Neurochemical Modeling & Profiling of Brain Metabolism
Tuesday 21 April 2009
Room 311 16:00-18:00


In-Young Choi and Ivan Tkac

16:00  347. Multimodal NMR Assessment of Erythropoietin as a Neuroprotective Agent Following Hypoxia-Ischemia on P3 Pup Rat Brain
    Yohan van de Looij1,2, Alexandra Chatagner1, Nicolas Kunz1,2, Petra S. Hüppi1, Rolf Gruetter3,4, Stéphane V. Sizonenko1
Division of Child Growth & Development, Department of Pediatrics, University of Geneva, Geneva, Switzerland; 2Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; 3Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne , Lausanne, Switzerland; 4Department of Radiology, University of Geneva and Lausanne, Switzerland
    The 3-day old rat (P3) shares some similarities in terms of cerebral development to the very preterm infant. Animal models of periventricular leukomalacia (most important cerebral alteration after premature birth) can be achieved by Hypoxia-Ischemia (HI). Here we investigated the neuroprotective effect of EPO in a model of neonatal HI injury in the P3 rat pup using DTI, MRS and immunohistochemistry. EPO appears able to reduce tissue loss and white matter injuries but it retains compromised metabolism consistent with incomplete recovery from EPO, giving a highly relevant new insight in the neuroprotective effect of EPO.
16:12 348. Neurochemical Profile of the Mouse Hypothalamus Using 1H MRS at 14.1T
    Hongxia Lei1,2, Carole Poitry-Yamate1, Frederic Preitner3, Bernard Thorens3, Rolf Gruetter1,4
Ecole Polytechnique Federale de Lausanne, Lausanne, Vaud, Switzerland; 2Radiology, University of Lausanne , Lausanne, Vaud, Switzerland; 3Institute of Physiology, University of Lausanne , Lasuanne, Vaud, Switzerland; 4Radiology, University of Geneva, Geneva, Switzerland
    MRS of hypothalamus in mice is very challenging due to its small volume and deep structure. In present study, we examine the feasibilities of 1H MRS of the hypothalamus in GLUT8 knockout mice at 14.1T. The quality spectra resulted in nearly 20 metabolites, so called the neurochemical profile of the mouse hypothalamus.
16:24 349. 1H MRS of the Visual Cortex Under Chronic Ocular Hypertension
    Kevin C. Chan1,2, Kwok-fai So3, Ed X. Wu1,2
Laboratory 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; 3Department of Anatomy, The University of Hong Kong, Hong Kong SAR, China
    This study aims to employ in vivo 1H MRS to monitor the metabolic changes in the visual cortex in an experimental model of chronic glaucoma. Five Sprague-Dawley rats were prepared to induce ocular hypertension unilaterally in the right eye by photocoagulating the episcleral and limbal veins using an argon laser. 1H MRS was performed to each side of the visual cortex 6 weeks after laser treatment. The results of this study suggest that glaucoma is associated with alterations in the metabolism of choline-containing compounds in the normally-appearing visual cortex. Measurement of the Cho:Cr reduction in the visual cortex may be a noninvasive biomarker for the disease.
16:36 350. Proton MRS Investigation of Human Glioma Models in Nude Mice at 14.1 T
    Vladimir Mlynarik1, Cristina Cudalbu1, Virginie Clément2, Denis Marino2, Ivan Radovanovic2, Rolf Gruetter1,3
Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; 2Dept. of Genetic Medicine and Development, University of Geneva School of Medicine, Geneva, Switzerland; 3Departments of Radiology, Universities of Lausanne and Geneva
    Injecting separated fresh or cultured human glioma-initiating cells into brain of nude mice produced tumors having two different phenotypes. The tumors from cultured cells grew fast and showed necrosis and Gd enhancement, while the gliomas from fresh cells grew slowly and showed no necrosis and very little Gd enhancement. Proton localized spectroscopy at 14.1 Tesla revealed different metabolic profiles in the two types of tumors. Characteristic changes of metabolite concentrations were observed in the brain tissue near the injection site of the cultured glioma-initiating cells before solid tumors were detected by MRI.


