Volume 3 • Issue 4 • 1000129 J Alzheimers Dis Parkinsonism ISSN: 2161-0460 JADP, an open access journal Open Access Research Article Schmitt et al., J Alzheimers Dis Parkinsonism 2013, 3:4 http://dx.doi.org/10.4172/2161-0460.1000129 Alzheimer’s Disease & Parkinsonism Keywords: MR-spectroscopy; C57BL/6; Brain metabolites; Absolute quantification Introduction Rodent models of human diseases are of high importance for biomedical research as they enable studying diseases under laboratory conditions to provide information on pathophysiology of the disease and to develop and evaluate treatment options. is is of special importance for orphan diseases such as the guanidinoacetate methyltransferase (GAMT) deficiency, where it has not been possible, due to the low number of patients, to evaluate and modify treatment strategies in a clinical setting. Further, in order to understand disease induced changes occurring during brain development, it is essential to have an accurate understanding of normal brain maturation and its biological variability [1]. Proton magnetic resonance spectroscopy ( 1 H MRS) is a well- established tool for non-invasive detection and quantification of brain metabolites such as taurine, creatine, choline, glutamate, glutamine, myo-inositol, and N-acetylaspartate [2]. 1 H MRS applied to the brain of mice and rats at different magnetic field strengths revealed metabolic patterns that are comparable to those observed in human brain [2- 5]. Studies of cerebral metabolite concentrations in different mouse strains, however, have also demonstrated small (<13%) inter-strain variations, which are limited to specific metabolites [4,6,7]. Metabolite changes occurring during post-natal mouse brain development have been studied in vivo with single-voxel spectroscopy [8-10] or a *Corresponding author: Andreas Schulze, The Hospital for Sick Children, The Research Institute, Genetics and Genome Biology, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada, Tel: +1 (416) 813 7654; Fax: +1 (416) 813 5345; E-mail: andreas.schulze@sickkids.ca Received August 27, 2013; Accepted November 09, 2013; Published November 13, 2013 Citation: Schmitt B, vonBoth I, Amara CE, Schulze A (2013) Quantitative Assessment of Metabolic Changes in the Developing Brain of C57BL/6 Mice by In Vivo Proton Magnetic Resonance Spectroscopy. J Alzheimers Dis Parkinsonism 3: 129. doi: 10.4172/2161-0460.1000129 Copyright: © 2013 Schmitt B, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Quantitative Assessment of Metabolic Changes in the Developing Brain of C57BL/6 Mice by In Vivo Proton Magnetic Resonance Spectroscopy Benjamin Schmitt 1 , Ingo vonBoth 2 , Catherine E Amara 3 and Andreas Schulze 4 * 1 Department of Radiology, Medical University of Vienna Centre for High-Field MR, Austria 2 Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada 3 Faculty of Kinesiology & Physical Education, University of Toronto, Canada 4 The Hospital for Sick Children, The Research Institute, Genetics and Genome Biology (Work was conducted here), University of Toronto, Canada Abstract Localized proton MRS was used to quantify cerebral metabolite concentrations in the thalamus of mice to assess the variation of major metabolites during brain development. Three sets of C57BL/6 mice were followed in a longitudinal study from a very early phase at post-natal day four (p4) until day 57 (p57). Experiments were conducted in accordance with Canadian animal care guidelines on a 7-Tesla small animal MR system. Specimens were examined under inhalation anesthesia using single-voxel MRS. A cubic volume with edge lengths of 1.9 mm was placed in the thalamus region of animals and point-resolved spectroscopy (PRESS) spectra were acquired with the following parameters (TR/TE/NEX=2500 ms/20 ms/600; Bandwidth=4000 Hz). Absolute metabolite quantification using LCModel was obtained by assigning water signal intensity measured by MRS to water concentrations determined by histobiochemical analysis and interpolation. Optimized anesthesia, immobilization, and careful monitoring led to a survival rate of 100% throughout the study. The brain water content was 84.8, 78.8, and 77.6% at p12, p31, and p66. Variation of metabolites revealed similar patterns for the total of creatine and phosphocreatine (tCr), glutamate and glutamine (Glx), and the total of N-acetyl aspartic compounds (tNAA), with steady increases from p4 to reaching a plateau after p21. The total of Choline- containing compounds (tCho) and myo-inositol (Ins) had high concentrations at early exam points, decreased to minima between p14 and p19, and increased to adult levels thereafter. Taurine (Tau) had highest levels at p4, decreased persistently but fast in the early development and slow in the later stages of brain development. Our results indicate that biological variance must be considered if results from studies on mouse models of pathologies are compared with results from healthy controls during development. This aspect seems to be especially important between p10 and p21. Due to the high temporal resolution used at early time points in our study and the inclusion of multiple groups of animals at time points, our data contribute important aspects to the existing literature about mouse brain development. multi-voxel approach in C57BL/6 mice, and in vitro with whole brain samples from C57BL/6 mice [11,12]. e four in vivo studies used different approaches for absolute metabolite quantification, namely advanced method for accurate, robust and efficient spectral fitting (AMARES), and linear combination of model spectra (LCModel). Additionally, the particular time points, the intervals between them, and the brain regions examined varied between the studies. While the results of studies seem fairly homogeneous, distinct differences in reported development patterns were found in a study by Larvaron et al. [8-11]. Differences between the study results may be attributed to the respective employed quantification strategies, e.g., the choice of using an external quantification or measured brain water content as