Applications of angiosome classification model for monitoring disease progression in the diabetic feet

Every 20 seconds there is a diabetes related amputation somewhere in the world”. Diabetes affects 382 million people in the world today and by 2035, at least 592 million people will have diabetesapproximately 10% of the world's adult population. One of the most sinister complications of diabetes is peripheral neuropathy, where patients loose the gift of pain in their feet. Presently, clinicians assess circulation, neuropathy, and plantar pressures to identify the risk of foot ulceration that when get infected lead to amputations. The key common factor that appears to be present both in dysfunctional healing and in predicting breakdown may be inflammation. Inflammation is a central unifying concept of medicine spanning across the spectrum of pathologies from a simple bruise to cancer. For a diabetic wound, uncontrolled inflammation produces staggering impact for the patients as well as the healthcare system. Currently, there are no objective means of measuring wound inflammation and surprisingly the status quo is ‘measurements of temperatures using back of the hand’. This paper presents a conceptual methodology for classification of thermograms based on the angiosomes of the feet. 1. DIABETIC WOUNDS “Every 20 seconds there is a diabetes related amputation somewhere in the world”. Diabetes affects 382 million people in the world today and by 2035, at least 592 million people will have diabetesapproximately 10% of the world's adult population. Half of the people with diabetes don’t know that they have it.[1] One of the most sinister complications of diabetes is peripheral neuropathy, where patients loose the gift of pain in their feet. Almost, 60-70% of those with diabetes will develop peripheral neuropathy, or lose sensation in their feet. This condition increases the risk of skin breakdown resulting in wounds or ulcers. Up to 25% of those with diabetes will develop a foot ulcer in their lifetime.[1] Almost 50% of these wounds become infected, 20% of which result in lower extremity amputations. After a major amputation, 50% of people will have their other limb amputated within 2 years. [2, 3] Identifying areas of injury by the presence of inflammation would allow patients or health care providers to take action to decrease the inflammation before a wound develops.[4, 5] Personal dermal thermometers already exist and have been shown to be clinically useful in reducing the rates of reulcerations.[6-8] However, significant involvement of microvascular disease predisposes skin tissue to ulceration and therefore, novel techniques are needed to differentiate between vascular and cellular indicators of metabolic status This may be deemed useful better clinical diagnosis especially in patients with a history of ulceration and/or amputations. 1.1. Inflammation Presently, clinicians assess circulation, neuropathy, and plantar pressures to identify the risk of foot ulceration.[9] Several studies have suggested prevention of foot ulcers by identifying individuals at high risk and treating for lower extremity complications. [10-12] Current assessment of severity of diabetic foot disease is subjective The key common factor that appears to be present both in dysfunctional healing and in predicting breakdown may be inflammation. Inflammation is a central unifying concept of medicine spanning across the spectrum of pathologies from a simple bruise to cancer. For a diabetic wound, uncontrolled inflammation produces staggering impact for the patients as well as the healthcare system. Currently, there are no objective means of measuring wound inflammation and surprisingly the status quo is ‘measurements of temperatures using back of the hand’. Thermography provides non-invasive imaging of inflammation and can be used to objectively assess changes on the skin surface to diagnose pathological disease states.[13-17] 1.2. Angiosomes Nagase et al. 2011 developed a novel classification system for planter thermal patterns based upon the angiosomes of the foot. The concept of angiosomes was defined in 1987 by Ian Taylor as separate three-dimensional anatomic units of tissue each fed by a source artery. The foot and ankle are comprised of six distinct angiosomes. Four angiosomes supply the plantar foot: the medial plantar artery (MPA) angiosome, lateral plantar artery (LPA) angiosome, medial calcaneal artery (MCA) angiosome, and lateral calcaneal artery (LCA) angiosome. Adjacent angiosomes are connected by small vessels known as choke vessels that dilate when the flow from a direct source artery is diminished or blocked. It can take days or weeks for the choke vessels to completely dilate. There are five possible patterns developed to illustrate the distal region (Figure 1). Type I shows the ‘bilateral butterfly pattern’ that was discovered in a previous study to be the most common pattern in normal subjects where the highest temperatures are located in the medial arch. Type II represents both the MPA and LPA undamaged. Type III represents when the MPA is compromised. Type IV represents when the LPA is compromised. Type V represents when both