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 language | English (US) |
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Pages (from-to) | 1197-1203 |
Number of pages | 7 |
Journal | NMR in biomedicine |
Volume | 26 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2013 |
Externally published | Yes |
Keywords
- Brain
- Dichloroacetate
- Glutamate
- Hyperpolarized C
- MRS
- Pyruvate
- Tricarboxylic acid cycle metabolism
ASJC Scopus subject areas
- Molecular Medicine
- Radiology Nuclear Medicine and imaging
- Spectroscopy