Penn CVI Vascular Research

Research

We are currently conducting a variety of studies on micro- and macro-vasculature. Please click on the links to learn more about some of the research being conducted at the PVRC:


Hyperpectral Imaging to Assess and Predict Diabetic Foot Ulcers 

This study focuses on bringing recent developments in in-vivo spectroscopy, hyperspectral imaging, and image processing together in the Medical HyperSpectral Imaging (MHSI) system to serve an unmet need for people with diabetes. By providing a better understanding of local physiology MHSI offers a method to identify tissue at risk, evaluate disease progression & monitor efficacy of therapy to prevent or mitigate diabetic foot ulcer complications.

In hyperspectral imaging (HSI) a two dimensional image is created that has spectral data inherent in each individual pixel. It is possible to correlate the spectrum of each pixel with the presence and concentration of various chemical species. This data can than be interpreted as a “gradient map” of these species in a surface. In essence, HSI is a method of “imaging spectroscopy” that combines the chemical specificity of spectroscopy with the spatial resolution of imaging. Light is separated into hundreds of wavelengths using any of several possible spectral separators and collected on a CMOS detector in much the same way that a picture is taken by an ordinary camera. A spectrum of 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 based on the chemistry of the region of interest.

The most important potential utility of MHSI technology in the area of diabetes care is its capability to create a gradient map which can highlight areas with subtle or preclinical physiologically relevant information. MHSI information may be useful in 3 main areas of patient care: prevention of disease, anatomic diagnosis, and monitoring of therapy. In each case it may have both research and clinical applications.

This study utilizes biomarkers of oxygen saturation and total hemoglobin in the upper layers of skin on the foot, as measured by MHSI, as a metric for assessing wound healing, a reflection of microvascular disease, and as a tool for determining tissue at risk for ulceration.

Evaluation of Endothelial Progenitor Cells in Patients with Chronic Kidney Disease with and without Diabetes Mellitus

Patients with renal failure have a high cardiovascular morbidity and mortality, and most die of complications related to atherosclerosis, namely myocardial infarction and stroke.  Several traditional and non-traditional cardiovascular risk factors are thought to play a role in increased cardiovascular events, but the vascular repair mechanisms are poorly understood. Recent research has identified bone marrow-derived endothelial progenitor cells (EPCs) as cells involved in the reparative processes in the cardiovascular system.  EPCs are considered to originate from CD-34 positive hematopoietic stem cells, which differentiate via separate pathways into erythrocytes, thrombocytes, various lineages of leukocytes, and endothelial cells.  The EPCs circulate in the vasculature, where they home and incorporate into sites of active neo-vascularization.  In patients with coronary artery disease, the number of EPCs correlates strongly with the number of cardiovascular risk factors.  The number of EPCs has also been found to correlate with the degree of endothelial dysfunction.  Patients with diabetes mellitus and chronic kidney disease exhibit impaired EPC function.
 
This study investigates the hypothesisthat impaired function of EPCs due to erythropoietin deficiency could be a potential cardiovascular risk factor contribution to morbidity and mortality in patients with diabetes mellitus and advanced chronic renal failure.  It examines whether patients with diabetes have reduced erythropoietin induced mobilization of EPCs from the bone marrow compared to non-diabetics. The number of circulating EPCs and EPC function will be compared between patients with advanced chronic kidney disease with and without diabetes mellitus before and after treatment with darbepoetin alfa.

Apex Pilot Study

The pathophysiology leading to development of claudication and decline in functional status in patients with peripheral arterial disease (PAD) is thought due to progression of atherothrombosis, the combination of atherosclerosis and thrombosis.  The combination of genes and cardiovascular risk factors such as smoking, diabetes mellitus, hypertension and dyslipidemia predispose to development of atherosclerosis in the leg arteries, with peak prevalence in those greater than 70 years.  Few patients present with symptoms of acute arterial occlusion manifest as painful and numb lower extremity, rather most have an insidious development of intermittent claudication. The natural history of atherosclerosis in the extremities involves progressive occlusion of the vessel, typically in susceptible regions where turbulent blood flow occurs such as the proximal superficial femoral artery and the popliteal artery at Hunter’s canal.

Patients with a reduced ankle pressure compared to the arm termed the ankle-brachial index (ABI) have disease present but may not have “classic” claudication symptoms and are therefore considered asymptomatic.  Transcutaneous arterial ultrasound is a noninvasive method to assess the location and severity of PAD.  Although still unclear, there is some evidence that atherosclerotic disease progression involves plaque hemorrhage or ulceration leading to acute vessel occlusion similar to that which occurs in the coronary arteries.   This study investigates the hypothesis that patients with ABI <0.09 but >0.60 who are asymptomatic or have atypical leg symptoms will convert to classic claudication symptoms from a rapid progression of an atherosclerotic lesion due to plaque rupture and thrombus formation. This pilot study will provide necessary information to calculate the sample size needed for a larger study aimed at reducing worsening stenosis and development of claudication.

Claudication: Exercise vs. Endoluminal Revascularization (CLEVER)

Peripheral arterial disease (PAD) is common, affecting up to 12% to 29% of the elderly.  Intermittent claudication is its most frequent symptom of PAD. Treatment options for those with intermittent claudication include modification of systemic risk of atherosclerotic ischemic events and treatments directed at improving physical functioning.  These latter options include medications, exercise training, angioplasty/stent placement, or bypass surgery. Many studies done before about angioplasty, bypass surgery, the significance of exercise training and medications for PAD but up to now it is not clear which of these treatments is most beneficial and safe. At the current time the most effective treatment for claudication is unknown.

The primary comparisons being made in this study are contrasting the relative superiority of aortoiliac stenting (ST) and supervised exercise therapy (SE) to optimal medical care (OMC) — as measured by maximum walking duration (MWD) at 6 months in patients with claudication due to aortoiliac peripheral arterial disease (PAD).  If these comparisons are positive, stenting will then be compared with supervised exercise training by sequential analysis. By sequential testing, the primary endpoints to be evaluated in this study are intended to demonstrate a 30% difference in improvement in MWD at 6 months in subjects undergoing either:

  1. Optimal medical care alone (OMC) versus optimal medical care and aortoiliac revascularization by stent placement (ST)
  2. Optimal medical care alone (OMC) versus optimal medical care and supervised exercise training (SE).
  3. Optimal medical care and supervised exercise training (SE) versus optimal medical care and aortoiliac revascularization by stent placement (ST).

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