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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,  13 C magnetic resonance spectroscopy (MRS) allows following the fate of  13 C-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  13 C MRS. In particular, the dynamic  13 C-labeling of pyruvate and lactate formed from  13 C-glucose was observed in real time. An ad-hoc synthesis to produce [2,3,4,6,6- 2 H 5 , 3,4- 13 C 2 ]-D-glucose was developed to improve the  13 C signal-to-noise ratio as compared to experiments performed following [U- 2 H 7 , U- 13 C]-D-glucose injections. The main advantage of only labeling C3 and C4 positions is the absence of  13 C- 13 C 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.

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