In vivo ¹³C MRS in the mouse brain at 14.1 Tesla and metabolic flux quantification under infusion of [1,6-¹³C₂]glucose

Abstract

In vivo ¹³C magnetic resonance spectroscopy (MRS) enables the investigation of cerebral metabolic compartmentation while, e.g. infusing ¹³C-labeled glucose. Metabolic flux analysis of ¹³C turnover previously yielded quantitative information of glutamate and glutamine metabolism in humans and rats, while the application to in vivo mouse brain remains exceedingly challenging. In the present study, ¹³C direct detection at 14.1 T provided highly resolved in vivo spectra of the mouse brain while infusing [1,6-¹³C₂]glucose for up to 5 h. ¹³C incorporation to glutamate and glutamine C4, C3, and C2 and aspartate C3 were detected dynamically and fitted to a two-compartment model: flux estimation of neuron-glial metabolism included tricarboxylic acid cycle (TCA) flux in astrocytes (V_g = 0.16 ± 0.03 µmol/g/min) and neurons (V_TCAⁿ= 0.56 ± 0.03 µmol/g/min), pyruvate carboxylase activity (V_PC = 0.041 ± 0.003 µmol/g/min) and neurotransmission rate (V_NT = 0.084 ± 0.008 µmol/g/min), resulting in a cerebral metabolic rate of glucose (CMR_glc) of 0.38 ± 0.02 µmol/g/min, in excellent agreement with that determined with concomitant ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸FDG PET).We conclude that modeling of neuron-glial metabolism in vivo is accessible in the mouse brain from ¹³C direct detection with an unprecedented spatial resolution under [1,6-¹³C₂]glucose infusion.