WO2007022508A2 - Technologie hyperspectrale permettant d'evaluer et de traiter la maladie des tissus et du pied diabetiques - Google Patents

Technologie hyperspectrale permettant d'evaluer et de traiter la maladie des tissus et du pied diabetiques Download PDF

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WO2007022508A2
WO2007022508A2 PCT/US2006/032593 US2006032593W WO2007022508A2 WO 2007022508 A2 WO2007022508 A2 WO 2007022508A2 US 2006032593 W US2006032593 W US 2006032593W WO 2007022508 A2 WO2007022508 A2 WO 2007022508A2
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Prior art keywords
tissue
pressure
foot
areas
oxygenation
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PCT/US2006/032593
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English (en)
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WO2007022508A3 (fr
Inventor
Jenny E. Freeman
Svetlana V. Panasyuk
Michael J. Hopmeier
Derek Brand
Kevin Schomacker
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Hypermed, Inc.
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Priority claimed from US11/396,941 external-priority patent/US8374682B2/en
Application filed by Hypermed, Inc. filed Critical Hypermed, Inc.
Priority to CA2656016A priority Critical patent/CA2656016C/fr
Publication of WO2007022508A2 publication Critical patent/WO2007022508A2/fr
Publication of WO2007022508A3 publication Critical patent/WO2007022508A3/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/2823—Imaging spectrometer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
    • A61B5/412—Detecting or monitoring sepsis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/44—Detecting, measuring or recording for evaluating the integumentary system, e.g. skin, hair or nails
    • A61B5/441—Skin evaluation, e.g. for skin disorder diagnosis
    • A61B5/445—Evaluating skin irritation or skin trauma, e.g. rash, eczema, wound, bed sore
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
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    • A61B5/48—Other medical applications
    • A61B5/4884—Other medical applications inducing physiological or psychological stress, e.g. applications for stress testing
    • A—HUMAN NECESSITIES
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    • A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7271—Specific aspects of physiological measurement analysis
    • A61B5/7275—Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
    • G—PHYSICS
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
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    • G—PHYSICS
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    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/49—Scattering, i.e. diffuse reflection within a body or fluid
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
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    • G16H30/00—ICT specially adapted for the handling or processing of medical images
    • G16H30/20—ICT specially adapted for the handling or processing of medical images for handling medical images, e.g. DICOM, HL7 or PACS
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    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
    • G16H50/20—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
    • G16H50/30—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indices; for individual health risk assessment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/01—Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/026—Measuring blood flow
    • A61B5/0261—Measuring blood flow using optical means, e.g. infrared light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/103—Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
    • A61B5/1036—Measuring load distribution, e.g. podologic studies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/103—Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
    • A61B5/1036—Measuring load distribution, e.g. podologic studies
    • A61B5/1038—Measuring plantar pressure during gait
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/103—Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
    • A61B5/107—Measuring physical dimensions, e.g. size of the entire body or parts thereof
    • A61B5/1074—Foot measuring devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
    • A61B6/50—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications
    • A61B6/507—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications for determination of haemodynamic parameters, e.g. perfusion CT
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N2021/4704—Angular selective
    • G01N2021/4709—Backscatter
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/314—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/359—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using near infrared light
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
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    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/4795—Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
    • G—PHYSICS
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    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H30/00—ICT specially adapted for the handling or processing of medical images
    • G16H30/40—ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing

Definitions

  • This invention relates generally to the evaluation and care of the extremities and tissues of persons affected by the disease diabetes or other ailments or injuries that may affect the ability to perfuse, oxygenate or heal tissue, particularly to the measurement of changes in tissue oxygenation by natural pressures applied to the foot or other tissues of the body that may lead to ulceration or tissue injury and using this information to offload pressure or provide treatment of injured areas or in areas at high risk and thereby treat or prevent ulceration or other tissue damage.
  • the present invention is directed to apparati and methods for assessing tissue oxygenation, hydration, oxygen delivery and/or oxygen extraction with hyperspectral imaging and, in particular, tissue oxygenation associated with the foot and other tissues.
  • Diabetes is a chronic disease that affects up to 6% of the US population. When diabetes is present, either the body produces less or no insulin, and/or does not properly use insulin. Insulin is a hormone necessary to maintain blood sugar concentration at normal levels. When insulin is not produced or used correctly by the body, glucose remains in the bloodstream instead of being shuttled into cells for energy production, resulting in high blood glucose, or high "blood sugar" levels. High blood sugar can manifest its presence through multiple symptoms, including thirst, frequent urination, weigHT loss, increased hunger, blurred vision, irritability, tingling or numbness in the hands or feet, frequent skin, bladder, or gum infection, wounds that do not heal, and extreme, unexplained fatigue.
  • diabetes can lead to death, and even diabetics undergoing doctor- supervised treatment suffer an increased death rate compared to the average population. Diabetes is also associated with progressive disease of the microvasculature. Diabetics also face risk of multiple complications during their lifetime arising from the disease.
  • Some of the more serious complications include: heart disease (the leading cause of death in diabetics); stroke (risk of stroke is 2 to 4 times greater for diabetics); high blood pressure (about 73% of diabetics); blindness (diabetic retinopathy causes 12,000 to 24,000 new cases each year and diabetes is the leading cause of new cases of blindness among adults 20-74 years old); kidney disease (diabetes is the leading cause of treated end stage renal disease, accounting for 43% of new cases); nervous system disease (60-70% of diabetics have mild to severe damage, such as impaired sensation of pain in the feet or hands, slowed digestion, and carpal tunnel syndrome); dental disease (almost one-third of diabetics have severe periodontal diseases); pregnancy complications (poorly controlled diabetes before conception and during the first trimester of pregnancy can cause major birth defects in 5-10% of pregnancies and spontaneous abortions in 15-20% of pregnancies); and amputations (more than 60% of non-traumatic lower-limb amputations in the United States occur among diabetics).
  • Diabetic neuropathic foot disease is the most common cause of amputation in the United States and arises as a sequella of several of the complications listed above. These complications often stem from the disturbance of the body's metabolism caused by the prolonged high blood sugar. The disturbance includes increased levels of serum cholesterol, triglycerides, and glucosylated hemoglobin, which lead to precipitation of the substances along the small blood vessels (especially capillaries) everywhere in the body, and more so in terminal blood vessels, like those found in the legs and feet. This then leads to damage to or stenosis of the blood vessels, ultimately resulting in a condition termed diabetic microangiopathy, or literally, disease of the capillaries related to diabetes.
  • microvascular disease Longstanding microvascular disease that is widespread may decrease the total capacity of blood circulation within the body, which both directly and indirectly through kidney damage contributes to the high blood pressure condition referenced above.
  • the most dangerous effect of microvascular disease is occurrence of ischemia (decreased blood supply). This is often manifest in symptoms in the foot and leg, although all tissues may suffer ischemic effects from microvascular disease. This condition can progress with inadequate supply of oxygen and nutrients, eventually producing devitalization and change of texture and color of the foot, often starting with a toe or portion of the forefoot, which can then spread to the rest of the limb. This can take the form of tissue ischemia or frank gangrene.
  • Diabetic patients also have increased risk of complications associated with their lower extremities, especially the feet, due to nervous system disease, as described above, that can lead to a partial or complete loss of feeling.
  • a healthy person that starts to feel pain when subjected to continuous local pressure may shift their body or make other suitable alterations to automatically lessen the discomfort; however, patients having a sensory loss are deprived of this protection and are therefore common victims of pressure sores and open wounds that can become ulcerated. They also tend to balance themselves differently which can cause progressive alteration in the bony structure of the foot.
  • protocols capable of diagnosing potential areas for the development of plantar ulcers would be of great value in decreasing and preventing diabetic foot amputation.
  • protocols directed at diagnosing other areas of potential ulceration in diabetic and non- diabetic people, such as sacral ulcers, ulcers on amputation stumps or foot ulcers in athletes would be useful.
  • Special utility would occur in patients with diseases or therapeutic circumstances in which the skin may become fragile such as with scleroderma or other collagen vascular diseases or treatment with steroids.
  • Diabetic foot lesions are an underlying cause of hospitalization, disability, morbidity, and mortality, especially among elderly people.
  • a protocol for early detection of plantar ulceration would avoid the need for follow-up examinations, supplementary examinations, local wound debridement, orthopedic appliances, and in some critical cases frequent hospitalization, and amputation.
  • Estimates have shown that between 2-6% of diabetic patients will develop a foot ulcer every year, 4 ' 5 and that the attributable cost for an adult male between 40 and 65 years of age is more than $27,000 in 1995 US dollars for the two years after diagnosis of the foot ulcer. 4
  • Devices are known for indicating to persons having diminished sensation in the foot that their feet are being exposed to excessive stress conditions that could possibly lead to plantar ulcers or worse. Many of these devices include shoes, which detect excess pressure through a force sensor and signal the wearer of the existence that a threshold pressure has been reached. Examples of such devices are described in U.S. Pat. No. 5,566,479, U.S. Pat. No. 4,610,253, U.S. Pat. No. 4,647,918, U.S. Pat. No. 5,642,096, and U.S. Pat. No. 6,918,883 B2.
  • Diabetes is a chronic, life-threatening disease for which there is no known cure. It is the fourth leading cause of death in the United States. Over 21 million people in the United States have diabetes and more than 1,000,000 new cases are diagnosed each year. It is estimated that there are at least 194 million people with diabetes worldwide. Type I (or juvenile) diabetes, the most severe form of the disease, comprises 5-10% of diabetes cases and requires daily treatment with insulin to sustain life.
  • Neuropathy results in a loss of protective sensation in the foot, exposing patients to undue, sudden or repetitive stress. It can lead to atrophy of the small intrinsic muscles, collapse of the arch, and loss of stability in the metatarsal-phalangeal joints. Neuropathy leads to lack of awareness of damage to the foot as it may be occurring, physical defects and deformities 9 which lead to greater physical stresses on the foot. In addition, it can lead to increased risk of cracking and the development of fissures in calluses (a potential entry for bacteria and increased risk of infection). 10
  • Microcirculatory changes are seen in people with in association with hyperglycemic damage. 11 Functional abnormalities occur at several levels. Hyaline basement membrane thickening and capillary leakage may impair diffusion of nutrients.
