Published Online
on October 16, 2003

A more recent version of this article appeared on November 1, 2003

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Submitted on April 4, 2003
Accepted on April 24, 2003

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

R. Markus MBChB, FRACP; D. C. Reutens MD, FRACP^*; S. Kazui MD; S. Read PhD, FRACP; P. Wright MBBS; B. R. Chambers MD, FRACP; J. I. Sachinidis PhD; H. J. Tochon-Danguy PhD; and G. A. Donnan MD, FRACP

From the Department of Medicine, University of Melbourne (R.M., D.C.R., P.W., B.R.C., G.A.D.); Department of Neurology (R.M., D.C.R., S.K., S.R., P.W., B.R.C., G.A.D.) and Centre for Positron Emission Tomography (D.C.R., J.I.S., J.H.T.-D.), Austin & Repatriation Medical Centre; and National Stroke Research Institute (R.M., D.C.R., S.K., S.R., P.W., B.R.C., G.A.D.), Melbourne, Australia.

^* To whom correspondence should be addressed. E-mail: reutens{at}austin.unimelb.edu.au.

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 ¹⁸F-fluoromisonidazole (¹⁸F-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 ¹⁸F-FMISO PET (n=19; <6 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 (P<0.05; >1 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]; P<0.05) 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; P<0.05).

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.

Key words: fluoromisonidazole • hypoxia • penumbra • stroke • tomography, emission computed

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