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

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.