As a model for guanidinoacetate methyltransferase (GAMT) deficiency in humans, a gene knockout mouse model was generated. Here we report on several metabolic abnormalities in these mice, observed by in vivo and in vitro MR spectroscopy. In 1 H MR spectra of brain and hindleg muscle a clearly reduced signal of creatine (Cr) was observed in GAMT-deficient (GAMT-/-) animals. Analysis of the 1 H MR spectra of GAMT-/-brain indicated little or no increase of a signal for guanidinoacetate (Gua). In proton MR spectra of muscle, a broad signal of low intensity was observed for Gua. However, substantial Gua accumulation in intact muscle tissue was unequivocally confirmed in high-resolution magic angle spinning spectra, in which the Gua signal was resolved as one clear sharp singlet. In 31 P MR analysis of brain and hindleg muscle a strongly reduced phosphocreatine (PCr) content was shown. In addition, a signal of phosphorylated Gua at 0.5 ppm upfield of PCr was observed, with much higher intensity in muscle than in brain. This signal decreased when ischemia was applied to the muscle and recovered after ischemia was released. Overall, the in vivo 31 P and 1 H MR spectroscopy of GAMT-/-mice is similar to that of human GAMT deficiency. This opens up new avenues for the fundamental study of tissue-type dependence of creatine synthesis and transport and for diagnostic and therapeutic aspects of creatine deficiencies in humans. Magn Reson Med 50: 936 -943, 2003.

The purpose of this paper is to evaluate the effect of the combination of magnetic resonance spectroscopic imaging (MRSI) data and magnetic resonance imaging (MRI) data on the classification result of four brain tumor classes. Suppressed and unsuppressed short echo time MRSI and MRI were performed on 24 patients with a brain tumor and four volunteers. Four different feature reduction procedures were applied to the MRSI data: simple quantitation, principal component analysis, independent component analysis and LCModel. Water intensities were calculated from the unsuppressed MRSI data. Features were extracted from the MR images which were acquired with four different contrasts to comply with the spatial resolution of the MRSI. Evaluation was performed by investigating different combinations of the MRSI features, the MRI features and the water intensities. For each data set, the isolation in feature space of the tumor classes, healthy brain tissue and cerebrospinal fluid was calculated and visualized. A test set was used to calculate classification results for each data set. Finally, the effect of the selected feature reduction procedures on the MRSI data was investigated to ascertain whether it was more important than the addition of MRI information. Conclusions are that the combination of features from MRSI data and MRI data improves the classification result considerably when compared with features obtained from MRSI data alone. This effect is larger than the effect of specific feature reduction procedures on the MRSI data. The addition of water intensities to the data set also increases the classification result, although not significantly. We show that the combination of data from different MR investigations can be very important for brain tumor classification, particularly if a large number of tumors are to be classified simultaneously.

This preliminary study indicates that HRMAS NMR of routinely obtained PNBs can provide detailed metabolic information of intact prostate tissue with clinical relevance.

Purpose To harmonize data acquisition and post-processing of single voxel proton magnetic resonance spectroscopy (1H-MRS) at 7 Tesla (7T), and to determine metabolite concentrations, accuracy and reproducibility of metabolite levels in the adult human brain. Experimental This study was performed in compliance with local Institutional Human Ethics Committees. The same seven subjects were each examined twice using four different 7T MR-systems from two different vendors using an identical semi-LASER spectroscopy sequence. Neurochemical profiles were obtained from the posterior cingulate cortex (GM) and the corona radiata (WM). Spectra were analyzed with LCModel, and sources of variation in concentrations (‘subject’, ‘institute’ & ‘random’) were identified with a variance components analysis. Results Concentrations of 10-11 metabolites, which were corrected for T1, T2, Magnetization Transfer-effects and partial volume effects, were obtained with mean Cramér-Rao Lower Bounds below 20%. Data variances and mean concentrations in GM and WM were comparable for all institutions. The primary source of variance for glutamate, myo-inositol, scyllo-inositol, total creatine and total choline was between-subjects. Variance sources for all other metabolites were associated to within-subject and system noise, except for total N-acetylaspartate, glutamine and glutathione, which related to differences in signal-to-noise and in shimming performance between vendors. Conclusion After multi-center harmonization of acquisition and post-processing protocols, metabolite concentrations and size and sources of their variations were established for neurochemical profiles in the healthy brain at 7T, which can be used as guidance in future studies quantifying metabolite and neurotransmitter concentrations with 1H-MRS at ultra-high magnetic field.

Purpose: To assess the reproducibility of 1 H-MR spectroscopic imaging (MRSI) of the human brain at 3T with volume selection by a double spin echo sequence for localization with adiabatic refocusing pulses (semi-LASER). Materials and Methods:Twenty volunteers in two different institutions were measured twice with the same pulse sequence at an echo time of 30 msec. Magnetic resonance (MR) spectra were analyzed with LCModel with a simulated basis set including an experimentally acquired macromolecular signal profile. For specific regions in the brain mean metabolite levels, within and between subject variance, and the coefficient of variation (CoV) were calculated (for taurine, glutamate, total N-acetylaspartate, total creatine, total choline, myo-inositol þ glycine, and glutamate þ glutamine).Results: Repeated measurements showed no significant differences with a paired t-test and a high reproducibility (CoV ranging from 3%-30% throughout the selected volume). Mean metabolite levels and CoV obtained in similar regions in the brain did not differ significantly between two contributing institutions. The major source of differences between different measurements was identified to be the between-subject variations in the volunteers. Conclusion:We conclude that semi-LASER 1 H-MRSI at 3T is an adequate method to obtain quantitative and reproducible measures of metabolite levels over large parts of the brain, applicable across multiple centers.