  • Hyaline basement membrane thickening and capillary leakage may impair diffusion of nutrients.
  • the endothelium-dependent and endothelium-independent cutaneous vasodilation is lower in the foot.
  • diabetes causes a thickening of the endothelial basement membrane which in turn may lead to impaired endothelial cell function.
  • Peripheral vascular disease is "microvascular disease” caused by atherosclerotic obstruction of large vessels resulting in arterial insufficiency. 13 It is more common and more severe in diabetics. 14 Like non-diabetics, people with diabetes may develop atherosclerotic disease of large-sized and medium-sized arteries, such as aortoiliac and femoropopliteal atherosclerosis. However, significant atherosclerotic disease of the infrapopliteal segments is particularly common in the diabetic population.
  • the reason for the prevalence of this form of arterial disease in diabetic persons is thougHT to result from a number of metabolic abnormalities, including high LDL and VLDL levels, elevated plasma von Willebrand factor, inhibition of prostacyclin synthesis, elevated plasma fibrinogen levels, and increased platelet adhesiveness.
  • Musculoskeletal abnormalities can lead to harmful changes in biomechanics and gait, increasing the pressures associated with various regions of the foot. Alteration or atrophy of fat pads in the foot from increased pressure can lead to skin loss or callus, both of which increase the risk of ulceration by two orders of magnitude.
  • a lower extremity ulcer develops in about 15% of patients with diabetes during their lifetime. Foot pathology associated with vascular disease is a major source of morbidity among diabetics and a leading cause of hospitalization. The infected and/or ischemic diabetic foot ulcer accounts for about 25% of all hospital days among patients with diabetes. Costs of foot disorder diagnosis and management are estimated at over $2 billion annually. Foot ulceration precedes 85% of lower extremity amputations. Proper prevention, evaluation and treatment of diabetic foot disease would clearly improve the quality of life for people with diabetes.
  • the current market for the diabetes device industry is over $4 billion dollars, and growing 18% annually. This has been primarily in the glucose self-testing area, but demonstrates the large dollars spent annually by patients and the health care system (Medicare and over 60% of other insurers now cover the costs of these devices and supplies.) to take the preventative steps of maintaining better glycemic control to minimize diabetic complications. This demonstrates the huge and growing scope of the overall diabetes market and that this defines the basis of a receptive community of patients and caregivers that will embrace innovative technologies to combat the complications of type 1 and type 2 diabetes such as diabetic foot ulcer.
  • Diabetic feet are at risk for a wide range of pathologies including infection, ulceration, deep tissue destruction, and/or metabolic complications. Cumulative risks for ulceration include neuropathy, foot-ankle deformity, high planar pressure, poor glucose control, and previous ulceration.
  • Noninvasive techniques now employed in screening for vascular related foot disease have not proven useful in predicting or preventing disease. There is currently no method to assess accurately, rapidly, and noninvasively the predisposition to serious foot complications, to define the real extent of disease or to track the efficacy of therapeutics over time.
  • Diabetic vascular disease was once thought to involve only the microvasculature. This belief has since been dispelled at both the histologic and surgical levels. It is now possible to perform pedal bypass on the ischemic diabetic leg with improved limb salvage rate and reduction in amputation rates. Although it is possible to have adequate inflow and outflow to the diabetic foot, the microvasculature of the diabetic foot is physiologically altered in terms of flow regulation such that tissue loss can continue to occur.
  • Diabetes through several molecular mechanisms, functions to decrease the amount of available nitric oxide and thus reduces vasodilatation. The loss of vasodilatation is then thought to lead to early nerve dysfunction through ischemia and nutrient deprivation. 15 As neuropathy worsens, the nociceptive C fibers are impaired leading to a loss of the ability to mount a hyperemic response to inflammation. 1 This places the foot at risk in terms of infection and the ability to heal minor wounds. Successful revascularization has shown to improve the microcirculation of the skin, but does not completely alter the vasoreactivity or the nociceptive C fiber response. 17 This places the revascularized patient still at risk for slow healing of ulcers and infection which may further compromise the foot in spite of adequate inflow.
  • ulcers Another form of ulcer is arterial or ischemic ulcer. These occur in patients with peripheral arterial disease, with or without diabetes. Over 12 million Americans have peripheral arterial disease and the incidence is rising. Ischemic ulcers arise from a lack of perfusion to the tissues adequate to meet the demands of maintaining tissue integrity or of healing a minor injury. The lack of perfusion can be due to blockage of a major vessel, smaller vessels or due to microcirculatory disease. Treatment often requires arterial vascular bypass if this is anatomically feasible. Because of the decrease in perfusion in these ulcers, compression or pressure of any kind is contraindicated.
  • peripheral arterial disease By reducing flow to the foot, peripheral arterial disease can impede healing; reducing the supply of oxygen and nutrients that tissue requires to maintain the repair process and the viability of the dermal barrier, and significantly amplify the problems associated with diabetic microvascular and neuropathic disease.
  • peripheral angiograms 100,000 peripheral bypasses performed for limb salvage and 135,000 amputations are performed. 82,000 of these amputations are on type 1 and type 2 diabetics. Symptoms and current diagnostic tests are not very sensitive indicators of disease progression or response to pharmacologic therapy.
  • ulcers can also occur primarily associated with venous disease in patients with or without diabetes. About 70% of all leg ulcers are venous ulcers. Venous leg ulcer occurs secondary to underlying venous disease whereby blockage or valve damage leading to valvar insufficiency of the superficial, deep or perforating veins leads to venous hypertension. The ulcer usually presents within the region of the leg just above the ankle. In general, venous ulcers are treated with compression stockings, wraps or bandages. graduated compression can reduce the elevated pressures in the superficial veins. Compression may also improve the competence of the valves.
  • Sacral and other decubitus ulcers and other forms of pressure sores represent other examples of tissue damage that are to date unable to be prevented or treated in an optimized fashion. They also lead to loss of quality of life, loss of life itself and also represent a huge burden to the health care system. Such ulcers occur in debilitated, hospitalized, paralyzed, malnourished patient groups and in other situations in which pressure is placed on a region of tissue that in some way compromises its viability.
  • Limp amputation Limb amputation is a significant problem due to a variety of causes including trauma, diabetic disease and atherosclerosis.
  • the prevalence of amputation in the United States is approximately 1 million, 20 and over 43,000 new major amputations are performed yearly 21 .
  • the amputee is not only challenged by having the underlying disease or cause of amputation to deal with but also having to learn to use the artificial limb and be beleaguered by the attendant complications that may arise from poor prosthetic fit.
  • This may include recurrent residual limb breakdown predisposing the patient to pain, stump or tissue ulceration or breakdown, osteomyelitis, and sepsis as well as abnormal gait which can occur with improper fit with a secondary result in safety concern, an increase in the energy cost of ambulation and the predisposition to developing osteoarthritis.
  • the evaluation of prosthetic fitting and the addressing of residual limb complications is largely based on limited objective criteria, symptoms and complaints of the amputee and a rather subjective examination of the residual limb, prosthesis, and gait pattern.
  • the implementation of an improved method of assessment of the design of prosthetics would be an advantage, which would encompass both pressure and perfusion or oxygenation data would be an advantage.
  • Spectroscopy like many other analytical techniques, has undergone an evolution in terms of the types of research fields in which it is being utilized. From its early beginnings, it was, and continues to be, a plentiful research field in the hands of physicists. Later, chemists discovered that spectroscopy was a useful tool for the investigation of complex molecular structures. Later still, biologists discovered the usefulness of spectroscopy in the analysis of the structures of biomolecules. 22
  • Spectra are known to be sensitive to subtle changes in molecular composition and conformation. Spectroscopic analysis of biomolecules is a well established field; and, as any chemist knows, the spectrum of a molecule forms a unique "fingerprint" of that compound. However, this maxim only holds true for pure compounds. Tissues, be they human or animal, are an incredibly complex and highly variable mixture of compounds. The typical spectra obtained from tissue are a weighted average of the spectral features of each of the chemical constituents being sampled within a given sample volume, and as such, these spectra contain information about the biochemical state of the entire sample.
  • the major obstacle in medical spectroscopy has been sorting out useful diagnostic information from the inter and intra-sample variability. It is not nearly enough to take a spectrum from a healthy piece of tissue and a diseased piece of tissue, compare them, and make valid claims regarding their disease state. It is necessary to take into account the range of disease expressions which occur over a population, as well as the intrinsic variability of tissue spectra during such analysis. This process requires either large, statistically relevant numbers of spectra or a methodology that takes into account the intrinsic inter-sample variability and spatial heterogeneity.
  • Spectroscopic investigations of medical interest can be roughly divided into three major areas: clinical chemistry, where the goal is to provide a quantitative analysis of blood or other fluid analytes; pathology, which attempts to provide an alternative pathological assessment of a tissue biopsy; and in vivo analyses, where the analysis is done without the need for an invasive procedure.
  • clinical chemistry where the goal is to provide a quantitative analysis of blood or other fluid analytes
  • pathology which attempts to provide an alternative pathological assessment of a tissue biopsy
  • in vivo analyses where the analysis is done without the need for an invasive procedure.
  • tissue scattering properties are governed by the bulk scattering properties as well as their absorbance. Variations in tissue or blood analyte composition and/or concentrations will affect visible and near-IR tissue absorbance, while changes in the tissue blood- volume will affect the scattering properties.
  • in-vivo reflectance data is further complicated in that most physical situations which modify tissue absorbance also affect tissue scattering. Visible and near-IR spectroscopic methods have been used for decades in operating theatres in the form of pulse oximeters. These simple systems utilize the different oxyhemoglobin and deoxyhemoglobin absorption bands to determine arterial oxygen saturation.
  • a small portion of visible light shining on the skin of the foot is reflected off the surface. Most of the light passes into the skin through the stratum corneum (-25 ⁇ m thick on the dorsal surface and considerably thicker on the plantar surface of the foot), the epidermis (-100 ⁇ m thick) and into the dermis.
  • the structural features of the dermis (collagen and elastin fibrils, arterial and venous plexus) backscatter the light .
  • This backscattered or re-emitted light maintains the same wavelength spectrum as the incident light , but the intensity is modified by the absorption of skin chromophores. 22"25
  • the intensity modification is directly related to the concentration of chromophores present in the volume of skin investigated.
