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

Positron emission tomography with O-15-labeled gases (O-15-PET) is important for invivo measurement of cerebral oxygen metabolism both in clinical and basic settings. However, there are currently no reports concerning O-15-PET in mice. Here, we developed an O-15-PET method applicable to mice with spontaneous respiration of O-15-gas without a tracheotomy catheter. Sequential O-15-PET was also performed in a mouse model of chronic cerebral hypoperfusion with bilateral common carotid artery stenosis (BCAS) induced by placement of microcoils. O-15-gas with isoflurane was supplied to the nose of mouse with evacuation of excess O-15-gas surrounding the body. O-15-PET was performed on days 3, 7, 14, 21, and 28 after surgery. Cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) were calculated in whole brains. A significant decrease in CBF and compensatory increase in OEF in the BCAS group produced CMRO2 values comparable to that of the sham group at three days post-operation. Although CBF and OEF in the BCAS group gradually recovered over the first 28 days, the CMRO2 showed a gradual decrease to 68% of sham values at 28 days post-operation. In conclusion, we successfully developed a noninvasive O-15-PET method for mice.