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


Lanz, Bernard; Uffmann, Kai; Wyss, Matthias T; Weber, Bruno; Buck, Alfred; Gruetter, Rolf (2012). A two-compartment mathematical model of neuroglial metabolism using [1-(11)C] acetate. Journal of Cerebral Blood Flow and Metabolism, 32(3):548-559.

Abstract

The purpose of this study was to develop a two-compartment metabolic model of brain metabolism to assess oxidative metabolism from [1-(11)C] acetate radiotracer experiments, using an approach previously applied in (13)C magnetic resonance spectroscopy (MRS), and compared with an one-tissue compartment model previously used in brain [1-(11)C] acetate studies. Compared with (13)C MRS studies, (11)C 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 (11)C 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(tca)(n) measured in dynamic (13)C MRS experiments. Assuming V(x)(g)=10 × V(tca)(g) and V(x)(n)=V(tca)(n), 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 (11)C tissue-activity curves obtained within 30 minutes in the rat cortex with a beta-probe after a bolus infusion of [1-(11)C] 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 (13)C MRS measurements.Journal of Cerebral Blood Flow & Metabolism advance online publication, 30 November 2011; doi:10.1038/jcbfm.2011.162.

The purpose of this study was to develop a two-compartment metabolic model of brain metabolism to assess oxidative metabolism from [1-(11)C] acetate radiotracer experiments, using an approach previously applied in (13)C magnetic resonance spectroscopy (MRS), and compared with an one-tissue compartment model previously used in brain [1-(11)C] acetate studies. Compared with (13)C MRS studies, (11)C 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 (11)C 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(tca)(n) measured in dynamic (13)C MRS experiments. Assuming V(x)(g)=10 × V(tca)(g) and V(x)(n)=V(tca)(n), 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 (11)C tissue-activity curves obtained within 30 minutes in the rat cortex with a beta-probe after a bolus infusion of [1-(11)C] 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 (13)C MRS measurements.Journal of Cerebral Blood Flow & Metabolism advance online publication, 30 November 2011; doi:10.1038/jcbfm.2011.162.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:04 Apr 2012 07:03
Last Modified:05 Apr 2016 15:39
Publisher:Nature Publishing Group
ISSN:0271-678X
Publisher DOI:https://doi.org/10.1038/jcbfm.2011.162
PubMed ID:22126912
Permanent URL: https://doi.org/10.5167/uzh-59862

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