest perfusion. The oxygen delivery in these tissues exceeds is very low. These tissues have the highest risk of ulceration.
Wounds other than on the foot can be similarly assessed, such as sacral decubiti, other areas of pressure necrosis, prosthesis stumps, skin flap tissue before, after or during surgery, areas of tissue breakdown after surgery, and burn injuries. In preferred embodiments of this invention, wounds that are assessed by this invention's imaging methods include wounds due to acute injuries such as lacerations, burns, bruises, wounds from high impact traumas, fractures, abrasions, bone dislocations, transfusion-related acute injuries, etc. Current optical methods for evaluating tissues for the conditions described above include:
10. Areas of decreased MHSI indicate tissue at risk for on-healing, ulcer extension, or primary ulceration.
Another embodiment can involve dividing the region of interest into radial segments, pie like segments or a combination of the two or into squares or other geometric shapes and using these segments to compare and contrast different regions of tissue: in the same field of view or as compared to a similar field of view on the contralateral extremity or on another part of the body (such as the forearm, the upper leg, etc.). The radial segments can also be compared to similar locations at different time points to demonstrate change over time in response to different therapeutic interventions, changes in tissue physiology, either local, regional or systemic due either to progression or remission of disease or of the effects of topical or systemic medications or therapies.
Such measurements can be used to quantify an increase in the vasculature around a wound, and can be used for comparisons to adjacent tissue. Embodiments of this invention can be used to quantify an increase in vasculature as the result of a proangiogenic agent. Proangiogenic agents include, but are not limited to, vascular endothelial growth factors (VEGF), epidermal growth factor (EGF), tumor necrosis factor (TNF-α), interleukin-1α, and substance P. Other embodiments quantify a decrease in vasculature as a result of an antiangiogenic agent. Antiangiogenic agents include, but are not limited to, angiostatin, interferon-α, metalloproteinase inhibitors, and other angiogenesis inhibitor drugs approved by the FDA. Other embodiments are used to quantify enhanced wound healing due to a proangiogenic agent. Preferably, enhanced wound healing is quantified due to a proangiogenic agent in diabetics. More preferably, embodiments are used to quantify enhanced wound healing in diabetic foot ulcers due to a proangiogenic agent. Other embodiments are used to quantify delayed wound healing due to an antiangiogenic agent. Other embodiments are used to quantify a decrease in cancer growth due to an antiangiogenic agent. Other embodiments are used to quantify enhanced wound healing due to negative pressure wound therapy. Other embodiments are directed to quantifying enhanced wound healing due to hyperbaric therapy.
MHSI can be used to determine the capability of tissue to heal after debridement and hence the relative safety of pursuing such an approach. Similarly, MHSI can be used to help determine the lowest level of amputation that can be performed with successful healing. Similarly MHSI can be used to determine whether elective surgery to the foot, lower extremity or other body part where evaluation and or quantitation of perfusion, oxygenation, or tissue metabolism would assist in determination of the safety of undertaking such a procedure or the location in which to direct such a procedure. MHSI can be utilized before debridement, amputation or other surgery to make this determination or during debridement, amputation\or other surgery to better assess tissue to improve surgical outcomes.
Such measurements can be used for the determination of which patients or which wounds are likely to improve with any of the above mentioned therapies, which patients or wounds or portions of wounds are healing or worsening, when a given therapy is sufficient (this could be during or immedialty after application of a therapy such as hyperbaric therapy or a debridement or a particular cleansing or pharmaceutical regimen or after a longer course of several days of therapy such as a vacuum therapy. MHSI criteria can be used to determine when a tissue will accept a skingraft or benefit from an allograft or other skin replacement.
One embodiment uses a single system that employs light wavelengths ranging from the UV through the far infrared portions of the electromagnetic spectrum, as well as either side of this range as new technologies are developed allowing for use of a greater portion of this spectrum (e.g. UV, visible, the near infrared, short wave infrared, mid infrared or far infrared portion of the electromagnetic spectrum). Another embodiment uses a system that uses one or more wavelengths from more than one of these wavelength regimes. One such system using wavelengths from more than one of these wavelength groupings is shown in figure two. In other embodiments, a single sensor could be used to collect light from more than one wavelength regime.
If the spectral separator 42 does not internally polarize the light, the first polarizer 43 is placed anywhere in the optical path, preferably in front of the receiving camera 46. The second polarizer 41 is placed in front of illuminating lights 20 such that the incident light polarization is controlled. The incident light is crossed polarized with the light recorded by the camera 46 to reduce specular reflection or polarization at different angles to vary intensity of the reflected light recorded by the camera.
In operation, a portable or, semi-portable apparatus is employed within line of site (or with optical access) of the object or area of interest, e.g., diabetic foot with or without an ulcer, or general area of interest. An operator begins by selecting a diagnostic protocol module using the input device. Each diagnostic protocol module is adapted to detect particular tissue characteristics of the target. The diagnostic module could be specific for diabetes, for peripheral vascular disease, for venous stasis disease or for a combination of these disease states. As another example, a screening protocol for feet without ulcers or a potential for healing protocol for feet with ulcers. In an alternative embodiment, the apparatus may contain only one diagnostic module adapted for general medical diagnosis.
