PROLONGED PERSISTENCE OF SUBSTANTIAL VOLUMES OF POTENTIALLY VIABLE BRAIN-TISSUE AFTER STROKE - A CORRELATIVE PET-CT STUDY WITH VOXEL-BASED DATA-ANALYSIS

Background and Purpose The existence in humans of brain tissue at risk for infarction but potentially viable leg, the penumbra) remains unpr oven. One retrospective operational definition of such tissue includes its final infarction despite a relatively preserved or even normal ce rebral metabolic rate of oxygen (CMRO(2)) in the early hours after str oke onset. Although previous positron emission tomography (PET) studie s identified tissue whose CMRO, declined from the acute to the subacut e stage, in principle compatible with deteriorating penumbra, they all lacked a coregistered CT scan mapping of final infarct and an objecti ve three-dimensional PET data analysis, while many patients were studi ed in the subacute (up to 48 hours) phase. We have evaluated whether t issue with CMRO(2) ranging above a threshold for presumably irreversib le damage in the first 18 hours of middle cerebral artery territory st roke, but below it in the chronic stage, could be retrospectively iden tified within the final infarct volume. Methods Our data bank comprise s 30 consecutive patients with first-ever middle cerebral artery terri tory stroke prospectively studied with PET within the first 18 hours a fter clinical onset; the O-15 equilibrium method was used to measure c erebral blood flow and CMRO(2). All survivors with the following crite ria were eligible for the present study: (1) technically adequate chro nic-stage PET performed in the same stereotaxic conditions, (2) coregi stered CT scan also performed in the chronic stage, and (3) an infarct of sufficient dimension (>16 mm diameter) on late CT. Corresponding e r scan cuts and PET slices were exactly realigned, and the outlines of CT hypodensities were superimposed on the corresponding CMRO(2) matri x. Infarcted voxels with CMRO: values less than or greater than 1.40 m L/100 mt per minute (ie, the generally accepted threshold for irrevers ible damage) were automatically identified and projected on matrices o f all other PET parameters and for both PET studies. Results Eight pat ients (mean age, 78 years) were eligible for the present study. The ac ute-stage PET study was performed 7 to 17 hours after stroke onset and the chronic-stage PET 13 to 41 days later. Within the final infarct, mean CMRO(2) fell significantly from the acute- to the chronic-stage P ET study (P<.001). Eventually infarcted voxels with acute-stage CMRO(2 ) values above the threshold were found in each of these eight patient s; they were most often situated near the infarct borders and constitu ted 10% to 52% (mean, 32%) of the final infarct volume. The acute-stag e CMRO(2) in these voxels ranged up to 4.13 mL/100 mt per minute but f ell below 1.40 mL/100 mt per minute in 93% of them at the chronic-stag e PET. In 7 of 8 patients the acute-stage mean cerebral blood flow ran ged from 10 to 22 mL/100 mt per minute, and the mean oxygen extraction fraction was markedly increased (>0.70) in these voxels, consistent w ith a penumbral state. Conclusions In a strictly homogeneous sample of prospectively studied patients, we have identified, up to 17 hours af ter stroke onset, substantial volumes of tissue with CMRO(2) well abov e the assumed threshold for viability that nevertheless spontaneously evolved toward necrosis. This tissue exhibited penumbral ranges of bot h cerebral blood flow and oxygen extraction fraction and thus could re present the part of penumbra that might be saved with appropriate ther apy.