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High-resolution spatial mapping of changes in the neurochemical profile after focal ischemia in mice

Authors

  • Malte F. Alf,

    Corresponding author
    1. Laboratory of Functional and Metabolic Imaging, Institute of the Physics of Biological System, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    • Department of Radiopharmacy, ETH Zurich, Switzerland
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  • Hongxia Lei,

    1. Laboratory of Functional and Metabolic Imaging, Institute of the Physics of Biological System, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    2. Department of Radiology, University of Lausanne, Lausanne, Switzerland
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  • Carole Berthet,

    1. Department of Clinical Neuroscience, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
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  • Lorenz Hirt,

    1. Department of Clinical Neuroscience, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
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  • Rolf Gruetter,

    1. Laboratory of Functional and Metabolic Imaging, Institute of the Physics of Biological System, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    2. Department of Radiology, University of Lausanne, Lausanne, Switzerland
    3. Department of Radiology, University of Geneva, Geneva, Switzerland
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  • Vladimir Mlynarik

    1. Laboratory of Functional and Metabolic Imaging, Institute of the Physics of Biological System, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
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M. F. Alf, ETH Zurich, Institute of Pharmaceutical Sciences, Department of Radiopharmacy, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.

E-mail: malte.alf@pharma.ethz.ch

Abstract

After ischemic stroke, the ischemic damage to brain tissue evolves over time and with an uneven spatial distribution. Early irreversible changes occur in the ischemic core, whereas, in the penumbra, which receives more collateral blood flow, the damage is more mild and delayed. A better characterization of the penumbra, irreversibly damaged and healthy tissues is needed to understand the mechanisms involved in tissue death. MRSI is a powerful tool for this task if the scan time can be decreased whilst maintaining high sensitivity. Therefore, we made improvements to a 1H MRSI protocol to study middle cerebral artery occlusion in mice. The spatial distribution of changes in the neurochemical profile was investigated, with an effective spatial resolution of 1.4 μL, applying the protocol on a 14.1-T magnet. The acquired maps included the difficult-to-separate glutamate and glutamine resonances and, to our knowledge, the first mapping of metabolites γ-aminobutyric acid and glutathione in vivo, within a metabolite measurement time of 45 min. The maps were in excellent agreement with findings from single-voxel spectroscopy and offer spatial information at a scan time acceptable for most animal models. The metabolites measured differed with respect to the temporal evolution of their concentrations and the localization of these changes. Specifically, lactate and N-acetylaspartate concentration changes largely overlapped with the T2-hyperintense region visualized with MRI, whereas changes in cholines and glutathione affected the entire middle cerebral artery territory. Glutamine maps showed elevated levels in the ischemic striatum until 8 h after reperfusion, and until 24 h in cortical tissue, indicating differences in excitotoxic effects and secondary energy failure in these tissue types. Copyright © 2011 John Wiley & Sons, Ltd.

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