title: High-resolution spatial mapping of changes in the neurochemical profile after focal ischemia in mice.
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 (1)H 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 T(2)-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.
authors.affiliation: Laboratory of Functional and Metabolic Imaging, Institute of the Physics of Biological System, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. malte.alf@pharma.ethz.ch
authors.forename: Malte F
authors.initials: MF
authors.lastname: Alf
authors.forename: Hongxia
authors.initials: H
authors.lastname: Lei
authors.forename: Carole
authors.initials: C
authors.lastname: Berthet
authors.forename: Lorenz
authors.initials: L
authors.lastname: Hirt
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mlynarik
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000150:complications / Q000378:metabolism / Q000473:pathology; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D017072:Neostriatum / Q000378:metabolism; D009448:Neurochemistry; D013654:Taurine / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D013654:Taurine; D001224:Aspartic Acid; D019344:Lactic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D005978:Glutathione