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Object: To determine whether glycine can be measured at 7 T in human brain with 1H magnetic resonance spectroscopy (MRS). Materials and methods: The glycine singlet is overlapped by the larger signal of myo-inositol. Density matrix simulations were performed to determine the TE at which the myo-inositol signal was reduced the most, following a single spin-echo excitation. 1H MRS was performed on an actively shielded 7 T scanner, in five healthy volunteers. Results: At the TE of 30ms, the myo-inositol signal intensity was substantially reduced. Quantification using LCModel yielded a glycine-to-creatine ratio of 0.14 ±0.01, with a Cramér-Rao lower bound (CRLB) of 7 ± 1%. Furthermore, quantification of metabolites other than glycine was possible as well, with a CRLB mostly below 10%. Conclusion: It is possible to detect glycine at 7 T in human brain, at the short TE of 30ms with a single spin-echo excitation scheme

Recently, the spin-echo full-intensity acquired localized (SPECIAL) spectroscopy technique was proposed to unite the advantages of short TEs on the order of milliseconds (ms) with full sensitivity and applied to in vivo rat brain. In the present study, SPECIAL was adapted and optimized for use on a clinical platform at 3T and 7T by combining interleaved water suppression (WS) and outer volume saturation (OVS), optimized sequence timing, and improved shimming using FASTMAP. High-quality single voxel spectra of human brain were acquired at TEs below or equal to 6 ms on a clinical 3T and 7T system for six volunteers. Narrow linewidths (6.6 +/- 0.6 Hz at 3T and 12.1 +/- 1.0 Hz at 7T for water) and the high signal-to-noise ratio (SNR) of the artifact-free spectra enabled the quantification of a neurochemical profile consisting of 18 metabolites with Cramer-Rao lower bounds (CRLBs) below 20% at both field strengths. The enhanced sensitivity and increased spectral resolution at 7T compared to 3T allowed a two-fold reduction in scan time, an increased precision of quantification for 12 metabolites, and the additional quantification of lactate with CRLB below 20%. Improved sensitivity at 7T was also demonstrated by a 1.7-fold increase in average SNR (= peak height/root mean square [RMS]-of-noise) per unit-time. Magn Reson Med 61:1279-1285, 2009. (C) 2009 Wiley-Liss, Inc.

We developed a short-echo-time (TE) sequence for proton localized spectroscopy by combining a 1D add-subtract scheme with a doubly slice-selective spin-echo (SE) sequence. The sequence preserves the full magnetization available from the selected volume of interest (VOI). By reducing the number of radiofrequency (RF) pulses acting on transverse magnetization, we were able to minimize the TE to the level that is achievable with the stimulated echo acquisition mode (STEAM) technique, and also gained a twofold increase in sensitivity. The use of an adiabatic pulse in the add-subtract localization improved the efficiency of excitation in spatially inhomogeneous RF fields, which are frequently encountered at high magnetic fields. The localization performance and sensitivity gains of this method, which is termed SPin ECho, full Intensity Acquired Localized (SPECIAL) spectroscopy, were demonstrated in vivo in rat brains. In conjunction with spectroscopic imaging, a 2-microl spatial resolution was accomplished with a signal-to-noise ratio (SNR) above 30, which is usually sufficient for reliable quantification of a large number of metabolites (neurochemical profile).

The development of new diagnostic criteria for Alzheimer's disease (AD) requires new in vivo markers reflecting early pathological changes in the brain of patients. Magnetic resonance (MR) spectroscopy has been shown to provide useful information about the biochemical changes occurring in AD brain in vivo. The development of numerous transgenic mouse models of AD has facilitated the evaluation of early biomarkers, allowing researchers to perform longitudinal studies starting before the onset of the pathology. In addition, the recent development of high-field animal scanners enables the measurement of brain metabolites that cannot be reliably quantified at lower magnetic fields. In this report, we studied a new transgenic mouse model of AD, the 5xFAD model, by in vivo proton and phosphorus MR spectroscopy. This model, which is characterized by an early-onset and a robust amyloid pathology, developed changes in the neurochemical profile, which are typical in the human disease, i.e., an increase in myo-inositol and a decrease in N-acetylaspartate concentrations, as early as in the 40th week of age. In addition, a significant decrease in the γ-aminobutyrate concentration was observed in transgenic mice at this age compared to controls. The pseudo-first-order rate constant of the creatine kinase reaction as well as relative concentrations of phosphorus-containing metabolites were not changed significantly in the 36 and 72-week old transgenic mice. Overall, these results suggest that mitochondrial activity in the 5 × FAD mice is not substantially affected but that the model is relevant for studying early biomarkers of AD.

Both ultrashort echo-time STEAM and MEGA-PRESS-edited spectroscopy were used to validate noninvasive quantification of vitamin C (ascorbate) in the developing rat brain, where changes in ascorbate concentration have been reported. Despite strong overlap with resonances from glutamine, glutamate, glutathione, and macromolecules, reliable quantification of ascorbate (Cramer-Rao lower bounds < 0.2 μmol/g) by LC-Model analysis of STEAM (TE = 2 ms) spectra was possible at 9.4 T. Ascorbate concentrations quantified from the STEAEM spectra were in very good agreement with concentrations calculated from fully resolved ascorbate resonances in MEGA-PRESS-edited spectra measured from identical volumes of interest. Ascorbate concentrations measured using STEAM decreased with increasing postnatal rat age, in agreement with published brain ascorbate concentrations measured in vitro using high-performance liquid chromatography (HPLC). © 2006 Wiley-Liss, Inc.

In the last decade, evidence has emerged indicating that the growth of a vast majority of tumors including gliomas is sustained by a subpopulation of cancer cells with stem cell properties called cancer initiating cells. These cells are able to initiate and propagate tumors and constitute only a fraction of all tumor cells. In the present study, we showed that intracerebral injection of cultured glioma-initiating cells into nude mice produced fast growing tumors showing necrosis and gadolinium enhancement in MR images, whereas gliomas produced by injecting freshly purified glioma-initiating cells grew slowly and showed no necrosis and very little gadolinium enhancement. Using proton localized spectroscopy at 14.1 Tesla, decreasing trends of N-acetylaspartate, glutamate and glucose concentrations and an increasing trend of glycine concentration were observed near the injection site after injecting cultured glioma-initiating cells. In contrast to the spectra of tumors grown from fresh cells, those from cultured cells showed intense peaks of lipids, increased absolute concentrations of glycine and choline-containing compounds, and decreased concentrations of glutamine, taurine and total creatine, when compared with a contralateral non-tumor-bearing brain tissue. A decrease in concentrations of N-acetylaspartate and -aminobutyrate was found in both tumor phenotypes after solid tumor formation. Further investigation is needed to determine the cause of the dissimilarities between the tumors grown from cultured glioma-initiating cells and those from freshly purified glioma-initiating cells, both derived from human glioblastomas. Copyright (C) 2011 John Wiley & Sons, Ltd.