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Pyruvate dehydrogenase (PDH) flux is a direct measure of cerebral mitochondrial function and metabolism. Detection of [<jats:sup>13<\/jats:sup>C]bicarbonate in the brain from hyperpolarized [1\u2010<jats:sup>13<\/jats:sup>C]pyruvate using carbon\u201013 (<jats:sup>13<\/jats:sup>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 <jats:sup>13<\/jats:sup>C MRS with hyperpolarized [1\u2010<jats:sup>13<\/jats:sup>C]pyruvate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From seven sedentary adults in good general health, time\u2010resolved [<jats:sup>13<\/jats:sup>C]bicarbonate production was measured in the brain using 90\u00b0 flip angles with minimal perturbation of its precursors, [1\u2010<jats:sup>13<\/jats:sup>C]pyruvate and [1\u2010<jats:sup>13<\/jats:sup>C]lactate, to test the hypothesis that the appearance of [<jats:sup>13<\/jats:sup>C]bicarbonate signals in the brain reflects the metabolic changes associated with neuronal activation. With a separate group of healthy participants (<jats:italic>n<\/jats:italic>\u2009=\u20093), the likelihood of the bolus\u2010injected [1\u2010<jats:sup>13<\/jats:sup>C]pyruvate being converted to [1\u2010<jats:sup>13<\/jats:sup>C]lactate prior to decarboxylation was investigated by measuring [<jats:sup>13<\/jats:sup>C]bicarbonate production with and without [1\u2010<jats:sup>13<\/jats:sup>C]lactate saturation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the course of visual stimulation, the measured [<jats:sup>13<\/jats:sup>C]bicarbonate signal normalized to the total <jats:sup>13<\/jats:sup>C signal in the visual cortex increased by 17.1%\u2009\u00b1\u200915.9% (<jats:italic>p<\/jats:italic>\u2009=\u20090.017), whereas no significant change was detected in [1\u2010<jats:sup>13<\/jats:sup>C]lactate. Proton BOLD fMRI confirmed the regional activation in the visual cortex with the stimuli. Lactate saturation decreased bicarbonate\u2010to\u2010pyruvate ratio by 44.4%\u2009\u00b1\u20099.3% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrated the utility of <jats:sup>13<\/jats:sup>C MRS with hyperpolarized [1\u2010<jats:sup>13<\/jats:sup>C]pyruvate for assessing the activation of cerebral PDH flux via the detection of [<jats:sup>13<\/jats:sup>C]bicarbonate production.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mrm.30015","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T11:33:37Z","timestamp":1706096017000},"page":"1822-1833","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Functional activation of pyruvate dehydrogenase in human brain using hyperpolarized 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