A two-compartment mathematical model of neuroglial metabolism using [1-11C] acetate

Abstract

The purpose of this study was to develop a two-compartment metabolic model of brain metabolism to assess oxidative metabolism from [1-11C] acetate radiotracer experiments, using an approach previously applied in 13C magnetic resonance spectroscopy (MRS), and compared with an onetissue compartment model previously used in brain [1-11C] acetate studies. Compared with 13C MRS studies, 11C radiotracer measurements provide a single uptake curve representing the sum of all labeled metabolites, without chemical differentiation, but with higher temporal resolution. The reliability of the adjusted metabolic fluxes was analyzed with Monte-Carlo simulations using synthetic 11C uptake curves, based on a typical arterial input function and previously published values of the neuroglial fluxes Vtca g , Vx, Vnt, and Vtca n measured in dynamic 13C MRS experiments. Assuming Vx g = 10Vtca g and Vx n = Vtca n , it was possible to assess the composite glial tricarboxylic acid (TCA) cycle flux Vgt g (Vgt g = Vx g Vtca g /(Vx g + Vtca g )) and the neurotransmission flux Vnt from 11C tissueactivity curves obtained within 30 minutes in the rat cortex with a beta-probe after a bolus infusion of [1-11C] acetate (n = 9), resulting in Vgt g = 0.136±0.042 and Vnt = 0.170±0.103 lmol/g per minute (mean±s.d. of the group), in good agreement with 13C MRS measurements.