Delayed calf muscle phosphocreatine recovery after exercise identifies peripheral arterial disease

Abstract

Objectives: In this study we intend to characterize phosphocreatine (PCr) recovery kinetics with phosphorus-31 ((31)P) 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.

Figures

Figure 1

Sequential phosphorous-31 spectra acquired after exercise in a subject with peripheral arterial disease. In this example the first three spectra (45 s) after exercise are shown. Note the incremental increase in phosphocreatine (PCr) and simultaneous decrease in inorganic phosphate reflecting PCr regeneration in the skeletal muscle tissue. ATP = adenosine triphosphate; PDE = phosphodiester; Pi = inorganic phosphate; PME = phosphomonester.

Figure 2

Representative phosphocreatine (PCr) recovery plots in control (top) and peripheral arterial disease (bottom) subjects. Note the steeper recovery curve in the control subject. The PCr recovery time constant was 34.4 s in the control subject and 121.1 s in the peripheral arterial disease patient.

Figure 3

In this graph of phosphocreatine (PCr) recovery time constants, the boxes extend from the 25th to the 75th percentile, and the horizontal lines depict the medians. The median PCr recovery time constant is longer in peripheral arterial disease (PAD) patients.

Figure 4

Receiver-operating characteristic curve for phosphocreatine (PCr) recovery kinetics. The points shown are the observed data.

Figure 5

Reproducibility analyzed using the method of Bland and Altman.