Note: Descriptions are shown in the official language in which they were submitted.
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HYPERSPECTRAL TECHNOLOGY FOR ASSESSING AND TREATING DIABETIC
FOOT AND TISSUE DISEASE
Background of the Invention
1. Field of the Invention
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.
2. Description of the Background
Diabetes (or diabetes mellitus) 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.
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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.
If left untreated, 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).
Studies of all patients with diabetes under primary care have delivered annual
rates of
ulcer formation of 5-6%. (Recently reported VA study with an overall annual
rate of 6.1% in all
patients 40 yrs),I Stratification into higher risk groups delivers an annual
de-novo ulcer
formation rate of 33% in patients with a history of amputation, 19% in
neuropathic patients with
bony deformity and no history of ulcer or amputation and 11% in neuropathic
patients with no
history of ulcer or amputation.2' 3
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
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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. 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. It is therefore desirable to detect the pressure
points or locations of
shear stress in the foot to prevent pressure sores and wounds so that a
patient who might not be
able to recognize existence of a pressure point inducing condition can take
curative or
preventative measures to eliminate or reduce the condition. More important to
just detecting
pressure points is to combine this information with the presence of vascular
compromise which
is the result of a decrease in tissue oxygenation that can be due to a
combination of
micro angiopathy or other influences on adequacy of systemic perfusion to the
tissue, large vessel
disease due to macrovascular atherosclerosis or obstruction and local factors
due to inflammation
to an extremity as measured by local tissue oxygenation.
The development of protocols capable of diagnosing potential areas for the
development
of plantar ulcers would be of great value in decreasing and preventing
diabetic foot amputation.
Similarly, protocols directed at diagnosing other areas of potential
ulceration in diabetic and non-
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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.
Although medical research experts have not yet found a cure, they have
discovered that
they can minimize the ravages of diabetes related complications by delineating
specific risks,
accurately assessing evolving pathologies, and ensuring the rapid institution
of effective therapy.
This is particularly true in providing appropriate care for the diabetic foot.
The development of an ulcer in the diabetic foot is commonly a result of a
break in the
barrier between the dermis of the skin and the subcutaneous fat that cushions
the foot during
ambulation. This rupture can lead to increased pressure on the dermis,
resulting in tissue
ischemia and eventual death, ultimately manifest in the form of an ulcer.6
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There are a number of factors that weigh heavily in the process of
ulceration.7 These
factors, such as neuropathy, microcirculatory changes, peripheral vascular
disease, obesity and
musculoskeletal abnormalities, affect different aspects of the foot, leading
to a synergy of effects
that greatly increase the risk of ulceration.8
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
deformities9 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). 1
Microcirculatory changes are seen in people with in association with
hyperglycemic
damage." Functional abnormalities occur at several levels. Hyaline basement
membrane
thickening and capillary leakage may impair diffusion of nutrients. When
comparing the
microcirculation of the forearm and foot in diabetic patients with and without
neuropathy, the
endothelium-dependent and endothelium-independent cutaneous vasodilation is
lower in the
foot.12 On a histologic level, it is well known that diabetes causes a
thickening of the endothelial
basement membrane which in turn may lead to impaired endothelial cell
function.
Peripheral vascular disease (PVD) is "macrovascular 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 (altered foot mechanics, limited joint mobility,
bony
deformities) can lead to harmful changes in biomechanics and gait, increasing
the pressures
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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.
People with diabetes are more likely to express a combination of the
aforementioned
factors than non-diabetics, leading the far greater incidence of diabetic foot
ulcers in type 1 and
type 2 diabetes compared to similar nondiabetics. Clearly, however, foot
ulcers can occur in non-
diabetics, especially ischemic ulcers seen in patients with peripheral
vascular disease and
associated with atherosclerosis, hypertension and a history of smoking.
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.
There is a huge unmet need in prevention, accurate diagnosis and monitoring of
therapeutics in diabetic foot disease. Currently the monitoring of
pharmacologic therapy is
grossly insufficient. Hyperspectral technology will be useful in both drug
development and in
evaluating clinical progress under a specific pharmacologic therapy. Surgical
decision-making
will be improved and necessary medical and surgical interventions can be
better timed. This will
provide huge savings to the health care system. Appropriate pairings of
hyperspectral
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measurements (to deliver a quantitative diagnostic) with therapeutics (both
pharmaceuticals and
devices) provide diagnostic/therapeutic pairings which can both help the
physician select and
monitor therapy.
Current solutions are ineffective or incomplete. 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.
Functional abnormalities in the microcirculation occur at several levels.
Hyaline
basement membrane thickening and capillary leakage may impair diffusion of
nutrients. When
comparing the micro circulation of the forearm and foot in diabetic patients
with and without
neuropathy, the endothelium-dependent and endothelium-independent cutaneous
vasodilatation
is lower in the foot.12 On a histologic level, it is well known that diabetes
causes a thickening of
the endothelial basement membrane which in turn may lead to impaired function
of the
endothelial cell. Nitric oxide is produced within the endothelial cell and
functions to relax
smooth muscle cells leading to dilation of the blood vessel. 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.16 This
places the foot at risk in terms of infection and the ability to heal minor
wounds. Successful
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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.
Although not every diabetic foot disorder can be prevented, it may be possible
to effect
dramatic reductions in their incidence and morbidity through appropriate
prevention and
management tools.
