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 (CMRO 2 ) in small animals, the steady-state method was applied to injectable 15 O 2 -PET ( 15 O 2 -positron emission tomography) using hemoglobin-containing vesicles ( 15 O 2 -HbV). Ten normal rats and 10 with middle cerebral arterial occlusion (MCAO) were studied using a small animal PET scanner. A series of 15 O-PET scans with C 15 O-labeled HbV, H 2 15 O, and 15 O 2 -HbV were performed with 10 to 15 minutes intervals to measure cerebral blood volume (CBV), cerebral blood flow (CBF), and CMRO 2 . 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 H 2 15 O and 15 O 2 -HbV scans. The radioactivity concentration of 15 O rapidly achieved equilibrium in the blood and whole brain at about 2 minutes after H 2 15 O and 15 O 2 -HbV administration, which was stable during the scans. The whole brain mean values of CBF, CBV, and CMRO 2 were 54.3 ± 2.0 mL per 100 g per minute, 4.9 ± 0.4 mL/100 g, and 2.8 ± 0.2 lmoL 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 15 O-labeled HbV is simple and useful to analyze hemodynamic changes in studies with model animals.

Sequential PET estimation of cerebral oxygen metabolism with spontaneous respiration of 15O-gas in mice with bilateral common carotid artery stenosis

“…Although precise evaluation of this estimation approach is needed because this is the first study to use the heart VOI in a 15 O-PET assay of oxygen metabolism by mice, the parameters in this study were obtained using ordinary equations that are widely applied both in clinical and basic settings and are similar to those reported in previous studies using rats (Supplementary Table). [8][9][10][11][12][13] Therefore, the OEF value obtained in this study appears to be adequate for mice. The recovery coefficient for the input function, which was obtained from the radioactivity concentration time course in the left ventricular cavity, was assumed to be 1.0 for calculations of CBF, CBV, OEF, and CMRO 2 .…”

“…where Hb and %Sat were hemoglobin concentration and O 2 saturation, which were fixed at 18.5 g/dl 9 and 96.7%, 12 respectively. Since several constants were assumed for the calculations as mentioned above, we simulated the effects of variations in the recovery coefficient on experimental parameters and present the results in a Supplementary document.…”

Quantitative Evaluation of Cerebral Blood Flow and Oxygen Metabolism in Normal Anesthetized Rats: 15O-Labeled Gas Inhalation PET with MRI Fusion

“…Reported values of OEF in rats under pentobarbital anesthesia are 54% 6 11% using the kinetic method with injectable 15 O-O 2 and 57% 6 13% using the surgical method based on the arterial-venous difference in oxygen concentration (4,20). Other studies using 15 O-O 2 hemoglobin-containing liposome vesicles reported OEF values in rats under chloral hydrate anesthesia of 61% 6 16% (6) and 56% 6 4% (27). OEF is a function of the 15 15 O-CO 2 count in the brain tissue.…”

Overview of Potential Clinical Applications of Hemoglobin Vesicles (HbV) as Artificial Red Cells, Evidenced by Preclinical Studies of the Academic Research Consortium

“…Injectable systems of 15 O 2 -carrier are expected to solve such problems. Injection of 15 O 2 -HbV has been proven to be effective for CMRO 2 to detect rat brain infarction [39,40]. …”