Peripheral arterial disease (PAD) is characterized by lower limb arterial obstruction due to atherosclerosis. Most of the over 10 million in the U.S. with PAD are elderly and the prevalence is increasing. Patients with PAD are under treated with potentially life-saving risk factor modification when compared to those with coronary disease. Presently used diagnostic methods are limited and modalities that will allow study of progression and regression of disease are clearly needed. Therefore, a multi-disciplinary team from cardiology, radiology, vascular surgery, biomedical engineering, exercise science, biostatistics and clinical trials management has been assembled to develop and refine such methods.
Aim #1 is to develop and test magnetic resonance imaging (MRI) methods to image the arterial wall and characterize atherosclerotic plaque in PAD. High-resolution multislice black-blood spiral MRI will be developed in normal subjects and tested in patients to rapidly survey the vessel wall and atherosclerotic plaque in the superficial femoral artery. Multi-spectral MRI will characterize plaque components in specific regions.
Aim #2 is to develop and test MRI and MR spectroscopic methods in the quantification of perfusion and energetics of skeletal muscle supplied by atherosclerotic peripheral arteries. Standardized plantarflexion exercise to a specific power output in the MRI will be performed. First-pass contrast-enhanced MRI at peak exercise will quantify the severity of calf muscle hypoperfusion. 31Phosphorus spectra acquired during exercise recovery will identify the metabolic evidence for ischemia. MR angiography will assess luminal obstruction. Functional studies will include 6-minute walk test and treadmill exercise with measures of V02 peak. With the hypothesis that statin therapy will reduce plaque burden, stabilize plaque components, and improve measures of end-organ function, Aim #3 is to use multi-modality magnetic resonance to test the efficacy of statin therapy on the vessel wall, atherosclerotic plaque, and skeletal muscle perfusion and energetics in PAD. 100 patients with PAD with an ankle-brachial index between 0.4 and 0.9 will be studied with comprehensive MR at baseline and yearly during 4 years of therapy with a high-dose statin. These studies will enhance the understanding of statin-mediated plaque regression and stabilization and improved end organ function in PAD and lay the groundwork for the study of other novel therapies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL075792-05
Application #
7276708
Study Section
Special Emphasis Panel (ZHL1-CSR-I (S1))
Program Officer
Reid, Diane M
Project Start
2003-09-22
Project End
2008-08-31
Budget Start
2007-07-01
Budget End
2008-08-31
Support Year
5
Fiscal Year
2007
Total Cost
$774,074
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
Mathew, Roshin C; Kramer, Christopher M (2018) Recent advances in magnetic resonance imaging for peripheral artery disease. Vasc Med 23:143-152
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
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
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

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