title: Infarct Volume Prediction by Early Magnetic Resonance Imaging in a Murine Stroke Model Depends on Ischemia Duration and Time of Imaging.
abstract: OBJECTIVE
  Despite standardization of experimental stroke models, final infarct sizes after middle cerebral artery occlusion (MCAO) vary considerably. This introduces uncertainties in the evaluation of drug effects on stroke. Magnetic resonance imaging may detect variability of surgically induced ischemia before treatment and thus improve treatment effect evaluation.
  
  
  METHODS
  MCAO of 45 and 90 minutes induced brain infarcts in 83 mice. During, and 3 and 6 hours after MCAO, we performed multiparametric magnetic resonance imaging. We evaluated time courses of cerebral blood flow, apparent diffusion coefficient (ADC), T1, T2, accuracy of infarct prediction strategies, and impact on statistical evaluation of experimental stroke studies.
  
  
  RESULTS
  ADC decreased during MCAO but recovered completely on reperfusion after 45 and partially after 90-minute MCAO, followed by a secondary decline. ADC lesion volumes during MCAO or at 6 hours after MCAO largely determined final infarct volumes for 90 but not for 45 minutes MCAO. The majority of chance findings of final infarct volume differences in random group allocations of animals were associated with significant differences in early ADC lesion volumes for 90, but not for 45-minute MCAO.
  
  
  CONCLUSIONS
  The prediction accuracy of early magnetic resonance imaging for infarct volumes depends on timing of magnetic resonance imaging and MCAO duration. Variability of the posterior communicating artery in C57Bl6 mice contributes to differences in prediction accuracy between short and long MCAO. Early ADC imaging may be used to reduce errors in the interpretation of post MCAO treatment effects on stroke volumes.
authors.affiliation: From the Department of Experimental Neurology, Charité Universitätsmedizin, Berlin, Germany (C.L., M.F., D.J., S.M., U.D., G.R.); Center for Stroke Research Berlin, Berlin, Germany (C.L., D.J., S.M., U.D., G.R.); NeuroCure Cluster of Excellence, Berlin, Germany (C.L., U.D.); German Center for Neurodegenerative Diseases (DZNE) (M.F., U.D.) and German Center for Cardiovascular Diseases (DZHK) (U.D.), Berlin site, Charitéplatz, Berlin, Germany; and Department of Neurology, University of Lübeck, Lübeck, Germany (G.R.). christoph.leithner@charite.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Leithner
authors.affiliation: From the Department of Experimental Neurology, Charité Universitätsmedizin, Berlin, Germany (C.L., M.F., D.J., S.M., U.D., G.R.); Center for Stroke Research Berlin, Berlin, Germany (C.L., D.J., S.M., U.D., G.R.); NeuroCure Cluster of Excellence, Berlin, Germany (C.L., U.D.); German Center for Neurodegenerative Diseases (DZNE) (M.F., U.D.) and German Center for Cardiovascular Diseases (DZHK) (U.D.), Berlin site, Charitéplatz, Berlin, Germany; and Department of Neurology, University of Lübeck, Lübeck, Germany (G.R.).
authors.forename: Martina
authors.initials: M
authors.lastname: Füchtemeier
authors.affiliation: From the Department of Experimental Neurology, Charité Universitätsmedizin, Berlin, Germany (C.L., M.F., D.J., S.M., U.D., G.R.); Center for Stroke Research Berlin, Berlin, Germany (C.L., D.J., S.M., U.D., G.R.); NeuroCure Cluster of Excellence, Berlin, Germany (C.L., U.D.); German Center for Neurodegenerative Diseases (DZNE) (M.F., U.D.) and German Center for Cardiovascular Diseases (DZHK) (U.D.), Berlin site, Charitéplatz, Berlin, Germany; and Department of Neurology, University of Lübeck, Lübeck, Germany (G.R.).
authors.forename: Devi
authors.initials: D
authors.lastname: Jorks
authors.affiliation: From the Department of Experimental Neurology, Charité Universitätsmedizin, Berlin, Germany (C.L., M.F., D.J., S.M., U.D., G.R.); Center for Stroke Research Berlin, Berlin, Germany (C.L., D.J., S.M., U.D., G.R.); NeuroCure Cluster of Excellence, Berlin, Germany (C.L., U.D.); German Center for Neurodegenerative Diseases (DZNE) (M.F., U.D.) and German Center for Cardiovascular Diseases (DZHK) (U.D.), Berlin site, Charitéplatz, Berlin, Germany; and Department of Neurology, University of Lübeck, Lübeck, Germany (G.R.).
authors.forename: Susanne
authors.initials: S
authors.lastname: Mueller
authors.affiliation: From the Department of Experimental Neurology, Charité Universitätsmedizin, Berlin, Germany (C.L., M.F., D.J., S.M., U.D., G.R.); Center for Stroke Research Berlin, Berlin, Germany (C.L., D.J., S.M., U.D., G.R.); NeuroCure Cluster of Excellence, Berlin, Germany (C.L., U.D.); German Center for Neurodegenerative Diseases (DZNE) (M.F., U.D.) and German Center for Cardiovascular Diseases (DZHK) (U.D.), Berlin site, Charitéplatz, Berlin, Germany; and Department of Neurology, University of Lübeck, Lübeck, Germany (G.R.).
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.affiliation: From the Department of Experimental Neurology, Charité Universitätsmedizin, Berlin, Germany (C.L., M.F., D.J., S.M., U.D., G.R.); Center for Stroke Research Berlin, Berlin, Germany (C.L., D.J., S.M., U.D., G.R.); NeuroCure Cluster of Excellence, Berlin, Germany (C.L., U.D.); German Center for Neurodegenerative Diseases (DZNE) (M.F., U.D.) and German Center for Cardiovascular Diseases (DZHK) (U.D.), Berlin site, Charitéplatz, Berlin, Germany; and Department of Neurology, University of Lübeck, Lübeck, Germany (G.R.).
authors.forename: Georg
authors.initials: G
authors.lastname: Royl
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology; D002560:Cerebrovascular Circulation; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D007091:Image Processing, Computer-Assisted; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015424:Reperfusion; D013997:Time Factors
keywords: brain; magnetic resonance imaging; mice; stroke