  • the log of the ratio of the re-emitted to the incident light intensity yields an absorption spectrum of the chromophores.
  • the primary absorbing chromophores in skin are oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) (present in the dermis), hemoglobin breakdown products such as bilirubin and methemoglobin, and melanin (present in the epidermis).
  • oxyHb oxyhemoglobin
  • deoxyHb deoxyhemoglobin
  • melanin present in the epidermis
  • the spectral properties have been reported. " Hemoglobin has distinct spectral signatures, depending on whether it is oxyHb or deoxyHb.
  • the in-vivo absorption spectra of these compounds have been well- characterized. 29 When compared to standard in-vivo absorption spectra, information about the type and also the relative concentration of chromophores in the region of investigation may be quantified. 30 ' 31
  • DR diffuse reflectance
  • HT or hyperspectral imaging is a method of "imaging” spectroscopy” that generates a "gradient map" of a region of interest based on local chemical compositions.
  • HT has been used in a wide variety of applications ranging from geological and agricultural to military and industrial, the major airborne applications are in mineral exploration, environmental monitoring and military surveillance. 3 2 HT has recently begun to be applied to medicine. 43"45 HT for medical applications has been shown to accurately predict viability and survival of tissue deprived of adequate perfusion, and to differentiate diseased (e.g. tumor) and ischemic tissue from normal tissue.
  • spectroscopy is used to monitor metabolic status in a variety of tissues; consider the spectroscopic methods used in pulse oximeters which utilize the different absorption bands oxy- & deoxy-Hb to estimate arterial oxygen saturation. No other method however provides information towards the spatial distribution or heterogeneity of the data.
  • Such spatial information is achieved by HT, where the multi-dimensional (spatial & spectral) data is represented in what is called a "hypercube" (see example in Figure 2).
  • the spectrum of reflected light is acquired for each pixel in a quadrant and each such spectrum is subjected to standard analysis. From this we create a map of the tissue based on the chemistry of the region of interest.
  • Tissues have optical signatures that reflect their chemical characteristics, can these can be measured using diffuse reflectance (DR) techniques with an optical probe placed at the site.
  • Tissues have two major optical chromophores of physiological relevance in the visible HgHT spectrum: oxyhemoglobin (OxyHb) and deoxyhemoglobin (DeoxyHb). When measured by hyperspectral technology, these chromophores delineate local oxygen delivery and extraction within the tissue microvasculature.
  • OxyHb oxyhemoglobin
  • DeoxyHb deoxyhemoglobin
  • these chromophores delineate local oxygen delivery and extraction within the tissue microvasculature.
  • ischemia such as in cases of limb ischemia or shock
  • the spatial composition of OxyHb and DeoxyHb varies across the skin, presenting a mottled appearance. This explains the variability and unreliability seen in tissue oximetry when measured at a single site.
  • Tissue undergoing wound healing also presents varying oxygenation status depending on where the probe is placed relative to the wound. This makes point measurements poor indicators of the wound healing process HT enables the efficient collection of data from over a million points, producing a 2-dimensional map of the state of tissue oxygenation including its spatial variation and thus provides an assessment of "oxygen anatomy".
  • Tissue oxygenation mapping is a compelling application of HT.
  • Single point DR spectroscopy has been used to study oxygen saturation in a variety of tissues and physiologic and pathologic conditions such as localized microcirculation, irritant-induced inflammation, ischemia-reperfusion injury, effect of UV irradiation, optical detection of cancer, and peripheral arterial disease.
  • a drawback of single point DR is that it provides no spatial information of tissue oxygenation and for complex systems it is clearly desirable to collect spatial information to monitor local variations, as different regions within the tissue may experience vastly different levels of blood flow, perfusion, and oxygen extraction. This is highly important when assessing either regional blood flow or the area around a wound. Systemic microvascular status, regional blood flow patterns and local physiology all play a role.
  • Hyperspectral imaging combines the chemical specificity of spectroscopy with the spatial resolution of imaging.
  • HT light is separated into hundreds of wavelengths using any of a number of possible spectral separators and collected on a charge-coupled device (CCD) in much the same way that a picture is taken by an ordinary camera.
  • CCD charge-coupled device
  • CMOS could be used instead of CCD, or some similar type of sensor.
  • a spectrum of penetrated and reflected light is acquired for each pixel in a region, and each such spectrum can be subjected to standard analysis. This allows the creation of an image representing the chemistry of the region of interest. 46
  • Hyperspectral Technology in one guise or another, has become a useful tool for the investigation of spatial heterogeneity in spectral properties in a variety of fields of study ranging from astronomy to medicine. Used for decades in airplane and satellite mounted systems for the mapping of land use and soil types, it has moved in the last five years into a large number of application areas. 39"41 Of particular interest here is the use of HT in the fields of biophysics and medicine. The combination of spectroscopic imaging and microscopy has proved very useful in the investigation of the spectral properties of slices of tissue. 42 ' 43 In addition to being useful for the investigation of microscopic structures, HT systems for imaging macroscopic structures have been shown to be useful in the monitoring of the spatial distribution of skin oxygenation. 44 ' 45 HT, however, allows mapping of the regional variations in hemodynamic parameters in response to tissue perfusion.
  • HT hyperspectral technology
  • Tissue which has insufficient oxygenation to remain viable is readily apparent from oxygen saturation maps calculated from near-IR spectral images acquired immediately following surgery; clinical signs of the loss of viability do not become apparent for 6 to 12 hours post-surgery. 8
  • HT has been studied in a hemorrhagic shock model.
  • An HT system was designed and built for in-vivo use on large animals and human subjects.
  • HT was performed on the ventral surface of the skin in a porcine model.
  • light pixels indicated areas of high relative oxygen saturation (O2-sat), whereas dark pixels indicated areas of low 02-sat.
  • O2-sat relative oxygen saturation
  • dark pixels indicated areas of low 02-sat.
  • HT demonstrated and quantified changes that were not visible to the naked eye. These data indicated early alterations in metabolism. As a more sensitive imaging tool, HT is useful to researchers and clinicians interested in understanding the underlying physiology or monitoring the effects of therapy in their patients. 49
  • Hyperspectral technology has several features making it a valuable technique for screening and evaluating the foot in diabetes and other peripheral vascular disorders.
  • the technique is noninvasive, rapid, and can be performed during regularly scheduled office visits without the necessity for prior patient preparation.
  • the clinical procedure takes under a minute and requires little more than positioning the patient carefully and taking a pre-programmed series of images at various wavelengths of light with the hyperspectral camera.
  • therapies are applied to the tissue.
  • the foot may be offloaded or pressure otherwise relieved from the injured area by bed rest, cut-outs in footwear, total contact casting or other similar treatments. Negative pressure may be applied to assist in healing.
  • compression stockings, bandages, wraps or mechanical pumping devices may be applied. Intermittent compression has been used to improve healing of tissue.
  • These therapies have also been applied to prevent tissue breakdown in tissue considered to be at risk for ulceration.
  • HT ulcerative colitis
  • Patients with peripheral vascular disease present with varying degrees of claudication, chronic wounds/ulcers, and gangrene.
  • Noninvasive clinical assessment of these patients is limited.
  • Ankle/brachial indices are limited by both inter- and intra-observer variability.
  • Ultrasound/laser Doppler only reveals flow within a vessel and not degree of perfusion in the tissue.
  • Transcutaneous oxygen tension can only evaluate a single point at a time.
  • HT bridges the gap between the above modalities and allows real time analysis of tissue perfusion in the entire limb.
  • one embodiment of the invention is directed to a gradient or index map for directing the treatment of ulceration of diabetic patient feet depicting the level of tissue oxygenation due to pressure from distribution of weight on the surface of the foot measured by hyperspectral technology, laser Doppler imaging, thermal imaging, or an analysis of angiographic, duplex ultrasound or MRA information.
  • Imaging or mapping data is collected while the patient is standing, walking or while seated, supine or prone.
  • Pressure information as measured by pressure mats or force plates and contour information measured through casting or laser surface scanning is used in combination with the HT oxygenation index map or other perfusion information to tailor make insoles or other orthotics to reduce pressure at high risk areas.
  • Some embodiments of the invention can be a method of ameliorating a disorder by determining a physiological state of a tissue in response to a physical stress comprising: determining the physiological state of the tissue, wherein said tissue is not subject to the physical stress, to obtained an unstressed physiological state; subjecting the tissue to a physical stress; determining the physiological state of the stressed tissue to obtain a stressed physiological state; and identifying areas of the tissue or corresponding aspects of the physical stress that can be modified to reduce the difference between the stressed and unstressed physiological states.
  • the method can comprise wherein determining the physiological state of the tissue, wherein said tissue is not subject to the physical stress to obtained an unstressed physiological state is determined from a control database of said physiological states.
  • the method can comprise comparing the stressed physiological state with the unstressed physiological state to identify areas of the tissue or corresponding aspects of the physical stress that can be modified to reduce the difference between the stressed and unstressed physiological states.
  • the tissue is a toe, a foot, a leg, a finger, a hand, an arm, or any portion thereof.
  • the physiological state comprises tissue oxygenation, tissue metabolism or tissue perfusion.
  • determining the physiological state is made by obtaining a hyperspectral or multispectral image of the tissue.
  • the invention can comprise a method for designing a prosthetic device comprising: generating HT gradient map of the stressed verses the unstressed tissue according to the method of claim 11 ; identifying areas of the tissue that are at risk for ulcer formation from said gradient map; and designing the prosthetic devise to reduce pressure to those areas of the tissue identified to be at risk from the gradient map.
  • the design reduces the risk of tissue ischemia in unbroken skin, formation of an ulcer or wound, formation of a plantar ulcer, venous stasis, venous ulcer disease or an infection.
  • inventions of the invention can comprise a method for orthotic treatment for preventing plantar ulcer formation comprising: generating a hyperspectral image, gradient map of the sole of a foot; identifying areas of the sole that are at risk for ulcer formation from said gradient map; redistributing pressure from said areas.
  • inventions of the invention can comprise a method for orthotic treatment in preventing ulcers on the tissue of a foot or limb stump comprising: obtaining a HT map of the tissue that combines information about pressure placed by a prosthetic device on the tissue and gravity, and adequacy of tissue oxygenation, tissue metabolism or tissue perfusion of the tissue; and modifying the prosthetic device to maximize tissue oxygenation, tissue metabolism or tissue perfusion of the tissue.
