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 ¹H T ₂* mapping and adiabatic pulse-acquire ³¹P-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 ³¹P-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.