Alena Horska¹, Syed Hasan¹, Xin Wang¹, Matthew Ryan², Richard Edden¹, Martha Denckla², Peter Barker^1,2, and Mark Mahone^1,2
1Johns Hopkins University, Baltimore, MD, United States, ²Kennedy Krieger Institute, Baltimore, MD, United States

Single voxel 1H MRS at 7T was used to measure glutamate concentrations in prefrontal and fronto-striatal regions in healthy 5-9 year old children. Reliability of glutamate measurement was assessed and the compliance with the MRI/MRS protocol was evaluated. Exploratory analyses were applied to examine the relationship between frontal Glu levels and neurobehavioral data.

Paul Gerald Mullins¹, Corinna Haenschel², Niall Lally^1,3, Mark Roberts¹, Darren Price^1,4, and Thomas Gruber^5
1Psychology, Bangor University, Bangor, Gwynedd, United Kingdom, ²School of Psychology, City University, London, United Kingdom, ³ICN, London, United Kingdom, ⁴Nottingham University, United Kingdom, ⁵Institut für Psychologie, Universität Osnabrück, Germany

We present the first concurrently acquired event-related Magnetic Resonance Spectroscopy (MRS) and Electroencephalography (EEG) study of neuronal activity. Using a 3T MR system, and MRI compatible EEG simultaneous MRS (from the lateral occipital cortex) and EEG data were collected during an event related visual repetition suppression paradigm. Collecting proton MRS and EEG measures simultaneously showed a significant correlation between Glutamate levels and the gama band response, providing a new window on the underlying neurochemical and electrophysiological substrates of neuronal activity.

João M.N. Duarte^1,2, and Rolf Gruetter^1,3
1Center for Biomedical Imaging, Ecole Polytechnique Federale Lausanne, Lausanne, Switzerland, ²Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland, ³Department of Radiology, Universities of Lausanne and Geneva, Lausanne and Geneva, Switzerland

We now investigated the metabolism of γ-aminobutyric acid (GABA) in the brain using localised 13C NMR spectroscopy at 14.1 T. Upon infusion of [1,6-13C]glucose, 11 time courses of 13C-enriched metabolites were quantified, to which we then fitted a 3-compartment model of cerebral metabolism, thus providing insight in GABA metabolism and GABAergic neurotransmission.

Golam M.I. Chowdhury¹, Mounira Banasr², Kevin L Behar¹, and Gerard Sanacora^3
1Department of Psychiatry and Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut, United States,²Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States, ³Department of Psychiatry and the Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut, United States

We investigated the effects of riluzole, a drug shown enhance of glial glutamate clearance and modulate presynaptic glutamate release, and ceftriaxone, a -lactam antibiotic known to elevate GLT1 expression, on neuronal and glial metabolism in awake rats subjected to chronic unpredictable stress (CUS), a rodent model of depression, or control conditions. The CUS animals were subjected to 12 stressors (2 per day for 35 days) and riluzole or ceftriaxone was administered once daily for the last 21 days. ¹³C enrichments of glutamate, GABA and glutamine were measured using ¹H-[¹³C]-NMR spectroscopy at 11.74T in extracts following infusions of either [1-¹³C]glucose, a substrate metabolized mainly in the neuronal TCA cycle, or [2-¹³C]acetate, a substrate metabolized by astrocytes labeling glutamine. CUS led to decreased ¹³C labeling from glucose and acetate suggesting altered neuronal and glial metabolism. Chronic riluzole treatment attenuated stress effects on neuron and glial neurotransmitter uptake/cycling, however, chronic ceftriaxone treatment mainly attenuated the neuronal effects with less prominent effects on glial cell metabolism.

Nuran Tunc-Skarka¹, Sandra Meier², Markus Sack¹, Wolfgang Weber-Fahr¹, Traute Demirakca¹, Thomas G. Schulze³, Carsten Diener⁴, and Gabriele Ende^1
1Neuroimaging, Central Insitute of Mental Health, Mannheim, Baden-Württemberg, Germany, ²Genetic Epidemiology in Psychiatry, Central Insitute of Mental Health, Mannheim, Baden-Württemberg, Germany, ³Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, ⁴Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Mannheim, Baden-Württemberg, Germany

Via MRS one of the most frequent findings in white matter of aging brains is a reduced NAA and an increased mI concentration. In our study we wanted to investigate if SCN1A has any effect on the age dependent metabolites in a sample of 49 healthy volunteers. SCN1A is been seen as a novel gene candidate for cognitive decline. We found reduced NAA and Glu and increased Cr and mI with age. Further we found increased mI in the SCN1A risk group.