Currently available tools for monitoring plantar pressures include pressure
sensitive mats
(RSscan Labs, UK) and thin in shoe pressure sensitive plates (Tekscan, Boston,
MA). Other tools
are available to measure the contour of the foot including plastic casts and
NIR surface scanners
(PedAlign., San Diego, CA). Specially tailored orthotics are then constructed
from information
gathered from these measurements that either offload pressure or evenly
distribute pressure to
the sole of the foot.
A study was recently performed using interferometry for detecting plantar
pressure
distribution involving a laser light oriented towards a compressed plate.18
This approach
involves a pressure plate, which compresses when subjected to a load. The
interferogram
produced represents the pattern of pressure distribution across the plate.
Such approaches as this
pose an improvement over the cumbersome, expensive footwear noted above, but
this method
still suffers from drawbacks, such as ease of use, mass availability, and
expense. Further, such
methods are only useful for analyzing the bottom or sole of the foot and fails
to account for
pressure points or locations of shear stress on other parts of the foot. These
other methods also do
not take into account generalized (systemic), regional or local influences
which may decrease
perfusion or oxygenation to a given region of the foot.
The effectiveness of these systems to reducing foot ulcerations is still
unanswered beyond
anecdotal evidence, with groups squaring off between measuring pressure or
contour as the
important endpoint. It has not been known to measure the spatial distribution
of local tissue
oxygenation, perfusion oxygen delivery or oxygen extraction while under
pressure.
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Peripheral Vascular Disease and "Islands of Ischemia"
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.
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. Each year 343,000 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.
Rhodes et al. coined the phrase "islands of ischemia" after observing non-
healing foot
ulcers in diabetic patients despite adequate peripheral bypass.I9 In one
experiment, a total of
fourteen patients were evaluated using Doppler, pulse volume recordings (PVR),
and
transcutaneous oxygen tensions (TcP02) in diabetic patients following distal
bypass. Group I
consisted of eleven patients with no evidence of ulcer following bypass, while
Group II consisted
of three patients with persistent ulcers despite revascularization. The two
groups were compared
based on their PVR and TcP02 results. Both groups were shown to have
statistically significant
increases in both PVR class and foot TcP02 (p<0.001). However, despite overall
increases in
foot TcP02, the non-healing ulcer group was found to have TcP02 values less
than 20 mm Hg
adjacent to the areas of ulceration. This suggests that despite adequate
inflow to the extremity
with peripheral bypass, "islands of ischemia" exist where inadequate perfusion
occurs, thus
making the area more susceptible to ulcer formation and inability to heal an
ulcer. The etiology
of "islands of ischemia" is considered multifactorial and involves abnormal
microvascular
regulatory mechanisms, histologic changes, and altered neurophysiology.
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Venous and Mixed Ulcers
In addition to the diabetic and ischemic ulcers described above, 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.
Mixed ulcers occur when there is both venous and arterial insufficiency.
Generally these
present as venous ulcers in someone with some degree of arterial
insufficiency. In this
circumstance, arterial vascular bypass may also be required. If this is not
possible, careful use of
compression may be undertaken to help decrease the venous pressure without
compromising
arterial flow, but this can be difficult to accomplish. Understanding the
adequacy of tissue
perfusion and oxygenation before undertaking compression therapy is important
as is monitoring
this during therapy.
Decubitus Ulcers
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.
There are also other situations in which abnormalities of skin, vasculature or
collagen
lead to tissue fragility. This can be associated with a variety of
circumstances including
malnutrition, cancer, catabolic state, debilitation, steroid use, collagen
vascular diseases, and
advanced age.
Limp amputation
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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,2 and over 43,000 new major amputations are performed
yearly21. 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. To date, 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 in Medicine
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
Over the last decade, spectroscopy has emerged into medicine. The natural
progression of
spectroscopy into medicine has paralleled another spectroscopic technique,
MRI. The original
investigations into problems of medical significance were based on the premise
that the
biochemistry of a tissue must change before changes in anatomy or morphology,
the current
standard criteria for many diagnoses, become apparent, and that these
biochemical changes will
be contained within the spectral signature. Therefore, chemical changes of a
disease state should
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be apparent by spectroscopic analyses prior to any clinical appearance. The
progress of research
thus far has consistently shown this to be a good premise.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. The vision of having a small, inexpensive, portable instrument
capable of making a
rapid, non-invasive assessment of some relevant medical parameter has provided
the driving
force behind the application of visible and near-IR spectroscopic techniques
to issues of medical
interest.
The optical properties of tissue 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. The interpretation of in-vivo reflectance data is
further complicated in
that most physical situations which modify tissue absorbance also affect
tissue scattering. Visible
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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.
Skin Spectroscopy
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 comeum (-25 pm
thick on the dorsal
surface and considerably thicker on the plantar surface of the foot), the
epidermis (-100 gm
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 @resent in the epidermis). The
spectral properties
have been reported.26-28 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
Single point diffuse reflectance (DR) spectroscopy has been used in a variety
of studies to
investigate the response of the in vivo microvasculature to stimulation. The
ratio oxyHb to
deoxyHb has been used to derive the oxygen extraction by the tissue, which
occurs with
metabolism. DR has been used to study oxygen saturation modulation in a
variety of tissues and
physiologic and pathologic conditions such as pancreatic microcirculation,32
irritant-induced
inflammation,33 ischemia-reperfusion injury34 and effect of UV irradiation,35
skin blanch tests.36
Work by Mansfield et al. has shown the utility of DR spectroscopy in the non-
subjective
diagnosis and monitoring of rheumatoid arthritis37 and basal cell carcinoma.38
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Point spectroscopy of the skin has been shown to be useful for some
applications. The
understanding derived from previous spectroscopic studies of complex
biological systems is
essential to accurate design of HT experiments as well as for optimizing the
interpretation of
imaging data. Understanding the spectroscopic properties of the human body and
the physiology
of the skin are prerequisites to interpreting HT results.
