Single voxel magnetic resonance spectroscopy with ultrashort echo time was implemented at 16.4 T to enhance the neurochemical profile of the rat brain in vivo. A TE of 1.7 msec was achieved by sequence optimization and by using short-duration asymmetric pulses. Macromolecular signal components were parameterized individually and included in the quantitative analysis, replacing the use of a metabolite-nulled spectrum. Because of the high spectral dispersion, several signals close to the water line could be detected, and adjacent peaks could be resolved. All 20 metabolites detected in this study were quantified with Cramé r-Rao lower bounds below 20%, implying reliable quantification accuracy. The signal of acetate was detected for the first time in rat brain in vivo with Cramé rRao lower bounds of 16% and a concentration of 0.52 mmol/g. Localized in vivo 1 H NMR spectroscopy provides a unique opportunity for measuring brain metabolite concentrations noninvasively, thus providing neurochemical information of in vivo processes (1). This capability has been shown to benefit from increasing magnetic field strength because of gains in signal-to-noise ratio (SNR) and chemical shift resolution. These advantages were demonstrated by detecting and quantifying 18 metabolites in the rat brain in vivo with an ultrashort echo time stimulated echo acquisition mode (STEAM) sequence at 9.4 T (2). Subsequently, the detection of ascorbate (Asc) was reported with both ultrashort TE STEAM and a J-difference editing technique (3), also at 9.4 T. Recently, several signals adjacent to the water peak, including N-acetylaspartate (NAA) at 4.38 ppm, glycerophosphorylcholine (GPC) at 4.31 ppm, and phosphorylcholine (PCho) at 4.27 ppm, were resolved with narrow RF bandwidths for water suppression, taking advantage of the increased spectral dispersion at 14.1 T (4).The availability of 16.4 T provides the potential of quantifying additional metabolites not detectable at lower field strength. Acetate (Ace), the anion of a shortchain organic acid, is widely recognized to be a substrate for glial cells (5). With in vivo 1 H NMR spectroscopy, the detection of the Ace methyl resonance at 1.9 ppm has not yet been possible due to its low concentration and virtually complete overlap with the methylene resonances of both g-aminobutyric acid (GABA) at 1.889 ppm and N-acetylaspartylglutamate (NAAG) at 1.9 ppm. Detection of Ace has, therefore, been limited to 1 H-[ 13 C]-NMR spectroscopy (6) and high resolution 1 H-NMR on perchloric acid (PCA) extracts of the rat brain (7).Although ultrashort TE makes it possible to obtain valuable metabolite information, it also leads to larger contributions from signals of macromolecules (MM); assessing this component is a critical factor in accurate metabolite quantification. Three different methods have been used to take account of the MM components in short TE in vivo 1 H NMR spectra. The first approach is to acquire an MM spectrum with an inversion-recovery metabolite-nulled measurement and then use this as a basis...

In vivo 1 H NMR spectroscopy was used to obtain the neurochemical profile in the posterior parts of the brain, the cerebellum and the medulla oblongata in comparison to the hippocampus and the thalamus. Using small voxel sizes between 16 and 32 ml to avoid partial volume effects, most metabolites demonstrated significant regional differences except acetate, g-aminobutyric acid, and phosphorylcholine. Noticeable regional differences in metabolite concentrations were the significant increase of total creatine in the cerebellum and the substantial decrease of taurine in thalamus and medulla oblongata. In particular, the glycine concentration in the medulla oblongata was determined to be 4.37 6 0.68 mmol/g (Cramé r-Rao lower bounds 7%) and thus significantly higher than in the other regions, consistent with findings reported in both in vivo 1 H NMR spectroscopy and in vitro biochemical assays. Intraindividual reproducibility and interindividual variability were investigated by acquiring spectra from the thalamus of the same rats in two sessions. No prominent influence on measurement session was observed in metabolite concentrations with coefficients of variations being below 20% in 16 metabolites. Magn Reson Med 66:11-17, 2011. V C 2011 Wiley-Liss, Inc. Key words: in vivo 1 H NMR spectroscopy; STEAM; ultra-short TE; CRLB; CV; regional differences; reproducibility Localized in vivo 1 H NMR spectroscopy of the brain is able to provide invaluable comprehensive and noninvasive information for investigating the healthy and diseased brain. In preclinical research, it has helped to understand pathologic changes in various disease models. Lately, the information content of in vivo 1 H NMR spectroscopy has been boosted by increasing magnetic field strengths available in modern MR instruments, making it possible to accurately quantify as many as 20 metabolites in the rat brain.An important factor for determining the applicability of in vivo 1 H NMR spectroscopy in preclinical studies is the quality of the localization, as metabolite concentrations have been shown to differ between tissues types. Thus, contamination from adjacent brain structures has to be strictly avoided. A double localization strategy, combining a stimulated echo acquisition mode volume selection with outer volume suppression (1), has been established as a reliable technique for many in vivo 1 H NMR spectroscopy studies, efficiently suppressing contributions from unwanted signal, while maximizing signal-to-noise ratio (SNR) and information by using short echo time (TE).Avoiding partial volume effects, however, is still difficult in many applications due to the large voxel sizes necessary to gather sufficient signal within acceptable measurement time. Thus, the selected volumes often contain more than one tissue type, which affects both the information content of the data as well as the reproducibility, as slight changes in the positioning of the voxel between sessions cause variations in the results. Thus, voxel size and accurate positioning are important f...

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The accuracy and precision of the quantification of metabolite concentrations in in vivo (1) H NMR spectroscopy are affected by linewidth and signal-to-noise ratio (SNR). To study the effect of both factors in in vivo (1) H NMR spectra acquired at ultrahigh field, a reference spectrum was generated by summing nine in vivo (1) H NMR spectra obtained in rat brain with a STEAM sequence at 16.4 T. By progressive deterioration of linewidth and SNR, 6400 single spectra were generated. In an accuracy study, the variation in the mean concentrations of five metabolites was mainly dependent on SNR, whereas 11 metabolites were predominantly susceptible to the linewidth. However, the standard deviations of the concentrations obtained were dependent almost exclusively on the SNR. An insignificant correlation was found between most of the heavily overlapping metabolite peaks, indicating independent and reliable quantification. Two different approaches for the consideration of macromolecular signals were evaluated. The use of prior knowledge derived by parameterization of a metabolite-nulled spectrum demonstrated improved fitting quality, with reduced Cramér-Rao lower bounds, compared to the calculation of a regularized spline baseline.