Functional activation of pyruvate dehydrogenase in human brain using hyperpolarized [1-13C]pyruvate
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5 2024
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Source: Magn Reson Med. 91(5):1822-1833
Details:
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Alternative Title:Magn Reson Med
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Personal Author:
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Description: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 [13C]bicarbonate in the brain from hyperpolarized [1-13C]pyruvate using 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 vivo13C MRS with hyperpolarized [1-13C]pyruvate.
Methods:
From 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.
Results:
In 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. 1H 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 13C MRS with hyperpolarized [1-13C]pyruvate for assessing the activation of cerebral PDH flux via the detection of [13C]bicarbonate production.
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Pubmed ID:38265104
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Pubmed Central ID:PMC10950523
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Funding:
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Volume:91
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Issue:5
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Supporting Files:No Additional Files