Hyperspectral Technology
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.39-42 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.
In medicine, 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 ligHT
spectrum: oxyhemoglobin (OxyHb) and deoxyhemoglobin (DeoxyHb). When measured
by
hyperspectral technology, these chromophores delineate local oxygen delivery
and extraction
within the tissue microvasculature. With 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
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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. In 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. In other
embodiments, 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 (HT), 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
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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 hemo dynamic
parameters in response
to tissue perfusion.
Changes in the absolute or relative amounts of oxyhemoglobin and
deoxyhemoglobin can
be measured. Additionally, determining the hemoglobin oxygen saturation (the
ratio of
oxyhemoglobin divided by the sum of oxyhemoglobin and deoxyhemoglobin) and the
total
hemoglobin (oxyhemoglobin plus deoxyhemoglobin) is relatively easy given the
differing
spectra of these two moieties. Unlike single point spectroscopy,23
hyperspectral technology (HT)
allows mapping of regional variations in hemodynamic parameters in response to
tissue
perfusion. Unlike infrared thermography, HT does not map the thermal emission
of the tissues.
Instead, it relies on the hemoglobin oxygen saturation and other biomarkers of
that tissue. One
application of HT is in the determination of tissue viability following
plastic surgery.47 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.48
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. After the image was processed and
false colors were
applied, light pixels indicated areas of high relative oxygen saturation (02-
sat), whereas dark
pixels indicated areas of low 02-sat. It is particularly interesting to note
that the mottling seen
during hemorrhagic shock features areas of very high tissue oxygenation,
alternating with areas
of very low tissue oxygenation. The most remarkable finding in these images is
the presence of
increased regional variability, or "subclinical mottling," during hemorrhagic
shock. As in the
plastic surgical model, here 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 perfoiined during regularly
scheduled office visits
without the necessity for prior patient preparation. The clinical procedure
takes under a minute
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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.
Treatment and Prevention of Tissue Breakdown
When tissue breakdown or ulceration is present, therapies are applied to the
tissue. In the
case of diabetic or ischemic ulcers of the foot, 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. In
the case of venous
ulcers, 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.
Generally in patients considered to be at risk for diabetic or ischemic ulcer
formation,
methods are undertaken to evenly distribute pressure to the tissue. In the
case of the foot this
takes the form of contoured shoe soles, footwear and orthotics and in the case
of bed ridden
patients air or water beds. However, it is important to understand that in
fact to optimize therapy,
it should not be uniform pressure that is the goal, but rather applying the
least amount of
pressure to the areas of tissue most at risk. It would be preferred to
identify areas of tissue most
at risk and combine this information 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. In order to prevent diabetic, ischemic, neuropathic or other
foot or tissue ulcers
patients need more than just uniform pressure relief. Known methods do not
solve the mismatch
between pressure, perfusion, oxygen delivery and oxygen extraction to meet the
demands of the
tissue. Foot or other tissue that is poorly perfused or metabolically unstable
is more susceptible
to the effects of pressure on the region. Therefore, there still remains a
need for a method for
detecting regions of the foot that are at risk in order to minimize pressure
and shear stress
especially in regions of poor tissue oxygenation or perfusion..
The applicability of HT in the care of patients with peripheral vascular
disease projects
into both the clinical setting and operating room. Patients with peripheral
vascular disease
present with varying degrees of claudication, chronic wounds/ulcers, and
gangrene. Non-
invasive 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
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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. This will allow the
vascular surgeon to
evaluate the anatomy specifically and determine which areas of the extremity
are non-perfused
and which are non-viable. This information will be able to help guide surgical
and medical
therapy. As an emerging technology, HT shows great promise in the evaluation
of tissue
perfusion.
Summary of the Invention
Accordingly, 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.
Other embodiments and technical advantages of the invention are set forth
below and
may be apparent from the drawings and the description of the invention which
follows, or may
be learned from the practice of the invention.
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.
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Further embodiments 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.
In further embodiments the method can comprise comparing the stressed
physiologieal
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. =
In other embodiments the tissue is a toe, a foot, a leg, a finger, a hand, an
arm, or any
portion thereof.
In other embodiments the physiological state comprises tissue oxygenation,
tissue
metabolism or tissue perfusion.
In other embodiments determining the physiological state is made by obtaining
a
hyperspectral or multispectra1 image of the tissue.
Some other embodiments 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 the present invention;
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.
In further embodiments, 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.
Other embodiments 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.
Other embodiments of the invention can comprise a method for orthotic
treatment in
preventing ulcers on the tissue of a foot or limb stump comprising:
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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.
Other embodiments 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.
In further embodiments of the invention the instrument further creates an
orthotic,
prosthetic or cushioned surface.
