Abstract
PURPOSE: Pyruvate, produced from either glucose, glycogen, or lactate, is the dominant precursor of cerebral oxidative metabolism. Pyruvate dehydrogenase (PDH) flux is a direct measure of cerebral mitochondrial function and metabolism. Detection of [(13) C]bicarbonate in the brain from hyperpolarized [1-(13) C]pyruvate using carbon-13 ((13) C) MRI provides a unique opportunity for assessing PDH flux in vivo. This study is to assess changes in cerebral PDH flux in response to visual stimuli using in vivo (13) C MRS with hyperpolarized [1-(13) C]pyruvate. METHODS: From seven sedentary adults in good general health, time-resolved [(13) C]bicarbonate production was measured in the brain using 90° flip angles with minimal perturbation of its precursors, [1-(13) C]pyruvate and [1-(13) C]lactate, to test the hypothesis that the appearance of [(13) C]bicarbonate signals in the brain reflects the metabolic changes associated with neuronal activation. With a separate group of healthy participants (n = 3), the likelihood of the bolus-injected [1-(13) C]pyruvate being converted to [1-(13) C]lactate prior to decarboxylation was investigated by measuring [(13) C]bicarbonate production with and without [1-(13) C]lactate saturation. RESULTS: In the course of visual stimulation, the measured [(13) C]bicarbonate signal normalized to the total (13) C signal in the visual cortex increased by 17.1% ± 15.9% (p = 0.017), whereas no significant change was detected in [1-(13) C]lactate. Proton BOLD fMRI confirmed the regional activation in the visual cortex with the stimuli. Lactate saturation decreased bicarbonate-to-pyruvate ratio by 44.4% ± 9.3% (p < 0.01). CONCLUSION: We demonstrated the utility of (13) C MRS with hyperpolarized [1-(13) C]pyruvate for assessing the activation of cerebral PDH flux via the detection of [(13) C]bicarbonate production.