title: Progress towards in vivo brain13C-MRS in mice: Metabolic flux analysis in small tissue volumes.
abstract: The combination of dynamic13C MRS data under infusion of13C-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 the13C 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 vivo13C 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 vivo13C 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 of13C in the different molecules and carbon positions.
authors.affiliation: Laboratory for Functional and Metabolic Imaging (LIFMET), École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. Electronic address: marta.lai@epfl.ch.
authors.forename: Marta
authors.initials: M
authors.lastname: Lai
authors.affiliation: Laboratory for Functional and Metabolic Imaging (LIFMET), École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; Department of Radiology, University of Geneva, 1205 Geneva, Switzerland; Department of Radiology, University of Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
authors.affiliation: Laboratory for Functional and Metabolic Imaging (LIFMET), École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lanz
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes / Q000032:analysis* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D064688:Metabolic Flux Analysis / Q000379:methods*; D051379:Mice; D008954:Models, Biological
chemical_list: D002247:Carbon Isotopes; D005947:Glucose
keywords: (13)C spectroscopy in vivo; Glucose metabolism; Metabolic modelling; Mouse brain metabolism