Dynamic Magnetic Resonance Measurements of Calf Muscle Oxygenation and Energy Metabolism in Peripheral Artery Disease

Background: Clinical assessments of peripheral artery disease (PAD) severity are insensitive to pathophysiological changes in muscle tissue oxygenation and energy metabolism distal to the affected artery. Purpose: To quantify the blood oxygenation level-dependent (BOLD) response and phosphocreatine (PCr) recovery kinetics on a clinical MR system during a single exercise-recovery session in PAD patients. Study.Type: Case control study. Subjects: Fifteen Fontaine stage II patients, and 18 healthy control subjects Field Strength/Sequence: Interleaved dynamic multiecho gradient-echo 1 H T2* mapping and adiabatic pulse-acquire P MR spectroscopy at 3T. Assessment: Blood pressure in the arms and ankles were measured to determine the ankle-brachial index (ABI). Subjects performed a plantar flexion exercise-recovery protocol. The gastrocnemius and soleus muscle BOLD responses were characterized using the T2* maps. High-energy phosphate metabolite concentrations were quantified by fitting the series of 31 P-MR spectra. The PCr recovery time constant (Tper) was derived as a measure of in vivo mitochondrial oxidative capacity. Statistical Tests: Comparisons between groups were performed using two-sided Mann Whitney U-tests. Relations between variables were assessed by Pearson's r correlation coefficients. Results: The amplitude of the functional hyperemic BOLD response in the gastrocnemius muscle was higher in PAD patients compared with healthy subjects (-3.8 1.4% vs. 1.4 0.3%; F' < 0.001), and correlated with the ABI (r= 0.79; F' < 0.001). PCr recovery was slower in PAD patients (Tpc, = 52.0 1 13.5 vs. 30.3 9.7 sec; P < 0.0001), and correlated with the ABI (r = 0.64; P < 0.001). Moreover, Tper correlated with the hyperemic BOLD response in the gastrocnemius muscle (r = 0.66; P < 0.01). Data Conclusion: MR readouts of calf muscle tissue oxygenation and high-energy phosphate metabolism were acquired essentially simultaneously during a single exercise-recovery session. A pronounced hypoxia-triggered vasodilation in PAD is associated with a reduced mitochondrial oxidative capacity.