Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI

• Main Authors: Sander, Christin Yen-Ming (Contributor), Rosen, Bruce R. (Contributor), Hooker, Jacob M. (Author), Catana, Ciprian (Author), Normandin, Marc D. (Author), Alpert, Nathaniel M. (Author), Knudsen, Gitte M. (Author), Vanduffel, Wim (Author), Mandeville, Joseph B. (Author)
• Other Authors: Harvard University- (Contributor), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Contributor)
• Format: Article
• Language: English
• Published: National Academy of Sciences (U.S.), 2014-03-24T16:48:46Z.
• Subjects: Article
• Online Access: Get fulltext

This study employed simultaneous neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to demonstrate the relationship between changes in receptor occupancy measured by PET and changes in brain activity inferred by fMRI. By administering the D2/D3 dopamine receptor antagonist [[superscript 11]C]raclopride at varying specific activities to anesthetized nonhuman primates, we mapped associations between changes in receptor occupancy and hemodynamics [cerebral blood volume (CBV)] in the domains of space, time, and dose. Mass doses of raclopride above tracer levels caused increases in CBV and reductions in binding potential that were localized to the dopamine-rich striatum. Moreover, similar temporal profiles were observed for specific binding estimates and changes in CBV. Injection of graded raclopride mass doses revealed a monotonic coupling between neurovascular responses and receptor occupancies. The distinct CBV magnitudes between putamen and caudate at matched occupancies approximately matched literature differences in basal dopamine levels, suggesting that the relative fMRI measurements reflect basal D2/D3 dopamine receptor occupancy. These results can provide a basis for models that relate dopaminergic occupancies to hemodynamic changes in the basal ganglia. Overall, these data demonstrate the utility of simultaneous PET/fMRI for investigations of neurovascular coupling that correlate neurochemistry with hemodynamic changes in vivo for any receptor system with an available PET tracer.
National Institutes of Health (U.S.) (Grant R90DA023427)
National Institutes of Health (U.S.) (Grant P41RR14075)
National Institutes of Health (U.S.) (Grant P30DA28800)
National Institutes of Health (U.S.) (Grant S10RR026666)
National Institutes of Health (U.S.) (Grant S10RR017208)
National Institutes of Health (U.S.) (Grant S10RR022976)
National Institutes of Health (U.S.) (Grant S10RR019933)