the MPA and LPA are compromised. The compromised angiosomes are supplied by choke vessels and therefore will have lower temperature readings than angiosomes that are intact. Figure 1: Conceptual model of plantar angiosomes (Courtesy: Journal of Plastic, Reconstructive & Aesthetic Surgery, Nagase et al. (2011) [18]). This paper presents a conceptual methodology for classification of thermograms based on the angiosomes of the feet. 2. METHODS Upon approval from the Institutional Review Board for this study, we enrolled 12 subjects 6-Diabetics with Peripheral Neuropathy (DMPN) & 6 controls. All subjects were recruited from the Southern Arizona Limb Salvage Alliance (SALSA) at the University of Arizona’s University Medical Center in Tucson. There were 3 study related visits – baseline, 6-week and 12-week. During the follow up visits we measured any potential signs of skin breakdown or ulcer. An ulcer is defined as the full thickness loss of epidermis and dermis layers including deeper structures. Patients were excluded from the study if they had any open ulcers or open amputation sites, active Charcot arthopathy, hammertoe, active foot infection, dementia, impaired cognitive function, history of alcohol or drug abuse within one (1) year of the study. As part of the study protocol, subjects were tested for neuropathy using 5.07 Semmes Weinstein monofilament and vibratory perception threshold (VPT). A VPT score of >25 was considered as presence of neuropathy. All subjects were clinically examined including visual assessment for the presence of callus, fissures, or dryness. A repetitive stress test was performed during each clinical visit. For this test, subjects were allowed to acclimatize with ambient conditions for 20 minutes after visual examination was performed. The room temperature and humidity will be maintained at 24C and less than 50% respectively with air conditioning. Then the foot temperature was measured using a handheld infrared scanner. After the first scan, patients were instructed to walk for 20 minutes and upon return their feet were again imaged using the infrared scanner. This measurement assessed the physiological response to stress. Subsequently, we waited for 10 minutes to acquire another thermal image to assess post stress recovery. Foot temperature were recorded for both right and left limbs at 5 sites with highest risk for ulceration. Nagase et al. conceptual model was then used to record the type of angiosome at each condition[18]. 3. RESULTS This was a cross-sectional study with 12 study subjects (6 DMPN and 6 Healthy Volunteers). For each study visit, each plantar thermographic image was allocated to the 20 different categories, (Figure 1), by one of the co-authors. To avoid observation bias, this allocation was further confirmed by an additional co-author. When the allocations differed among the investigators, the images were reviewed again by both investigators to make a final decision. If the images did not correspond to any of the 20 categories, they were designated as ‘atypical’. The classification framework was directly applied from the prior works of Nagase et al (2011). [18] However, due to a small sample size we did not identify any atypical categories. Nagase et al. (2011) have reported 15% atypical feet (control group) and 12.8% atypical feet in patient group, in their study of 129 healthy controls and 32 diabetic patients. Tables 1 & 2 summarize the angiosomes classification for both groups respectively. Additionally, Figure 2 illustrates the delta temperatures at 6 high risk sites for a healthy volunteer. Similar computations were carried out for all subjects and averaged to provide a mean delta temperature at each of the high risk site (Table 3). Healthy Right Left Right Left Right Left 1 Baseline IVd$ Id IIa$ IIa$ IIa$ IIa$ 62Week Vd Vd IIa$ IIa$ IIb$ IId$ 122Week IVa$ Id IIa$ IIa$ IVa$ IVd$ 2 Baseline Id Vd IIa$ IIa$ IIa$ IIa$ 62Week Vd Vd IIa$ IIa$ IIa$ IIa$ 122Week IIa$ IIa$ IIa$ IIb$ IIa$ IIa$ 3 Baseline Id Id Id Id Id Id 62Week Id Id Id Id Id Id 122Week IId$ Id IId$ IId$ Id Id 4 Baseline Id Id IVc$ Ia Vd Vd 62Week Id Id IVa$$ Vc Id Id 122Week Vd Id Vd Vd Vd Id 5 Baseline IId$ Id IId$ IIId$ IId$ IIId$ 62Week IIId$ IIId IIa IIa IIId$ IIId 122Week IId Id IIId Vd IIId IIId$ 6 Baseline Vd Vd Vd IVd Vd Vd 62Week Id Ia IId$ IIa$ IVd IVa 122Week Id Ia Id Vd Id Ia Rest Post;Stress Recovery Table 1: Summary of angiosomes classification for 6 Healthy Volunteers. DMPN Right Left Right Left Right Left 1 Baseline Ib Id IIIa IIIa IIIb IIb% 64Week IIa% IIa% IIa% IIa% IIa% IIa% 124Week Id Id IIIa IIa% Vd Vd 2 Baseline IIa IIa% IIa IIa% IIa IIa% 64Week n/a n/a n/a n/a n/a n/a 124Week n/a n/a n/a n/a n/a n/a 3 Baseline IVa% IVa% Va IVa% Vc IVa% 64Week IVa% IIa Vc IVa% Vc IVa% 124Week Vc IIa Vc Vc Vc Vc 4 Baseline IIId IIa% Vd IIa% Vd IIId 64Week IIIa n/a IIIa n/a IIa% n/a 124Week Vd Vd Vd Vd Vd Vd 5 Baseline IIa% IIa IIa% IIa IIa% IIa 64Week IIa% IIa IIa% IIa IIc% IIb% 124Week IIa% IIa IIa% IIa% IIc% IIb% 6 Baseline n/a IVa% n/a IIa n/a IIa 64Week n/a IIa% n/a IIa% n/a Vd 124Week n/a Id n/a IIId n/a Vd Rest Post<Stress Recovery Table 2: Summary of angiosomes classification for 6 DMPN Subjects.