UCSF

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) ¹³C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP ¹³C-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 ¹³C-pyruvate, ¹³C-lactate and ¹³C-bicarbonate, following intravenous administration of [1-¹³C]-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 ¹³C 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 mm³ (¹³C-pyruvate) and 12 × 12 × 21 mm³ (¹³C-lactate, ¹³C-bicarbonate). ¹³C-pyruvate and ¹³C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial ¹³C-pyruvate-SNR, ¹³C-lactate-SNR, ¹³C-bicarbonate-SNR, ¹³C-lactate/pyruvate ratio, ¹³C-pyruvate-to-lactate conversion rate, k_PL, and ¹³C-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 ¹³C-pyruvate MRI that aims to reflect LDH and PDH activity.