Refining and testing the PWI–DWI mismatch hypothesis

Mismatch between a perfusion-weighted image (PWI) deficit and a smaller diffusion-weighted image (DWI) lesion, putatively provides a visual representation of the ischemic penumbra. The mismatch concept is certainly biologically plausible and there is a growing body of supportive evidence. Indeed, many clinical centers have begun to utilize PWI and DWI in the selection of potential acute stroke thrombolysis patients. Unfortunately, the hypothesis that patients with PWI–DWI mismatch are the optimal responders to thrombolytic therapy remains unproven. Furthermore, there is at this point no accepted or standardized definition of exactly what constitutes mismatch. Multiple perfusion and diffusion parameters are available. In addition, it has become increasingly apparent that the PWI deficits tend to overestimate the true volume of tissue at risk of infarction. Various methods of compensating for this have been developed, primarily based on the application of image intensity thresholds. Thus, a bewildering number of PWI–DWI mismatch definitions are possible in any given patient. The Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) tests the hypothesis that patients with PWI–DWI mismatch patterns will respond optimally to treatment with tissue plasminogen activator (tPA). The primary endpoint is an MRI surrogate; volume change between the acute DWI hyper-intense lesion and final infarct volume seen on T2-weighted images at 90 days. The ability of various PWI–DWI mismatch definitions to predict DWI expansion is assessed. These data make it clear that reperfusion is a much stronger predictor of tissue fate than any definition of mismatch. We have found that absolute diffusion and perfusion thresholds for infarction cannot be defined accurately, as they are highly dependent on time to reperfusion. Thus, it appears that the concepts of penumbral thresholds and mismatch are both oversimplifications of complex and dynamic pathophysiological processes. Although, the mismatch hypothesis needs to be proven, and will undoubtedly be refined by future studies, it does seem certain that it will play an increasingly important role in patient management. If MRI is to be a more widely used clinical tool, however, reliable and rapid assessment methods will be required. We have adapted the Alberta Stroke Program Early CT Score (ASPECTS) system to DWI and PWI images. We have developed an MRI ASPECTS mismatch score, which predicts PWI–DWI mismatch by volume with high specificity. If it can be shown that these patients are the ideal tPA candidates, this system may permit widespread application of PWI–DWI mismatch selection criteria in the near future.