  • inventions of the invention can comprise an instrument which comprises: a collector for collecting data on pressure or shear stress of a tissue; another collector for collecting data on tissue oxygenation or perfusion; a register for combining both sets of data into a single tissue map.
  • the instrument further creates an orthotic, prosthetic or cushioned surface.
  • the orthotic, prosthetic or cushioned surface created serves to protect diseased tissue or tissue at risk for disease.
  • inventions of the invention can comprise a method for diagnosing a tissue comprising: collecting first information on pressure or shear stress of said tissue; collecting second information on tissue oxygenation, tissue metabolism or tissue perfusion information of said tissue; and combining both first and second information to identify portions of said tissue that are diseased or susceptible to disease
  • the method provides information about the tissue of a patient which is then used in modifying the environment of a patient or treat disease of said tissue.
  • inventions of the invention can comprise a method for treating a disease or disorder comprising: combining information regarding pressure or shear stress on a tissue with tissue oxygenation, tissue metabolism or tissue perfusion information of said tissue; identifying from the combined information portions of said tissue that are diseased or susceptible to disease; and modifying the environment of a patient to prevent or treat the disease or disorder.
  • Other embodiments of the invention can comprise a method of ameliorating a disorder by determining a physiological state of a tissue comprising: determining tissue oxygenation, tissue metabolism or tissue perfusion information of said tissue; determining pressure or shear stress on said tissue; identifying areas of the tissue or corresponding aspects of the physical stress that are indicative of susceptibility to disease; and modifying an environment around said identified susceptible tissue.
  • FIG 1 The image illustrates a normal foot with characteristically lower HT values seen in the absence of a wound. Note the registration target that allows the proper registration of sequential scans to form the tissue maps presented. In this image a pressure point is denoted cause by recent pressure from a tightly fitting shoe.
  • FIG 2 Picture of claudicated foot at baseline and after exercise.
  • Angiography showed evidence of L common femoral artery occlusion. Long segment occlusion precluded successful angioplasty/stent.
  • the study showed reconstitution before the SFA/profunda bifurcation with good distal runoff.
  • the top row demonstrates changes due to vascular compromise seen at baseline, including an "island of ischemia" in the center of the left forefoot. Before we started the study the subject pointed to this region as the place that had dysesthesias and discomfort long before claudication started.
  • the bottom row shows dramatic changes after brief exercise (until pain occurred while he was carrying a box and walking briskly for 1 minute, which is typical of his work requirements). An island of ischemia is observed in the right foot following exercise.
  • FIG 3 Ulcer healing prediction algorithm using HT -oxy > 45 to predict healing in ulcer subjects from Phase I. IfHT COM-OXY is greater than 45, then it is likely the ulcer will heal.
  • FIG 4 Type 1 diabetic subject with a deep ulcer located under the 1 st metatarsophalangeal joint. The Left Panel presents the color image of the ulcer. This image demonstrates use of a mosaic formed from two separate images and a method of analysis using a radial map and segments around the ulcer. The right image shows the hyperspectral composite image with a radial map centered on the ulcer. The radial map has 20 circles spaced 1 mm apart that are divided into 8 segments forming a maximum of 200 segments in which the mean values of oxyhemoglobin and deoxyhemoglobin are calculated and presented.
  • FIG. 1 The regions of ulcer extension (non-healing set) provide a surrogate for definition of tissue at risk in a foot with unbroken skin.
  • Each Point consists of illumination/excitation and collection fibers at a defined spacing (or spacings) or a defined geometric arrangement.
  • the collection fibers are aligned spatially on a detector such as a CCD or a diode array such that the spatial location of the fibers is defined, therefore maintaining the spatial information obtained.
  • a spectral separator either prior to the light entering the illumination fibers or prior to the emitted light falling on the detector or detectors, this allows the spectral separation of the light and for MHSI to be conducted.
  • Each fiber could also have a strain detector to measure pressure.
  • Embodiments of the invention combine in-vivo spectroscopy and hyperspectral technologies with an understanding of physiology, wound care, foot care and conditions and the clinical management of people with diabetes, peripheral vascular disease, venous disease and metabolic disturbances or other medical conditions that impair wound healing or tissue integrity.
  • Hyperspectral technologies and/or hyperspectral imaging such also includes multispectral imaging.
  • a tissue oxygenation map as measured by hyperspectral technology is used by itself or in combination with contour or pressure maps to define areas of tissue at risk of ulceration.
  • An HT map is designed to show the spatial distribution of oxyhemoglobin and deoxyhemoglobin in tissue.
  • the pseudo-colors and brightness level presented in the image depend on the levels of these two components as determined on a pixel by pixel basis. Sites having low values of oxyhemoglobin (high risk) are typically depicted as grayish yellow while areas of high oxygenation are reddish purple.
  • Tailored orthotics insoles for shoes as one example
  • Pressure maps as measured by force plates and contours as measured by scanning methods or from casts can be further used to distribute the remaining pressure to the rest of the foot.
  • the tailored orthotics can take the shape of the foot while having areas designed to offload pressure at selected sites.
  • the insole can be made with a high density plastic or rubber material with a lower density foam or polymer at the sites at risk. Pockets of silicone gels or fluids can be used to further reduce impact pressures.
  • HT maps are taken with the patient seated or lying down, with no weight bearing. This information is then paired with digital or digitalized data obtained from pressure or contour measuring devices in order to generate an advanced orthotic. Image registration techniques are used to fuse the images and an algorithm applied to instruct the orthotic any one or any combination of these measurements is used to assess the adequacy of tissue perfusion to optimize an orthotic for use under real world conditions.
  • images of the foot taken after walking in a given shoe, footwear, or orthotic is used to determine points of increased irritation of the foot to assist in optimizing the footwear.
  • Figure 1 shows an HT map which demonstrates a pressure point created by suboptimal foot wear. This map provides novel information for use to modify standard methods of orthotic or footwear construction to relieve pressure in areas identified by HT mapping.
  • tissue is not on the foot sole, and standard methods to create an orthotic pressure measurement or molding while standing would not address this area on the lateral/dorsal foot surface.
  • HT maps is obtained of an amputation stump either with or without weight bearing and with or without exercise for evaluation of an existing prosthesis or design of a new one.
  • the HT map is obtained after exercise on a treadmill.
  • Figure 2 demonstrates a patient with left leg claudication with an obvious "island of ischemia" demonstrated by a localized region of low oxyhemoglobin readings on the HT map of his left foot sole at rest.
  • the right foot which has no major abnormalities at rest, demonstrates an area of decreased tissue oxygenation after exercise.
  • This HT map after exercise can be used in conjunction with contour or pressure measurements to create optimized footwear.
  • Measurement of tissue perfusion, oxygenation, oxygen delivery or oxygen extraction by HT provides additional information to assist the physician in early diagnosis, prevention, treatment selection and treatment monitoring in such a way as to provide benefit to patients with tissue breakdown or those at risk for tissue breakdown.
  • HT maps are taken when pressure is off of the area of interest and compared with those taken after the area of interest is positioned on a given surface. This is used for modifying the surface or providing cushioning in appropriate locations, hi one embodiment this takes the form of a specifically contoured "doughnut".
  • the HT map provides information relative to the adequacy or inadequacy of the bed or wheelchair padding or pressure and provides information or recommends local modifications of the surface supporting the body to minimize pressure in areas most at risk. For example, an HT map of a paralyzed patient's buttocks is taken while lying prone and then again after sitting in his wheelchair. Pressure points noted by HT are identified and the chair contour or consistency of material modified in these regions. Because of the spatial map generated by HT has a spatial resolution of 100 microns, the contour of the seating material can be very precisely constructed.
  • HT measurements provide information about all of the surrounding tissue and the adequacy of perfusion elsewhere.
  • HT measurements are taken with the patient prone and the ulcer and surrounding skin in the baseline, non weight bearing state.
  • HT measurements are taken from underneath the surface, through a transparent surface on which the patient is lying. .
  • two sets of HT measurements are taken, one while the tissue is not exposed to weight bearing and one after the patient was lying on whatever surface was used to position him/her.
  • a feedback loop is created to develop a "smart bed” or “smart cushion” which was transparent and allowed for measurement of HT in real time.
  • tissue oxygenation decreases in a certain region due to pressure, the bed or cushion would shift its properties to decrease pressure on areas of decreased perfusion. This is done by hydraulic, air pressure, thermal or other means.
  • HT mapping information is utilized to direct the administration of other therapies to alter the relationship between oxygen delivery and oxygen demand in any given region such as providing heat, cooling, vasodilators, or other pharmacologic agents.
  • Patients with early stage peripheral vascular disease with only the early manifestations of mild claudication may have islands of ischemia visible by HT either at rest or after exercise as on a treadmill. These patients may benefit from either earlier angiography and endovascular or vascular surgical repair or by construction of orthotics or footwear that protects the areas demonstrated either before or after exercise to have a decrease in HT measurements of tissue oxygenation.
  • HT oxygenation mapping combines information about oxyhemoglobin and deoxyhemoglobin into a two dimensional colorized representation.
  • One embodiment of the invention speaks to the use of HT oxygenation mapping for the adjustment of pressure on tissue regions to prevent tissue breakdown.
  • Tissue demonstrated to be at risk by HT oxygenation mapping is treated by delivering reduced pressure to the site, by delivering reduced pressure to the site, by delivery of additional pressure to the site (as in the case of venous ulcers or to instill medications ), by delivery of essentially zero pressure to the site or by delivery of negative pressure to the site.
  • HT measurement is combined with pressure measurements obtained from the sole of the foot while standing or walking or from any other body part that is in prolonged contact with a surface such as a wheelchair or bed.
  • HT measurements are combined with pressure measuring techniques in an index map that reflects both measurements. To do so, HT measurements and an image of the foot created by one of the pressure measuring techniques are co-registered into a single index map.
  • modifications of the HT measurement system optics and instrumentation are undertaken to acquire data from underneath the patient's foot while standing simultaneously with measurements of tissue contour achieved with a NIR scanning technique. The images will be co- registered and an algorithm for synthesizing the pressure and tissue oxygenation or perfusion data will be utilized to generate an index map which delivers an optimized pressure profile for orthotic, footwear, prosthetic or cushion construction.
