Measuring Mitochondrial Metabolism in Rat Brain in Vivo Using Mr Spectroscopy of Hyperpolarized [2-C-13]Pyruvate


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-C-13]pyruvate. NMR in Biomedicine, 26(10), 1197-1203.


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.

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