In further embodiments of the invention the orthotic, prosthetic or cushioned
surface
created serves to protect diseased tissue or tissue at risk for disease.
Other embodiments 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
In further embodiments of the invention 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.
Other embodiments 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.
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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.
Brief Description of the Figures
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 100 is denoted cause by
recent pressure from a
tightly fitting shoe.
FIG 2: Picture of claudicated foot at baseline and after exercise. HT mapping
of a mild/moderate
claudicator with pain while functioning as a facilities maintenance man during
his work day.
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" 100 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 ischernia 300 and pressure points 200 are observed in the right
foot following exercise.
FIG 3: Ulcer healing prediction algorithm using LIT -oxy > 45 to predict
healing in ulcer subjects from
Phase I. Ill-IT COM-OXY is greater than 45, then it is likely the ulcer will
heal.
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FIG 4: Type I diabetic subject with a deep ulcer located under the I
metatarsophalangeal joint. The Left
Panel presents the color image of the ulcer 400. 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 I 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 5. The regions of ulcer extension (non-healing set) provide a surrogate
for definition of tissue at risk
in a foot with unbroken skin.
Description of the Invention and Examples
The present invention now will be described more fully hereinafter with
reference to preferred
embodiments of the invention. This invention may, however, be embodied in many
different forms and
should not be construed as limited to the embodiments set forth herein;
rather, these embodiments are
provided so that this disclosure will be thorough and complete, and will fully
convey the scope of the
invention to those skilled in the art.
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.
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When referring to Hyperspectral technologies and/or hyperspectral imaging,
such also
includes multispectral imaging.
In one embodiment a tissue oxygenation map as measured by hyperspectral
technology
(HT) 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) can then be designed
that offload
pressure at selected sites identified as high risk. 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 taken while a patient is standing barefoot, walking barefoot or taken
with no
weight placed on the foot, as when seated or lying down, each provide
different information as to
the relationship between pressure and adequate tissue perfusion. In one
embodiment, 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.
In another embodiment, 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. In Figurethe
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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.
In another embodiment of the invention, 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.
In another embodiment of the invention, 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. After exercise perfusion is globally decreased,
but the central region
where the tissue is most at risk is enlarged. 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.
In one embodiment, 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. In
one embodiment
this takes the form of a specifically contoured "doughnut". In another
embodiment 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.
In another embodiment, in the evaluation and treatment of a sacral decubitus
ulcer, in
addition to removing pressure from the region of the ulcer, HT measurements
provide
information about all of the surrounding tissue and the adequacy of perfusion
elsewhere. In one
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embodiment HT measurements are taken with the patient prone and the ulcer and
surrounding
skin in the baseline, non weight bearing state. In another embodiment HT
measurements are
taken from underneath the surface, through a transparent surface on which the
patient is lying. .
In a third embodiment, 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. In another embodiment, 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. In this
embodiment, as 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. In another embodiment
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.
This can also occur following a variety of surgical procedures including those
in which a
portion of the patient is casted or positioned in a particularly chosen
position.
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.
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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.
For measuring pressure or contour of the foot, in general the patient stands
or walks on
the device, however similar pressure measurements can be taken by placing a
pressure measuring
pad or device in a shoe or orthotic for continuous measurement. In one
embodiment, 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. In
another embodiment,
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.
In another embodiment, the pressure measurements could be done with
pedobarogaph
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. In another embodiment, a clear surface is
used and NIR
scanning provides contour information for use in conjunction with HT maps as
described above.
In one embodiment, 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. In another embodiment, the
combination of HT
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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.
In one embodiment, 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. In another
embodiment, 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.
In other embodiments, 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:
Tekskan system
Video pedobarograph system
Podotrack
Optical pedobarograph
PressureStat
Kistler force platform
Spiral computed tomography and planar pressure measurements
KScan System
Prosthetic System
Grip System
Hoof and Saddle System
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
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ischemia, pressure points are manifest by a decrease in tissue oxygenation and
total hemoglobin
from baseline after exercise.
In one embodiment HT mapping is combined with data derived from a method of
measuring pressures and forces applied to the foot is via an ultrasonic
method. Here,
simultaneous measurement of force applied to the tissue during a quasi-static
computer
controlled compression and ultrasonic images of the underlying bone are
obtained. In this
technique, 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).5 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.
In another embodiment, 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.51
Another embodiment combines HT mapping or tissue perfusion measurements with
an
instrument] devised for the in vivo examination of the dynamic biomechanical
stifthess and
visebplasticity properties of skin such as the dynamic biomechanical skin
measurement (DBSM)
probe described by Elizabeth K Dawes-Higgs et al.52
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,54 spiral CT scan55 of the amputated extremity or pressure
measuring pads,
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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. By
measuring not only tissue perfusion, but the adequacy of that perfusion, HT is
also used to
quantitatively determine the spatial distribution of well and poorly perfused
regions of the skin
on the foot and thereby determine which regions of the foot are susceptible to
ulceration.
Changes in these regions may be tracked over time.
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
TcP02 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
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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.
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
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.
In one embodiment, 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.
Prevention: 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
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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.
Diagnosis: In the patient with a visible foot ulcer, 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.
Monitoring of Therapeutics: 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.
Assessment of General Microvascular Status/Progression of Disease:
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.
Although not every diabetic foot disorder can be prevented, it may be possible
to effect
dramatic reductions in their incidence and morbidity through appropriate
prevention and
management tools. Routine application of a simple non-invasive monitoring
device over the
extended period of disease of patients with diabetes will prove especially
useful.