  • the pressure measurements could be done with pedobarograph or other pressure measurements and HT maps being performed sequentially and then integrated later. If the pressure measurement technique provides a hard copy of the information not in digitized format, one embodiment of the invention will scan in the pressure data, place in digital format, coregister with HT mapping data, run an algorithm for synthesizing the pressure and tissue oxygenation or perfusion data to generate an index map which delivers an optimized pressure profile for orthotic, footwear, prosthetic or cushion construction.
  • Similar measurements can be taken by placing a pressure pad on the bed or wheelchair surface of a debilitated patient to demonstrate areas of increased pressure on the skin due to bony structures or body conformation.
  • a clear surface is used and NIR scanning provides contour information for use in conjunction with HT maps as described above.
  • modification of the surface or device to alter the pressure on the tissue can be undertaken on the basis of HT mapping data alone, which inherently contains some data related to pressure or shear stress on the tissue.
  • HT mapping data alone, which inherently contains some data related to pressure or shear stress on the tissue.
  • combination of HT maps or other oxygenation or perfusion information with tissue pressure or contour information are used to modify the surface or device to alter the pressure on the tissue.
  • a "smart system” can be created to obtain HT data in a continuous or intermittent fashion and the pressure can be automatically adjusted either continuously or intermittently based on the HT map or other oxygenation or perfusion measurement.
  • a care giver can obtain the information and make the adjustments to the pressure modifying device.
  • One embodiment of the invention here pertains to utilizing HT mapping to identify areas of tissue most at risk and combining this with contour or pressure mapping data that has been used to apply uniform pressure, to design orthotics or cushions to deliver pressure tailored to the needs of the tissue.
  • HT mapping will be paired with any of the following pressure measuring techniques. To do so appropriate modifications of both the HT instrumentation and the pressure measuring devices will be undertaken to achieve data most useful for combination. Unique algorithms will be required for pairing with any one of the specific devices or technologies listed:
  • HT mapping demonstrates pressure points in most patients by delivering measurements with increases in tissue oxygenation and total hemoglobin to the area. In some patients with ischemia, pressure points are manifest by a decrease in tissue oxygenation and total hemoglobin from baseline after exercise.
  • HT mapping is combined with data derived from a method of measuring pressures and forces applied to the foot is via an ultrasonic method.
  • simultaneous measurement of force applied to the tissue during a quasi-static computer controlled compression and ultrasonic images of the underlying bone are obtained.
  • a cylindrical pexiglassrod is attached to the end of an trasound probe.
  • a force transducer is mounted with the probe, and the plexiglass rod is slowly advanced into the tissue until the applied pressure reaches a specified amount (such as approximately 400 kPa).
  • 50 HT maps are recorded as are ultrasonic images of the foot and the magnitude of the applied force are continuously recorded throughout the experiment. These data are then used to construct force- displacement curves and combined pressure/oxygenation index maps of the tissue.
  • HT mapping could be integrated into the biomechanical assessment of human-based load carriage system assessment for the objective evaluation of biomechanical aspects of load-bearing webbing, vests, packs and their components.
  • Another embodiment combines HT mapping or tissue perfusion measurements with an instrument] devised for the in vivo examination of the dynamic biomechanical stiffness and viscoelasticity properties of skin such as the dynamic biomechanical skin measurement (DBSM) probe described by Elizabeth K Dawes-Higgs et al. 52
  • DBSM dynamic biomechanical skin measurement
  • Another embodiment combines HT or other tissue oxygenation or perfusion information with mapping data generated by a compound ultrasound sensor and pressure transducer system such array system described by Wang et al. 53 for use in the measurement of buttock soft tissue in vivo to assess susceptibility to pressure ulcer formation.
  • Another embodiment combines HT or other tissue oxygenation or perfusion information with pressure and/or shear stress and/or ambulatory motion information provided by videofluoroscopy, spiral CT scan of the amputated extremity or pressure measuring pads, transducers other or devices placed in prosthetic devices in order to optimize prosthetic fit and prevent complications.
  • Another embodiment of the invention is directed to a method of measuring tissue oxygenation changes associated with tissue ischemia or damage.
  • HT measurements are used to demonstrate not only tissue oxygenation but also adequacy of oxygenation for the tissue to either remain viable (in the as yet uninjured situation) or to heal if an ulcer or area of breakdown is already present.
  • HT provides information regarding both tissue perfusion and metabolism, displaying images that identify specific areas of the foot or other tissue that may be at risk for ulceration, and deliver information to the physician to assist him in identifying specific protective measures to lower the risk of ulcer formation, such as orthotics or offloading.
  • HT tissue perfusion
  • Hyperspectral imaging has several features that may lead to it becoming a valuable technique for screening and evaluation of the foot in diabetes and other peripheral vascular disorders. Among other capabilities, hyperspectral imaging technology can identify and assess areas of tissue at risk and islands of ischemia. Point measurements such as TcPO2 or global measurements such as duplex scanning, PVR or ABI will not identify such problem areas. In one embodiment, however, the orthotic design is modified by applying a scalar value associated with one of the point measurement or regional measurement techniques described above.
  • HT oxygenation mapping combines information about oxyhemoglobin and deoxyhemoglobin into a two dimensional colorized representation.
  • One embodimenet of the invention speaks to the use of HT oxygenation mapping for the adjustment of pressure on tissue regions to prevent tissue breakdown.
  • Tissue demonstrated to be at risk by HT oxygenation mapping could be treated by delivering reduced pressure to the site, by delivering reduced pressure to the site, by delivery of additional pressure to the site (as in the case of venous ulcers or to instill medications ), by delivery of essentially zero pressure to the site or by delivery of negative pressure to the site.
  • HT measurement could be combined with pressure measurements obtained from the sole of the foot while standing or walking or from any other body part that is in prolonged contact with a surface such as a wheelchair or bed.
  • Measurements that measure pressure or contour of the foot have been described.... In general the patient stands or walks on the device, but similar pressure measurements can be taken by placing a pressure measuring pad or device in a shoe or orthotic for continuous measurement.
  • Modification of pressure to tissue can be undertaken on the basis of HT mapping data or on the combination of HT maps or other oxygenation or perfusion information with tissue pressure or contour information.
  • this can occur in a continuous fashion and the pressure can be automatically adjusted based on the HT map or other oxygenation or perfusion measurement.
  • Other embodiments can include the prevention of further disease, diagnosis of disease, the monitoring of therapy, and a general assessment of microvascular status and progressive of disease.
  • HT processes both perfusion and metabolic data, thereby displaying images that identify specific areas of the foot that may be at risk for ulceration, and thereby lead to institution of specific protective measures to lower the risk of ulcer formation, such as orthotics.
  • HT is used to quantitatively determine the spatial distribution of well and poorly perfused regions of the skin on the foot and thereby determine which part of the foot is susceptible to ulceration. By tracking non- visible changes over time HT provides early warning of the need for additional non-surgical intervention.
  • HT mapping defines a level of tissue ischemia which would make debridement unsafe. A reduction in tissue oxygenation will allows the doctor to determine whether the ulcer will heal or will require some level of amputation to close the wound.
  • HT can determine and objectively quantify the size, shape and severity of existing ulcers to monitor the efficacy of treatment. Additional potential strengths of hyperspectral technology include the ability to repeat studies periodically to obtain objective longitudinal follow-up.
  • Hyperspectral technology provides information about microcirculatory disease that cannot be assessed by conventional visualization techniques. It is useful at both the research and direct patient care level. Given that an abnormal ABI has been shown to be associated with increased risk of cardiovascular disease and death, HT may be even more useful as an early screening test for coronary artery disease and stroke in patients with diabetes. It also provides information relative to neuropathy and its progression.
  • HT Medical Hyperspectral Technology
  • HT delivers information at the level of the tissue which combines influences from the local surrounding, from physiology or pathology related to the macrovessels responsible for regional blood flow and from systemic microvascular status, both baseline and as affected by medications, state of hydration, anemia, etc.
  • HT specifically examines the microvasculature that is thought to be one of the prime targets of hyperglycemic damage.
  • HT provides information and diagnostics to assist in research on improving local or systemic therapies useful in prevention of foot ulcers and other microvascular complications.
  • HT has the potential of becoming a standard clinical tool for the definition of tissue at risk and the prediction or early detection of vascular foot and tissue lesions, wounds and ulcers of ischemic, neuopathic, venous or other origins more than just foot.
  • early warning by HT provides the foundation for preventing the occurrence of ulcer formation by the institution of specific therapies or protective measures such as orthotics or define the need for revascularization procedures.
  • HT can detect clinically significant changes in the cutaneous microvascular circulation and in tissue properties of the feet of people with diabetes at an early stage, and these changes can be used to predict the subsequent risk of foot ulceration. Studies were performed in three phases to further understanding of the disease.
  • the technique is noninvasive, rapid, and can be performed during regularly scheduled office visits without the necessity for prior patient preparation.
  • the clinical procedure takes under a minute and requires little more than positioning the patient carefully and taking a preprogrammed series of images at various wavelengths of light with the hyperspectral camera.
  • HT information is useful in three main areas of patient care: prevention of disease, anatomic diagnosis, and monitoring of therapy. In each case utility is for both research and clinical applications.
  • HT can be used to identify areas of high risk for the potential outbreak of ulcers, especially plantar ulcers.
  • HT can be used to generate a gradient map or index map of the plantar region of the foot, or other areas of interest.
  • the HT map can show the tissue oxyhemoglobin, deoxyhemoglobin and oxygen saturation levels of the area of the tissue analyzed.
  • Low levels of oxygen saturation can indicate a high risk for onset of ulcer formation.
  • the determination of low levels of oxygen saturation can be determined by comparing different points the HT image where lower level regions can be indicative of high risk.
  • testing can be conducted over time and comparing the relative change of oxygen saturation in an individual's foot.
  • oxygen saturation levels can be compared between one person's feet, or there can be a large sampling of individuals to establish a baseline level of appropriate oxygenation.
  • oxygenation and ulcer formation can be highly dependent on an individual's own characteristics.
