In Vivo Simultaneous Measurement of Glutamine Synthetase and Glutamate Dehydrogenase Activity in the Hyperammonemic Rat Brain Using Localized ¹H and ¹⁵N MRS
Cristina Cudalbu¹, Bernard Lanz², Paul R. Vasos³, Yves Pilloud², Vladimír Mlynárik², Rolf Gruetter^2,4
1Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL) , Lausanne, Switzerland; ²Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; ³Laboratory for Biomolecular Magnetic Resonance, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland; ⁴2Departments of Radiology, Universities of Lausanne and Geneva, Switzerland

15N MRS is an alternative approach to 13C MRS in studying glutamate-glutamine metabolism and can provide a more straightforward interpretation. For this study we developed a new pulse sequence in order to simultaneously measure [5-15N]Gln and [2-15N]Gln+Glu for a direct measurement of the net glutamine synthesis rate (Vsyn-Vnt), Vsyn and VGDH under 15N-labeled ammonia infusion in the rat brain, using in vivo localized 15N MRS interleaved with 1H MRS. We obtained from the 1H data a net synthesis flux (Vsyn-Vnt)=0.035±0.001µmol/min/g. By fitting the in vivo 5-15N Gln and 2-15N Glu+Gln time courses, Vsyn=0.24±0.03µmol/min/g, VGDH=0.030±0.001µmol/min/g. Finally, the apparent neurotransmission rate, Vnt=0.21±0.03µmol/min/g.

GABA Concentration in Frontal Eye Field Predicts Oculomotor Distractibility
Richard AE Edden^1,2, Petroc Sumner³, Aline Bompas³, Krish D. Singh^3
1Russell H Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins University, Baltimore, MD, United States; ²FM Kirby Research Center for Functional MRI, Kennedy Krieger Institute, Baltimore, MD, United States; ³CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom

Recent developments in the quantitation of GABA through edited MRS allow the behavioural consequences of individual differences in local GABA concentration to be studied. Such studies provide an important window into the workings of the healthy brain and a multimodal probe to investigate pathology.  Eye movements, known to be altered in many pathologies, are  thought to be planned in frontal eye fields (FEF). In this study we measure GABA concentration in a functionally-localised FEF region and show that GABA predicts saccade distractibility in healthy controls; this novel approach suggests further studies into the biochemical origins of neuropathologic behavioural deficits.

MR Spectroscopy Without Water Suppression for the Determination of Proton Exchange Rates in the Human Brain
Erin Leigh MacMillan¹, Daniel Guo Quae Chong¹, Wolfgang Dreher², Anke Henning³, Chris Boesch¹, Roland Kreis^1
1Department of Clinical Research, University of Bern, Bern, Switzerland; ²Dept. Chemistry, University of Bremen, Bremen, Germany; ³Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

MRS without water suppression can detect exchangeable proton resonances, particularly downfield of water.  Employing a two-acquisition scheme with alternating up- or down-field metabolite inversion prior to PRESS, both the metabolite and water spectra were obtained from the human brain in-vivo.  The experiment was performed with and without a water inversion prepulse with varying inversion times (TI).  The magnetization transfer curves were fit with a Bloch-McConnell two-site exchange model to determine exchange rates, with initial estimates yielding lifetimes (1/Km�¨w) ranging from 90ms to >2s, which offer information about pH and chemical microenvironments, and may aid in the understanding of CEST effects.

Modeling of ¹³C MRS Data of Cerebral Glucose Metabolism Comparing Mild Hypoglycemia with Euglycemia in Humans
Kim C.C. van de Ven¹, Marinette van der Graaf^1,2, Alexander A. Shestov³, Bastiaan E. de Galan⁴, Cees J.J. Tack⁴, Pierre-Gilles Henry³, Arend Heerschap^1
1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; ²Clinical Physics Laboratory, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; ³Center for Magnetic Resonance Research, University of Minneapolis, Minneapolis, MN, United States; ⁴General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

During hypoglycemia the supply of the brain with glucose is reduced. The aim of this study was to examine the direct effects of hypoglycemia on cerebral glucose metabolism by ¹³C MRS with infusion of [1-¹³C]glucose. ¹³C-label from glucose gets incorporated into isotopic positions in downstream amino acids. To estimate metabolic kinetics the time dependent uptake curves were modeled with a one-compartment model of cerebral glucose metabolism. Assuming similar labeling in plasma [3-¹³C]lactate, the flux through the TCA cycle, given by V_TCA , were comparable for both groups indicating that brain metabolism is maintained during mild hypoglycemia.

Quantification and Differentiation of CK and ATPase Fluxes Between Human GM and WM Using 3D ³¹P CSI and Saturation Transfer - not available
Xiao-Hong Zhu¹, Fei Du¹, Qiang Xiong¹, Hongyan Qiao¹, Xiao Liu¹, Jianyi Zhang², Xiaoliang Zhang³, Kamil Ugurbil¹, Wei Chen^1
1Center for Magnetic Resonance Research, Department of Radiology, Minneapolis, MN, United States; ²Department of Medicine, University of Minnesota, Minneapolis, MN, United States; ³University of California San Francisco, San Francisco, CA, United States

In vivo ³¹P MRS in combine with saturation transfer provides a useful tool for noninvasively measuring the cerebral metabolic fluxes of creatine kinase (CK) and ATPase reactions. However, 3D imaging of these metabolic fluxes in human brain is challenging owing to limited sensitivity and complicated quantification model when a short (desired) repetition time is used. In this study, we demonstrate that with advanced ³¹P MRS imaging approach and a newly developed quantification method, it is possible to image the CK and ATPase reaction rate constants and fluxes in human brain at 7T. We found that these fluxes were several folds higher in the grey matter than white matter. This study demonstrates not only the superior sensitivity achievable at high/ultrahigh field, but also the great potential of ³¹P approach for studying cerebral HEP metabolism and neuroenergetics associated with brain function and dysfunction.

