title: Assessment of metabolic fluxes in the mouse brain in vivo using 1H-[13C] NMR spectroscopy at 14.1 Tesla.
abstract: (13)C magnetic resonance spectroscopy (MRS) combined with the administration of (13)C labeled substrates uniquely allows to measure metabolic fluxes in vivo in the brain of humans and rats. The extension to mouse models may provide exclusive prospect for the investigation of models of human diseases. In the present study, the short-echo-time (TE) full-sensitivity (1)H-[(13)C] MRS sequence combined with high magnetic field (14.1 T) and infusion of [U-(13)C6] glucose was used to enhance the experimental sensitivity in vivo in the mouse brain and the (13)C turnover curves of glutamate C4, glutamine C4, glutamate+glutamine C3, aspartate C2, lactate C3, alanine C3, γ-aminobutyric acid C2, C3 and C4 were obtained. A one-compartment model was used to fit (13)C turnover curves and resulted in values of metabolic fluxes including the tricarboxylic acid (TCA) cycle flux VTCA (1.05 ± 0.04 μmol/g per minute), the exchange flux between 2-oxoglutarate and glutamate Vx (0.48 ± 0.02 μmol/g per minute), the glutamate-glutamine exchange rate V(gln) (0.20 ± 0.02 μmol/g per minute), the pyruvate dilution factor K(dil) (0.82 ± 0.01), and the ratio for the lactate conversion rate and the alanine conversion rate V(Lac)/V(Ala) (10 ± 2). This study opens the prospect of studying transgenic mouse models of brain pathologies.
authors.affiliation: 1] Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland [2] Unit for Research in Schizophrenia, Department of Psychiatry, Center for Psychiatric Neuroscience, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
authors.forename: Lijing
authors.initials: L
authors.lastname: Xin
authors.affiliation: Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lanz
authors.affiliation: 1] Department of Radiology, University of Geneva, Geneva, Switzerland [2] Animal Imaging and Technology Core (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Lei
authors.affiliation: 1] Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland [2] Department of Radiology, University of Geneva, Geneva, Switzerland [3] Department of Radiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology; D002247:Carbon Isotopes / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D008954:Models, Biological; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D051381:Rats; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D002247:Carbon Isotopes; D019275:Radiopharmaceuticals; D013549:Sweetening Agents; D019344:Lactic Acid; D005947:Glucose