title: Multisite longitudinal reliability of tract-based spatial statistics in diffusion tensor imaging of healthy elderly subjects.
abstract: Large-scale longitudinal neuroimaging studies with diffusion imaging techniques are necessary to test and validate models of white matter neurophysiological processes that change in time, both in healthy and diseased brains. The predictive power of such longitudinal models will always be limited by the reproducibility of repeated measures acquired during different sessions. At present, there is limited quantitative knowledge about the across-session reproducibility of standard diffusion metrics in 3T multi-centric studies on subjects in stable conditions, in particular when using tract based spatial statistics and with elderly people. In this study we implemented a multi-site brain diffusion protocol in 10 clinical 3T MRI sites distributed across 4 countries in Europe (Italy, Germany, France and Greece) using vendor provided sequences from Siemens (Allegra, Trio Tim, Verio, Skyra, Biograph mMR), Philips (Achieva) and GE (HDxt) scanners. We acquired DTI data (2 × 2 × 2 mm(3), b = 700 s/mm(2), 5 b0 and 30 diffusion weighted volumes) of a group of healthy stable elderly subjects (5 subjects per site) in two separate sessions at least a week apart. For each subject and session four scalar diffusion metrics were considered: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial (AD) diffusivity. The diffusion metrics from multiple subjects and sessions at each site were aligned to their common white matter skeleton using tract-based spatial statistics. The reproducibility at each MRI site was examined by looking at group averages of absolute changes relative to the mean (%) on various parameters: i) reproducibility of the signal-to-noise ratio (SNR) of the b0 images in centrum semiovale, ii) full brain test-retest differences of the diffusion metric maps on the white matter skeleton, iii) reproducibility of the diffusion metrics on atlas-based white matter ROIs on the white matter skeleton. Despite the differences of MRI scanner configurations across sites (vendors, models, RF coils and acquisition sequences) we found good and consistent test-retest reproducibility. White matter b0 SNR reproducibility was on average 7 ± 1% with no significant MRI site effects. Whole brain analysis resulted in no significant test-retest differences at any of the sites with any of the DTI metrics. The atlas-based ROI analysis showed that the mean reproducibility errors largely remained in the 2-4% range for FA and AD and 2-6% for MD and RD, averaged across ROIs. Our results show reproducibility values comparable to those reported in studies using a smaller number of MRI scanners, slightly different DTI protocols and mostly younger populations. We therefore show that the acquisition and analysis protocols used are appropriate for multi-site experimental scenarios.
authors.affiliation: Center for Mind/Brain Sciences (CIMEC), University of Trento, Rovereto, Italy. Electronic address: jorge.jovicich@unitn.it.
authors.forename: Jorge
authors.initials: J
authors.lastname: Jovicich
authors.affiliation: LENITEM Laboratory of Epidemiology, Neuroimaging, & Telemedicine - IRCCS San Giovanni di Dio-FBF, Brescia, Italy.
authors.forename: Moira
authors.initials: M
authors.lastname: Marizzoni
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, and IDIBAPS, Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bosch
authors.affiliation: Department of Psychiatry and Clinical Psychobiology, Universitat de Barcelona and IDIBAPS, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Bartrés-Faz
authors.affiliation: LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Essen, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Arnold
authors.affiliation: LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Essen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Benninghoff
authors.affiliation: LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Essen, Germany; Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.affiliation: Department of Neuroradiology, IRCSS San Martino University Hospital and IST, Genoa, Italy; Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Roccatagliata
authors.affiliation: Department of Neuroscience, Ophthalmology, Genetics and Mother-Child Health (DINOGMI), University of Genoa, Genoa, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Picco
authors.affiliation: Department of Neuroscience, Ophthalmology, Genetics and Mother-Child Health (DINOGMI), University of Genoa, Genoa, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Nobili
authors.affiliation: Pharmacology, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille University - CNRS, UMR 7289, Marseille, France.
