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- Title
Measuring mitochondrial metabolism in rat brain in vivo using MR Spectroscopy of hyperpolarized [2-<sup>13</sup>C]pyruvate.
- Authors
Park, Jae Mo; Josan, Sonal; Grafendorfer, Thomas; Yen, Yi ‐ Fen; Hurd, Ralph E.; Spielman, Daniel M.; Mayer, Dirk
- 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. Copyright © 2013 John Wiley & Sons, Ltd.
- Publication
NMR in Biomedicine, 2013, Vol 26, Issue 10, p1197
- ISSN
0952-3480
- Publication type
Article
- DOI
10.1002/nbm.2935