Abstract

The penumbra--tissue perfused below the flow threshold for functional disturbance but above that for maintenance of morphological integrity--is the target for therapy in acute ischemic stroke. Irreversible tissue damage and penumbra can be reliably identified by multitracer positron emission tomography (PET) which has severe limitations due to complexity, invasiveness and radiation exposure. Therefore other modalities served as surrogate markers, with diffusion/perfusion-weighted magnetic resonance imaging (DW/PW-MRI) and perfusion computed tomography (PCT) being applied widely in clinical routine. In order to evaluate the limitations of DW/PW-MRI a comparative study was performed in acute stroke patients in whom cerebral perfusion was assessed by perfusion-weighted magnetic resonance imaging (PW-MRI) and H2(15)O-PET, tissue damage was estimated by diffusion-weighted magnetic resonance imaging (DW-MRI) and 11C-flumazenil (FMZ) PET and DW/PW-MRI mismatch was related to the tissue with increased oxygen extraction fraction (OEF) as an indicator of penumbra. The lesions in DW-MRI and in FMZ-PET were reliable predictors of final infarct on late MRI, but DW-MRI showed a high false positive rate. PW-MRI was limited in estimating flow and yielded values comparable to H2(15)O-PET only in the range between 20 and 30 ml/100 g/min. The DW/PW-MRI mismatch overestimated the penumbra as determined by increased OEF. These limitations of DW/PW-MRI have to be considered if used for selection of patients for treatment and might have an impact on the outcome of clinical trials based on this surrogate marker.

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