Quantitative evaluation of cerebral blood flow and oxygen metabolism in normal anesthetized rats: ¹⁵O-Labeled gas inhalation PET with MRI fusion

PET with ¹⁵O gas has been used for the quantitative measurement of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO ₂), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in humans. However, several technical difficulties limit its use in experiments on small animals. Herein, we describe the application of the ¹⁵O gas steady-state inhalation method for normal anesthetized rats. Methods: Eight normal male Sprague-Dawley rats (mean body weight ± SD, 268 ± 14 g) under anesthesia were investigated by ¹⁵O-labeled gas PET. After tracheotomy, an airway tube was placed in the trachea, and the animals were connected to a ventilator (tidal volume, 3 cm³; frequency, 60/min). The CBF and OEF were measured according to the original steady-state inhalation technique under artificial ventilation with ¹⁵O-CO₂ and ¹⁵O-O₂ gases delivered through the radioactive gas stabilizer. CBV was measured by ¹⁵O-CO gas inhalation and corrected for the intravascular hemoglobinbound ¹⁵O-O₂. Arterial blood sampling was performed during each study to measure the radioactivity of the whole blood and plasma. MR image was performed with the same acrylic animal holder immediately after the PET. Regions of interest were placed on the whole brain of the PET images with reference to the semiautomatically coregistered PET/MR fused images. Results: The data acquisition time for the whole PET experiment in each rat was 73.3 ± 5.8 (range, 68-85) min. In both the ¹⁵O-CO₂ and the ¹⁵O-O₂ studies, the radioactivity count of the brain reached a steady state by approximately 10 min after the start of continuous inhalation of the gas. The quantitative PET data of the whole brain were as follows: CBF, 32.3 ± 4.5 mL/100 mL/min; CMRO₂, 3.23 ± 0.42 mL/100 mL/min; OEF, 64.6% 6 9.1%; and CBV, 5.05 ± 0.45 mL/100 mL. Conclusion: Although further technical improvements may be needed, this study demonstrated the feasibility of quantitative PET measurement of CBF, OEF, and CMRO₂ using the original steady-state inhalation method of ¹⁵O-CO₂ and ¹⁵O-O₂ gases and measurement of CBV using the ¹⁵O-CO gas inhalation method in the brain of normal anesthetized rats.