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

Author:

Zaidi Maheen1,Ma Junjie12,Thomas Binu P.13,Peña Salvador1,Harrison Crystal E.1,Chen Jun1,Lin Sung‐Han1ORCID,Derner Kelley A.1,Baxter Jeannie D.1,Liticker Jeff1,Malloy Craig R.13ORCID,Bartnik‐Olson Brenda4,Park Jae Mo135ORCID

Affiliation:

1. Advanced Imaging Research Center The University of Texas Southwestern Medical Center Dallas Texas USA

2. GE Precision Healthcare Jersey City New Jersey USA

3. Department of Radiology The University of Texas Southwestern Medical Center Dallas Texas USA

4. Department of Radiology Loma Linda University Loma Linda California USA

5. Department of Biomedical Engineering The University of Texas Southwestern Medical Center Dallas Texas USA

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.

Funder

U.S. Army

Muscular Dystrophy Association

Publisher

Wiley

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