Dynamic magnetic resonance measurements of calf muscle oxygenation and energy metabolism in peripheral artery disease

Abstract

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 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 T₂ * 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.

Keywords: atherosclerosis; exercise stress; interleaved scanning; intermittent claudication; metabolic hyperemia; mitochondrial dysfunction.