title: Individual-reader diagnostic performance and between-reader agreement in assessment of subjects with Parkinsonian syndrome or dementia using 123I-ioflupane injection (DaTscan) imaging.
abstract: Establishing an early, accurate diagnosis is fundamental for appropriate clinical management of patients with movement disorders or dementia. Ioflupane (123)I Injection (DaTscan, (123)I-ioflupane) is an important adjunct to support the clinical diagnosis. Understanding individual-reader diagnostic performance of (123)I-ioflupane in a variety of clinical scenarios is essential.
  
  
  METHODS
  Sensitivity, specificity, interreader, and intrareader data from 5 multicenter clinical studies were reviewed. The different study designs offered an assortment of variables to assess the effects on the diagnostic performance of (123)I-ioflupane: on-site versus 3-5 blinded image readers, number of image evaluations, early/uncertain versus late/confirmed clinical diagnosis as reference standard, and subjects with movement disorders versus dementia.
  
  
  RESULTS
  Eight hundred eighteen subjects had individual-reader efficacy data available for analysis. In general, sensitivity and specificity were high and comparable between on-site versus blinded independent readers. In subjects with dementia, when the clinical diagnosis was made at month 12 versus baseline, specificity improved from 77.4%-91.2% to 81.6%-95.0%. In subjects with movement disorders, this effect was observed to an even greater extent, when diagnostic performance using month-18 diagnosis as a reference standard (sensitivity, 67.0%-73.7%; specificity, 75.0%-83.3%) was compared versus month-36 diagnosis (77.5%-80.3% and 90.3%-96.8%, respectively). Diagnostic performance was similar in subjects with dementia (74.4%-89.9% and 77.4%-95.0%, respectively) and subjects with movement disorders (67.0%-97.9% and 71.4%-98.4%, respectively). In most of the comparisons, between-reader agreement was very good (almost perfect), with κ ranging from 0.81 to 1.00. Within-reader agreement, measured in 1 study, was 100% for 3 blinded readers.
  
  
  CONCLUSIONS
  Individual-reader diagnostic performance, as assessed by measuring sensitivity and specificity of (123)I-ioflupane to detect the presence or absence of striatal dopaminergic deficit, using the clinical diagnosis as a reference standard, was high in subjects with either movement disorders or dementia and was similar in on-site readers versus blinded analyses. Between- and within-reader agreements were very good (almost perfect). Longer follow-up between imaging and clinical diagnosis improved the diagnostic accuracy, most likely due to improvement in the clinical diagnosis reference standard, rather than changes in reader accuracy.
authors.affiliation: Institute for Neurodegenerative Disorders, New Haven, Connecticut jseibyl@mnimaging.com.
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.affiliation: Department of Neurology and Stereotactic Neurosurgery, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kupsch
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Booij
authors.affiliation: Institute of Neurological Sciences, Southern General Hospital and University of Glasgow, Glasgow, Scotland.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Grosset
authors.affiliation: Nuclear Medicine-Radiopharmacology, Champalimaud Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal.
authors.forename: Durval C
authors.initials: DC
authors.lastname: Costa
authors.affiliation: Departments of Neurology, Molecular Pharmacology and Physiology, USF Health Byrd Parkinson's Disease and Movement Disorders Center, National Parkinson Foundation Center of Excellence, Tampa, Florida.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.affiliation: Department of Nuclear Medicine, Centre Antoine Lacassagne, TIRO Research Group, University of Nice Sophia-Antipolis, Nice, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Darcourt
authors.affiliation: Department of Clinical Neurology, National Parkinson's Foundation International Centre of Excellence, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre Campus, Nottingham, United Kingdom.
authors.forename: Nin
authors.initials: N
authors.lastname: Bajaj
authors.affiliation: Division of Psychiatry, University College London, London, United Kingdom North Essex Partnership University NHS Foundation Trust, Essex, United Kingdom.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Walker
authors.affiliation: Institute for Neurodegenerative Disorders, New Haven, Connecticut.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Marek
authors.affiliation: Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: McKeith
authors.affiliation: Department of Psychiatry, University of Cambridge School of Clinical Medicine and Cambridgeshire and Peterborough Foundation NHS Trust, Cambridge, United Kingdom.
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
authors.affiliation: Department of Nuclear Medicine, Municipal Hospital Karlsruhe, Inc., Karlsruhe, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Tatsch
authors.affiliation: Neurology Service, Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.affiliation: Departments of Radiology, Nuclear Medicine, and Molecular Imaging, University Medical Centre Groningen, Groningen, The Netherlands; and.
authors.forename: Rudi A
authors.initials: RA
authors.lastname: Dierckx
authors.affiliation: Medical Affairs, Life Sciences, GE Healthcare, Princeton, New Jersey.
authors.forename: Igor D
authors.initials: ID
authors.lastname: Grachev
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002986:Clinical Trials as Topic; D003704:Dementia / Q000000981:diagnostic imaging*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009662:Nortropanes / Q000008:administration & dosage; D015588:Observer Variation; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging*; D012680:Sensitivity and Specificity; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
chemical_list: D009662:Nortropanes; C519528:ioflupane
keywords: DaTscan; Ioflupane 123I Injection; diagnostic performance; sensitivity; specificity