title: A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System.
abstract: The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4) and the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of positron emission tomography (PET) and magnetic resonance imaging (MRI) scans acquired in a total of 210 healthy individuals. Comparison of the regional PET binding measures with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (in picomoles per milliliter). We also assessed the regional association between protein concentration and mRNA expression in the human brain by comparing the 5-HT density across the atlas with data from the Allen Human Brain atlas and identified receptor- and transporter-specific associations that show the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system of the human brain.
  
  
  
  We present a high-resolution positron emission tomography (PET)- and magnetic resonance imaging-based human brain atlas of important serotonin receptors and the transporter. The regional PET-derived binding measures correlate strongly with the corresponding autoradiography protein levels. The strong correlation enables the transformation of the PET-derived human brain atlas into a protein density map of the serotonin (5-hydroxytryptamine, 5-HT) system. Next, we compared the regional receptor/transporter protein densities with mRNA levels and uncovered unique associations between protein expression and density at high detail. This new in vivo neuroimaging atlas of the 5-HT system not only provides insight in the human brain's regional protein synthesis, transport, and density, but also represents a valuable source of information for the neuroscience community as a comparative instrument to assess brain disorders.
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet.|Faculty of Health and Medical Sciences.
authors.forename: Vincent
authors.identifier: 0000-0001-7805-279X
authors.initials: V
authors.lastname: Beliveau
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet.
authors.forename: Melanie
authors.identifier: 0000-0002-9120-8098
authors.initials: M
authors.lastname: Ganz
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet.
authors.forename: Ling
authors.identifier: 0000-0001-5102-051X
authors.initials: L
authors.lastname: Feng
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet.|Department of Public Health, Section of Biostatistics, and.
authors.forename: Brice
authors.identifier: 0000-0001-9694-2956
authors.initials: B
authors.lastname: Ozenne
authors.affiliation: Faculty of Health and Medical Sciences.|PET and Cyclotron Unit, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Højgaard
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet.
authors.forename: Patrick M
authors.identifier: 0000-0002-8115-0611
authors.initials: PM
authors.lastname: Fisher
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet.
authors.forename: Claus
authors.identifier: 0000-0001-7811-1825
authors.initials: C
authors.lastname: Svarer
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts 02129, and.|Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Greve
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, gmk@nru.dk.|Faculty of Health and Medical Sciences.
authors.forename: Gitte M
authors.identifier: 0000-0003-1508-6866
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D001271:Atlases as Topic; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D049268:Positron-Emission Tomography; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin
keywords: 5-HT; MRI; PET; atlas; autoradiography; mRNA