Diagnostic processor 38 responds to the operator's input by obtaining a series of transfer functions and an image, processing protocol and an image processing protocol from the selected diagnostic protocol module 56. The diagnostic processor provides the filtering transfer functions to the spectral separator 42 via its filter control interface 52 and then instructs the image acquisition interface 50 to acquire and store the resulting filtered image from the image sensor 46. The general-purpose operating module 54 repeats these filtering and acquiring steps one or more times, depending on the number of filter transfer functions stored in the selected diagnostic protocol module. The filtering transfer functions can represent bandpass, multiple bandpass, or other filter characteristics and can include wavelengths in preferably the UV, preferably the visible, preferably the NIR and preferably, the IR electromagnetic spectrum.
The unique cool illumination provided by the LED prevents overheating of skin which may result in poor imaging resolution. Preferably, the LED provides sufficient light while producing no other physical or physiologic effects such as, for example, minimal or no increase in skin temperature. This lighting system in combination with the polarizer allows adequate illumination while preventing surface glare from internal organs and overheating of skin. In certain embodiments, illumination can arise from any source meeting the needs of the device such as, for example, more passive sources such as room light or from sunlight.
In a preferred embodiment, a calibrator is included in, the system. Calibrator has an area colored with a pattern of two (or more) colors. To optimize use of the calibrator for this particular application where oxyHb and deoxyHb are important components of the solution, colors are chosen that have a distinct absorption band in the wavelength range similar to oxyHb and deoxyHb—preferably in the range 500-600 nm. The colors are placed into a pattern, preferably, a checker-board pattern, where 1 out of 4 squares has color1, and 3 out of 4 squares have color2. Thus, approximately 25% of the squares are color1 and 75% of the squares are color2. The system takes a hypercube being slightly out of focus—that provides blurring of colors into each pixel. From the spectra for each pixel, a linear composition of two spectra: one from color1 and another from color2 are observed. The recorded spectra are decomposed in a manner similar to a system that decomposes skin spectra into oxyHb & deoxyHb components. However, in this instance it takes pure color1 and color2 spectra from library instead of oxyHb & deoxyHb. Valid calibration reports concentrations of 75% for color2 and 25% for color1. Results are similar to skin analysis, where the output is approximately 90% of oxyHb and 10% of deoxyHb. Other embodiments include but are not limited to, changes to the pattern, the color concentration & intensity, and the number of colors.
In summary, the calibrator simulates the way the biological mixture (oxyHb+deoxyHb) is observed by using “optical” mixture via combination of pattern (with known spatial concentrations) and analog blurring (defocusing—for speed. Defocusing can also be done in the software through the use of computational filters) in such a way as to ensure that the entire MHSI system is functioning correctly and accurately.
In another preferred embodiment, diagnostic, protocol modules 56, printer 62, display 12, or any combination thereof; may be omitted from portable device 10. In this embodiment, acquired images are stored in storage device 60 during the medical procedure. At a later time, these images are transferred via a communications link to a second device or computer located at a remote location, for example, hospital medical records, for backup or reviewing at a later time. This second device can have the omitted diagnostic protocol modules, printer, display, or any combination thereof. In another embodiment, the stored images are transferred from portable device 10, located in the clinic, via a communications link to a remote second device in real time.
In a preferred embodiment the system has facility to project real-time hyperspectral data onto the operation field, region of interest, or viewing window positioned above the operating site through use of a Heads Up Display or other suitable technique allowing the user to overlay the image in a useful manner. Also, display completely separately for remote guidance (i.e. on a wall screen for a group of people to review in real time, or post procedure). The projected information has precise one-to-one mapping to the illuminated surface (e.g. wound, operating surface, tissue) and provides the user with necessary information in efficient and non-distractive way. When projected onto an overhang viewing window, the images (real-color and/or pseudo-color) can be zoomed in/out to provide variable magnification. This subsystem consists of the following elements: 1) image projector with field-of-view precisely co-aligned with the field-of-view of the hyperspectral imager, 2) miniature remote control device which allows the surgeon or podiatrist to switch projected image on and off without turning from the site of debridement and change highlight structure and/or translucency on the projected image to improve visibility of the features of interest as well as projected image brightness and intensity, 3) real-time data processing package which constructs projected image based on hyperspectral data and operator/surgeon input, 4) optional viewing window positioned above the operating site that is translucent for real observation or opaque for projecting pseudo-color solution or higher resolution images.
FIG. 2 shows the preferred system specifications along with a diagram of our focusing methodology and the optical design of the Spectral. Imager. In this embodiment, a liquid crystal tunable filters (LCTF's) was used as the wavelength selector and are coupled to complementary metal oxide semiconductor (CMOS) imaging sensors. Fitted with macro lenses and the positional light focusing system described below, the system has a preferred working focal length of roughly 1 to 2 feet.
