Imaging the ischemic penumbra and treatment effects by PET.

Abstract

Active treatment of acute ischemic stroke can only be successful as long as tissue in the area of ischemic compromise is still viable. Therefore, the identification of the area of irreversible damage, and its distinction from the penumbral zone, i.e., tissue with impaired function but preserved morphology, may improve the estimation of the potential efficacy of various therapeutic strategies. This can be achieved by multi-tracer positron emission tomography (PET), perfusion-weighted and diffusion-weighted magnetic resonance imaging in experimental models. Neuroimaging modalities applied in patients with acute ischemic stroke cannot reliably identify penumbra tissue and detect irreversible damage in the first hours after stroke, when treatment must be initiated to have the potential for success: multitracer studies for the assessment of flow and irreversible metabolic damage usually are limited in the clinical setting, and arterial blood sampling necessary for quantitative determinations is prohibited under certain circumstances, e.g., when thrombolysis is planned. The range of the penumbra can be assessed by combining determinations of flow and benzodiazepine receptor binding by PET of H2(15)O and 11C-flumazenil (FMZ) and relating flow values and FMZ binding to the final state of the tissue. By this approach, cumulative probability curves can be computed to predict eventual infarction or non-infarction and to define the penumbral range. The computed values are in good agreement with results from other studies proving the validity of the concept of the penumbra which was also demonstrated in several therapeutic studies in which thrombolytic treatment reversed critical ischemia and decreased the volume of the final infarcts. Such neuroimaging findings might serve as surrogate targets in the selection of other therapeutic strategies for large clinical trials.