title: Reperfusion Beyond 6 Hours Reduces Infarct Probability in Moderately Ischemic Brain Tissue.
abstract: OBJECTIVE
  We aimed to examine perfusion changes between 3 and 6 and 6 and 24 hours after stroke onset and their impact on tissue outcome.
  
  
  METHODS
  Acute ischemic stroke patients underwent perfusion magnetic resonance imaging at 3, 6, and 24 hours after stroke onset and follow-up fluid-attenuated inversion recovery at 1 month to assess tissue fate. Mean transit time prolongation maps (MTTp=MTT-[median MTT of contralateral hemisphere]) were obtained at 3 (MTTp3 h), 6 (MTTp6 h), and 24 hours (MTTp24 h). Perfusion changes between 3 and 6 hours (ΔMTTp3_6) and 6 and 24 hours (ΔMTTp6_24) were calculated. A 2-step analysis was performed to evaluate the impact of ΔMTTp3_6 and ΔMTTp6_24 on tissue fate. First, a voxel-based multivariable logistic regression was performed for each individual patient with MTTp3 h, ΔMTTp3_6, and ΔMTT6_24 as independent variables and tissue fate as outcome. Second, Wilcoxon signed-rank tests on logistic regression coefficients were performed across patients to evaluate whether ΔMTTp3_6 and ΔMTT6_24 had significant impact on tissue fate for varying severities of baseline perfusion.
  
  
  RESULTS
  Perfusion change was common during both time periods: 85% and 81% of patients had perfusion improvement during 3- to 6- and 6- and 24-hour time intervals, respectively. ΔMTT3_6 significantly influenced 1-month infarct probability across a wide range of baseline perfusion (MTTp 0-15 s). ΔMTT6_24 also impacted 1-month infarct probability, but its influence was restricted to tissue with milder baseline ischemia (MTTp 0-10 s).
  
  
  CONCLUSIONS
  Brain tissue with mild to moderate ischemia can be salvaged by reperfusion even after 6 hours. Such tissue could be targeted for intervention beyond current treatment windows.
authors.affiliation: From the Mallinckrodt Institute of Radiology (H.A., C.E., K.D.V., J.-M.L.) and Department of Neurology (A.L.F., Y.C., J.-M.L.), Washington University, School of Medicine; and Department of Biostatistics (H.Z.), Department of Neurology (W.J.P., W.L.), and Department of Radiology (W.L.), University of North Carolina at Chapel Hill.
authors.forename: Hongyu
authors.initials: H
authors.lastname: An
authors.affiliation: From the Mallinckrodt Institute of Radiology (H.A., C.E., K.D.V., J.-M.L.) and Department of Neurology (A.L.F., Y.C., J.-M.L.), Washington University, School of Medicine; and Department of Biostatistics (H.Z.), Department of Neurology (W.J.P., W.L.), and Department of Radiology (W.L.), University of North Carolina at Chapel Hill.
authors.forename: Andria L
authors.initials: AL
authors.lastname: Ford
authors.affiliation: From the Mallinckrodt Institute of Radiology (H.A., C.E., K.D.V., J.-M.L.) and Department of Neurology (A.L.F., Y.C., J.-M.L.), Washington University, School of Medicine; and Department of Biostatistics (H.Z.), Department of Neurology (W.J.P., W.L.), and Department of Radiology (W.L.), University of North Carolina at Chapel Hill.
authors.forename: Cihat
authors.initials: C
authors.lastname: Eldeniz
authors.affiliation: From the Mallinckrodt Institute of Radiology (H.A., C.E., K.D.V., J.-M.L.) and Department of Neurology (A.L.F., Y.C., J.-M.L.), Washington University, School of Medicine; and Department of Biostatistics (H.Z.), Department of Neurology (W.J.P., W.L.), and Department of Radiology (W.L.), University of North Carolina at Chapel Hill.
authors.forename: Yasheng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: From the Mallinckrodt Institute of Radiology (H.A., C.E., K.D.V., J.-M.L.) and Department of Neurology (A.L.F., Y.C., J.-M.L.), Washington University, School of Medicine; and Department of Biostatistics (H.Z.), Department of Neurology (W.J.P., W.L.), and Department of Radiology (W.L.), University of North Carolina at Chapel Hill.
authors.forename: Katie D
authors.initials: KD
authors.lastname: Vo
authors.affiliation: From the Mallinckrodt Institute of Radiology (H.A., C.E., K.D.V., J.-M.L.) and Department of Neurology (A.L.F., Y.C., J.-M.L.), Washington University, School of Medicine; and Department of Biostatistics (H.Z.), Department of Neurology (W.J.P., W.L.), and Department of Radiology (W.L.), University of North Carolina at Chapel Hill.
authors.forename: Hongtu
authors.initials: H
authors.lastname: Zhu
authors.affiliation: From the Mallinckrodt Institute of Radiology (H.A., C.E., K.D.V., J.-M.L.) and Department of Neurology (A.L.F., Y.C., J.-M.L.), Washington University, School of Medicine; and Department of Biostatistics (H.Z.), Department of Neurology (W.J.P., W.L.), and Department of Radiology (W.L.), University of North Carolina at Chapel Hill.
authors.forename: William J
authors.initials: WJ
authors.lastname: Powers
authors.affiliation: From the Mallinckrodt Institute of Radiology (H.A., C.E., K.D.V., J.-M.L.) and Department of Neurology (A.L.F., Y.C., J.-M.L.), Washington University, School of Medicine; and Department of Biostatistics (H.Z.), Department of Neurology (W.J.P., W.L.), and Department of Radiology (W.L.), University of North Carolina at Chapel Hill.
authors.forename: Weili
authors.initials: W
authors.lastname: Lin
authors.affiliation: From the Mallinckrodt Institute of Radiology (H.A., C.E., K.D.V., J.-M.L.) and Department of Neurology (A.L.F., Y.C., J.-M.L.), Washington University, School of Medicine; and Department of Biostatistics (H.Z.), Department of Neurology (W.J.P., W.L.), and Department of Radiology (W.L.), University of North Carolina at Chapel Hill. leejm@neuro.wustl.edu weili_lin@med.unc.edu.
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Lee
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000175:diagnosis* / Q000601:surgery*; D002544:Cerebral Infarction / Q000175:diagnosis / Q000601:surgery; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000639:trends; D008875:Middle Aged; D011446:Prospective Studies; D015424:Reperfusion / Q000639:trends*; D020521:Stroke / Q000175:diagnosis* / Q000601:surgery*; D013997:Time Factors
keywords: MR perfusion imaging; brain; ischemia; reperfusion; stroke; tissue outcome