title: Image-derived input function derived from a supervised clustering algorithm: methodology and validation in a clinical protocol using [11C](R)-rolipram.
abstract: Image-derived input function (IDIF) obtained by manually drawing carotid arteries (manual-IDIF) can be reliably used in [(11)C](R)-rolipram positron emission tomography (PET) scans. However, manual-IDIF is time consuming and subject to inter- and intra-operator variability. To overcome this limitation, we developed a fully automated technique for deriving IDIF with a supervised clustering algorithm (SVCA). To validate this technique, 25 healthy controls and 26 patients with moderate to severe major depressive disorder (MDD) underwent T1-weighted brain magnetic resonance imaging (MRI) and a 90-minute [(11)C](R)-rolipram PET scan. For each subject, metabolite-corrected input function was measured from the radial artery. SVCA templates were obtained from 10 additional healthy subjects who underwent the same MRI and PET procedures. Cluster-IDIF was obtained as follows: 1) template mask images were created for carotid and surrounding tissue; 2) parametric image of weights for blood were created using SVCA; 3) mask images to the individual PET image were inversely normalized; 4) carotid and surrounding tissue time activity curves (TACs) were obtained from weighted and unweighted averages of each voxel activity in each mask, respectively; 5) partial volume effects and radiometabolites were corrected using individual arterial data at four points. Logan-distribution volume (V T/f P) values obtained by cluster-IDIF were similar to reference results obtained using arterial data, as well as those obtained using manual-IDIF; 39 of 51 subjects had a V T/f P error of <5%, and only one had error >10%. With automatic voxel selection, cluster-IDIF curves were less noisy than manual-IDIF and free of operator-related variability. Cluster-IDIF showed widespread decrease of about 20% [(11)C](R)-rolipram binding in the MDD group. Taken together, the results suggest that cluster-IDIF is a good alternative to full arterial input function for estimating Logan-V T/f P in [(11)C](R)-rolipram PET clinical scans. This technique enables fully automated extraction of IDIF and can be applied to other radiotracers with similar kinetics.
authors.affiliation: Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Chul Hyoung
authors.initials: CH
authors.lastname: Lyoo
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States of America ; University of Bordeaux, CNRS, INCIA, UMR 5287, Talence, France.
authors.forename: Paolo
authors.initials: P
authors.lastname: Zanotti-Fregonara
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Sami S
authors.initials: SS
authors.lastname: Zoghbi
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Jeih-San
authors.initials: JS
authors.lastname: Liow
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Victor W
authors.initials: VW
authors.lastname: Pike
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D000465:Algorithms; D002250:Carbon Radioisotopes; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology; D016022:Case-Control Studies; D016000:Cluster Analysis; D003865:Major Depressive Disorder / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008297:Male; D049268:Positron-Emission Tomography; D020889:Rolipram / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D020889:Rolipram