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(Stroke. 2005;36:1153.)
© 2005 American Heart Association, Inc.

Original Contributions

Refining the Perfusion–Diffusion Mismatch Hypothesis

K.S. Butcher, MD, PhD, FRCP(C); M. Parsons, PhD, FRACP; L. MacGregor, MBBS, MmedSc; P.A. Barber, PhD, FRACP; J. Chalk, PhD, FRACP; C. Bladin, PhD, FRACP; C. Levi, FRACP; T. Kimber, FRACP; D. Schultz, FRACP; J. Fink, FRACP; B. Tress, FRACR; G. Donnan, MD, FRACP; S. Davis, MD, FRACP for the EPITHET Investigators

From the Departments of Neurology (K.S.B., S.D.), Clinical Epidemiology (L.M.), and Radiology (B.T.), Royal Melbourne Hospital, University of Melbourne, Australia; the Department of Neurology, John Hunter Hospital, Newcastle, Australia (M.P., C.L.); the Department of Neurology, Auckland Hospital, New Zealand (P.A.B.); the Department of Neurology, Box Hill Hospital, Melbourne, Australia (C.B.); the Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia (T.K.); the Department of Neurology, Flinders Medical Centre, Adelaide, Australia (D.S.); the Department of Neurology, Christchurch Hospital, New Zealand (J.F.); and the Department of Neurology, Austin Hospital, Melbourne, Australia (G.D.).

Correspondence to Kenneth S. Butcher, Royal Melbourne Hospital, Grattan St, Parkville, Victoria, Australia 3050. E-mail kenneth.butcher{at}mh.org.au

Background and Purpose— 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 (PWI_vol-DWI_vol) 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 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.

Key Words: magnetic resonance imaging, diffusion-weighted • magnetic resonance imaging, perfusion-weighted • thrombolysis

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