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
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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. By tracking non-
obvious changes over
time, 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.
Individuals having diabetes type 1 or type 2, or other diseases or infirmities
which may
lead to foot or skin ulcers as a result of improper oxygen saturation levels
may use HT for
prevention or reduce the potential for the development of such ulcers. In the
past, much of the
diagnosis and emphasis for reducing the occurrence of ulcers, especially
plantar ulcers, focused
on the distribution of plantar pressure as the primary cause or indicator of
resulting ulcers.
However, HT widens the focus to the view tissue oxygen delivery, oxygen
extraction and
oxygen saturation as a contributing cause of ulcers.
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. 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.
Therefore, 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.
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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.
Furthermore,
testing can be conducted over time and comparing the relative change of oxygen
saturation in an
individual's foot. Furthermore, 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. However, as described elsewhere, 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.
Once high risk areas have been determined, orthotics can then be applied as
part of the
methodology of preventing ulcer formation. In the past, orthotics has been
directed merely to
alleviating high pressure areas, or equalizing pressure of the plantar region
of the foot. However,
by identifying high risk areas based on HT data, orthotics can be directed to
redistributing
pressure to alleviate low tissue oxygenation or oxygen saturation areas. In
preferred
embodiments, it is desirable to have no pressure, or as little pressure as
possible on such poorly
oxygenated or perfused areas. However, additionally, pressure data can be also
taken into
account in pressure redistribution. Not only HT data is taken into account,
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.
Pedobarograph System
1.) 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.
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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.
3.) Pressure sensitive ink sheets - Semi-quantitative as low cost alternatives
to force plate
pedobarograph. Identifies high pressure (>12.3 kg/cm2) 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. In a separate
embodiment, 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. For sequential measurements, 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.
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In another embodiment, 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.
Clinical Data:
In summary, over 3500 clinical HT values have been collected and data have
been
published in the Lancet, Vascular Medicine and Diabetes.44' 56' 57 HT provides
more clinically
useful information about tissue microcirculation and pathophysiology than
other methods. 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 macrovascular 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.
During HT measurements, the baseline oxyhemoglobin (HT-Oxy) was reduced in
both
non-neuropathic and neuropathic groups compared to controls (p <0.0001).
Resting
deoxyhemoglobin (deoxyHb) showed a non-significant inverse trend in control,
non-neuropathic
and neuropathic group (p=NS). Tissue hemoglobin oxygen saturation (SHT 02 or
HT-Sat was
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different among all three groups, being highest in controls followed by non-
neuropathic and
neuropathic groups (p <0.001).
Similar results were observed in the measurements at the dorsum of the foot.
However,
the main differences with the forearm results were that the baseline HT-Oxy
was reduced in the
neuropathic group when compared to non-neuropathic and control groups (p
<0.0011) As a
results of this, the baseline HT-Sat was higher in the controls and non-
neuropathic compared to
the neuropathic group (p <0.05).
The conclusions drawn from these data were that:
1) 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;
2) HT measurements performed at the dorsal foot surfaces, in turn, 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; and
3) skin oxygenation is impaired in the diabetic foot and this may be major
contributing
factor for the observed impaired wound healing of the diabetic foot ulcers.
These data
suggest that 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.
Iontophoresis Studies
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. By applying acetylcholine chloride, the endothelium-dependent
vasodilatation may
be measured, while the use of sodium nitroprusside measures the endothelium-
independent
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vasodilatation. The MIC1 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. In order to avoid the measurement of a non-specific response
to the 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.
The iontophoresis study demonstrated that 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. 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. However, 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).
The use of 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). Skin spectra show the characteristic doublet of oxyHb as
their major
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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.
Following iontophoresis of ACh or NP, there is an increase in the 02-sat
levels and an
increase in total Hb determined by HSI in the areas affected by the drug
infusion.44 By fitting the
reference oxyHb and deoxyHb spectra into the subject's spectra, an 02-sat
percentage and a
measure of total hemoglobin (tHb) are obtained for each pixel in the image.
Subtracting the pre-
iontophoresis 02-sat and Hb images from the correlative post-iontophoresis
images enables the
determination of the percent change.
Following iontophoresis of ACh or NP, there is an increase in the
oxyhemoglobin, a
decrease in the deoxyhemoglobin, an increase in 02-sat levels and an increase
in total Hb
determined by HT in the areas affected by the drug infusion.44 This quantifies
the visible
reddening of the skin seen in the same regions. The increase of total Hb as
measured by HT is
comparable to the blood flow changes seen in laser Doppler imaging but with
far improved
spatial resolution.44' 60 The 02-sat information offers the more important
information as to the
oxygen extraction by the tissue. In the face of vasodilatation, these images
confirm the theory
that with tissue metabolism relatively constant and an increase in local blood
flow we will see
less oxygen removed per unit of blood passing through the tissue and a
relative increase in the
oxyHb to deoxyHb ratio.
These results show that 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 02-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 02-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 02-sat image reflects more
closely the increased
oxygen delivery as well as oxygen extraction and metabolic state of the
tissue.
In another study, 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
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(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.
Two sites on each plantar foot were chosen, the skin directly above the 1st
and the 3rd
metatarsophalangeal joint (MTPJ). For each site on each foot, both the
relative 02-sat and total
Hb values as determined from the HT data were averaged within an approximately
1 cm2 area.
