title: Topography and temporal evolution of hypoxic viable tissue identified by 18F-fluoromisonidazole positron emission tomography in humans after ischemic stroke.
abstract: OBJECTIVE
  We sought to characterize the spatial and temporal evolution of human cerebral infarction. Using a novel method of quantitatively mapping the distribution of hypoxic viable tissue identified by 18F-fluoromisonidazole (18F-FMISO) PET relative to the final infarct, we determined its evolution and spatial topography in human stroke.
  
  
  METHODS
  Patients with acute middle cerebral artery territory stroke were imaged with 18F-FMISO PET (n=19; <6 hours, 4; 6 to 16 hours, 4; 16 to 24 hours, 5; 24 to 48 hours, 6). The hypoxic volume (HV) comprised voxels with significant (P<0.05; >1 mL) uptake on statistical parametric mapping compared with 15 age-matched controls. Central, peripheral, and external zones of the corresponding infarct on the anatomically coregistered delayed CT were defined according to voxel distance from the infarct center and subdivided into 24 regions by coronal, sagittal, and axial planes. Maps ("penumbragrams") displaying the percentage of HV in each region were generated for each time epoch.
  
  
  RESULTS
  Higher HV was observed in the central region of the infarct in patients studied within 6 hours of onset (analysis of covariance [ANCOVA]; P<0.05) compared with those studied later, in whom the HV was mainly in the periphery or external to the infarct. HV was maximal in the superior, mesial, and posterior regions of the infarct (ANCOVA; P<0.05).
  
  
  CONCLUSIONS
  These observations suggest that infarct expansion occurs at the expense of hypoxic tissue from the center to the periphery of the ischemic region in humans, similar to that seen in experimental animal models. These findings have important pathophysiological and therapeutic implications.
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Markus
authors.forename: D C
authors.initials: DC
authors.lastname: Reutens
authors.forename: S
authors.initials: S
authors.lastname: Kazui
authors.forename: S
authors.initials: S
authors.lastname: Read
authors.forename: P
authors.initials: P
authors.lastname: Wright
authors.forename: B R
authors.initials: BR
authors.lastname: Chambers
authors.forename: J I
authors.initials: JI
authors.lastname: Sachinidis
authors.forename: H J
authors.initials: HJ
authors.lastname: Tochon-Danguy
authors.forename: G A
authors.initials: GA
authors.lastname: Donnan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology; D002470:Cell Survival; D018450:Disease Progression; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D002534:Hypoxia, Brain / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011237:Predictive Value of Tests; D020521:Stroke / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology; D014055:Tomography, Emission-Computed
chemical_list: D005462:Fluorine Radioisotopes; C031843:fluoromisonidazole; D008920:Misonidazole