title: Free water elimination improves test-retest reproducibility of diffusion tensor imaging indices in the brain: A longitudinal multisite study of healthy elderly subjects.
abstract: Free water elimination (FWE) in brain diffusion MRI has been shown to improve tissue specificity in human white matter characterization both in health and in disease. Relative to the classical diffusion tensor imaging (DTI) model, FWE is also expected to increase sensitivity to microstructural changes in longitudinal studies. However, it is not clear if these two models differ in their test-retest reproducibility. This study compares a bi-tensor model for FWE with DTI by extending a previous longitudinal-reproducibility 3T multisite study (10 sites, 7 different scanner models) of 50 healthy elderly participants (55-80 years old) scanned in two sessions at least 1 week apart. We computed the reproducibility of commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AXD: axial diffusivity), derived either using a DTI model or a FWE model. The DTI metrics were evaluated over 48 white-matter regions of the JHU-ICBM-DTI-81 white-matter labels atlas, and reproducibility errors were assessed. We found that relative to the DTI model, FWE significantly reduced reproducibility errors in most areas tested. In particular, for the FA and MD metrics, there was an average reduction of approximately 1% in the reproducibility error. The reproducibility scores did not significantly differ across sites. This study shows that FWE improves sensitivity and is thus promising for clinical applications, with the potential to identify more subtle changes. The increased reproducibility allows for smaller sample size or shorter trials in studies evaluating biomarkers of disease progression or treatment effects. Hum Brain Mapp 38:12-26, 2017. © 2016 Wiley Periodicals, Inc.
authors: Center for Mind/Brain Sciences (CIMEC), University of Trento, Rovereto, Italy.
authors: Angela
authors: A
authors: Albi
authors: Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors: Ofer
authors: O
authors: Pasternak
authors: Center for Mind/Brain Sciences (CIMEC), University of Trento, Rovereto, Italy.
authors: Ludovico
authors: L
authors: Minati
authors: LENITEM Laboratory of Epidemiology, Neuroimaging, & Telemedicine-IRCCS San Giovanni di Dio-FBF, Brescia, Italy.
authors: Moira
authors: M
authors: Marizzoni
authors: Department of Psychiatry and Clinical Psychobiology, Universitat de Barcelona and IDIBAPS, Barcelona, Spain.
authors: David
authors: D
authors: Bartrés-Faz
authors: Department of Neuroradiology and Magnetic Resonance Image core Facility, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors: Núria
authors: N
authors: Bargalló
authors: Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic, and IDIBAPS, Barcelona, Spain.
authors: Beatriz
authors: B
authors: Bosch
authors: Department Geriatrics Neuroscience & Orthopedics, Catholic University, Policlinic Gemelli, Rome, Italy.|IRCSS S.Raffaele Pisana, Rome, Italy.
authors: Paolo Maria
authors: PM
authors: Rossini
authors: Center for Neuropsychological Research, Catholic University, Rome, Italy.
authors: Camillo
authors: C
authors: Marra
authors: LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Essen, Germany.
authors: Bernhard
authors: B
authors: Müller
authors: LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Essen, Germany.
authors: Ute
authors: U
authors: Fiedler
authors: LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Essen, Germany.|Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg August University, Göttingen, Germany.
authors: Jens
authors: J
authors: Wiltfang
authors: Department of Neuroradiology, IRCSS San Martino University Hospital and IST, Genoa, Italy.|Department of Health Sciences, University of Genoa, Genoa, Italy.
authors: Luca
authors: L
authors: Roccatagliata
authors: Department of Neuroscience, Ophthalmology, Genetics and Mother-Child Health (DINOGMI), University of Genoa, Genoa, Italy.
authors: Agnese
authors: A
authors: Picco
authors: Department of Neuroscience, Ophthalmology, Genetics and Mother-Child Health (DINOGMI), University of Genoa, Genoa, Italy.