These data are summarized below in the following Table.
Sample
Variable by Site Mean Std Dev Minimum Maximum
Size
Relative Oxygen Saturation
Left 1st MTPJ 37.19 7.28 26.36 48.07 12
RigHT 1st MTPJ 37.04 9.00 23.83 54.92 11
Left 3rd MTPJ 35.24 8.92 17.43 48.93 12
RigHT 3rd
34.03 11.62 9.69 50.27 11
MTPJ
Total Hemoglobin
Left 1st MTPJ 0.71 0.18 0.46 1.04 12
RigHT 1st MTPJ 0.66 0.17 0.37 0.85 11
Left 3rd MTPJ 0.67 0.20 0.36 0.99 12
RigHT 3rd 0.71 0.22 0.26 1.19 11
MTPJ
One subject had had his right foot amputated. Thus, for relative 02-sat and
for tHb, we
obtained 12 measurements of left feet and 11 measurements of right feet at two
foot-sites
(hereafter site).
The age of the 12 males subjects ranged from 47 to 79 (with a mean of 62.4 and
SD of
11.4 years). Among the 12 subjects, 6 had diabetes, 4 had coronary artery
disease, 7 had
hyperlipidemia, 6 were smokers, 6 were hypertensive, and 8 had claudication.
This defined six
binary factors; namely, diabetes, coronary artery disease, hyperlipidemia,
smoker, hypertension,
and claudication.
For each of these six we used the t-test to compare the two mean values for
the categories
'condition present' or 'condition absent'. This was done for each relative
oxygen saturation and
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total hemoglobin measure. Because age correlated with some of relative oxygen
saturation
measures, we re-ran these t-tests controlling for age.
Age significantly (p < 0.05) correlated with relative 02-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 significantly lower mean
values of relative 02-
sat at the 3 sites and nearly significant at the right 3rd MTPJ site (p
<0.10). For tHb, subjects
with claudication had a lower mean value at the right 3rd MTPJ site, but it
was not quite
significant (p < 0.10).
The mean 02-sat and total Hb measures did not differ with respect to any other
binary
factor (diabetes to hypertension). This negative result held when the
comparisons were adjusted
for age.
Next we defined a 'better' foot and a 'worse' foot for patients with two feet.
The better
foot had the higher average scan measurements over all sites for a combined
measure of relative
02-sat and tHb, where relative 02-sat and tHb values were resealed to make the
values
comparable. We also averaged left and rigHT feet for these 11 subjects. For
all six binary
factors t-tests were run on each of these newly defined variables. There were
significant results
for only the factor, claudication. These claudication results held only for
the oxygen measures,
but did so at both the sites, 1st MTPJ and 3rd MTPJ. The t-tests were
significant when comparing
either the better foot or the worse foot. Only the average of the two feet at
the 1st MTPJ site was
significant.
The conclusions from these data were:
= Relative 02-sat images appear more likely to distinguish between healthy
and less
healthy tissue in the feet than total hemoglobin
= Relative 02-sat measures appear to distinguish subjects with and without
claudication.
Although these results come from a sample where n = 12, there is a strong
indication that
peripheral circulatory compromise, as evidenced by the early symptom of
claudication, causes a
decrease in the relative 02-sat level in the foot. This provides strong
evidence that HT methods
are useful in determining the vascular status of diabetic feet. Larger sample
sizes will allow an
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exploration of the spatial heterogeneity of these results. We can track
changes in tissue
oxygenation correlating to claudication, which is very early in the
progression of vascular
compromise.
Clinical Diabetic Ulcer Study Results
The mean values for 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.
Site Group (NO HT -Oxy HT -Deoxy HT -Sat
Control (21) 29 7 41 16 42 17
Forearm - Baseline Low-risk diabetics (36) 20 5 44 10 32 8
High-risk diabetics (51) 19 7 49 10 28 8
Control (21) 25 13 44 18 38 22
Dorsum of Foot - ________________________________________________________
Low-risk diabetics (36) 24 9 41 11 37 12
Baseline
High-risk diabetics (51) 19 9 45 13 30 12
Control (21) 50 1 12 52 15 49 10
Forearm ¨ Post -
Low-risk diabetics (36) 41 8 50 10
iontophoresis
High-risk diabetics (51) 38 9 50 9 43 7
Control (21) 47 15 50 17 49 15
Dorsum of Foot ¨ ________________________________________________________
Low-risk diabetics (36) 39 11 44 11 47 11
Post-iontophoresis ______________________________________________________
High-risk diabetics (51) 32 9 47 15 41 10
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
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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).
We applied this radial profile methodology to examine our data from a study in
which 10
diabetic subjects with 17 ulcers were enrolled. Twenty-one separate radial
maps were performed
on the 17 ulcers. Of the 21 separate ulcer locations, 14 were reported to heal
clinically while 7
did not heal clinically. An increase in oxyHb and deoxyHb was noted when using
a linear mixed
model of hyperspectral tissue oxygenation values determined in tissue
surrounding the ulcer
(Table Below). Interestingly, the percent hemoglobin oxygen saturation did not
differ between
the two groups suggesting that the blood supply is meeting the oxygen demands
for the healing
ulcer by increasing the amount of blood delivered to the wound while no
response is noted for
the nonhealing ulcers because the nonhealing ulcer is not communicating with
the systemic
circulation.
