Abstract
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Objectives Since oxygen is a key energy source in living brains, 15O PET measurement of cerebral oxygen metabolism is an important tool for clinical diagnoses. Although the mouse is an economic and useful animal model for a variety of diseases, to date there are no reports concerning 15O PET measurement in mice. Thus, we developed an 15O PET method for noninvasive measurement of cerebral oxygen metabolism in mice with spontaneous respiration of 15O-gas to evaluate the usefulness of this technique for assessing surgically induced bilateral common carotid artery stenosis (BCAS) in mice with chronic low perfusion.
Methods BCAS mice were prepared by placing 0.18 mm diameter coils on both sides of the common carotid arteries of C57BL6/J mice. The inlet and outlet tubes were placed on a microPET animal bed for spontaneous administration of 15O-gas under isoflurane anesthesia and efficient evacuation of excess 15O-gas surrounding the animal’s body. 15O-gas PET was performed on BCAS or sham-operated mice at 3, 7, 14, 21, and 28 days after surgery. PET images were reconstructed using a 2D FBP method to calculate cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) in whole brains following the 3-step ARG method.
Results Using an evacuation rate that was ~10-fold faster than the supply rate, we could inhibit radioactivity accumulation around the mouse body during 15O-gas PET scanning to obtain clear PET images of brains. These images could then be used to calculate cerebral metabolic parameters of whole brains. The results clearly indicated a significantly decreased CBF and compensatory increased OEF in day 3 BCAS mice, leading to CMRO2 values that were comparable to sham-operated mice. Although the CBF and OEF values gradually recovered to levels similar to those obtained for sham mice over 28 days, the CMRO2 showed a gradual decrease and by day 28 was about 60% of the values for sham mice.
Conclusions We successfully developed an 15O-gas PET method for estimating cerebral oxygen metabolism in mice. This method is completely noninvasive with spontaneous respiration of 15O-gas under isoflurane anesthesia.