authors: Flavio Mariano
authors: FM
authors: Nobili
authors: Pharmacology, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University-CNRS, UMR, Marseille, 7289, France.
authors: Oliver
authors: O
authors: Blin
authors: CRMBM-CEMEREM, UMR 7339, Aix Marseille Université-CNRS, Marseille, France.
authors: Julien
authors: J
authors: Sein
authors: CRMBM-CEMEREM, UMR 7339, Aix Marseille Université-CNRS, Marseille, France.
authors: Jean-Philippe
authors: JP
authors: Ranjeva
authors: APHM, CHU Timone, Service de Neurologie et Neuropsychologie, Marseille, France.|Aix Marseille Université, Inserm, INS UMR_S 1106, Marseille, 13005, France.
authors: Mira
authors: M
authors: Didic
authors: Université de Lille, Inserm, CHU Lille, U1171-Degenerative and vascular cognitive disorders, Lille, F-59000, France.
authors: Stephanie
authors: S
authors: Bombois
authors: Université de Lille, Inserm, CHU Lille, U1171-Degenerative and vascular cognitive disorders, Lille, F-59000, France.
authors: Renaud
authors: R
authors: Lopes
authors: Université de Lille, Inserm, CHU Lille, U1171-Degenerative and vascular cognitive disorders, Lille, F-59000, France.
authors: Régis
authors: R
authors: Bordet
authors: 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: Hélène
authors: H
authors: Gros-Dagnac
authors: 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: Pierre
authors: P
authors: Payoux
authors: Department of Neuroradiology, General Hospital, Verona, Italy.
authors: Giada
authors: G
authors: Zoccatelli
authors: Department of Neuroradiology, General Hospital, Verona, Italy.
authors: Franco
authors: F
authors: Alessandrini
authors: Department of Neuroradiology, General Hospital, Verona, Italy.
authors: Alberto
authors: A
authors: Beltramello
authors: 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: Antonio
authors: A
authors: Ferretti
authors: 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: Massimo
authors: M
authors: Caulo
authors: IRCCS SDN, Naples, Italy.
authors: Marco
authors: M
authors: Aiello
authors: IRCCS SDN, Naples, Italy.
authors: Carlo
authors: C
authors: Cavaliere
authors: IRCCS SDN, Naples, Italy.|University of Naples Parthenope, Naples, Italy.
authors: Andrea
authors: A
authors: Soricelli
authors: Section of Neurology, Centre for Memory Disturbances, University of Perugia, Perugia, Italy.
authors: Lucilla
authors: L
authors: Parnetti
authors: Medical Physics Unit, Perugia General Hospital, Perugia, Italy.
authors: Roberto
authors: R
authors: Tarducci
authors: Neuroradiology Unit, Perugia General Hospital, Perugia, Italy.
authors: Piero
authors: P
authors: Floridi
authors: 3rd Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors: Magda
authors: M
authors: Tsolaki
authors: Interbalkan Medical Center of Thessaloniki, Thessaloniki, Greece.
authors: Manos
authors: M
authors: Constantinidis
authors: Interbalkan Medical Center of Thessaloniki, Thessaloniki, Greece.|Department of Radiology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors: Antonios
authors: A
authors: Drevelegas
authors: 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: Giovanni
authors: G
authors: Frisoni
authors: Center for Mind/Brain Sciences (CIMEC), University of Trento, Rovereto, Italy.
authors: Jorge
authors: J
authors: Jovicich
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D016880:Anisotropy; D001921:Brain / Q000000981:diagnostic imaging*; D056324:Diffusion Tensor Imaging; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D021621:Imaging, Three-Dimensional; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D014867:Water / Q000378:metabolism*; D066127:White Matter / Q000000981:diagnostic imaging
chemical_list: D014867:Water
keywords: brain diffusion tensor imaging; free-water imaging; healthy elderly; longitudinal; multisite diffusion MRI; test-retest reproducibility