Changho Choi¹, Sandeep Ganji¹, Abhishek Banerjee¹, Ivan Dimitrov¹, Subroto Ghose¹, and Carol Tamminga^1
1University of Texas Southwestern Medical Center, Dallas, Texas, United States

Measurement of glycine (Gly) in gray and white matter (GM and WM) in the human brain by 1H-MRS at 7T is reported. A Gly-optimized PRESS sequence was used for measuring Gly from various brain regions in 10 healthy volunteers. The Gly signal intensity, following the normalization to the water signal, was larger in GM-dominant regions than in WM-dominant regions. From a linear regression of the Gly estimates vs. fractional GM content, the Gly concentrations in GM and WM were estimated to be 0.99 and 0.04 mM, respectively.

Chloé Najac^1,2, Charlotte Marchadour^1,2, Martine Guillermier^1,2, Philippe Hantraye^1,2, Vincent Lebon^1,2, and Julien Valette^1,2
1CEA-MIRCen, Fontenay-aux-Roses, France, ²CEA-CNRS URA 2210, Fontenay-aux-Roses, France

In vivo diffusion-weighted spectroscopy offers unique insights into cell architecture. At long diffusion times td, the geometry of the compartment where diffusion occurs deeply affects the apparent diffusion coefficient (ADC). In the present study, we investigated brain metabolites ADC variation at long and ultra-long td (up to 1 second). No strong dependence of NAA, creatine and choline ADC on td was observed over the large time-window. Data modeling using geometrically constrained diffusion models leads to the conclusion that a major fraction of brain metabolites diffuse in long fibers such as axons and dendrites.

Jieun Kim¹, In-Young Choi^1,2, Karen Duff³, and Phil Lee^1,4
1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States, ²Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States, ³Department of Integrative Neuroscience, Columbia University Medical Center, New York, NY, United States, ⁴Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States

Effects of tauopathies in cerebral metabolism are not well described. This study aims to characterize neurochemical alterations associated with the development of tau pathologies in tau transgenic mice (rTau) that express a repressible human tau variant. Longitudinal assessment of neurochemical levels in the hippocampus showed alterations already at 5 months of age (mos), when they start to develop progressive age-related NFTs, neuronal loss, and behavioral impairments. Neurochemical alterations were more pronounced at 9 mos and further progressed at 12 mos, demonstrating 1H MRS as a sensitive tool to monitor disease progression with age in tauopathies.

Ivan Tkac¹, Katie Czerniak², Amy Hurst³, Barbara Felt³, Michael K Georgieff², and Raghavendra Rao^2
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Department of Pediatrics, University of Minnesota, Minneapols, MN, United States, ³Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States

In vivo ¹H NMR spectroscopy and qPCR method were used to investigate long-term effect of two different iron repletion therapy protocols on neurochemical profiles and gene expression in prefrontal cortex and hippocampus of neonatally iron deficient rats at adulthood. Region specific differences in NAA, NAAG, PE and GPC+PC were in agreement with observed gene expression. Observed dose-dependent effects of iron repletion protocol potentially may be helpful in optimizing therapy for neonatal iron deficiency.

Iris Y. Zhou^1,2, Russell W. Chan^1,2, Leon C. Ho^1,2, Patrick P. Gao^1,2, and Ed X. Wu^1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong SAR, China

In this study, in vivo 1H MRS was employed to investigate the metabolic differences between pregnant and non-pregnant rats in hippocampus and thalamus. Significantly higher level of hippocampal NAA of pregnant rats indicates the increased density of neurons in this region, facilitating supporting behaviors that involving learning and memory. Reduced level of choline in the maternal brain during pregnancy reflects high fetal demands. The raised lactate level in thalamus might be related to the hyperventilation of pregnancy. The results of this study provide neurochemical evidence of the behavioral changes associated with pregnancy.