Improved Quantification of Mitochondrial Exchange, TCA Cycle Rate and Neurotransmission Flux Using ¹H{¹³C} MRS Measurements of C4 and C3 of Glutamate and Glutamine
Bernard Lanz¹, Lijing Xin¹, Rolf Gruetter^1,2
1Laboratory for functional and metabolic imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; ²Departments of Radiology, Universities of Lausanne and Geneva, Lausanne and Geneva, Switzerland

[2-¹³C]acetate infusion coupled with ¹³C MRS enables the separated assessment of glial and neuronal Krebs cycle fluxes with higher accuracy than ¹³C labeled glucose, due to the asymetric metabolism of acetate in the brain. However, the faster neuronal Krebs cycle induces a strong dilution of the ¹³C labeled glutamate on the neuronal side, resulting in lower ¹³C MRS signal than with glucose. In this study, we analyzed with Monte-Carlo simulations the precision of the fitted metabolic fluxes with separated GluC3/GlnC3 curves obtained with ¹H{¹³C} MRS as well as the impact of the neuroglial partition of glutamate on the fluxes.

Composition of Fatty Acids in Adipose Tissue by In Vivo ¹³ MRS at 7T
Ivan Dimitrov¹, Jimin Ren², Deborah Douglas², Jeannie Davis², A Dean Sherry², Craig R. Malloy^2
1Philips Medical Systems, Cleveland, OH, United States; ²Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

The risk of many chronic diseases may be influenced by the composition of fatty acids in adipose tissue, particularly the ratio of saturated to unsaturated fats and the ratio of omega-6 to omega-3 fats. However, the chemical shift dispersion of ¹H MRS is not sufficient for full analysis of chemical composition. Broadband proton-decoupled ¹³C NMR spectra of subcutaneous adipose tissue were obtained in healthy subjects.  After corrections for T₁ and nuclear Overhauser effects, the poly-, mono-, and saturated fat composition was 18%, 49%, and 32%, respectively. ¹³C NMR is a rich source of information about adipose composition in humans.

Influence of Regional Macromolecule Baseline on the Quantification of Neurochemical Profile in Rat Brain
Lijing Xin¹, Vladimir Mlynárik¹, Hongxia Lei², Rolf Gruetter^1,2
1Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; ²Department of Radiology, University of Lausanne, Lausanne, Switzerland

The aim of present study was to measure the macromolecule baselines from four different volumes of interest including cortex, hippocampus, striatum and a mixture of brain structures, and then to assess their influence on the quantification of metabolites. Minor differences were found between the macromolecules acquired from specific regions and a large volume containing various cerebral structures. A slight variability in the shape of the macromolecule baseline introduced by data processing can affect calculated concentrations of less well characterized metabolites. The use of a generic experimental macromolecule baseline provides a sufficiently accurate measurement of the neurochemical profile in rat brain.

Short Echo Time H¹ Chemical Shift Imaging Data Quantification in the Mouse Brain at 11.7T Using a Constrained Parametric Macromolecular Model
Hélène Ratiney¹, Yann Le Fur², Michaël Sdika², Sophie Cavassila^3
1Université de Lyon, CREATIS-LRMN; CNRS UMR 5220; Inserm U630; INSA-Lyon; Université Lyon 1, Villeurbanne, France; ²Université Aix-Marseille II, CRMBM, CNRS UMR 6612, Marseille, France; ³Université de Lyon,, CREATIS-LRMN; CNRS UMR 5220; Inserm U630; INSA-Lyon; Université Lyon 1, Villeurbanne, France

Short echo time chemical shift imaging (SE-CSI) data quantification at 11.7T in the mouse brain is challenging because the magnetic field inhomogeneity impact the quality of both water suppression and  spectral resolution and macromolecular contamination can vary from voxel to voxel. We propose to derive from macromolecular CSI acquisition a constrained parametric macromolecular model to incorporate strong prior knowledge into the fitting of the SE-CSI. Evaluation of this approach on in vivo data acquisition is proposed and discussed.

Spectroscopy of the Human Prostate at 3 Tesla Using Surface Coil: Age-Related Changes
Jan Weis¹, Antonina Bergman¹, Francisco Ortiz-Nieto¹, Mikael Häggman², Håkan Ahlström^1
1Dept. of Radiology, Uppsala University Hospital, Uppsala, Sweden; ²Dept. of Urology, Uppsala University Hospital, Uppsala, Sweden

Single-voxel spectroscopy and 2D spectroscopic imaging of the prostate at 3 T was performed using standard surface coil. Spectra of 53 healthy volunteers were processed using customized LCModel. It was found that metabolite-to-citrate spectral intensity ratios were significantly lower in older individuals than in younger. Our results demonstrate that the prostate spectroscopy at 3 T is feasible using surface coil. LCModel provides a high level of accuracy for analysis of prostate spectra. Our results indicate that each 1H MRS study of the human prostate should include age-matched controls.