Ischemic Core and Penumbra in Human Stroke

Abstract

Background and Purpose —The ischemic core and penumbra have not been thoroughly characterized after acute cerebral thromboembolic occlusion in humans. Differentiation between areas of potentially viable and irreversibly injured ischemic tissue may facilitate assessment and treatment of stroke patients. Methods —Cerebral blood flow (CBF) was measured in 20 patients with acute middle cerebral artery (MCA) occlusion between 60 and 360 minutes after stroke onset, with the stable xenon computerized tomography (CT) technique. Threshold displays were generated at a single level, and the percentages of hemisphere with CBF ≤6, ≤10, 11 to 20, 21 to 30, and >30 cm 3 · 100 g −1 · min −1 were measured. The corresponding images on 12 available follow-up CT scans were similarly assessed to determine the area of final infarct. Comparisons were analyzed with a paired Student’s t test and Pearson’s correlation coefficient. Results —Discrete and confluent areas of CBF ≤20 cm 3 · 100 g −1 · min −1 were identified in all patients, ipsilateral to the symptomatic MCA territory. The average area of CBF ≤20 cm 3 · 100 g −1 · min −1 within the ipsilateral hemisphere was 66±17% compared with 36±12% contralaterally ( P <0.001). A difference in the extent of low CBF was due primarily to areas with CBF ≤10 cm 3 · 100 g −1 · min −1 (48±18% versus 16±7%, P <0.001). The area of most severe ipsilateral ischemia (≤6 cm 3 · 100 g −1 · min −1 ) best corresponded to the final area of infarction (37±18% versus 40±24%; correlation coefficient, 0.866; P <0.01). The acute ischemic core destined to infarction was not surrounded by a widened rim of moderate ischemia because the area with CBF 11 to 20 cm 3 · 100 g −1 · min −1 was similar bilaterally (19±4% versus 20±7%, P =0.792, thus not significant). Conclusions —Our study in acute human stroke involving MCA occlusion indicates that a severely ischemic core (CBF ≤6 cm 3 · 100 g −1 · min −1 ), observed between 1 to 6 hours after stroke onset, corresponds to the cerebral tissue destined to infarction. The ischemic penumbra with flow values between 7 and 20 cm 3 · 100 g −1 · min −1 surrounding the ischemic core is very narrow. Therefore, strategies to improve the outcome of many patients with acute MCA occlusion must either include interventions to reverse the ischemic process within a few minutes of onset or increase the cerebral tolerance of ischemia and thereby prolong the potential therapeutic window.