Measuring mitochondrial metabolism in rat brain in vivo using MR Spectroscopy of hyperpolarized [2-13C]pyruvate

Jae Mo Park, Sonal Josan, Thomas Grafendorfer, Yi Fen Yen, Ralph E. Hurd, Daniel M. Spielman, Dirk Mayer

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34 Scopus citations

Abstract

Hyperpolarized [1-13C]pyruvate ([1-13C]Pyr) has been used to assess metabolism in healthy and diseased states, focusing on the downstream labeling of lactate (Lac), bicarbonate and alanine. Although hyperpolarized [2-13C]Pyr, which retains the labeled carbon when Pyr is converted to acetyl-coenzyme A, has been used successfully to assess mitochondrial metabolism in the heart, the application of [2-13C]Pyr in the study of brain metabolism has been limited to date, with Lac being the only downstream metabolic product reported previously. In this study, single-time-point chemical shift imaging data were acquired from rat brain in vivo. [5-13C]Glutamate, [1-13C]acetylcarnitine and [1-13C]citrate were detected in addition to resonances from [2-13C]Pyr and [2-13C]Lac. Brain metabolism was further investigated by infusing dichloroacetate, which upregulates Pyr flux to acetyl-coenzyme A. After dichloroacetate administration, a 40% increase in [5-13C]glutamate from 0.014±0.004 to 0.020±0.006 (p=0.02), primarily from brain, and a trend to higher citrate (0.002±0.001 to 0.004±0.002) were detected, whereas [1-13C]acetylcarnitine was increased in peripheral tissues. This study demonstrates, for the first time, that hyperpolarized [2-13C]Pyr can be used for the in vivo investigation of mitochondrial function and tricarboxylic acid cycle metabolism in brain.

Original languageEnglish (US)
Pages (from-to)1197-1203
Number of pages7
JournalNMR in biomedicine
Volume26
Issue number10
DOIs
StatePublished - Oct 1 2013

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Keywords

  • Brain
  • Dichloroacetate
  • Glutamate
  • Hyperpolarized C
  • MRS
  • Pyruvate
  • Tricarboxylic acid cycle metabolism

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

Cite this

Park, J. M., Josan, S., Grafendorfer, T., Yen, Y. F., Hurd, R. E., Spielman, D. M., & Mayer, D. (2013). Measuring mitochondrial metabolism in rat brain in vivo using MR Spectroscopy of hyperpolarized [2-13C]pyruvate. NMR in biomedicine, 26(10), 1197-1203. https://doi.org/10.1002/nbm.2935