A metabolic threshold of irreversible ischemia demonstrated by PET in a middle cerebral artery occlusion-reperfusion primate model

Objective - to evaluate the predictive value of measurements of regional ce rebral blood flow (CBF), oxygen metabolism (CMRO2) and oxygen extraction ra tio (OER) for assessment of the fate of ischemic brain tissue. Materials an d Methods - Sequential PET measurements were performed during middle cerebr al artery occlusion (MCAO; 2 h) and 12-24 h (mean 18 h) of reperfusion in a primate model (Macaca mulatta, n = 8). A penumbra region was delineated on the MCAO PET image (OER > 125% and CMRO2 greater than or equal to 45% of t he values observed in the contralateral hemisphere, respectively) and an in farction region was delineated on the last PET image (CMRO2 < 45% of the va lues observed in the contralateral hemisphere). The penumbra regions deline ated during MCAO and the infarction regions delineated at the final PET, we re copied on to the images from all other PET sessions for measurements of CBF, CMRO2 and OER. Ratios were calculated by dividing the mean values obta ined by the values of the corresponding contralateral region. Results - His topathology verified the adequacy of the criteria applied in the last PET f or delineation of the infarction region. The penumbra region and infarction region were separated in all cases, except in two cases where a minimal ov erlap was seen. CBF and OER showed considerable variation over time and the re was no consistent difference between the penumbra and infarction regions . CMRO2 showed a more stable pattern and the difference between penumbra an d infarction regions was maintained from the time of MCAO throughout the en tire reperfusion phase. With CMRO2 as predictor, all 50 observations could be correctly predicted as penumbra or infarction when using an optimal thre shold ratio value estimated to be in the interval of 61% to 69% of the corr esponding contralateral region. CBF and OER proved to have low power as pre dictors. Conclusions - The results indicate that CMRO2 is the best predicto r of reversible or irreversible brain damage and the critical metabolic thr eshold level appears to be a reduction of oxygen metabolism to between 61% and 69% of the corresponding contralateral region.