Chapter 4 - Applicability of Experimental PET in Animal Models for the Interpretation of Incidental Findings in Human Stroke

Abstract

This chapter presents a test of a commercial high-resolution scanner designed for clinical positron emission tomography (PET) studies for its applicability to investigations of cerebral metabolism and blood flow in cats. Cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), cerebral blood volume (CBV), and cerebral glucose metabolic rate (CMRglc) are determined by using 15O-steady-state or bolus injection oxygen methods and 18F-fluorodeoxyglucose (FDG). Metabolic and blood flow images of 14 contiguous, 3 mm PET slices are also compared to histological sections in four control animals. In another 12 cats, hemodynamic and metabolic changes were followed by serial multitracer PET for 24 hours after permanent and 30- and 60-minute occlusion of the left middle cerebral artery (MCA). The pattern and extent of the changes of the physiological variables were related to the final infarct verified in matched histological sections. At the scanner's spatial resolution, the gross anatomy of the cat's brain could be distinguished best in FDG images. The values of CBF, CMRO2, and CMRglc measured in cortex, white matter, and basal ganglia were in the range of common autoradiographic results. Immediately after MCA occlusion, there was a widespread decrease in blood flow, but metabolism was preserved at values suggesting viable tissue. In permanent occlusion, the areas of increased oxygen extraction fraction (OEF) moved with time from the center to the periphery of the MCA territory, and OEF and CMRglc subsequently declined, indicating transformation to the large infarcts later found in corresponding histologic sections. Reopening the MCA after 30 minutes induced short-lasting hyperperfusion and fast normalization of metabolism; no cortical infarcts were found. After a 60-minute occlusion, hyperperfusion lasted for extended periods; CMRO2, OEF, and CMRglc were permanently depressed; and large infarcts were found. These results demonstrate that high-resolution positron emission tomography is a valuable tool for clinically oriented experimental research.