Background: Mitochondrial dysfunction and inflammation are representative metabolic phenotypes of muscular dystrophy (MD) and precede overt muscle damage, suggesting a causal role for impaired aerobic respiration and energy metabolism in the pathogenesis of MD. Patients with MD have reduced glucose availability in skeletal and cardiac muscle, likely leading to diminished downstream metabolites such as lactate and consequent energetic insufficiency. Pyruvate occupies a central metabolic junction linking glycolysis to mitochondrial oxidative metabolism and inflammatory pathways, yet its metabolic fate in the myocardium of MD patients remains unexplored. Hyperpolarized (HP) carbon-13 (13C) MRI with intravenous injection of HP [1-13C]pyruvate enables noninvasive, real-time assessment of pyruvate utilization and downstream metabolic fluxes at the cellular level in vivo, providing a unique opportunity to interrogate altered myocardial metabolism in MD.
Objectives: This study is to demonstrate the feasibility and utility of imaging myocardial metabolism using HP [1-13C]pyruvate MRI in patients with Duchenne and Becker muscular dystrophy.
Results: Five male MD patients (2 Duchenne, 3 Becker; 10-63 years) and five male healthy controls (13-26 years) were recruited. High-sensitivity cardiac troponin T levels were elevated in patients (15-107 ng/L) compared with controls (<7 ng/L). Participants underwent a comprehensive 13C/1H-integrated MR protocol (<1.5 hours) on a clinical 3T scanner, including standard 1H cine MRI and metabolite-interleaved 13C MRI following intravenous bolus injection of HP [1-13C]pyruvate. All subjects tolerated the protocol without adverse events. The normalized HP product signals (relative to the sum of all HP 13C products) was lower for [13C]bicarbonate and higher for [1-13C]lactate in MD patients compared with healthy controls, resulting in a lower bicarbonate/lactate ratio in patients (0.88+/-0.17) than in controls (1.03+/0.06).
Conclusions: This study demonstrates the feasibility and safety of assessing myocardial metabolism using HP [1-13C]pyruvate MRI in patients with MD. The presence of detectable HP 13C-bicarbonate suggests preserved mitochondrial oxidative capacity in the myocardium during the pathogenesis of MD-associated cardiomyopathy. These findings establish a foundation for future studies using HP metabolic imaging to characterize disease heterogeneity and monitor metabolic progression or therapeutic response in MD.