title: Refining the perfusion-diffusion mismatch hypothesis.
abstract: OBJECTIVE
  The Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) tests the hypothesis that perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch predicts the response to thrombolysis. There is no accepted standardized definition of PWI-DWI mismatch. We compared common mismatch definitions in the initial 40 EPITHET patients.
  
  
  METHODS
  Raw perfusion images were used to generate maps of time to peak (TTP), mean transit time (MTT), time to peak of the impulse response (Tmax) and first moment transit time (FMT). DWI, apparent diffusion coefficient (ADC), and PWI volumes were measured with planimetric and thresholding techniques. Correlations between mismatch volume (PWIvol-DWIvol) and DWI expansion (T2(Day 90-vol)-DWI(Acute-vol)) were also assessed.
  
  
  RESULTS
  Mean age was 68+/-11, time to MRI 4.5+/-0.7 hours, and median National Institutes of Health Stroke Scale (NIHSS) score 11 (range 4 to 23). Tmax and MTT hypoperfusion volumes were significantly lower than those calculated with TTP and FMT maps (P<0.001). Mismatch > or =20% was observed in 89% (Tmax) to 92% (TTP/FMT/MTT) of patients. Application of a +4s (relative to the contralateral hemisphere) PWI threshold reduced the frequency of positive mismatch volumes (TTP 73%/FMT 68%/Tmax 54%/MTT 43%). Mismatch was not significantly different when assessed with ADC maps. Mismatch volume, calculated with all parameters and thresholds, was not significantly correlated with DWI expansion. In contrast, reperfusion was correlated inversely with infarct growth (R=-0.51; P=0.009).
  
  
  CONCLUSIONS
  Deconvolution and application of PWI thresholds provide more conservative estimates of tissue at risk and decrease the frequency of mismatch accordingly. The precise definition may not be critical; however, because reperfusion alters tissue fate irrespective of mismatch.
authors.affiliation: Department of Neurology, Royal Melbourne Hospital, University of Melbourne, Australia. kenneth.butcher@mh.org.au
authors.forename: K S
authors.initials: KS
authors.lastname: Butcher
authors.forename: M
authors.initials: M
authors.lastname: Parsons
authors.forename: L
authors.initials: L
authors.lastname: MacGregor
authors.forename: P A
authors.initials: PA
authors.lastname: Barber
authors.forename: J
authors.initials: J
authors.lastname: Chalk
authors.forename: C
authors.initials: C
authors.lastname: Bladin
authors.forename: C
authors.initials: C
authors.lastname: Levi
authors.forename: T
authors.initials: T
authors.lastname: Kimber
authors.forename: D
authors.initials: D
authors.lastname: Schultz
authors.forename: J
authors.initials: J
authors.lastname: Fink
authors.forename: B
authors.initials: B
authors.lastname: Tress
authors.forename: G
authors.initials: G
authors.lastname: Donnan
authors.forename: S
authors.initials: S
authors.lastname: Davis
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000473:pathology; D002536:Cerebral Arteries / Q000473:pathology; D002544:Cerebral Infarction; D002560:Cerebrovascular Circulation; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D017352:Echo-Planar Imaging / Q000379:methods*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008875:Middle Aged; D010477:Perfusion; D020521:Stroke / Q000175:diagnosis* / Q000473:pathology*; D015912:Thrombolytic Therapy; D013997:Time Factors; D016896:Treatment Outcome