MRS of Normal & Fundamental Physiology
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Tuesday 8 May 2012
Room 109-110  16:00 - 18:00 Moderators: Sylvia Mangia, Jullie W. Pan

16:00 0295.   Assessment of Prefrontal and Fronto-Striatal Glutamate Concentration in Healthy Children at 7T
Alena Horska1, Syed Hasan1, Xin Wang1, Matthew Ryan2, Richard Edden1, Martha Denckla2, Peter Barker1,2, and Mark Mahone1,2
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.

 
16:12 0296.   The relationship between Glutamate and oscillatory activity in a repetition suppression paradigm – a combined MR-spectroscopy and EEG study
Paul Gerald Mullins1, Corinna Haenschel2, Niall Lally1,3, Mark Roberts1, Darren Price1,4, and Thomas Gruber5
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.

 
16:24 0297.   
Brain metabolism in glutamatergic and GABAergic compartments detected by in vivo 13C NMR spectroscopy at 14.1 T
João M.N. Duarte1,2, and Rolf Gruetter1,3
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.

 
16:36 0298.   1H-[13C]-NMR spectroscopy measures of chronic stress effects on TCA cycle flux and glutamate-glutamine cycling are attenuated by riluzole or ceftriaxone treatment in awake rat prefrontal cortex
Golam M.I. Chowdhury1, Mounira Banasr2, Kevin L Behar1, and Gerard Sanacora3
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 lower case Greek beta-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.

 
16:48 0299.   
Myo-Inositol increase with age shows SCN1A dependency: a 3T MRS study
Nuran Tunc-Skarka1, Sandra Meier2, Markus Sack1, Wolfgang Weber-Fahr1, Traute Demirakca1, Thomas G. Schulze3, Carsten Diener4, and Gabriele Ende1
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.

 
17:00 0300.   Measurement of glycine in gray and white matter in the human brain by 1H-MRS at 7.0 T in vivo
Changho Choi1, Sandeep Ganji1, Abhishek Banerjee1, Ivan Dimitrov1, Subroto Ghose1, and Carol Tamminga1
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.

 
17:12 0301.   The major fraction of intracellular metabolites in the primate brain is localized in long fibers rather than in cell bodies, as shown by diffusion-weighted spectroscopy at long and ultra-long diffusion times
Chloé Najac1,2, Charlotte Marchadour1,2, Martine Guillermier1,2, Philippe Hantraye1,2, Vincent Lebon1,2, and Julien Valette1,2
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.

 
17:24 0302.   Longitudinal Neurochemical changes in brains of Tau transgenic mouse model
Jieun Kim1, In-Young Choi1,2, Karen Duff3, and Phil Lee1,4
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.

 
17:36 0303.   Long-term dosage effects in iron repletion treatment on neurochemical profiles and gene expression in rat model of neonatal iron deficiency
Ivan Tkac1, Katie Czerniak2, Amy Hurst3, Barbara Felt3, Michael K Georgieff2, and Raghavendra Rao2
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.

 
17:48 0304.   
Proton Magnetic Resonance Spectroscopy of Regional Metabolic Changes in Rat Brain during Pregnancy
Iris Y. Zhou1,2, Russell W. Chan1,2, Leon C. Ho1,2, Patrick P. Gao1,2, and Ed X. Wu1,2
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.