Functional activation of pyruvate dehydrogenase in human brain using hyperpolarized [1‐13C]pyruvate

Abstract

AbstractPurposePyruvate, 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 [13C]bicarbonate in the brain from hyperpolarized [1‐13C]pyruvate using carbon‐13 (13C) 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 13C MRS with hyperpolarized [1‐13C]pyruvate.MethodsFrom seven sedentary adults in good general health, time‐resolved [13C]bicarbonate production was measured in the brain using 90° flip angles with minimal perturbation of its precursors, [1‐13C]pyruvate and [1‐13C]lactate, to test the hypothesis that the appearance of [13C]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 [1‐13C]pyruvate being converted to [1‐13C]lactate prior to decarboxylation was investigated by measuring [13C]bicarbonate production with and without [1‐13C]lactate saturation.ResultsIn the course of visual stimulation, the measured [13C]bicarbonate signal normalized to the total 13C signal in the visual cortex increased by 17.1% ± 15.9% (p = 0.017), whereas no significant change was detected in [1‐13C]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).ConclusionWe demonstrated the utility of 13C MRS with hyperpolarized [1‐13C]pyruvate for assessing the activation of cerebral PDH flux via the detection of [13C]bicarbonate production.