title: Measuring mitochondrial metabolism in rat brain in vivo using MR Spectroscopy of hyperpolarized [2-¹³C]pyruvate.
abstract: 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.
authors.affiliation: Department of Electrical Engineering, Stanford University, Stanford, CA, USA; Department of Radiology, Stanford University, Stanford, CA, USA.
authors.forename: Jae Mo
authors.initials: JM
authors.lastname: Park
authors.forename: Sonal
authors.initials: S
authors.lastname: Josan
authors.forename: Thomas
authors.initials: T
authors.lastname: Grafendorfer
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Yen
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Hurd
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Spielman
authors.forename: Dirk
authors.initials: D
authors.lastname: Mayer
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D002247:Carbon Isotopes; D011773:Pyruvates
keywords: MRS; brain; dichloroacetate; glutamate; hyperpolarized 13C; pyruvate; tricarboxylic acid cycle metabolism
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