Progress towards in vivo brain 13C-MRS in mice: Metabolic flux analysis in small tissue volumes

The combination of dynamic 13C MRS data under infusion of 13C-labelled substrates and compartmental models of cerebral metabolism enabled in vivo measurement of metabolic fluxes with a quantitative and distinct determination of cellular-specific activities. The non-invasive nature and the chemical specificity of the 13C dynamic data obtained in those tracer experiments makes it an attractive approach offering unique insights into cerebral metabolism. Genetically engineered mice present a wealth of disease models particularly interesting for the neuroscience community. Nevertheless, in vivo 13C NMR studies of the mouse brain are only recently appearing in the field due to the numerous challenges linked to the small mouse brain volume and the difficulty to follow the mouse physiological parameters within the NMR system during the infusion experiment. This review will present the progresses in the quest for a higher in vivo 13C signal-to-noise ratio up to the present state of the art techniques, which made it feasible to assess glucose metabolism in different regions of the mouse brain. We describe how experimental results were integrated into suitable compartmental models and how a deep understanding of cerebral metabolism depends on the reliable detection of 13C in the different molecules and carbon positions.