Imaging of central benzodiazepine receptors in chronic cerebral ischemia

Abstract

In patients with atherosclerotic internal carotid artery (ICA) or middle cerebral artery (MCA) occlusive disease, fluctuation of cerebral perfusion under conditions of chronic hemodynamic compromise may cause not only cerebral infarction but also selective neuronal damage in the cerebral cortex that is not detectable as infarction on CT or MRI. Imaging of the central-type benzodiazepine receptors (cBZR), which are expressed by most cortical neurons, has enabled visualization of neuronal alterations induced by ischemia in vivo, in humans. Using PET and 11C-flumazenil, we showed that selective neuronal damage demonstrated as a decrease in cBZR in the normal-appearing cerebral cortex was associated with increased oxygen extraction fraction (OEF), the so-called misery perfusion, in patients with atherosclerotic ICA or MCA occlusive disease in the chronic stage. Follow-up examinations of the patients without ischemic episode showed that a decrease in cBZR was associated with an increase in OEF (hemodynamic deterioration). A decrease in cBZR was also associated with executive dysfunction. Chronic hemodynamic ischemia causes selective neuronal damage observed as a decrease in cBZR that has an impact on the functional outcomes. Therapies for preventing neuronal damage are needed, and imaging of cBZR may be useful to monitor the effects of such therapies.