16:48 351. Redox Dependence and Compartmentation of [13C]Pyruvate in the Brain of Deuterated Rats Bearing Implanted C6 Gliomas
    Tiago Brandao Rodrigues1, Pilar Lopez-Larrubia1, Sebastián Cerdán1
LISMAR, Instituto de Investigaciones Biomédicas CSIC, Madrid, Spain
    We investigated the redox dependence and compartmentation of the pyruvate pool in the brain of partially deuterated rats bearing C6 gliomas. The rats were infused with [1-13C]glucose and [2-13C]pyruvate or [U-13C3]lactate. The relative amounts of [3-13C]lactate derived from glucose to the [2-13C] or [U-13C3]lactate isotopomers derived from monocarboxylates decreased in the order contralateral>ipsilateral>tumor regions, revealing a progressive reduction in glycolysis for regions containing increasing endogenous lactate concentrations. Deuterated animals bearing C6 tumors, infused with [1-13C]glucose and [2-13C]pyruvate, showed different deuterium enrichments in the methyl groups of cerebral [3-13C] and [2-13C]lactate, revealing a slow mixing of the [3-13C] and [2-13C]pyruvate precursors in the 2H exchange timescale of their methyl groups.
17:00 352. In Situ 3D MR Metabolic Imaging of Microwave-Irradiated Rodent Brain: A New Tool for Metabolomics Research
    Robin A. de Graaf1, Golam MI Chowdhury1, Peter B. Brown1, Douglas L. Rothman1, Kevin L. Behar1
MRRC, Yale University, New Haven, CT, USA
    High-resolution and high-sensitivity MR imaging and spectroscopy on microwave-irradiated rat brain is demonstrated. Structural integrity and metabolic stability are confirmed for at least 12 hours through the use of DTI and T2-weighted MRI and 1H MRS. 1H MR spectra of microwave-irradiated rat brain are indistinguishable from in vivo 1H MR spectra. When combined with in vivo infusion of 13C-labeled compounds, the in situ 1H MRSI data allows the detection of metabolic fluxes at high spatial resolution.
17:12 353.

Quantification of Brain Glycogen Concentration and Turnover Through Localized 13C NMR of Both the C1 and C6 Resonance

    Ruud Bernardus van Heeswijk1, Florence D. Morgenthaler1, Lijing Xin1, Rolf Gruetter1,2
Center for BioMedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, VD, Switzerland; 2Departments of Radiology, Universities of Lausanne and Geneva, Lausanne and Geneva, Switzerland
    Brain glycogen concentration and turnover were determined in vivo in the rat by simultaneously monitoring both the C1 and C6 resonances with 13C NMR. These resonances lie 3.9 kHz apart at 9.4 T, so to prevent a chemical shift displacement artifact a sequence based on the Fourier series window was implemented. After bringing the C1 resonance in steady state through 'pre-labeling' with 1-13C1 glucose, an acute infusion of 1,6-13C2 glucose was used to label the C6 resonance of glycogen and so estimate its turnover time, while the C1 resonance was used to monitor for concentration changes.
17:24 354. 17O T1/T2* Tissue-Relaxation Rates with Anatomical Contrast in the Rat Brain at 16.4 T
    Hannes M. Wiesner1, David Z. Balla1, Rolf Pohmann1, Wei Chen2, Kamil Ugurbil2, Kamil Uludag1
High-Field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany; 2Radiology, Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, MN, USA
    The direct NMR detection of 17O benefits particularly from higher field strengths and is a promising tool in the study of cerebral oxygen metabolism. The aim of this study was to acquire anatomical MRS images of H217O at natural abundance concentration in the rat head at 16.4 Tesla. Intra-cortical contrast and differences in tissue-specific relaxation of brain and muscle tissue were found, enabling optimizations in contrast and sensitivity. Based on these results implications on the spatial specificity of oxygen consumption (CMRO2) measurements using 17O2-enriched gas will be discussed.
17:36 355. Effect of Short- And Long-Term Type 1 Diabetes on the Neurochemical Profile in STZ-Induced Diabetic Rats at 9.4 T
    Wen-Tung Wang1, Sang-Pil Lee2,3, Irina Smirnova4, In-Young Choi1,5
Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA; 21Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA; 32Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA; 4Department of Physical Therapy and Rehabilitation Sciences, University of Kansas Medical Center, Kansas City, KS, USA; 52Department of Neurology, Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA
    The neurological consequences of diabetes mellitus were assessed during short- and long-term streptozotocin-induced diabetes in the rat brain. Early yet subtle changes of neurochemical contents in the streptozotocin(STZ)-induced diabetes were detected using in vivo ultra-short echo time 1H MRS at 9.4 T. Acute hyperglycemia led to significant changes in alanine, ß-hydroxybutyrate, glutamine, myo-inositol, lactate, taurine, and choline compounds (GPC+PCho). While glutamine showed a transient increase during the short-term hyperglycemic period, others maintained persistent changes through the chronic stage. Four weeks after the STZ-injection, aspartate, glutathione and N-acetylaspartate started to show significant decreases, indicating increased oxidative stress and neuronal loss during the disease progression.
17:48 356. Dynamic Metabolic Modeling of [2-13C]Acetate Metabolism in the Rat Brain
    Alexander A. Shestov1, Dinesh K. Deelchand1, Pierre-Gilles Henry1
Radiology, University of Minnesota Medical School, Minneapolis, MN, USA
    Carbon-13 MRS combined with metabolic modeling allows measurement of metabolic rates in vivo. Most 13C metabolic modeling studies have been performed using 13C-glucose as the infused substrate. Acetate, a glial-specific substrate, is an attractive alternative to glucose for the study of neuronal-glial interactions. Here we report kinetic parameters for acetate transport and utilization, as well as dynamic metabolic modeling of glutamate and glutamine 13C turnover curves obtained during 13C-acetate infusion with a two-compartment neuronal-glial model.