Cerebellum as the normal reference for the detection of increased cerebral oxygen extraction

Hemispheric ratios of oxygen extraction fraction (OEF), a proven methodology for the detection of severe hemodynamic impairment and stroke risk, are not sensitive for detecting bilateral hemispheric increases in OEF. The aim of this study was to investigate the use of cerebellum as the reference normal. We analyzed positron emission tomographic (PET) measurements of count-based OEF and clinical data from 57 patients with unilateral atherosclerotic carotid occlusion and 13 controls enrolled in a prospective study of stroke risk. The ipsilateral, contralateral, and total cerebellum were each evaluated as possible reference regions, and the ratios of the middle cerebral artery (MCA) hemispheric OEF counts against those in each reference region were determined. A statistically significant correlation (P<0.0001) was observed with all three MCA-to-cerebellar ratios when compared with the gold standard of ipsilateral-to-contralateral MCA hemispheric ratio. Kaplan-Meier analyses showed all MCA-to-cerebellar ratios to be predictive of stroke. By using the total cerebellum method, 7 strokes were found to have occurred in 20 patients with increased OEF (P=0.0007), compared with 7 strokes out of 16 patients with elevated OEF using the ipsilateral or contralateral cerebellum methods (P<0.0001). These methods may be useful for categorizing the hemodynamic status of patients with bilateral cerebral occlusive diseases, including atherosclerosis and moyamoya, to determine the association with the risk of subsequent stroke.