Hybrid imaging using PET/MRI has emerged as a platform for elucidating novel neurobiology, molecular and functional changes in disease, and responses to physiological or pharmacological interventions. For the central nervous system, PET/MRI has provided insights into biochemical processes, linking selective molecular targets and distributed brain function. This review highlights several examples that leverage the strengths of simultaneous PET/MRI, which includes measuring the perturbation of multi-modal imaging signals on dynamic timescales during pharmacological challenges, physiological interventions or behavioral tasks. We discuss important considerations for the experimental design of dynamic PET/MRI studies and data analysis approaches for comparing and quantifying simultaneous PET/MRI data. The primary focus of this review is on functional PET/MRI studies of neurotransmitter and receptor systems, with an emphasis on the dopamine, opioid, serotonin and glutamate systems as molecular neuromodulators. In this context, we provide an overview of studies that employ interventions to alter the activity of neuroreceptors or the release of neurotransmitters. Overall, we emphasize how the synergistic use of simultaneous PET/MRI with appropriate study design and interventions has the potential to expand our knowledge about the molecular and functional dynamics of the living human brain. Finally, we give an outlook on the future opportunities for simultaneous PET/MRI.
Keywords: Dopamine; opioid; pharmacology; serotonin; simultaneous PET/MRI.