7. Adjust the color resolution of the pseudo-color image according to quality of apparent concentration of oxygenated Hb, or deoxygenated Hb, or their mathematical combination, e.g. total Hb, oxygen saturation, etc. Preferably, reduce resolution of hue and saturation color planes by binning the image (e.g. by 2, 3, 4, etc. pixels), or/and by resizing the image, or/and by smoothing the image through filtering higher frequency components out. Interpolate the smoothed color planes on the grid of higher resolution intensity (value) plane
{right arrow over (S)}ij =∥c 1{right arrow over (OxyHb)}+c 2{right arrow over (DeoxyHb)}+c 3{right arrow over (Offset+c 4Slope)}∥2
Data in the following table represent typical oxyHb, deoxyHb, and SHSIO2 values for two body positions, forearm and foot, and for various stages of diabetes: nondiabetics, diabetics without peripheral neuropathy, and diabetics with peripheral neuropathy. In general, the value for oxyHb and SHSIO2 are lower in the feet of diabetic subjects with, neuropathy compared to the other two groups, a group at high risk for developing foot ulcers. In addition, the values for oxyHb, deoxyHb, and SHSIO2 depend on body location, that once calibrated can be accounted for by the diagnostic module.
MHSI oximetry values at baseline (prior
to iontophoresis of acetylcholine)
MSHI images have the ability to differentiate between regions of tissue associated with a present foot ulcer on the basis of biomarkers such as the oxyHb and deoxyHb coefficients. FIG. 6 shows an ulcer on the sole of the foot of a type 1 diabetic patient (ulcer 1). From the visible image on the left, little distinguishes one area of the ulcer from another. However when looking at the image with the MHSI, there is obvious discriminatory power between the state of tissue seen in the purple oval, which is likely to heal, and that surrounded by the black oval, which is tissue at risk for further ulceration. It is important to note that the skin on the sole of this patient's feet is highly calloused, with a thick stratum corneum, but one is still able to differentiate tissue based on its spectral signatures. Given, that the sole of the foot is often the site of the thickest stratum corneum on the body; the device works on all naturally or surgically exposed tissue or tissue otherwise visualized with laparoscopy, endoscopy, retinoscopy or other visualization techniques. Ulcer 2 was located on the dorsal surface of the foot, on the patient's big toe (FIG. 6). These images further show the ability to differentiate between tissue at risk and tissue likely to heal. Additionally, tissue surrounding a fungal infection on the patient's middle toe (bottom right-hand corner of the image) has an MHSI that can demonstrate inflamed or infected tissue.
The potential of hyperspectral imaging in diagnosing global microcirculatory insufficiencies and impacting on other complications of diabetes associated with the microvasculature besides foot ulcers. In FIG. 7, hyperspectral measurements from the feet of four patients, with the first two columns of images showing the MHSI of the soles of both feet, and the second two columns showing images of the dorsal surfaces of both feet after the application of ACH via iontophoresis. In the first three patients, an MHSI is seen that is much healthier than that of the fourth patient. Consequently, the fourth patient had a foot ulcer at the time of this study and has a previous history of ulceration. While the contrast between the data from the soles in these patients is striking, there is complementary information in, the data from the microvascular response shown in the two columns on the right. Note that the first three patients all have MHSI scores that contain purple information in response to vasodilation, while the fourth patient shows what would be considered an MHSI that was indicative of tissue that was at risk. Microcirculatory changes associated with the progression of diabetes can also be modified by different treatment and therapeutic regimens and with the overlay of other systemic diseases (such as congestive heart failure or hypertension) or treatments or therapies for systemic diseases.
Each radial pie segment was evaluated for signs of healing, nonhealing or progression in subsequent visits. MHSI measurements and clinical healing results were compared. MHSI algorithms were developed to identify changes associated with ulcer healing, nonhealing and progression. A primary endpoint evaluated the specific sectors of tissue around an ulcer that would heal, not heal or progress. The group estimates for oxyHb, deoxyHb, and O2Sat are given in the following table using a linear mixed effects regression model. Significant differences were seen for healing for the oxyHb and deoxyHb values. Patients who did not heal also demonstrated increased heterogeneity in distant foot and in arm measurements. For the 21 ulcers studied, the algorithm predicted 6 of 7 ulcers that did not heal and 10 of 14 ulcers that healed. Conclusion: MHSI identifies microvascular abnormalities in the diabetic foot and provides early information assist in managing foot ulceration and predict outcomes in patients with diabetes.
As depicted in FIG. 10, 50-micron resolution images of a rabbit's ear were taken with MHSI over a ten day period. In FIG. 10(a), the color image was reconstructed from MHSI data, showing a party of the observed area 50-by-40 mm, recorded at the baseline on day 1. The pseudo-image (b) was obtained as a result of hyperspectral processing, showing a distribution of the oxygenated (oxy) and deoxygenated (deoxy) hemoglobin in the underlying tissue at the same time.
Other embodiments and uses of the invention will be apparent to those skilled in from consideration of the specification and practice of the invention disclosed herein. All references cited herein, including all publications, U.S. and foreign patents, and patent and provisional applications, and all publications and documents cited herein for any reason, are specifically and entirely incorporated by reference. It is intended that the specification and examples be considered exemplary only.
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