Impact of Mechanical Ventilation and Anesthesia on PET Tracer Kinetics for Combined PET/fMRI Studies in Rats

Abstract Purpose Positron Emission Tomography (PET), a crucial tool in molecular brain imaging, has evolved into hybrid system through integration with functional MRI (fMRI). This advancement facilitates simultaneous recording of molecular and functional data in animal models, offering in-sights into neuroreceptor and neurotransmitter dynamics and their effects on brain function. While mechanical ventilation is often used in small animal fMRI to stabilize physiological blood gas levels, its effects on PET tracer kinetics remain underexplored. Procedures: This study examines the kinetics of [¹¹C]raclopride, a dopamine-sensitive PET tracer targeting D2/D3 receptors, under various respiratory conditions and anesthesia protocols frequently used in small animal fMRI and PET. Results Results indicate significant variations in tracer kinetics: increased peak levels, a shorter time to peak, and a faster tracer equilibrium in the striatum-cerebellum distribution volume ratio were observed in spontaneously breathing animals versus those under mechanical ventilation. Anesthesia type also strongly influenced the tracer kinetics: α-chloralose anesthesia reduced brain uptake, whereas isoflurane led to a more rapid equilibrium. Conclusions These findings underscore the profound impact of mechanical ventilation and anesthesia selection on PET tracer kinetics in hybrid PET/fMRI studies. The study highlights that those protocols established for fMRI are not directly transferable to PET imaging in small animals, emphasizing the necessity for a careful investigation of the influence of anesthesia and ventilation techniques on tracer kinetics.