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In vivo detection of intermediate metabolic products of [1-(13) C]ethanol in the brain using (13) C MRS.

ABSTRACT: In this study, in vivo (13) C MRS was used to investigate the labeling of brain metabolites after intravenous administration of [1-(13) C]ethanol. After [1-(13) C]ethanol had been administered systemically to rats, (13) C labels were detected in glutamate, glutamine and aspartate in the carboxylic and amide carbon spectral region. (13) C-labeled bicarbonate HCO 3- (161.0 ppm) was also detected. Saturating acetaldehyde C1 at 207.0 ppm was found to have no effect on the ethanol C1 (57.7 ppm) signal intensity after extensive signal averaging, providing direct in vivo evidence that direct metabolism of alcohol by brain tissue is minimal. To compare the labeling of brain metabolites by ethanol with labeling by glucose, in vivo time course data were acquired during intravenous co-infusion of [1-(13) C]ethanol and [(13) C(6) ]-D-glucose. In contrast with labeling by [(13) C(6) ]-D-glucose, which produced doublets of carboxylic/amide carbons with a J coupling constant of 51 Hz, the simultaneously detected glutamate and glutamine singlets were labeled by [1-(13) C]ethanol. As (13) C labels originating from ethanol enter the brain after being converted into [1-(13) C]acetate in the liver, and the direct metabolism of ethanol by brain tissue is negligible, it is suggested that orally or intragastrically administered (13) C-labeled ethanol may be used to study brain metabolism and glutamatergic neurotransmission in investigations involving alcohol administration. In vivo (13) C MRS of rat brain following intragastric administration of (13) C-labeled ethanol is demonstrated.

SUBMITTER: Xiang Y

PROVIDER: S-EPMC3400341 | biostudies-other | 2011 Nov

REPOSITORIES: biostudies-other

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Project description:Diffusion-weighted (DW-) MRS investigates non-invasively microstructural properties of tissue by probing metabolite diffusion in vivo. Despite the growing interest in DW-MRS for clinical applications, little has been published on the reproducibility of this technique. In this study, we explored the optimization of a single-voxel DW-semi-LASER sequence for clinical applications at 3 T, and evaluated the reproducibility of the method under different experimental conditions. DW-MRS measurements were carried out in 10 healthy participants and repeated across three sessions. Metabolite apparent diffusion coefficients (ADCs) were calculated from mono-exponential fits (ADCexp ) up to b = 3300 s/mm2 , and from the diffusional kurtosis approach (ADCK ) up to b = 7300 s/mm2 . The inter-subject variabilities of ADCs of N-acetylaspartate + N-acetylaspartylglutamate (tNAA), creatine + phosphocreatine, choline containing compounds, and myo-inositol were calculated in the posterior cingulate cortex (PCC) and in the corona radiata (CR). We explored the effect of physiological motion on the DW-MRS signal and the importance of cardiac gating and peak thresholding to account for signal amplitude fluctuations. Additionally, we investigated the dependence of the intra-subject variability on the acquisition scheme using a bootstrapping resampling method. Coefficients of variation were lower in PCC than CR, likely due to the different sensitivities to motion artifacts of the two regions. Finally, we computed coefficients of repeatability for ADCexp and performed power calculations needed for designing clinical studies. The power calculation for ADCexp of tNAA showed that in the PCC seven subjects per group are sufficient to detect a difference of 5% between two groups with an acquisition time of 4 min, suggesting that ADCexp of tNAA is a suitable marker for disease-related intracellular alteration even in small case-control studies. In the CR, further work is needed to evaluate the voxel size and location that minimize the motion artifacts and variability of the ADC measurements.

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In vivo detection of intermediate metabolic products of [1-(13) C]ethanol in the brain using (13) C MRS.

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