Development of an H215O Steady-State Method Combining a Bolus and Slow Increasing Injection with a Multiprogramming Syringe Pump
An 15O-labeled water (H215O) steady-state method for quantitative measurement of cerebral blood flow ( CBF), which is less stressful to small animals with a few point blood sampling, was developed. After a simulation using a dose meter to achieve stable H215O radioactivity in the blood with a multiprogramming syringe pump programmed for slowly increasing injection volume, 10 rats were studied with the injection method. Arterial blood was sampled every minute during 6-minute positron emission tomography (PET) scans. After the PET scan, N-isopropyl- p-[125I]-iodoamphetamine (125I-IMP) was injected into the same rat to measure CBF using the autoradiography method based on a microsphere model. Regions of interest were placed on the whole brain in H215O-PET and 125I-IMP-autoradiography images, and CBF values calculated from both methods were compared. Radioactivity in the dose meter achieved equilibrium ~1 minute after starting the H215O injection. In rat studies, radioactivity in the blood and brain rapidly achieved equilibrium at 2 minutes after administration. The correlation of CBF values of H215O PET (49.2 ± 5.4 mL per 100 g per minute) and those of 125I-IMP autoradiography (49.1 ± 5.2 mL per 100 g per minute) was excellent ( y = 1.01 x −0.37, r2 = 0.97). The H215O steady-state method with a continuously increasing injection is useful for CBF measurement in small animal studies, especially when multiple scans are required in the same animal.