  • Evaluation of high risk areas can be conducted on the basis of HT data alone, that is oxygen saturation, or in combination with pressure data as well. Pressure distribution of the foot combined with information regarding tissue perfusion, oxygenation or oxygen saturation can result in greater confidence in preventing ulcer formation.
  • orthotics can then be applied as part of the methodology of preventing ulcer formation.
  • orthotics has been directed merely to alleviating high pressure areas, or equalizing pressure of the plantar region of the foot.
  • orthotics can be directed to redistributing pressure to alleviate low tissue oxygenation or oxygen saturation areas.
  • pressure data can be also taken into account in pressure redistribution.
  • high pressure areas can be taken into consideration to redistribute pressure in such a way that high pressure areas are alleviated as well as low oxygenation areas.
  • Optical force plates (US Patent 5,722,287) - a video gait analysis system used to measure the pressure at the bottom of the foot through all the stages of the gait cycle. While walking across a force plate fitted with an illuminated glass plate, the pressure from each step deflects the glass plate which in turns reflects the illumination light downwards. The reflect light is capture with a video camera and is proportional to the force of the foot hitting the plate. System can measure static and dynamic (while walking) pressures. 2.) Electrical Force plates - Capacitive pressure 1344 sensors from Novel Inc, Germany having 2 sensors per square centimeter, F-Mat/F-Scan having 1.4 sensors per square centimeter (TekScan, Boston), or similar technology can be used as the force plate. Interpolation of the data produces high resolution isobarographs. System can measure static and dynamic (while walking) pressures.
  • Pressure sensitive ink sheets Semi-quantitative as low cost alternatives to force plate pedobarograph. Identifies high pressure (>12.3 kg/cm 2 ) areas on the plantar surface. Based on ink impression sheets, a pressure chart is used to quantify pressure. Sheets can be used to measure static and dynamic pressures. Examples include Podotrack (Foot Care Technology) and PressureStat (Footlogic, Inc.).
  • the current invention proposes a new means for measuring the plantar pressure by creating by hyperspectral technology a tissue oxygenation map of the foot tissue at baseline.
  • the invention measures the change in tissue oxygenation while standing on or walking across a transparent platform, or on a surface that measures pressure while walking or standing.
  • Hyperspectral imaging can also be used in combination with the above technologies to assess tissue for the risk of ulceration, especially when evaluating the feet of patients with diabetes and/or peripheral arterial disease.
  • the HT map can be used to identify pressure points on the tissue surface and an orthotic insole can then be designed where the pressure at this site is reduced or offloaded.
  • Combining hyperspectral technology with contour or pedobarographic methods can be done sequentially or in some cases simultaneously.
  • the HT map can be overlaid on the contour or pressure maps using image registration techniques. Sequential methods are more relevant when recording dynamic pressure or other forms of measurements. Offloading would be advised in cases where areas of high pressure coincides with low tissue Dxygenation.
  • simultaneous HT mapping is coupled with optical contour or optical pedobarographic measurements. Contour mapping by optical scanning of the foot and hyperspectral mapping can be done having nearly coincidental optical axes. Both imaging systems would be housed underneath the transparent platform.
  • HT values correlate with ulcer healing ( Figure 3) with both a sensitivity and specificity of 86%, and vascular symptoms correlate significantly with HT values (p ⁇ 0.01).
  • 56 HT reveals significant pathologic impairment in the microvasculature of the feet of diabetic patients which is accentuated in the presence of neuropathy. Differences in the underlying microvasculature of diabetics also are found in the forearm, and it has been concluded that these microvascular changes contribute to the development of foot ulceration and could preclude the healing of existing ulcers.
  • Micro- and macro vascular abnormalities of the diabetic foot were studied in collaboration with Dr. Aristidis Veves and colleagues at the Microvascular Laboratory at Harvard's Beth- Israel Deaconess Medical Center. Data were presented on 108 subjects divided into healthy non- diabetic subjects, non-neuropathic diabetic subjects and neuropathic diabetic subjects collected under funding from the American Diabetes Association. 44 Changes in large vessels and microcirculation of the diabetic foot play an important role in the development of foot ulceration and subsequent failure to heal existing ulcers and we evaluated the correlation of HT data with the circulatory status of tissue with diabetes and sub-populations at greater risk for foot disease. The paper describes significant changes in oxygen delivery & extraction reported by HT measurements of the skin of the forearm and foot of diabetic patients, with or without neuropathy.
  • HT measurements performed at the forearm level provide a measure of the systemic microvasculature, as the forearm represents an area that is traditionally not differentially afflicted by microvascular or macrovascular disease to the extent of the lower extremities;
  • HT measurements performed at the dorsal foot surfaces provide regional information, potentially indicative of both microvascular and macrovascular changes associated with atherosclerotic disease in large vessels exacerbated by diabetes and that HT is able to differentiate the level of this damage on either the right or left lower extremity;
  • HT measurements can provide physiological information about the baseline condition of tissue that is relevant to determining the wound healing capacity of a given individual or given extremity.
  • Microvascular reactivity measurements have been performed using iontophoresis at both the forearm and dorsum of the foot level of the non-dominant side. This ensures the testing of an area that was not usually affected by neuropathy (forearm) and affected area (dorsum of the foot).
  • the term iontophoresis denotes the introduction of soluble ions into the human skin by applying electric current. It is a non-invasive technique, which avoids any systemic effects of the used drugs.
  • acetylcholine chloride By applying acetylcholine chloride, the endothelium-dependent vasodilatation may be measured, while the use of sodium nitroprusside measures the endothelium-independent vasodilatation.
  • the MICl iontophoresis system (Moor Instruments Ltd, Millwey, Devon, England) is used in this invention. Specifically, a small quantity ( ⁇ 1 ml) of 1% acetylcholine chloride solution is used on the forearm of the participating subjects; subsequently a constant current of 200 microampere will be applied for 60 seconds achieving a dose of 6 mC-cm-2.
  • the erythema typically takes the form of a uniform redness under the wrist strap electrode, while under the drug containment electrode, the tissue may exhibit either uniform or mottled redness.
  • vehicle de- ionized water
  • both the response to the vehicle and to the active substances will be measured.
  • the dose-response curves have been previously established for acetylcholine and nitroprusside in healthy subjects. Research experiments were designed to create two distinct alterations in cutaneous physiology by iontophoresis of two vasodilators: 1) sodium nitroprusside (endothelium independent); and 2) acetylcholine chloride (endothelium-dependent).
  • HT provided quantitative information over the physiologic range of local changes in the microcirculation of the foot induced by focal iontophoretic application of the endothelial dependent and endothelial independent vasodilators nitroprusside or acetylcholine.
  • HT tissue oxygenation maps change significantly and quantitatively during vasodilatation and confirm existing laser Doppler imaging (LDI) data that the microcirculatory responses of type 1 and type 2 diabetic feet.
  • LPI laser Doppler imaging
  • HT methods of determining the tissue oxygenation and relative oxygen saturation and total hemoglobin content in skin give results that are correlated with laser Doppler imaging (LDI)methods.
  • LDI and HT measure different physical properties (LDI measures blood flow while HT measures oxy and deoxyhemoglobin that contribute to oxygenation status and total amounts of hemoglobin).
  • HT mapping following iontophoretic application of vasodilators constitutes another embodiment.
  • An iontophoretic vasodilator model was used successfully to study the microvasculature of diabetics by Drs. Veves, Arora and others.
  • 58 ' 59 We obtained HT maps of oxyhemoglobin, deoxyhemoglobin, relative hemoglobin (Hb) concentration and 02-sat (hemoglobin oxygen saturation) from in vivo spectra of the skin before and after iontophoresis of endothelial independent and endothelial dependent vasodilators nitroprusside (NP) and acetylcholine (ACh).
  • NP nitroprusside
  • ACh acetylcholine
  • Skin spectra show the characteristic doublet of oxyHb as their major spectral feature. Control spectra were taken from a region not infused with the drug, while the green were taken from a NP infused region. Comparison shows the increase in oxyHb in the spectra following NP iontophoresis. These data demonstrate the utility of HT in monitoring drugs that cause vasodilatation such as antihypertensives and cardiac unloading agents. Similarly, HT can be used to monitor the effects of systemic or locally applied vasoconstrictors.
  • HT has the sensitivity and specificity to operate in the range of change that occurs physiologically in this model and can be used to monitor changes in blood flow and O2-sat in-vivo following iontophoresis.
  • the spatial distribution of 02-sat and Hb following drug application is of particular interest.
  • the increase in both relative O2-sat and total Hb appears to be more diffuse for ACh than for NP.
  • the total Hb here reflects the total blood present in the region of interest, whereas the O2-sat image reflects more closely the increased oxygen delivery as well as oxygen extraction and metabolic state of the tissue.
  • HT measurements were acquired from the feet of 12 men at the VAMC in Washington, DC. A typical subject required 20 minutes to be scanned at 4 sites on their feet (dorsal and plantar surfaces of each foot). HT data were acquired and processed as described below. To simplify initial analyses in this pilot, we collapsed these data as follows to obtain a single intensity for both relative 02-sat and tHb at each site on the foot.
  • the age of the 12 males subjects ranged from 47 to 19 (with a mean of 62.4 and SD of 11.4 years).
  • 6 had diabetes
  • 4 had coronary artery disease
  • 7 had hyperlipidemia
  • 6 were smokers
  • 6 were hypertensive
  • 8 had claudication.
  • Age significantly (p ⁇ 0.05) correlated with relative O2-sat at the left 1st MTPJ, rigHT 1st MTPJ and left 3rd MTPJ sites with respectively r -0.70 -0.69 -0.81, but not with tHb at any of the sites.
  • subjects with claudication had a lower mean value at the right 3rd MTPJ site, but it was not quite significant (p ⁇ 0.10).
  • oxyhemoglobin, deoxyhemoglobin, and hemoglobin oxygen saturation are given in the following table for high risk diabetic subjects, low risk diabetic subjects and control nondiabetic subjects at baseline and post-iontophoresis.
  • Bold-face values denote significant changes.
  • a radial map analysis routine is used for evaluating sites with ulcers.
  • the radial maps reduce the hyperspectral image data into mean oxyHb and deoxyHb values measured at 200 separate locations around the ulcer. In this way different tissue regions can be compared and tissue immediately adjacent to the wound margin can be assessed and compared to tissue that is further away. Typically measurements within the wound are avoided due to the exudates that interfere with the measurement.
