A two-compartment mathematical model of neuroglial metabolism using 1- 11 C 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 one-tissue 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 V tcag, V x, V nt, and V tcan measured in dynamic 13C MRS experiments. Assuming V xg 10 × V tcag and V xn V tcan, it was possible to assess the composite glial tricarboxylic acid (TCA) cycle flux V gtg (V gtg V xg × V tcag/(V xg V tcag)) and the neurotransmission flux V nt from 11C tissue-activity 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 V gtg= 0.136±0.042 and V nt 0.170±0.103 μmol/g per minute (mean=s.d. of the group), in good agreement with 13C MRS measurements. © 2012 ISCBFM All rights reserved.