Toward an in Vivo Neurochemical Profile: Quantification of 18 Metabolites in Short-Echo-Time 1H NMR Spectra of the Rat Brain

Abstract

Localized in vivo1 H NMR spectroscopy was performed with 2-ms echo time in the rat brain at 9.4 T. Frequency domain analysis with LCModel showed that the in vivo spectra can be explained by 18 metabolite model solution spectra and a highly structured background, which was attributed to resonances with fivefold shorter in vivo T 1 than metabolites. The high spectral resolution (full width at half maximum approximately 0.025 ppm) and sensitivity (signal-to-noise ratio approximately 45 from a 63-L volume, 512 scans) was used for the simultaneous measurement of the concentrations of metabolites previously difficult to quantify in 1 H spectra. The strongly represented signals of Nacetylaspartate, glutamate, taurine, myo-inositol, creatine, phosphocreatine, glutamine, and lactate were quantified with Cramér-Rao lower bounds below 4%. Choline groups, phosphorylethanolamine, glucose, glutathione, ␥-aminobutyric acid, Nacetylaspartylglutamate, and alanine were below 13%, whereas aspartate and scyllo-inositol were below 22%. Intra-assay variation was assessed from a time series of 3-min spectra, and the coefficient of variation was similar to the calculated Cramér-Rao lower bounds. Interassay variation was determined from 31 pooled spectra, and the coefficient of variation for total creatine was 7%. Tissue concentrations were found to be in very good agreement with neurochemical data from the literature.

Automatic quantitation of localized in vivo1H spectra with LCModel

“…In all of these studies the concentrations of the other metabolites remained constant with time to within experimental error, as would be expected. Detailed studies 3,7,8 of intra-assay and inter-assay reproducibility with LCModel are discussed below.…”

Proton MRS of early post‐natal mouse brain modifications in vivo

“…Modulations of major metabolite pools have been observed in human brain during childhood and adolescence (3) and in various pathological processes (4)(5)(6). At a higher field (9.4 T), by in vivo MRS, in 63 mL voxel, quantification of 18 metabolites has been performed in adult rat (7) and mouse (8) brains. More recently, developmental changes of metabolite concentrations have been determined in various areas (11 mL) of healthy rat brains (9).…”

Temperature dependence of 1H NMR chemical shifts and its influence on estimated metabolite concentrations

“…Additionally, the presence of more brain metabolites than considered in this study may cause additional spectral overlapping and thus even more severe quantification problems [4].…”

“…The metabolite concentrations were adjusted to mimic a rat brain [4,5,45]. Data sets were simulated for 40, 37, 35, and 32 °C to analyse the potential influence of pyrexia and experimentally induced cooling.…”

“…In vivo localised 1 H NMR spectroscopy (MRS) allows to non-invasively measure numerous metabolites in brain tissue, thus offering the possibility to study characteristic metabolic changes and identify biomarkers of diseases [1][2][3][4][5][6][7]. Therefore, a reliable quantification of brain metabolites is essential for the relevance of in vivo MRS.…”