title: Magnetic resonance imaging-based cerebral tissue classification reveals distinct spatiotemporal patterns of changes after stroke in non-human primates.
abstract: BACKGROUND
  Spatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood. Aims of this study were three-fold: (1) to determine unique temporal magnetic resonance imaging (MRI) patterns at the acute, subacute and chronic stages after stroke in macaques by combining quantitative T2 and diffusion MRI indices into MRI 'tissue signatures', (2) to evaluate temporal differences in these signatures between transient (n = 2) and permanent (n = 2) middle cerebral artery occlusion, and (3) to correlate histopathology findings in the chronic stroke period to the acute and subacute MRI derived tissue signatures.
  
  
  RESULTS
  An improved iterative self-organizing data analysis algorithm was used to combine T2, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps across seven successive timepoints (1, 2, 3, 24, 72, 144, 240 h) which revealed five temporal MRI signatures, that were different from the normal tissue pattern (P < 0.001). The distribution of signatures between brains with permanent and transient occlusions varied significantly between groups (P < 0.001). Qualitative comparisons with histopathology revealed that these signatures represented regions with different histopathology. Two signatures identified areas of progressive injury marked by severe necrosis and the presence of gitter cells. Another signature identified less severe but pronounced neuronal and axonal degeneration, while the other signatures depicted tissue remodeling with vascular proliferation and astrogliosis.
  
  
  CONCLUSIONS
  These exploratory results demonstrate the potential of temporally and spatially combined voxel-based methods to generate tissue signatures that may correlate with distinct histopathological features. The identification of distinct ischemic MRI signatures associated with specific tissue fates may further aid in assessing and monitoring the efficacy of novel pharmaceutical treatments for stroke in a pre-clinical and clinical setting.
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street CNY 2301, Charlestown, MA, 02129, USA. mark@invivonmr.uu.nl.|Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands. mark@invivonmr.uu.nl.
authors.forename: Mark J R J
authors.initials: MJ
authors.lastname: Bouts
authors.affiliation: New England Primate Research Center, Pathology, Southborough, MA, USA. susan.westmoreland@abbvie.com.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Westmoreland
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street CNY 2301, Charlestown, MA, 02129, USA. decrespigny.alex@gene.com.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: de Crespigny
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street CNY 2301, Charlestown, MA, 02129, USA. yutongliu@unmc.edu.|Department of Radiology, The University of Nebraska Medical Center, Omaha, NE, USA. yutongliu@unmc.edu.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street CNY 2301, Charlestown, MA, 02129, USA. vangel@nmr.mgh.harvard.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Vangel
authors.affiliation: Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands. r.m.dijkhuizen@umcutrecht.nl.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Dijkhuizen
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street CNY 2301, Charlestown, MA, 02129, USA. ona@nmr.mgh.harvard.edu.
authors.forename: Ona
authors.initials: O
authors.lastname: Wu
authors.affiliation: Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street CNY 2301, Charlestown, MA, 02129, USA. helen@mrvision.com.
authors.forename: Helen E
authors.initials: HE
authors.lastname: D'Arceuil
mesh_terms: D000208:Acute Disease; D000465:Algorithms; D000818:Animals; D001921:Brain / Q000473:pathology*; D002908:Chronic Disease; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D018450:Disease Progression; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D020244:Infarction, Middle Cerebral Artery; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D012189:Retrospective Studies; D020521:Stroke / Q000473:pathology*