Enhancing Metabolic Imaging of Energy Metabolism in Traumatic Brain Injury Using Hyperpolarized [1-13C]Pyruvate and Dichloroacetate

Stephen J DeVience; Xin Lu; Julie L Proctor; Parisa Rangghran; Juliana A Medina; Elias R Melhem; Rao P Gullapalli; Gary Fiskum; Dirk Mayer

doi:10.3390/metabo11060335

Enhancing Metabolic Imaging of Energy Metabolism in Traumatic Brain Injury Using Hyperpolarized [1-¹³C]Pyruvate and Dichloroacetate

Metabolites. 2021 May 24;11(6):335. doi: 10.3390/metabo11060335.

Authors

Stephen J DeVience^{1

2}, Xin Lu^{1

2}, Julie L Proctor³, Parisa Rangghran³, Juliana A Medina³, Elias R Melhem^{1

2}, Rao P Gullapalli^{1

2}, Gary Fiskum³, Dirk Mayer^{1

2}

Affiliations

¹ Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
² Center for Metabolic Imaging & Therapeutics (CMIT), University of Maryland Medical Center, Baltimore, MD 21201, USA.
³ Department of Anesthesiology and the Center for Shock, Trauma, and Anesthesiology Research (S.T.A.R.), University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Abstract

Hyperpolarized magnetic resonance spectroscopic imaging (MRSI) of [1-¹³C]pyruvate metabolism has previously been used to assess the effects of traumatic brain injury (TBI) in rats. Here, we show that MRSI can be used in conjunction with dichloroacetate to measure the phosphorylation state of pyruvate dehydrogenase (PDH) following mild-to-moderate TBI, and that measurements can be repeated in a longitudinal study to monitor the course of injury progression and recovery. We found that the level of ¹³C-bicarbonate and the bicarbonate-to-lactate ratio decreased on the injured side of the brain four hours after injury and continued to decrease through day 7. Levels recovered to normal by day 28. Measurements following dichloroacetate administration showed that PDH was inhibited equally by PDH kinase (PDK) on both sides of the brain. Therefore, the decrease in aerobic metabolism is not due to inhibition by PDK.

Keywords: controlled cortical impact; hyperpolarized metabolic imaging; magnetic resonance spectroscopic imaging; pyruvate dehydrogenase; traumatic brain injury.

Grants and funding

R21 NS096575/NH/NIH HHS/United States