title: Metabolic Modeling of Dynamic (13)C NMR Isotopomer Data in the Brain In Vivo: Fast Screening of Metabolic Models Using Automated Generation of Differential Equations.
abstract: Most current brain metabolic models are not capable of taking into account the dynamic isotopomer information available from fine structure multiplets in (13)C spectra, due to the difficulty of implementing such models. Here we present a new approach that allows automatic implementation of multi-compartment metabolic models capable of fitting any number of (13)C isotopomer curves in the brain. The new automated approach also makes it possible to quickly modify and test new models to best describe the experimental data. We demonstrate the power of the new approach by testing the effect of adding separate pyruvate pools in astrocytes and neurons, and adding a vesicular neuronal glutamate pool. Including both changes reduced the global fit residual by half and pointed to dilution of label prior to entry into the astrocytic TCA cycle as the main source of glutamine dilution. The glutamate-glutamine cycle rate was particularly sensitive to changes in the model.
authors.affiliation: Commissariat à l'Energie Atomique (CEA), Molecular Imaging Research Center (MIRCen), 92260, Fontenay-aux-Roses, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Tiret
authors.affiliation: Center for Magnetic Resonance Research (CMRR), University of Minnesota, 2021 6th St SE, Minneapolis, MN, 55455, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Shestov
authors.affiliation: Commissariat à l'Energie Atomique (CEA), Molecular Imaging Research Center (MIRCen), 92260, Fontenay-aux-Roses, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Valette
authors.affiliation: Center for Magnetic Resonance Research (CMRR), University of Minnesota, 2021 6th St SE, Minneapolis, MN, 55455, USA. henry@cmrr.umn.edu.
authors.forename: Pierre-Gilles
authors.initials: PG
authors.lastname: Henry
mesh_terms: D000465:Algorithms; D000818:Animals; D001331:Automation; D001923:Brain Chemistry / Q000502:physiology*; D003198:Computer Simulation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008954:Models, Biological; D008962:Models, Theoretical; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism
keywords: 13C; Metabolic modeling; Neuronal-glial metabolism; Two-compartment