Regional quantification of cardiac metabolism with hyperpolarized [1-(13)C]-pyruvate MRI evaluated in an oral glucose challenge

BACKGROUND: The heart has metabolic flexibility, which is influenced by fed/fasting states, and pathologies such as myocardial ischemia and hypertrophic cardiomyopathy (HCM). Hyperpolarized (HP) (13)C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP (13)C-MRI have yet to demonstrate regional quantification of metabolism, which is important in regional ischemia and HCM patients with asymmetric septal/apical hypertrophy. METHODS: We developed and applied methods for whole-heart imaging of (13)C-pyruvate, (13)C-lactate and (13)C-bicarbonate, following intravenous administration of [1-(13)C]-pyruvate. The image acquisition used an autonomous scanning method including bolus tracking, real-time magnetic field calibrations and metabolite-specific imaging. For quantification of metabolism, we evaluated (13)C metabolite images, ratio metrics, and pharmacokinetic modeling to provide measurements of myocardial lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) mediated metabolic conversion in 5 healthy volunteers (fasting & 30 min following oral glucose load). RESULTS: We demonstrate whole heart coverage for dynamic measurement of pyruvate-to-lactate conversion via LDH and pyruvate-to-bicarbonate conversion via PDH at a resolution of 6×6×21 mm(3) ((13)C-pyruvate) and 12×12×21 mm(3) ((13)C-lactate, (13)C-bicarbonate) . (13)C-pyruvate and (13)C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial (13)C-pyruvate-SNR, (13)C-lactate-SNR, (13)C-bicarbonate-SNR, (13)C-lactate/pyruvate ratio, (13)C-pyruvate-to-lactate conversion rate, k(PL), and (13)C-pyruvate-to-bicarbonate conversion rate, k(PB), all had statistically significant increases following oral glucose challenge. k(PB), reflecting PDH activity and pyruvate entering the Krebs Cycle, had the highest correlation with blood glucose levels and was statistically significant. CONCLUSIONS: We demonstrate first-in-human regional quantifications of cardiac metabolism by HP (13)C-pyruvate MRI that aims to reflect LDH and PDH activity.