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CLINICAL RESEARCH: CARDIAC IMAGING

Multifactorial Determinants of Functional Capacity in Peripheral Arterial Disease

Uncoupling of Calf Muscle Perfusion and Metabolism

Justin D. Anderson, MD^_*, Frederick H. Epstein, PhD^,, Craig H. Meyer, PhD^,, Klaus D. Hagspiel, MD^_*,, Hongkun Wang, PhD, Stuart S. Berr, PhD^,, Nancy L. Harthun, MD^||, Arthur Weltman, PhD^_*, Joseph M. DiMaria, BA, Amy M. West, MD^_* and Christopher M. Kramer, MD^_*,,_*

^_* Department of Medicine, University of Virginia Health System, University of Virginia, Charlottesville, Virginia
Department of Radiology, University of Virginia Health System, University of Virginia, Charlottesville, Virginia
Department of Biomedical Engineering, University of Virginia Health System, University of Virginia, Charlottesville, Virginia
Department of Public Health Sciences, University of Virginia Health System, University of Virginia, Charlottesville, Virginia
^|| Department of Surgery, University of Virginia Health System, University of Virginia, Charlottesville, Virginia

Manuscript received August 6, 2008; revised manuscript received January 6, 2009, accepted January 14, 2009.

^_* Reprint requests and correspondence: Dr. Christopher M. Kramer, University of Virginia Health System, Departments of Medicine and Radiology, Lee Street, Box 800170, Charlottesville, Virginia 22908 (Email: ckramer{at}virginia.edu).

Objectives: We aimed to investigate the pathophysiology of peripheral arterial disease (PAD) by examining magnetic resonance imaging (MRI) and spectroscopic (MRS) correlates of functional capacity.

Background: Despite the high prevalence, morbidity, and cost of PAD, its pathophysiology is incompletely understood.

Methods: Eighty-five patients (age 68 ± 10 years) with mild-to-moderate PAD (ankle-brachial index 0.69 ± 0.14) had their most symptomatic leg studied by MRI/MRS. Percent wall volume in the superficial femoral artery was measured with black blood MRI. First-pass contrast-enhanced MRI calf muscle perfusion and ³¹P MRS phosphocreatine recovery time constant (PCr) were measured at peak exercise in calf muscle. All patients underwent magnetic resonance angiography (MRA), treadmill testing with maximal oxygen consumption measurement, and a 6-min walk test.

Results: Mean MRA index of number and severity of stenoses was 0.84 ± 0.68 (normal 0), % wall volume 74 ± 11% (normal 46 ± 7%), tissue perfusion 0.039 ± 0.015 s^–1 (normal 0.065 ± 0.013 s^–1), and PCr 87 ± 54 s (normal 34 ± 16 s). MRA index, % wall volume, and ankle-brachial index correlated with most functional measures. PCr was the best correlate of treadmill exercise time, whereas calf muscle perfusion was the best correlate of 6-min walk distance. No correlation was noted between PCr and tissue perfusion.

Conclusions: Functional limitations in PAD are multifactorial. As measured by MRI and spectroscopy, atherosclerotic plaque burden, stenosis severity, tissue perfusion, and energetics all play a role. However, cellular metabolism is uncoupled from tissue perfusion. These findings suggest a potential role for therapies that regress plaque, increase tissue perfusion, and/or improve cellular metabolism. (Comprehensive Magnetic Resonance of Peripheral Arterial Disease; NCT00587678)

Key Words: magnetic resonance imaging • spectroscopy • peripheral vascular disease • blood flow • atherosclerosis

Abbreviations and Acronyms   ABI = ankle-brachial index   CRP = C-reactive protein   MRA = magnetic resonance angiography   MRI = magnetic resonance imaging   MRS = magnetic resonance spectroscopy   PAD = peripheral arterial disease   PCr = phosphocreatine recovery time constant   VO 2 = maximal oxygen consumption

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