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Measuring mitochondrial metabolism in rat brain in vivo using MR Spectroscopy of hyperpolarized [2‐ 13 C]pyruvate
Author(s) -
Park Jae Mo,
Josan Sonal,
Grafendorfer Thomas,
Yen YiFen,
Hurd Ralph E.,
Spielman Daniel M.,
Mayer Dirk
Publication year - 2013
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.2935
Subject(s) - citric acid cycle , acetylcarnitine , metabolism , in vivo , chemistry , glutamate receptor , biochemistry , citrate synthase , pyruvate dehydrogenase complex , biology , receptor , microbiology and biotechnology , enzyme
Hyperpolarized [1‐ 13 C]pyruvate ([1‐ 13 C]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‐ 13 C]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‐ 13 C]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‐ 13 C]Glutamate, [1‐ 13 C]acetylcarnitine and [1‐ 13 C]citrate were detected in addition to resonances from [2‐ 13 C]Pyr and [2‐ 13 C]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‐ 13 C]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‐ 13 C]acetylcarnitine was increased in peripheral tissues. This study demonstrates, for the first time, that hyperpolarized [2‐ 13 C]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.