title: Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI.
abstract: 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 [(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.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA. csander@mit.edu
authors.forename: Christin Y
authors.initials: CY
authors.lastname: Sander
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.forename: Ciprian
authors.initials: C
authors.lastname: Catana
authors.forename: Marc D
authors.initials: MD
authors.lastname: Normandin
authors.forename: Nathaniel M
authors.initials: NM
authors.lastname: Alpert
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
authors.forename: Wim
authors.initials: W
authors.lastname: Vanduffel
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Rosen
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Mandeville
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D065127:Dopamine D2 Receptor Antagonists; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008959:Models, Neurological; D049268:Positron-Emission Tomography / Q000379:methods; D020891:Raclopride / Q000008:administration & dosage / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride
keywords: NHP; displacement; dynamic binding potential; monkey