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

AUTHORS: Lanz B, Uffmann K. Wyss M, Weber B, Buck A, Gruetter R

Journal of Cerebral Blood Flow and Metabolism, 32(3): 548–559, March 2012

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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_tca^g, V_x, V_nt, and V_tcaⁿ measured in dynamic ¹³C MRS experiments. Assuming V_x^g=10 × V_tca^g and V_xⁿ=V_tcaⁿ, it was possible to assess the composite glial tricarboxylic acid (TCA) cycle flux V_gt^g (V_gt^g=V_x^g × V_tca^g/(V_x^g+V_tca^g)) 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_gt^g=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.

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Module: PET