  • the individual segments can be used to identify regions that surround a healing ulcer from those that surround an ulcer that is not healing or extending. ( Figure 5).
  • HT HT identifies microvascular abnormalities in the diabetic foot and provides early information regarding the healing capacity of diabetic foot ulcers. This information can assist in managing foot ulceration, and predict outcomes.
  • establishing a broad spectral library has enabled us to determine a baseline for assessing diabetic foot problems and other tissue problems in a broad group of people with diabetes. Many other factors could potentially modify the nature of HT spectral signatures. We have assessed how age, skin color, and disease duration correlate with HT features. We have determined how other demographic and anthropomorphic variables correlate with HT features.
  • HT better predicts healing potential of skin wounds and amputation sites than other available techniques especially in diabetics.
  • This technique assesses perfusion at the skin level to find out that whether despite palpable pulses, the formation of ulcers is due to microcirculatory changes or skin islands of ischemia.
  • Pressure sensitive mats, or gels, or gel shoe inserts can be used. Orthotics can be specially tailored to properly redistribute pressures on the basis of HT gradient map and/or pressure.
  • PedAlign - infrared optical scanner that measures the shape of the foot including foot contours and arch height measurements and contour and uses this information when designing custom orthotics.
  • Orthotics are composed of semi-rigid polypropylene or graphite composite shells with different heal cup depths.
  • Casting plaster casts or foams that remember the shape of the foot when stepped on.
  • HT maps and index measurements created by the combination of HT maps or other metrics of tissue oxygenation and perfusion and pressure measurements combined with HT maps or other metrics of tissue oxygenation and perfusion is not limited to the sole of the foot or feet, but also to limbs, amputee limbs, or other extremities and areas of tissue of the body of interest.
  • HT maps are evaluated independently or paired with any of the following data: past medical history, past surgical history, medications, physical examination, ankle/brachial indices (ABIs), TcPO2, and pulse volume recording (PVR).
  • the HT maps are then evaluated independently or compared with degree of clinical disease and level of perfusion to determine.
  • Combination of HT data with ankle brachial index, pulse volume recording, duplex scan, angiogram, MRA images and/or transcutaneous oxygen tension measurements may also be undertaken to determine the level of perfusion and oxygenation at the skin level.
  • pre and postoperative images may be compared to determine if there is a change in the level of perfusion at the skin level.
  • HT studies may be performed with and without exercise to enhance information about tissue perfusion and islands of ischemia.
  • the present invention is directed to a process for directly measuring pressure and the characteristics of tissue health related to adequacy of perfusion and as can be described by metrics of tissue oxygenation including oxygen delivery, oxygen extraction and oxygenation in the foot of diabetic and non-diabetic patients and in other tissues of the body subjected to pressure.
  • Charcot foot disease is known as a neuropathic osteoarthropathy and can be observed in diabetics. The exact etiology is still unknown; however, the most common theory involves hyperperfusion of the foot.
  • the autonomic component of the neuropathy leads to vasodilatation and hyperperfusion.
  • the perfusion causes demineralization of the bones. Weight bearing forces cause the bones to begin to fragment and fracture, leading to collapse of the arch.
  • the long-term sequelae of a rockerbottom-shaped foot leads to high-pressure areas that are prone to ulceration.
  • Charcot ulcerations are typically mechanical in nature but can become infected within the soft tissue and osseous structures. A midfoot collapse with tissue loss and radiographic signs of osteomyelitis in addition to clinical signs of edema and erythema often lead to a confusing and difficult-to-diagnose condition. Charcot osteoarthropathies often are diagnosed as an osteomyelitis by plain radiographs. Scintigraphic studies help in determining the nature of these changes.
  • the present invention provides a combination of information regarding pressure exerted on the foot while standing or walking with information about perfusion of the foot is obtained by thermal imaging, hyperspectral imaging (HT), duplex scanning, angiography, MRA or laser Doppler imaging and provides a map and perfusion of the foot. This map is translated into maximal protection of the foot. This concept can be translated into the assessment and protection of other tissues and body parts.
  • the combined data is transferred to an orthotic manufacturing device which utilizes digital information to create the desired contour.
  • One embodiment combines a HT map with digitized information regarding the pressure measured from the foot or other tissue of the body while it is weight bearing.
  • an index map is created which combines oxygenation and pressure information according to an algorithm that permits the construction of an orthotic, prosthetic or cushion which then delivers less pressure to the foot or other tissue in regions of decreased oxygenation.
  • This algorithm modifies the standard construction of the orthotic or cushion with a factor which changes it from providing even distribution of pressure to less pressure where tissue oxygenation is compromised.
  • Hyperspectral technology offers the ability to directly measure tissue damage, or clearly related biomarkers related to tissue damage, rather than merely parameters indirectly related to it. Otherwise stated, foot tissue that is poorly perfused or metabolically unstable is more susceptible to the effects of pressure on the region.
  • a hyperspectral tissue map which provides information relative to the oxyHb and deoxyHb present in tissue in the region of interest on a pixel by pixel basis has been created and applied to the assessment of diabetic feet with and without foot ulceration.
  • Such a map of the perfusion and metabolism of the tissue helps us to provide information concerning what tissue will heal and what tissue is at risk for ulceration.
  • this HT map is paired with a spatial map of the pressure exerted by the weight of the patient and/or the pressure between the tissue and a shoe surface to provide a composite image that would indicate areas where pressure needed to be minimized to prevent ulceration in a region at particular risk.
  • HT measurements taken after walking in particular foot wear or with a prosthetic or orthotic could demonstrate areas of subclinical tissue damage on either platar or dorsal foot surfaces or on amputation stump due to shear stress and guide orthotic or prosthetic or footwear remodeling.
  • HT measurements of venous ulcers guide the selection of pressure to be applied. This would be especially important in the case of mixed arterial and venous ulcers.
  • HT measurements could be taken of the distal portions of the extremity through a transparent wrap during venous compression therapy.
  • HT measurements could help guide the selection of compression strength based on evaluation of arterial or ischemic disease and potential islands of ischemia.
  • HT maps could be used to guide the application of negative pressure therapy in both location and degree based on the assessment of both the wound and the surrounding tissue .
  • HT maps could be used prior to application of negative pressure or through a transparent material during therapy to assess the effects on the tissue during therapy.
  • a mask/optically clear window is used to analyze perfusion while changing pressure.
  • the window can be static in either a flat or conformal shape, or dynamic varying based either on exerted pressure or some other control schema. It can also provide temperature variation (make the tissue hot or cold) or vibration to enhance circulation. A combination of all of these occurring across a surface in contact with the tissue can also occur.
  • Such a method is also applied to situations of other orthotic appliances such as amputation prostheses or the treatment of decubiti or other wounded areas.
  • a variety of forms including imaging of the patient while reclined, taking images of the top, bottom and soles of the feet and a pressure measurement while standing on a special plate or walking in special shoes or boots to record pressure over different regions of tissue are used.
  • a hyperspectral image taken through a transparent plate incorporates the effects of pressure on the tissue while the patient is standing.
  • a hyperspectral image with the patient lying down and no pressure on the foot with one taken with the patient standing, or one taken immediately after walking is performed.
  • Other uses include performing the HT in free fligHT /fall, such as space. Also, it is used to assess the degree of healing and functionality of therapy for severely burned patients where you need to adjust the mask/bandage on the tissue.
  • Other uses include using in a hospital bed adjustment, overlying pad on bed, or wound suction device adjustment as in the VAC FreedomTM device (Kinetics Concepts, Inc.).
  • liquid crystals are used for mapping the pressure detected on the foot.
  • a thin film filled with viscous fluid is provided. The patient steps on the film applying pressure from body weigHT . The high pressure areas pushes the fluid out, causing the high pressure areas to appear transparent. The low pressure areas are filled with fluid.
  • tissue healing and/or rate of progression of infection through tissue also includes a means of measuring tissue healing and/or rate of progression of infection through tissue, an application for measurement of effectiveness of a tourniquet, determining proper fit of clothing such as brassieres, gas masks, shock absorbing plates for body armor, etc, measurement of absorption of trans-dermal drugs into tissue, both instantaneous and time release, measurement of fit of airline seats, wheel chairs, etc. to look at impact (deep vein thrombosis, bed sores, etc.), measurement of fit of boots/shoes to avoid blisters and the fit of riding tack on horses to reduce blisters, passive biometric ID through mapping of unique vascular structure non-invasively, and measurement of response to toxins, such as anaphylactic shock, prior to full onset and seizures or respiratory distress.
  • Image registration could be facilitated by the use of proprietary fiducial marks and proprietary registration software.
  • Calibration could be facilitated by proprietary calibrators or calibration routines.
  • a baseline HT measurement of the forearm is required as a part of each examination to provide data regarding the systemic microcirculation.
  • HT measurements are taken at different sites to assess the location and severity of regional ischemic disease and local microvascular changes.
  • the patient is positioned on the examining table in such a way as to expose and stabilize the areas to be studied.
  • the operator enters patient information into the machine and calibrates the HT equipment by placing the "Calibration Check Pad” in its holder and taking a measurement from the "Calibration Check Pad” to ensure appropriate calibration, focus and correction for background UgHT ing.
  • the forearm site is generally the first to be studied.
  • An HT "Measurement Check Target” (7 mm pad with hydrogel backing) is placed on the patient's forearm.
  • the instrument head is adjusted until the focusing beams converge on the target.
  • a data set from a 10 cm x 13 cm region is then acquired by the operator over a 15 second interval.
  • the data collected from the tissue region is presented as a map of the tissue on the monitor for inspection by the operator.
  • HT COM-Oxy Quantitative measurements of oxyhemoglobin (HT COM-Oxy), deoxyhemoglobin (HT COM- Deoxy, and oxygen saturation (HT COM-Sat) over the central area of the tissue region is displayed on a computer screen along with a colorized tissue map reflecting the HT COM-Oxy and the HT COM-Deoxy levels.
  • the operator obtains additional quantitative data from specific region(s) of interest within the area examined (e.g., around an ulcer).
  • the operator repeats the steps (other than calibration) above for each additional site: (e.g. the dorsum (top) of the foot, the plantar surface (sole) of the foot, the calf, an ulcer).
