Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized 13C magnetic resonance

Mor Mishkovsky, Brian Anderson, Magnus Karlsson, Mathilde H. Lerche, A. Dean Sherry, Rolf Gruetter, Zoltan Kovacs, Arnaud Comment

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Abstract

The mammalian brain relies primarily on glucose as a fuel to meet its high metabolic demand. Among the various techniques used to study cerebral metabolism, 13C magnetic resonance spectroscopy (MRS) allows following the fate of 13C-enriched substrates through metabolic pathways. We herein demonstrate that it is possible to measure cerebral glucose metabolism in vivo with sub-second time resolution using hyperpolarized 13C MRS. In particular, the dynamic 13C-labeling of pyruvate and lactate formed from 13C-glucose was observed in real time. An ad-hoc synthesis to produce [2,3,4,6,6-2H5, 3,4-13C2]-D-glucose was developed to improve the 13C signal-to-noise ratio as compared to experiments performed following [U-2H7, U-13C]-D-glucose injections. The main advantage of only labeling C3 and C4 positions is the absence of 13C-13C coupling in all downstream metabolic products after glucose is split into 3-carbon intermediates by aldolase. This unique method allows direct detection of glycolysis in vivo in the healthy brain in a noninvasive manner.

Original languageEnglish (US)
Article number11719
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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