Linear mixed effects model results of tissue oxygenation values in tissue
surrounding an
ulcer.
Group Estimates (SEM)
Mean ( SEM)
MITT p-value
Control Foot
Not Healing Healing
oxyHb 36.4 2.2 51.9 1.8 <.0001
53.2 0.7
deoxyHb 34.2+ 1.9 47.8 1.6 <.0001 47.7 0.5
02-sat 0.51 0.01 0.51 0.01 0.8646 0.514
0.004
A simple algorithm was deduced from the linear mixed effects model results.
Namely if
the mean value of oxyHb determined from tissue surrounding a wound is larger
than 45, the
ulcer is predicted to heal while if the value is less than 45 the ulcer is
predicted to not heal. Using
this algorithm, 6 of the 7 (sensitivity = 86%) clinically nonhealing ulcers
were predicted to not
heal while 12 of the 14 clinically healing ulcers were predicted to heal
(specificity = 86%). A
scatterplot of these results are shown in FIG 2.
The results of these analyses conclude
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= HT showed significant differences in hyperspectral tissue oxygenation
measurements
between ulcers that healed and ulcers that did not heal.
= These results indicate that increased oxygen delivery to the ulcer area
is associated with
an increased healing rate.
= 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.
= Inherent in the radial profile analysis was the definition of areas of
"tissue at risk" not
originally adjacent to the ulcer that then went on over the six month period
to ulcerate.
We have compared HT foot images to current and past clinical measurements in
the patient's
clinical history. We also contrasted the HT images of subjects with and
without ulcers, and
contrast the feet of subjects with one ulcerated foot and one ulcer-free foot.
This determined
which features and summary variables of HT tissue oxygenation maps correlate
with ulceration
and risk factors related to ulceration. Patients with existing peripheral
vascular disease were
evaluated clinically in terms of symptoms (claudication, rest pain), tissue
loss, other vascular lab
studies (ankle-brachial index, transcutaneous oxygen tension, neuropathy
symptom score pulse
volume recording and laser Doppler iontophoresis, LDI), and using
hyperspectral imaging.
In addition, 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. In this group of patients we
commonly find lower
extremity skin lesions in the form of ulceration despite the presence of
palpable pulses or
adequate flow by conventional vascular lab studies. 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.
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There are many methods of orthotics known to one of skill in the art. 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.
Foot Contouring
1.) 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.
2.) Casting ¨ plaster casts or foams that remember the shape of the foot when
stepped on.
It should also be understood that the use of 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), TcP02, 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. Finally, for patients undergoing
revascularization, pre and post-
operative 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.
As embodied and broadly described here, the present invention is directed to a
process
for directly measuring pressure and the characteristics of tissue health
related to adequacy of
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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. Scintigcaphic 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. In one embodiment 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.
Using image
registration techniques, 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.
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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 (reflecting oxygen
delivery and
oxygen extraction), helps us to provide information concerning what tissue
will heal and what
tissue is at risk for ulceration. In one embodiment, 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.
In one embodiment, 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. In
one embodiment, HT measurements could be taken of the distal portions of the
extremity
through a transparent wrap during venous compression therapy. In another
embodiment, HT
measurements could help guide the selection of compression strength based on
evaluation of
arterial or ischemic disease and potential islands of ischemia.
In the case of a wound, 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.
In another embodiment, 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
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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.
In another embodiment, 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.).
In another embodiment, 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.
Other uses for this system 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.
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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.
Other embodiments and uses of the invention will be apparent to those skilled
in the art from
consideration of the specification and practice of the invention disclosed
herein. The scope of the
claims should not be limited by the preferred embodiments set forth in the
examples, but should be
given the broadest interpretation consistent with the description as a whole.
HT Procedure
A baseline HT measurement of the forearm is required as a part of each
examination to
provide data regarding the systemic microcirculation. In the lower extremity,
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 ligHT 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.
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 then 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
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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. These sites provide information about
local, regional,
and systemic effects on tissue oxygenation in the lower extremity.
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 Clinical Applications:
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:
= Predict healing in diabetic foot ulcers by using the correlation of
degree of tissue oxygenation
with healing (HT COM-Oxy >45 associated with healing and <45 associated with
non-
healing) 56'61
= Deliver information about the progression of microcirculatory disease in
diabetes by
demonstrating lower levels of tissue oxygenation in the feet and forearms of
diabetics
afflicted with more advanced disease
= Define the presence and quantitate the severity of neuropathy
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= Provide an early demonstration of claudication and islands of ischemia
which to identify
those patients requiring earlier angiographic evaluation and intervention
= Provide a tool for diagnosis and directing treatment of critical limb
ischemia
= Identify smaller regions of ischemia, provide a quantitative metric for
their assessment and
track their response to therapy
= Provide an assessment of tissue viability relevant in making decisions as
to when and where
to amputate
= Provide information as to adequacy of tissue oxygenation around a wound
to help the
physician determine safety of debridement, avoid debridement of an ischemic
region and
refer for vascular evaluation re intervention when necessary
= Provide information to help define tissue at risk for ulceration and
initiate a prevention
program (i.e. skin care, orthotics, vascular evaluation, elective foot surgery
to improve
biomechanics)
= Direct off-weigHT ing including accommodative orthotic device or shoegear
to reduce
pressure and treat or prevent ulceration
= Assist in the timing and level of amputation
= Assist in the assessment of adequacy of tissue oxygenation after
interventional stent
placement or surgical distal bypass
= Assist in the assessment of steal phenomenon in AV fistulas placed for
use in dialysis of
chronic renal failure patients
= Provide a screening tool to evaluate viability of tissue for use in
surgical flaps prior to
reconstruction or amputation
= Assist in assessing whether early surgical intervention is needed to
reduce pressure
(prophylactic surgery)
= Provide a screening tool for pre-operative assessment (which provides
better information
than ABIs) for diabetes patients prior to elective surgery
= Provide a general screening tool for tissue oxygenation assessment with
the capability of
summing effects of local, regional and systemic disease in an anatomically
relevant fashion
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(which may become as standard as checking pulses and sensation for all
patients with
diabetes)
= Deliver information about systemic physiology and metabolism in
hemorrhagic shock and
hypovolemic decompensation useful in the early determination of hemodynamic
compromise
and impending shock 44
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. Within the HT tissue map, 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.
