Metabolic modelling and time-resolved mapping of glucose oxidative metabolism in rats brain by indirect deuterium detection with 1H-FID-MRSI at 9.4T

Abstract

ObjectThe present study exploits newly developed dynamic indirect 1H-[2H]-FID-MRSI at 9.4T, combined with a dedicated metabolic model, to enable regional and quantitative characterization of glucose oxidative metabolism flux in the rat brain with minimal metabolic assumptions, by measuring both 2H-labelled Glx turnover and pool size along a controlled 2H-Glc infusion protocol. Materials and MethodsSeven rats underwent dynamic 2D 1H-FID-MRSI during a 2-hour infusion of [6,6-2H2] glucose. Consecutive 13-min acquisitions quantified Glx-C4 1H-signal decay, converted to 2H-Glx concentrations using baseline metabolite pool sizes. A three-pool kinetic model including 2H-label loss was fitted to regional turnover curves to estimate oxidative flux (Vgt) and pyruvate dilution (Kdil). Model performance and parameter robustness were finally assessed with Monte-Carlo simulations. ResultsIn vivo 2H-Glx turnover showed a saturated exponential rise ([~]60 min), with a labelling plateau higher in striatum (1.85 mol/g) than hippocampus (1.55 mol/g). Metabolic modelling provided region-specific oxidative fluxes: Vgt = 0.27 {+/-} 0.07 mol/g/min (hippocampus) and Vgt = 0.40 {+/-} 0.06 mol/g/min (striatum), with consistent Kdil across regions. Simulations confirmed a good model robustness in retrieving Vgt over a large range of experimental conditions. DiscussionThis work shows the appropriateness of indirect dynamic 1H-[2H]-FID-MRSI for quantitative metabolic flux mapping of cerebral glucose oxidative metabolism.