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CLINICAL RESEARCH: CARDIAC IMAGING

Delayed Calf Muscle Phosphocreatine Recovery After Exercise Identifies Peripheral Arterial Disease

David C. Isbell, MD^_*, Stuart S. Berr, PhD^,, Alicia Y. Toledano, ScD^||, Frederick H. Epstein, PhD^,, Craig H. Meyer, PhD, Walter J. Rogers, PhD^_*,, Nancy L. Harthun, MD, Klaus D. Hagspiel, MD, Arthur Weltman, PhD^_* 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 Surgery, University of Virginia Health System, University of Virginia, Charlottesville, Virginia
^|| Center for Statistical Sciences, Brown University, Providence, Rhode Island

Manuscript received September 23, 2005; revised manuscript received December 20, 2005, accepted December 30, 2005.

^_* 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: In this study we intend to characterize phosphocreatine (PCr) recovery kinetics with phosphorus-31 (³¹P) magnetic resonance spectroscopy in symptomatic peripheral arterial disease (PAD) patients compared with control subjects and determine the diagnostic value and reproducibility of this parameter.

BACKGROUND: Due to the inconsistent relationship between flow and function in PAD, novel techniques focused on the end-organ are needed to assess disease severity and measure therapeutic response.

METHODS: Fourteen normal subjects (5 men, age 45 ± 14 years) and 20 patients with mild-to-moderate symptomatic PAD (12 men, age 67 ± 10 years, mean ankle brachial index 0.62 ± 0.13) were studied. Subjects exercised one leg to exhaustion while supine in a 1.5-T magnetic resonance scanner using a custom-built plantar flexion device. Surface coil-localized, free induction decay acquisition localized to the mid-calf was used. Each ³¹P spectrum consisted of 25 signal averages at a repetition time of 550 ms. The PCr recovery time constant was calculated by monoexponential fit of PCr versus time, beginning at exercise completion.

RESULTS: Median exercise time was 195.0 s in normal subjects and 162.5 s in PAD patients (p = 0.06). Despite shorter exercise times in patients, the median recovery time constant of PCr was 34.7 s in normal subjects and 91.0 s in PAD patients. Area under the receiver-operating characteristic curve was 0.925 ± 0.045. Test-retest reliability was excellent.

CONCLUSIONS: The PCr recovery time constant is prolonged in patients with symptomatic PAD compared with normal subjects. The method is reproducible and may be useful in the identification of disease. Further study of this parameter’s ability to track response to therapy as well as its prognostic capability is warranted.

Abbreviations and Acronyms   ABI = ankle brachial index   ATP = adenosine triphosphate   PAD = peripheral arterial disease   PCr = phosphocreatine   Pi = inorganic phosphate   31P MRS = phosphorus-31 magnetic resonance spectroscopy   ROC = receiver-operating characteristic

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