title: [123I]FP-CIT ENC-DAT normal database: the impact of the reconstruction and quantification methods.
abstract: BACKGROUND
  [123I]FP-CIT is a well-established radiotracer for the diagnosis of dopaminergic degenerative disorders. The European Normal Control Database of DaTSCAN (ENC-DAT) of healthy controls has provided age and gender-specific reference values for the [123I]FP-CIT specific binding ratio (SBR) under optimised protocols for image acquisition and processing. Simpler reconstruction methods, however, are in use in many hospitals, often without implementation of attenuation and scatter corrections. This study investigates the impact on the reference values of simpler approaches using two quantifications methods, BRASS and Southampton, and explores the performance of the striatal phantom calibration in their harmonisation.
  
  
  RESULTS
  BRASS and Southampton databases comprising 123 ENC-DAT subjects, from gamma cameras with parallel collimators, were reconstructed using filtered back projection (FBP) and iterative reconstruction OSEM without corrections (IRNC) and compared against the recommended OSEM with corrections for attenuation and scatter and septal penetration (ACSC), before and after applying phantom calibration. Differences between databases were quantified using the percentage difference of their SBR in the dopamine transporter-rich striatum, with their significance determined by the paired t test with Bonferroni correction. Attenuation and scatter losses, measured from the percentage difference between IRNC and ACSC databases, were of the order of 47% for both BRASS and Southampton quantifications. Phantom corrections were able to recover most of these losses, but the SBRs remained significantly lower than the "true" values (p < 0.001). Calibration provided, in fact, "first order" camera-dependent corrections, but could not include "second order" subject-dependent effects, such as septal penetration from extra-cranial activity. As for the ACSC databases, phantom calibration was instrumental in compensating for partial volume losses in BRASS (~67%, p < 0.001), while for the Southampton method, inherently free from them, it brought no significant changes and solely corrected for residual inter-camera variability (-0.2%, p = 0.44).
  
  
  CONCLUSIONS
  The ENC-DAT reference values are significantly dependent on the reconstruction and quantification methods and phantom calibration, while reducing the major part of their differences, is unable to fully harmonize them. Clinical use of any normal database, therefore, requires consistency with the processing methodology. Caution must be exercised when comparing data from different centres, recognising that the SBR may represent an "index" rather than a "true" value.
authors.affiliation: Department of Medical Physics, University Hospital Southampton NHS Foundation Trust, Southampton, UK. livia.bolt@uhs.nhs.uk.
authors.forename: Livia
authors.initials: L
authors.lastname: Tossici-Bolt
authors.affiliation: Institute of Nuclear Medicine, University College London Hospital NHS Foundation Trust, London, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Dickson
authors.affiliation: Department of Nuclear Medicine and Euromedic Szeged, University of Szeged, Szeged, Hungary.
authors.forename: Terez
authors.initials: T
authors.lastname: Sera
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: Department of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Asenbaun-Nan
authors.affiliation: Medical Physics Unit, Az. Ospedaliera Universitaria San Martino, Genoa, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Bagnara
authors.affiliation: Nuclear Medicine Division, Mont-Godinne Medical Center, Université Catholique de Louvain, Yvoir, Belgium.
authors.forename: Thierry Vander
authors.initials: TV
authors.lastname: Borght
authors.affiliation: Department of Nuclear Medicine, Medical Physics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Cathrine
authors.initials: C
authors.lastname: Jonsson
authors.affiliation: Neurobiology Research Unit and Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Robin
authors.initials: R
authors.lastname: de Nijs
authors.affiliation: Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Swen
authors.initials: S
authors.lastname: Hesse
authors.affiliation: Nuclear Medicine Department, Centre Antoine Lacassagne, University of Nice-Sophia Antipolis, Nice, France.
authors.forename: Pierre M
authors.initials: PM
authors.lastname: Koulibaly
authors.affiliation: Department of Nuclear Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Umit O
authors.initials: UO
authors.lastname: Akdemir
authors.affiliation: Nuclear Medicine, University Hospital and K.U. Leuven, Leuven, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Koole
authors.affiliation: Department of Nuclear Medicine, Municipal Hospital of Karlsruhe Inc., Karlsruhe, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Tatsch
authors.affiliation: Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Varrone
keywords: 123I; Calibration; FP-CIT; Quantification; Reconstruction; SPECT; Specific binding ratio