title: Mapping the distribution of serotonin transporter in the human brainstem with high-resolution PET: Validation using postmortem autoradiography data.
abstract: The human brainstem is a complex structure with several small nuclei and neural pathways of interest in the pathophysiology of central nervous system (CNS) disorders. In common with other monoaminergic systems, serotoninergic neurons originate from a group of nuclei located in the brainstem. The present study was designed to validate a user-independent approach for a detailed in vivo quantification of serotonin transporter (5-HTT) availability in the human brainstem using a template-based approach that consisted of three steps. First, 3T-MR images and parametric binding potential (BPND) [(11)C]MADAM images of ten healthy subjects were used to generate a PET template of 5-HTT availability. In the second step, volumes of interest (VOIs) for different brainstem nuclei were obtained using a method in which VOIs are initially delineated on MRI images using anatomical landmarks and then are finally tailored on the distribution of 5-HTT binding using a thresholding approach applied to the 5-HTT template. In the final step, the VOIs were transformed and applied individually to BPND images of 16 healthy subjects (14M/2F, 20-64years). The in vivo distribution of BPND values obtained with the template-based method were in good agreement with an individual-based approach taken as gold standard. Results were also in agreement with 5-HTT quantification using in vitro binding data obtained with autoradiography (ARG) studies using [(3)H]MADAM. The proposed template-based method can be applied to PET data acquired in several CNS disorders in which serotonin neurons in the brainstem might be affected.
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. Electronic address: patrik.fazio@ki.se.
authors.forename: P
authors.initials: P
authors.lastname: Fazio
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Schain
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Varnäs
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Halldin
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; AstraZeneca Translational Science Centre, PET CoE, Karolinska Institutet, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Farde
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Varrone
mesh_terms: D000328:Adult; D000368:Aged; D001344:Autopsy / Q000379:methods; D001345:Autoradiography / Q000379:methods*; D001596:Benzylamines / Q000493:pharmacokinetics*; D001933:Brain Stem / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D001596:Benzylamines; C470437:N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: Brainstem nuclei; PET template-based analysis; Serotonin transporter