Topography and Temporal Evolution of Hypoxic Viable Tissue Identified by ¹⁸ F-Fluoromisonidazole Positron Emission Tomography in Humans After Ischemic Stroke

Abstract

Background and Purpose-We sought to characterize the spatial and temporal evolution of human cerebral infarction.Using a novel method of quantitatively mapping the distribution of hypoxic viable tissue identified by 18 Ffluoromisonidazole ( 18 F-FMISO) PET relative to the final infarct, we determined its evolution and spatial topography in human stroke. Methods-Patients with acute middle cerebral artery territory stroke were imaged with 18 F-FMISO PET (nϭ19; Ͻ6 hours, 4; 6 to 16 hours, 4; 16 to 24 hours, 5; 24 to 48 hours, 6). The hypoxic volume (HV) comprised voxels with significant (PϽ0.05; Ͼ1 mL) uptake on statistical parametric mapping compared with 15 age-matched controls. Central, peripheral, and external zones of the corresponding infarct on the anatomically coregistered delayed CT were defined according to voxel distance from the infarct center and subdivided into 24 regions by coronal, sagittal, and axial planes. Maps ("penumbragrams") displaying the percentage of HV in each region were generated for each time epoch. Results-Higher HV was observed in the central region of the infarct in patients studied within 6 hours of onset (analysis of covariance [ANCOVA]; PϽ0.05) compared with those studied later, in whom the HV was mainly in the periphery or external to the infarct. HV was maximal in the superior, mesial, and posterior regions of the infarct (ANCOVA; PϽ0.05). Conclusions-These observations suggest that infarct expansion occurs at the expense of hypoxic tissue from the center to the periphery of the ischemic region in humans, similar to that seen in experimental animal models. These findings have important pathophysiological and therapeutic implications.

Impact of Retrievable Stents on Acute Ischemic Stroke Treatment

“…The present study verified that the use of a Demographic data, treatment modalities, recanalization results, time to recanalization, and NIHSS scores on admission and 1 day after intervention of patients treated with (group A) and without retrievable stent significantly reduces the time to recanalization in a multimodal approach to endovascular stroke treatment. Because ischemic penumbral tissue irreversibly turns into damaged brain tissue over time, 22,23 faster recanalization should result in less infarct growth and better outcome. We observed a more pronounced reduction of the NIHSS score during the first 24 hours after stroke onset in patients of group A compared with group B, which might be explained by the significantly faster recanalization achieved in group A.…”

Applications of Nitroimidazole In Vivo Hypoxia Imaging in Ischemic Stroke

“…39,40,41 This tissue was found predominantly superior, mesial and posterior to the center of the final infarct. Furthermore, this tissue was preferentially seen in the center of the final infarct in patients studied Ͻ6 hour from onset, while it was mostly peripheral or external to it at later times.…”

Heterogeneity in the penumbra

“…Another marker of the penumbra, 18 F misonidazol is trapped in viable hypoxic tissue (Takasawa et al, 2007). In early stroke, increased 18 F misonidazol uptake surrounds the core, and there is a strong association between the extent of 18 F misonidazol-binding tissue that survives and functional outcome (Markus et al, 2003). 18 F misonidazol uptake also assesses hypoxia in the white matter, where progression of ischemic damage is slower (Heiss et al, 2000; Spratt et al, 2007).…”