Cerebral Oxygen Metabolism of Rats using Injectable 15O-Oxygen with a Steady-State Method

Abstract

To develop a less-stressful and simple method for measurement of the cerebral metabolic rate of oxygen ( CMRO2) in small animals, the steady-state method was applied to injectable 15O2-PET (15O2-positron emission tomography) using hemoglobin-containing vesicles (15O2-HbV). Ten normal rats and 10 with middle cerebral arterial occlusion (MCAO) were studied using a small animal PET scanner. A series of 15O-PET scans with C15O-labeled HbV, H215O, and 15O2-HbV were performed with 10 to 15 minutes intervals to measure cerebral blood volume (CBV), cerebral blood flow (CBF), and CMRO2. Positron emission tomography scans were started with a tracer injection using a multiprogramming syringe pump, which provides a slowly increasing injection volume to achieve steady-state radioactivity for H215O and 15O2-HbV scans. The radioactivity concentration of 15O rapidly achieved equilibrium in the blood and whole brain at about 2 minutes after H215O and 15O2-HbV administration, which was stable during the scans. The whole brain mean values of CBF, CBV, and CMRO2 were 54.3 ± 2.0 mL per 100 g per minute, 4.9 ± 0.4 mL/100 g, and 2.8 ±0.2 μmoL per g per minute (6.2 ± 0.4 mL per 100 g per minute) in the normal rats, respectively. In the MCAO model rats, all hemodynamic parameters of the infarction area on the occlusion side significantly decreased. The steady-state method with 15O-labeled HbV is simple and useful to analyze hemodynamic changes in studies with model animals.