  • the quantitative oxygenation measurements obtained for each site are recorded along with the colorized tissue maps.
  • the operator saves the data collected and the maps displayed on the screen to the instrument's hard drive to record the quantitative HT measurements along with the location from which they were derived.
  • the physician reviews and interprets a print out of the maps of the tissue and the quantitative tissue oxygenation measurements for each site. This review includes additional regions of interest selected by the operator and/or the physician within a data collection area.
  • the physician compares HT measurements from multiple collection sites in order to obtain information on systemic, regional and local microvascular pathophysiology.
  • the physician may also review HT maps stored on the computer to obtain additional oxygenation measurements from any other regions of interest which may be identified during his review in order to complete his/her review and interpretation.
  • the physician also may review previous studies and the HT data from the current analysis with HT measurements obtained during previous sessions.
  • the physician documents and records his/her interpretation in the patient's medical record and sends a report describing the findings to the referring physician.
  • HT provides quantitative and anatomically relevant information about local tissue condition.
  • HT oxygenation measurements reflect the summation of effects of systemic microvascular disease, regional macrovascular disease and local tissue pathophysiology (i.e. response to wounding). Given its capabilities for providing quantitative information related to tissue oxygenation (oxygen delivery and oxygen extractions), HT can be useful in the following settings:
  • HT is useful clinically because it measures local tissue oxygenation based upon the total as well as relative pathophysiologic contributions of systemic, regional and local macro- and micro-vascular pathology to local tissue damage.
  • HT measures both oxygen delivery to and oxygen extraction by tissue in an anatomically relevant format, producing a colorized map of the area of tissue being studied.
  • every pixel contains information regarding oxyhemoglobin and deoxyhemoglobin levels and oxygen saturation.
  • the HT map displays the amount of tissue oxygenation throughout the area being assessed with a spatial resolution of 100 microns. This localized and quantitative information about tissue oxygenation can be used to assist in the evaluation of ischemic tissue or other damaged tissue such as that around a wound.
  • One group of tests e.g. duplex scan
  • these tests provide no information about the contribution of microvascular disease to the pathophysiology and no information as to the adequacy of perfusion.
  • a second group of tests such as transcutaneous oxygen monitoring, do not provide the same level of anatomic localization as HT COM, do not assess the adequacy of the circulation, and cannot be applied successfully to regions on the plantar surface of the foot or regions that are not flat or that are near a wound.
  • HT delivers information assessing the impact of both macrovascular and microvascular ⁇ isease on the tissue being evaluated.
  • HT is a clinical alternative to other non-invasive ⁇ ysiologic studies of the arterial system. It provides more reliable, more anatomically relevant, md more specific information about the oxygenation of tissue and general physiologic state than the currently performed procedures (non-invasive physiologic studies of upper or lower extremity arteries, single level, bilateral or non-invasive physiologic studies of upper or lower extremity arteries, multiple levels or with provocative functional maneuvers, complete bilateral study).
  • no other technology other than HT provides a complete assessment as to whether the microcirculation and oxygenation status of the tissue surrounding a diabetic's ulcer or wound is adequate to meet the physiologic needs for healing).
  • Examples include diabetic foot ulcers, neuropathic foot ulcers, ischemic ulcers, stasis [venous] ulcers, sacral ulcers, symptomatic arterial insufficiency, diabetic microvascular disease, trauma to the extremities, tissue viability after attempted revascularization, tissue flaps, burns, and post-debridement tissue viability.
  • HT is a more versatile measurement of tissue oxygenation than TCPO2:
  • IT is more relevant that ABI or PVR in reporting local, anatomically relevant information in lderly and diabetic patients with calcified or inelastic vessels:
  • ⁇ nstrumentation n one embodiment there is a methodology to integrate components of existing contour neasuring devices designed to deliver uniform pressure to the foot via an orthotic with a iyperspectral technology map to provide information to modify the creation of the orthotic to incorporate information relative to tissue oxygenation so that "the least pressure can be placed on the tissue most at risk".
  • One embodiment requires the construction of a novel device which ⁇ ncorporates aspects of both parent devices. To achieve data fusion it is necessary to coregister data from the HT map and whatever contour or pressure measuring technology is chosen, here described for the Pedalign PMI system.
  • Both instruments are assembled as a single unit and mounted rigidly with respect to each other as well as stepping platform. They have overlapping fields of view and the measurements are conducted simultineously.
  • the fields of view can be coregistered during the process of the instrument integration using special calibrator.
  • This calibrator will consist of a rectangular pattern of small rubber pads pressured against the stepping platform. The property of this calibrator is that it can produce an image of rectangular pattern visible in both PMI and FootVu data. After numerical processing of the corresponding data from the both instruments the transformation algorithm will be obtained. When applied to the consequently measured FootVu data this algorithm will compensate for effects of parallax, scaling and rotational factors and precisely coregister FootVu data with the data from PMI.
  • HT data A correlation has been established between HT data and clinical disease in diabetes and in peripheral vascular disease. Patients with existing peripheral vascular disease were evaluated clinically in terms of symptoms (claudication, rest pain), tissue loss, conventional vascular lab studies (ABI, transcutaneous oxygen tension, toe pressures), and using hyperspectral imaging. The HT data was analyzed in conjunction with the other data, and a correlation with severity of disease determined. In diabetic foot disease we have compared this technology to other available techniques that evaluate extremity perfusion: ankle brachial index, pulse volume recording, transcutaneous oxygen tension, and toe pressures. HT has been shown to better predict healing potential of skin wounds in diabetics, with a sensitivity of 86% and a specificity of 86%.
  • HT mapping can evaluate patients after endovascular or operative revascularization.
  • Vascular bypasses reconstruct major named vessels that can be evaluated by detection of blood flow in the bypassed arteries; but the perfusion at the skin level cannot be easily or accurately evaluated. This technique offers an opportunity to do so.
  • HT data offers the greatest benefit as an early indicator of the risk of foot ulcers. This allows the physician to adjust the treatment plan to prevent or delay the occurrence of an ulcer.
  • the present invention performs HT on tissue under the circumstances of wound healing with and without arterial occlusion in the ear of diabetic or non- diabetic rabbits.
  • HT can track wound healing and identify and quantify the angiogenesis and effects of EPCs on wound healing.
  • the spectra of tissue oxy and deoxy hemoglobin and the calculated tissue oxygen saturation reflect the oxygen delivery, oxygen extraction and metabolic state of tissue.
  • These HT maps could be useful in designing or tailoring surfaces or devices to optimize the pressure to the healing surface. This could be by providing zero pressure, a specified amount of positive pressure or negative pressure to different regions of tissue to optimize healing or prevent breakdown.
  • NIR hyperspectral imaging has been used to visualize otherwise undetectable variations in tissue perfusion and predict tissue viability following plastic surgery long before they can be determined clinically. 47 End tissue of a long pedicle flap in the rat that has insufficient oxygenation to remain viable is readily apparent in these local tissue maps calculated from NIR images acquired immediately following surgery. By contrast, visible clinical signs of impending necrosis do not become apparent for 12 hours after surgery. The compromised tissue goes on to slough 72 hours later.
  • hyperspectral technology is used to assess human subjects under circumstances of hemodynamic compromise.
  • the whole body is compromised and the this embodiment speaks to the design of beds or cushions for patients with shock or low flow.
  • Oxyhemoglobin is a quantifiable measure of experimentally induced chronic tretinoin inflammation and accommodation in photodamaged skin. Skin Pharmacol 1997;10(3):135-143.
  • Morag E Cavanagh PR. Radiographic and ultrasonic methods to study foot structure. In: Third Symposium on Footwear Biomechanics, Session 4; 1997; Tokyo; 1997.

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Abstract

Cette invention concerne d'une manière générale une carte-index comprenant des informations à la fois de pression et de perfusion relatives au pied d'un patient diabétique à des fins de traitement. La carte-index peut également être une carte de perfusion et/ou métabolisme des tissus (reflétant l'apport d'oxygène et l'extraction d'oxygène) obtenue par imagerie thermique, imagerie hyperspectrale ou par balayage par ultrasons duplex, angiographie par résonance magnétique (ARM), tomographie par ordinateur (CT) ou imagerie Doppler à laser. Ces informations contribuent au traitement en prévention de l'ulcération et de l'amputation du pied diabétique et au traitement de tissus touchés en prévention de la perte de tissus dans d'autre régions du corps.
PCT/US2006/032593 2005-08-19 2006-08-21 Technologie hyperspectrale permettant d'evaluer et de traiter la maladie des tissus et du pied diabetiques WO2007022508A2 (fr)

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US11/396,941 US8374682B2 (en) 2005-04-04 2006-04-04 Hyperspectral imaging in diabetes and peripheral vascular disease

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US9274046B2 (en) 2010-04-30 2016-03-01 Chemimage Corporation System and method for gross anatomic pathology using hyperspectral imaging
JP2017000836A (ja) * 2016-09-27 2017-01-05 Hoya株式会社 電子内視鏡装置
CN107389601A (zh) * 2017-08-25 2017-11-24 天津商业大学 基于高光谱的芒果冲击损伤后可滴定酸含量预测方法
US11883128B2 (en) 2016-08-24 2024-01-30 Mimosa Diagnostics Inc. Multispectral mobile tissue assessment

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US5088503A (en) * 1987-05-21 1992-02-18 Peter Seitz Method and apparatus for the production of inserts
US6122846A (en) * 1999-08-30 2000-09-26 Frank B. Gray Force monitoring shoe
US20030139667A1 (en) * 2000-04-13 2003-07-24 Hewko Mark D. Tissue viability/health monitor utilizing near infrared spectroscopy

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9274046B2 (en) 2010-04-30 2016-03-01 Chemimage Corporation System and method for gross anatomic pathology using hyperspectral imaging
US11883128B2 (en) 2016-08-24 2024-01-30 Mimosa Diagnostics Inc. Multispectral mobile tissue assessment
JP2017000836A (ja) * 2016-09-27 2017-01-05 Hoya株式会社 電子内視鏡装置
CN107389601A (zh) * 2017-08-25 2017-11-24 天津商业大学 基于高光谱的芒果冲击损伤后可滴定酸含量预测方法

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