Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI
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 dopa...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2013-07, Vol.110 (27), p.11169-11174 |
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| creator | Sander, Christin Y. Hooker, Jacob M. Catana, Ciprian Normandin, Marc D. Alpert, Nathaniel M. Knudsen, Gitte M. Vanduffel, Wim Rosen, Bruce R. Mandeville, Joseph B. |
| description | 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 [ ¹¹C]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. |
| doi_str_mv | 10.1073/pnas.1220512110 |
| format | Article |
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By administering the D2/D3 dopamine receptor antagonist [ ¹¹C]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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1220512110</identifier><identifier>PMID: 23723346</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences</publisher><subject>Animals ; antagonists ; Binding sites ; Biological and medical sciences ; Biological Sciences ; blood volume ; Brain ; Brain - blood supply ; Brain - drug effects ; Brain - metabolism ; Cerebellum ; Cerebrovascular Circulation - drug effects ; Dopamine ; Dopamine Antagonists - administration & dosage ; Dopamine Antagonists - pharmacokinetics ; Dopamine D2 Receptor Antagonists ; dopamine receptors ; Dosage ; Fundamental and applied biological sciences. Psychology ; ganglia ; Imaging ; Ligands ; Macaca mulatta ; Magnetic resonance imaging ; Magnetic Resonance Imaging - methods ; Male ; Models, Neurological ; Neurochemistry ; Neurotransmitters ; NMR ; Nuclear magnetic resonance ; Pharmacology ; Positron emission tomography ; Positron-Emission Tomography - methods ; Primates ; Putamen ; Raclopride - administration & dosage ; Raclopride - pharmacokinetics ; Receptors ; Receptors, Dopamine D2 - metabolism ; Receptors, Dopamine D3 - antagonists & inhibitors ; Receptors, Dopamine D3 - metabolism ; Tomography ; Vertebrates: nervous system and sense organs</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2013-07, Vol.110 (27), p.11169-11174</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>2014 INIST-CNRS</rights><rights>Copyright National Academy of Sciences Jul 2, 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c555t-5618e9e1b802f4f5dc48b51d7fc9456b49e3418f898cf21f79ad4cef20d60af63</citedby><cites>FETCH-LOGICAL-c555t-5618e9e1b802f4f5dc48b51d7fc9456b49e3418f898cf21f79ad4cef20d60af63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/110/27.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/42706393$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/42706393$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27566526$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23723346$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sander, Christin Y.</creatorcontrib><creatorcontrib>Hooker, Jacob M.</creatorcontrib><creatorcontrib>Catana, Ciprian</creatorcontrib><creatorcontrib>Normandin, Marc D.</creatorcontrib><creatorcontrib>Alpert, Nathaniel M.</creatorcontrib><creatorcontrib>Knudsen, Gitte M.</creatorcontrib><creatorcontrib>Vanduffel, Wim</creatorcontrib><creatorcontrib>Rosen, Bruce R.</creatorcontrib><creatorcontrib>Mandeville, Joseph B.</creatorcontrib><title>Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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 [ ¹¹C]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.</description><subject>Animals</subject><subject>antagonists</subject><subject>Binding sites</subject><subject>Biological and medical sciences</subject><subject>Biological Sciences</subject><subject>blood volume</subject><subject>Brain</subject><subject>Brain - blood supply</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Cerebellum</subject><subject>Cerebrovascular Circulation - drug effects</subject><subject>Dopamine</subject><subject>Dopamine Antagonists - administration & dosage</subject><subject>Dopamine Antagonists - pharmacokinetics</subject><subject>Dopamine D2 Receptor Antagonists</subject><subject>dopamine receptors</subject><subject>Dosage</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>ganglia</subject><subject>Imaging</subject><subject>Ligands</subject><subject>Macaca mulatta</subject><subject>Magnetic resonance imaging</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Male</subject><subject>Models, Neurological</subject><subject>Neurochemistry</subject><subject>Neurotransmitters</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Pharmacology</subject><subject>Positron emission tomography</subject><subject>Positron-Emission Tomography - methods</subject><subject>Primates</subject><subject>Putamen</subject><subject>Raclopride - administration & dosage</subject><subject>Raclopride - pharmacokinetics</subject><subject>Receptors</subject><subject>Receptors, Dopamine D2 - metabolism</subject><subject>Receptors, Dopamine D3 - antagonists & inhibitors</subject><subject>Receptors, Dopamine D3 - metabolism</subject><subject>Tomography</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1v1DAQhiMEoqVw5gREQkhctjvjz_iChNoClcqHoD1bXsdessrGwY4r9d_jaJctcPJhnpnXr56qeo5wiiDpchxMOkVCgCNBhAfVMYLChWAKHlbHAEQuGkbYUfUkpQ0AKN7A4-qIUEkoZeK4Ml9cjuHWJJt7E2sb8th3w7qeQn1Olue0bsNott3g6uisG6cQ62BtHs1g7-qcZjR129xPZnAhp_rbxfXS58FOXRhMX3_-fvm0euRNn9yz_XtS3Xy4uD77tLj6-vHy7P3VwnLOpwUX2DjlcNUA8czz1rJmxbGV3irGxYopRxk2vlGN9QS9VKZl1nkCrQDjBT2p3u3ujnm1da11wxRNr8fYbU2808F0-t_J0P3U63CrqQSqhCoH3u4PxPAruzTpbZes6_tdNY0NUEQUBAr6-j90E3IshQtFlUIlEUihljvKxpBSdP7wGQQ969OzPn2vr2y8_LvDgf_jqwBv9kAxZnofi4cu3XOSC8HJzNV7bk44xJZcIvVcYq77YodsUrF6YBiRIKiiZf5qN_cmaLOOJebmBwEUAEglJ5z-BuDUwQU</recordid><startdate>20130702</startdate><enddate>20130702</enddate><creator>Sander, Christin Y.