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 T(2)* mapping and adiabatic pulse‐acquire (31)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 T(2)* maps. High‐energy phosphate metabolite concentrations were quantified by fitting the series of (31)P‐MR spectra. The PCr recovery time constant (τ(PCr)) 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%; P < 0.001), and correlated with the ABI (r = 0.79; P < 0.001). PCr recovery was slower in PAD patients (τ(PCr) = 52.0 ± 13.5 vs. 30.3 ± 9.7 sec; P < 0.0001), and correlated with the ABI (r = –0.64; P < 0.001). Moreover, τ(PCr) 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. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:98–107.