Currently, no other tests provide the information delivered by HT COM. Other
non-
invasive tests have fallen short of providing actionable information.
= One group of tests (e.g. duplex scan) primarily assess large vessel
disease and the level of
an obstruction to flow, but do not provide information about the effects of
such an
obstruction on specific tissue regions. Unlike HT COM, 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.
= A third group of tests which include pulse volume recordings and ankle
brachial indices
are inaccurate in the presence of calcified vessels, whereas HT measurements
are not
affected by the presence of calcification of the macrovascular tree.
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HT delivers information assessing the impact of both macrovascular and
microvascular
lisease on the tissue being evaluated. HT is a clinical alternative to other
non-invasive
physiologic studies of the arterial system. It provides more reliable, more
anatomically relevant,
ind 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
Dxtremity 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). For example, no other technology other than HT provides a complete
assessment as to
whether the micro circulation 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 TCP02:
= Providing anatomically relevant data of the specific tissue region under
evaluation with high
spatial resolution
= Providing data from locations in which TCP02 cannot be used (the foot
sole or areas around
a wound),
= Delivering data that is not rendered inaccurate by small area of sampling
by the TCP02
probe which does not take into account tissue heterogeneity
= Delivering data of skin under normal conditions and not after high
temperature induced
vasodilatation used in the TCP02 technique
= Preventing operator errors by the technician related to the more complex
procedures required
for proper TCP02 probe siting and application vs turnkey HT scan
= Delivering more relevant information which sums the contributions of
local, regional and
systemic disease and is not rendered inaccurate by hardening or inelasticity
of peripheral
vessels a better metric of HT measurements have relevance in the assessment of
the
following conditions:
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IT is more relevant that ABI or PVR in reporting local, anatomically relevant
information in
lderly and diabetic patients with calcified or inelastic vessels:
= Providing information about specific tissue regions
= Providing an indication of oxygen extraction and the adequacy of
perfusion or oxygen
delivery
= Providing information that is much easier and quicker to collect and less
operator dependent
rnstrumentation
In 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
[ncorporate 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.
The process of coregistration depends on the level of integration between both
instruments. The
following are three possible forms of integration:
1) 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.
In this case 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
compansate for
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effects of parallax, scaling and rotational factors and precisely coregister
FootVu data with the
data from PMI.
2) The instruments are manufactured as separate units but can measure data
from the same
stepping platform simultaneously. In this case the coregistration can be
achieved based the
contour of the area where foot skin touches the platform. This contour is
easily detectable both
on PMI and FootVu images. By feeding both images to the special numerical
coregistration
procedure which will deduce the "touching contours" the transformation
algorithm will be
derived. Just like in the previous case, this algorithm will modify the FootVu
data to make the
image to be coregistered with PMI data.
3) In the case when the instrument units are not intergrated and measurements
by PMI and
FootVu are taken separately fiduciary registration marks will be used. These
marks are four
small circular pads which can be applied to the foot close to the edges of the
area registered in
both PMI and FootVu data. The position of these pads will not change between
PMI and FootVu
measurements. By locating the positions of these pads on the corresponding PMI
and FootVu
images the special numerical procedure will derive the transformation
algorithm which will be
then applied to FootVu image to achieve coregistration.
Application of similar principles for different measurements of pressure or
tissue assessment
with HT mapping should be obvious to those skilled in the art.
Examples
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.
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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%. In
this group of patients
we commonly find lower extremity skin lesions in the form of ulceration
despite the presence of
palpable pulses or adequate flow by conventional vascular lab studies. This
technique includes
the influences of systemic microvascular and local factors in its assessment
of the adequacy of
oxygenation at the skin level to define where, despite palpable pulses, the
formation of ulcers is
likely to occur, and demonstrates islands of ischemia, and differences along
angiosomes. This
demonstration of islands of ischemia can be obtained in some instances at rest
and in some cases
appears after exercise. These underperfused regions can be defined as regions
of tissue at risk
that warrant protection from pressure or shear stress.
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.
In another embodiment, 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. In this circumstance, 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. Using spectral features, NW
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
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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.
In another embodiment, hyperspectral technology is used to assess human
subjects under
circumstances of hemodynamic compromise. Here the whole body is compromised
and the this
embodiment speaks to the design of beds or cushions for patients with shock or
low flow.
56
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