authors.forename: Oliver
authors.initials: O
authors.lastname: Blin
authors.affiliation: Department of Neurology, EA1046, Lille University, Lille, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bombois
authors.affiliation: Department of Neuroradiology, EA1046, Lille University, Lille, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Lopes
authors.affiliation: Department of Pharmacology, EA1046, Lille University, Lille, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
authors.affiliation: CRMBM-CEMEREM, UMR 7339, Aix Marseille Université - CNRS, Marseille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Chanoine
authors.affiliation: CRMBM-CEMEREM, UMR 7339, Aix Marseille Université - CNRS, Marseille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Ranjeva
authors.affiliation: APHM, CHU Timone, Service de Neurologie et Neuropsychologie, Marseille, France; Aix-Marseille Université, INSERM U 1106, Marseille, France.
authors.forename: Mira
authors.initials: M
authors.lastname: Didic
authors.affiliation: INSERM, Imagerie cérébrale et handicaps neurologiques, UMR 825, Toulouse, France; Université de Toulouse, UPS, Imagerie cérébrale et handicaps neurologiques, UMR 825, CHU Purpan, Place du Dr Baylac, Toulouse Cedex 9, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Gros-Dagnac
authors.affiliation: INSERM, Imagerie cérébrale et handicaps neurologiques, UMR 825, Toulouse, France; Université de Toulouse, UPS, Imagerie cérébrale et handicaps neurologiques, UMR 825, CHU Purpan, Place du Dr Baylac, Toulouse Cedex 9, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Payoux
authors.affiliation: Department of Neuroradiology, General Hospital, Verona, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Zoccatelli
authors.affiliation: Department of Neuroradiology, General Hospital, Verona, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Alessandrini
authors.affiliation: Department of Neuroradiology, General Hospital, Verona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Beltramello
authors.affiliation: Department of Neuroradiology and Magnetic Resonace Image core Facility, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Bargalló
authors.affiliation: Department of Neuroscience Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti, Italy; Institute for Advanced Biomedical Technologies (ITAB), University "G. d'Annunzio" of Chieti, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferretti
authors.affiliation: Department of Neuroscience Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti, Italy; Institute for Advanced Biomedical Technologies (ITAB), University "G. d'Annunzio" of Chieti, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Caulo
authors.affiliation: IRCCS SDN, Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Aiello
authors.affiliation: IRCCS SDN, Naples, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Ragucci
authors.affiliation: IRCCS SDN, Naples, Italy; University of Naples Parthenope, Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Soricelli
authors.affiliation: Section of Neurology, Centre for Memory Disturbances, University of Perugia, Perugia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Salvadori
authors.affiliation: Medical Physics Unit, Perugia General Hospital, Perugia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Tarducci
authors.affiliation: Neuroradiology Unit, Perugia General Hospital, Perugia, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Floridi
authors.affiliation: 3rd Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: Interbalkan Medical Center of Thessaloniki, Thessaloniki, Greece.
authors.forename: Manos
authors.initials: M
authors.lastname: Constantinidis
authors.affiliation: Interbalkan Medical Center of Thessaloniki, Thessaloniki, Greece; Department of Radiology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Drevelegas
authors.affiliation: Dept. Geriatrics, Neuroscience & Orthopaedics, Catholic University, Policlinic Gemelli, Rome, Italy; IRCSS S.Raffaele Pisana, Rome, Italy.
authors.forename: Paolo Maria
authors.initials: PM
authors.lastname: Rossini
authors.affiliation: Center for Neuropsychological Research, Catholic University, Rome, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Marra
authors.affiliation: Department of Neuroradiology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Josephin
authors.initials: J
authors.lastname: Otto
authors.affiliation: Department of Neuroradiology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reiss-Zimmermann
authors.affiliation: Department of Neuroradiology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Karl-Titus
authors.initials: KT
authors.lastname: Hoffmann
authors.affiliation: LENITEM Laboratory of Epidemiology, Neuroimaging, & Telemedicine - IRCCS San Giovanni di Dio-FBF, Brescia, Italy.
authors.forename: Samantha
authors.initials: S
authors.lastname: Galluzzi
authors.affiliation: LENITEM Laboratory of Epidemiology, Neuroimaging, & Telemedicine - IRCCS San Giovanni di Dio-FBF, Brescia, Italy; Memory Clinic and LANVIE, Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D056324:Diffusion Tensor Imaging / Q000295:instrumentation / Q000379:methods / Q000592:standards*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D066127:White Matter / Q000033:anatomy & histology*
keywords: Brain diffusion tensor imaging; Multi-center; Multi-site MRI; Reliability; Reproducibility; Tract-based spatial statistics