A Two-compartment Mathematical Model of Neuroglial Metabolism Using [1-(11)C] Acetate

Overview

Journal J Cereb Blood Flow Metab

Publisher Sage Publications

Specialties Cardiology & Vascular Diseases
Endocrinology
Neurology

Date 2011 Dec 1

PMID 22126912

Citations 7

Authors

Bernard Lanz

Kai Uffmann

Matthias T Wyss

Bruno Weber

Alfred Buck

Rolf Gruetter

Affiliations

Soon will be listed here.

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.

Citing Articles

Refined Analysis of Brain Energy Metabolism Using In Vivo Dynamic Enrichment of 13C Multiplets.

Dehghani M M, Lanz B, Duarte J, Kunz N, Gruetter R ASN Neuro. 2016; 8(2).

PMID: 26969691 PMC: 4790427. DOI: 10.1177/1759091416632342.

Oxidative metabolism of astrocytes is not reduced in hepatic encephalopathy: a PET study with [(11)C]acetate in humans.

Iversen P, Mouridsen K, Hansen M, Jensen S, Sorensen M, Bak L Front Neurosci. 2014; 8:353.

PMID: 25404890 PMC: 4217371. DOI: 10.3389/fnins.2014.00353.

Why are astrocytes important?.

Verkhratsky A, Nedergaard M, Hertz L Neurochem Res. 2014; 40(2):389-401.

PMID: 25113122 DOI: 10.1007/s11064-014-1403-2.

Metabolic Flux and Compartmentation Analysis in the Brain In vivo.

Lanz B, Gruetter R, Duarte J Front Endocrinol (Lausanne). 2013; 4:156.

PMID: 24194729 PMC: 3809570. DOI: 10.3389/fendo.2013.00156.

Computational approaches for understanding energy metabolism.

Shestov A, Barker B, Gu Z, Locasale J Wiley Interdiscip Rev Syst Biol Med. 2013; 5(6):733-50.

PMID: 23897661 PMC: 3906216. DOI: 10.1002/wsbm.1238.

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