</creator><creator>Hooker, Jacob M.</creator><creator>Catana, Ciprian</creator><creator>Normandin, Marc D.</creator><creator>Alpert, Nathaniel M.</creator><creator>Knudsen, Gitte M.</creator><creator>Vanduffel, Wim</creator><creator>Rosen, Bruce R.</creator><creator>Mandeville, Joseph B.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20130702</creationdate><title>Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI</title><author>Sander, Christin Y. ; Hooker, Jacob M. ; Catana, Ciprian ; Normandin, Marc D. ; Alpert, Nathaniel M. ; Knudsen, Gitte M. ; Vanduffel, Wim ; Rosen, Bruce R. ; Mandeville, Joseph B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c555t-5618e9e1b802f4f5dc48b51d7fc9456b49e3418f898cf21f79ad4cef20d60af63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>antagonists</topic><topic>Binding sites</topic><topic>Biological and medical sciences</topic><topic>Biological Sciences</topic><topic>blood volume</topic><topic>Brain</topic><topic>Brain - blood supply</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Cerebellum</topic><topic>Cerebrovascular Circulation - drug effects</topic><topic>Dopamine</topic><topic>Dopamine Antagonists - administration & dosage</topic><topic>Dopamine Antagonists - pharmacokinetics</topic><topic>Dopamine D2 Receptor Antagonists</topic><topic>dopamine receptors</topic><topic>Dosage</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>ganglia</topic><topic>Imaging</topic><topic>Ligands</topic><topic>Macaca mulatta</topic><topic>Magnetic resonance imaging</topic><topic>Magnetic Resonance Imaging - methods</topic><topic>Male</topic><topic>Models, Neurological</topic><topic>Neurochemistry</topic><topic>Neurotransmitters</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Pharmacology</topic><topic>Positron emission tomography</topic><topic>Positron-Emission Tomography - methods</topic><topic>Primates</topic><topic>Putamen</topic><topic>Raclopride - administration & dosage</topic><topic>Raclopride - pharmacokinetics</topic><topic>Receptors</topic><topic>Receptors, Dopamine D2 - metabolism</topic><topic>Receptors, Dopamine D3 - antagonists & inhibitors</topic><topic>Receptors, Dopamine D3 - metabolism</topic><topic>Tomography</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sander, Christin Y.</creatorcontrib><creatorcontrib>Hooker, Jacob M.</creatorcontrib><creatorcontrib>Catana, Ciprian</creatorcontrib><creatorcontrib>Normandin, Marc D.</creatorcontrib><creatorcontrib>Alpert, Nathaniel M.</creatorcontrib><creatorcontrib>Knudsen, Gitte M.</creatorcontrib><creatorcontrib>Vanduffel, Wim</creatorcontrib><creatorcontrib>Rosen, Bruce R.</creatorcontrib><creatorcontrib>Mandeville, Joseph B.</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sander, Christin Y.</au><au>Hooker, Jacob M.</au><au>Catana, Ciprian</au><au>Normandin, Marc D.</au><au>Alpert, Nathaniel M.</au><au>Knudsen, Gitte M.</au><au>Vanduffel, Wim</au><au>Rosen, Bruce R.</au><au>Mandeville, Joseph B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2013-07-02</date><risdate>2013</risdate><volume>110</volume><issue>27</issue><spage>11169</spage><epage>11174</epage><pages>11169-11174</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><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 [ ¹¹C]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.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences</pub><pmid>23723346</pmid><doi>10.1073/pnas.1220512110</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2013-07, Vol.110 (27), p.11169-11174 |
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| subjects | Animals antagonists Binding sites Biological and medical sciences Biological Sciences blood volume Brain Brain - blood supply Brain - drug effects Brain - metabolism Cerebellum Cerebrovascular Circulation - drug effects Dopamine Dopamine Antagonists - administration & dosage Dopamine Antagonists - pharmacokinetics Dopamine D2 Receptor Antagonists dopamine receptors Dosage Fundamental and applied biological sciences. Psychology ganglia Imaging Ligands Macaca mulatta Magnetic resonance imaging Magnetic Resonance Imaging - methods Male Models, Neurological Neurochemistry Neurotransmitters NMR Nuclear magnetic resonance Pharmacology Positron emission tomography Positron-Emission Tomography - methods Primates Putamen Raclopride - administration & dosage Raclopride - pharmacokinetics Receptors Receptors, Dopamine D2 - metabolism Receptors, Dopamine D3 - antagonists & inhibitors Receptors, Dopamine D3 - metabolism Tomography Vertebrates: nervous system and sense organs |
| title | Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI |
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