Assessing the optimal preparation strategy to minimize the variability of cardiac pyruvate dehydrogenase flux measurements with hyperpolarized MRS

Hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy can measure cardiac pyruvate dehydrogenase (PDH) flux in vivo through 13C-label incorporation into bicarbonate. Using this technology, substrate availability, as well as pathology have been shown to modulate PDH flux. Clinical protocols attempt to standardize PDH flux with oral glucose loading prior to scanning, while rodents in preclinical studies are usually scanned in the fed state. We aimed to establish which strategy is optimal to maximise PDH flux and minimise its variability in both control and diabetic rats, without affecting the pathological variation being assessed. We found a similar variance in both fed and glucose-loaded animals, which showed no statistically significant differences. Furthermore, glucose loading did not alter the low PDH flux seen in type II diabetic rats. Overall this suggests that preclinical cardiac hyperpolarized magnetic resonance studies could be performed either in the fed or in the fasted and glucose-loaded state. Centres planning to start new clinical studies with cardiac hyperpolarized magnetic resonance in man may find it beneficial to run small proof-of concept trials to determine whether metabolic standardisations by oral or intravenous glucose load are beneficial compared to scanning patients in the fed state.