Peripheral arterial disease (PAD) is characterized by lower limb arterial obstruction due to atherosclerosis. There are 8.5 million people with PAD in the U.S over the age of 40. Over the past 14 years, our multi-disciplinary team of investigators has developed several novel magnetic resonance imaging (MRI) endpoints for clinical trials for PAD patients with intermittent claudication (IC). Creatine chemical exchange saturation transfer (CrCEST) is a novel non-spectroscopic imaging method that allows measurement of creatine kinetics in a spatially localized manner at 3T that could increase the applicability of the measure and allow spatial matching to muscle perfusion. We hypothesize that CrCEST kinetics will distinguish PAD and normals in a highly reproducible manner and will correlate with PCr kinetics. Thus, Specific Aim 1 is to demonstrate that CrCEST kinetics distinguishes PAD patients from age-matched normal subjects and reproducibly measures calf muscle energetics with exercise. We will study 23 patients with PAD compared to 23 normal controls. We will also study reproducibility and examine correlation with PCr kinetics. Critical limb ischemia (CLI) presents as rest pain, ischemic ulceration, or gangrene due to the inability of resting blood flow to meet tissue metabolic demands. We plan to study CLI patients to both improve understanding of its pathophysiology and expand the reach of these novel methods beyond their application to IC. In recent years, endovascular revascularization has increased while surgery has declined and outcomes have improved. We hypothesize that catheter-based revascularization improves perfusion and energetics to a greater extent and sooner than surgical intervention. Therefore, Specific Aim 2 is to compare the effects of catheter-based and surgical revascularization on the time course of change in calf muscle perfusion and energetics in PAD. 120 patients (30 patients in each of 4 groups (IC with catheter-based or surgical revascularization, CLI with catheter-based or surgical revascularization) will be studied. Prognosis of CLI is significantly worse than IC with a combined mortality and amputation rate of 25-33% at 1 year. We hypothesize that lower calf muscle perfusion and worse energetics leads to worse outcome in CLI. Thus, Specific Aim 3 is to correlate muscle group specific perfusion and energetics with amputation- free survival in non-revascularized CLI. 65 patients with CLI that do not subsequently undergo revascularization will be studied and cuff/occlusion hyperemia measures of tissue perfusion with ASL before and 8-12 weeks after revascularization. Amputation-free survival will be tracked over 1-3 years.

Public Health Relevance

Peripheral arterial disease (PAD) affects 8.5 million in the U.S. and techniques to evaluate potential benefits of new treatments are sorely lacking. This study aims to further develop and test new techniques using magnetic resonance imaging. We will use these techniques to compare the benefits of stents versus surgery in improving leg muscle blood flow and energy levels. In addition, we will aim to understand whether leg muscle blood flow and energy levels can predict how patients with the severest forms of PAD do over time.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL075792-12A1
Application #
9446530
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Reid, Diane M
Project Start
2003-09-22
Project End
2021-11-30
Budget Start
2017-12-15
Budget End
2018-11-30
Support Year
12
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Virginia
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Balfour Jr, Pelbreton C; Gonzalez, Jorge A; Kramer, Christopher M (2017) Non-invasive assessment of low- and intermediate-risk patients with chest pain. Trends Cardiovasc Med 27:182-189
McDermott, Mary M; Kramer, Christopher M; Tian, Lu et al. (2017) Plaque Composition in the Proximal Superficial Femoral Artery and Peripheral Artery Disease Events. JACC Cardiovasc Imaging 10:1003-1012
McDermott, Mary M; Carroll, Timothy; Carr, James et al. (2017) Femoral artery plaque characteristics, lower extremity collaterals, and mobility loss in peripheral artery disease. Vasc Med 22:473-481
Fielden, Samuel W; Meyer, Craig H (2015) A simple acquisition strategy to avoid off-resonance blurring in spiral imaging with redundant spiral-in/out k-space trajectories. Magn Reson Med 73:704-10
Lopez, David; Pollak, Amy W; Meyer, Craig H et al. (2015) Arterial spin labeling perfusion cardiovascular magnetic resonance of the calf in peripheral arterial disease: cuff occlusion hyperemia vs exercise. J Cardiovasc Magn Reson 17:23
Kramer, Christopher M (2015) Novel magnetic resonance imaging end points for physiologic studies in peripheral arterial disease: elegance versus practicality. Circ Cardiovasc Imaging 8:
Kramer, Christopher M (2015) Role of Cardiac MR Imaging in Cardiomyopathies. J Nucl Med 56 Suppl 4:39S-45S
Kramer, Christopher M; Chandrashekhar, Y; Narula, Jagat (2015) Is it T1me for tissue characterization in myocarditis? JACC Cardiovasc Imaging 8:115-7
Shaw, Peter W; Kramer, Christopher M (2015) The case for CMR. J Nucl Cardiol 22:968-70
Fielden, Samuel W; Mugler 3rd, John P; Hagspiel, Klaus D et al. (2015) Noncontrast peripheral MRA with spiral echo train imaging. Magn Reson Med 73:1026-33

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