In vivo Positron Emission Tomography (PET) measurement of cerebral oxygen metabolism in small animals

Abstract

The cerebral metabolic rate for oxygen (CMRO2) and cerebral oxygen extraction fraction (OEF) are two fundamental parameters used to characterize the pathophysiologic status of cerebral tissues. Although the O-15-labeled gas inhalation method is used to measure these parameters in clinical studies, applying this method to small animals requires many intensive procedures. Thus the development of a new method to measure CMRO2 and OEF in small animals is of interest. This study aimed to develop a method to assess CMRO2 and OEF using intravenously injectable oxygen (injectable 15O-O2) and Positron Emission Tomography (PET) for small animals such as rats. Injectable 15O-O2 was obtained after 15O-O2 gas circulation into an artificial lung. The OEF in normal rats was calculated using the same equation as that used for the bolus inhalation in the 15O-O2 gas method. The obtained value of 0.54±0.11 of OEF was similar to the value determined from the arterial-venous difference in the oxygen concentration. Furthermore, we evaluated the usefulness of the injectable 15O-O2 system in rats occluded in the right middle cerebral artery. A decrease in cerebral blood flow (CBF) and compensatory increase in OEF were observed 1 h after occlusion. In contrast, a marked decrease in CBF and CMRO2 and a collapse of the compensatory OEF mechanism were found 24 h after occlusion. Thus injectable 15O-O2 with PET can be used to estimate oxygen metabolism reliably in stroke animal models, and may be useful for accelerating basic research on cerebral diseases. © 2008 The Pharmaceutical Society of Japan.