Functional activation of pyruvate dehydrogenase in human brain using hyperpolarized [1-13C]pyruvate
Maheen Zaidi, Junjie Ma, Binu P. Thomas, Salvador Peña, Crystal E. Harrison, Jun Chen, Sung-Han Lin, Kelley A. Derner, Jeannie D. Baxter, Jeff Liticker, Craig R. Malloy, Brenda Bartnik-Olson, Jae Mo Park
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 [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.
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. 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 13C MRS with hyperpolarized [1-13C]pyruvate for assessing the activation of cerebral PDH flux via the detection of [13C]bicarbonate production.