Sonal Josan1, 2, Jae Mo Park3, Yi-Fen Yen4, Ralph Hurd4, Adolf Pfefferbaum1, 5, Daniel Spielman2, 3, Dirk Mayer1, 2
1Neuroscience Program, SRI International, Menlo Park, CA, United States; 2Radiology, Stanford University, Stanford, CA, United States; 3Electrical Engineering, Stanford University, Stanford, CA, United States; 4Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States; 5Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States
Hyperpolarized [1-13C]-pyruvate MRS has been used to measure changes in cardiac pyruvate dehydrogenase (PDH) flux, with up-regulation by dichloroacetate demonstrating an increase in 13C-bicarbonate production. This work investigates the metabolic fate of the corresponding increase in acetyl-CoA generated by the up-regulated PDH flux, using [2-13C]-pyruvate to follow the 13C label into the Krebs cycle. The increase in bicarbonate from [1-13C]-pyruvate was compared to the increase in [5-13C]-glutamate from [2-13C]-pyruvate and provides information about the relative fraction of pyruvate going through PDH that enters the Krebs cycle vs. other metabolic pathways.