title: Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease.
abstract: Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan-rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease.
authors.affiliation: University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, Paris, France DHU NeuroVasc, Sorbonne Paris Cité, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: De Guio
authors.affiliation: University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, Paris, France DHU NeuroVasc, Sorbonne Paris Cité, Paris, France Department of Neurology, AP-HP, Lariboisière Hospital, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Jouvent
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Geert Jan
authors.initials: GJ
authors.lastname: Biessels
authors.affiliation: Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
authors.affiliation: Department of Public Health and Primary Care, Cambridge University, Cambridge, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: Brayne
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Christopher
authors.initials: C
authors.lastname: Chen
authors.affiliation: University of Lille, CHU Lille, Inserm U1171, Lille, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cordonnier
authors.affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Department of Neurology, Nijmegen, The Netherlands.
authors.forename: Frank-Eric
authors.initials: FE
authors.lastname: De Leeuw
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilian-University (LMU), Munich, Germany Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.affiliation: Department of Neuroimaging Sciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
authors.forename: Fergus
authors.initials: F
authors.lastname: Doubal
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilian-University (LMU), Munich, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Duering
authors.affiliation: Inserm UMR897, University of Bordeaux, Bordeaux, France
authors.forename: Carole
authors.initials: C
authors.lastname: Dufouil
authors.affiliation: Department of Cognitive Neurology and Dementia Research, University of Magdeburg, Magdeburg, Germany.
authors.forename: Emrah
authors.initials: E
authors.lastname: Duzel
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.affiliation: Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Hachinski
authors.affiliation: Department of Radiology and Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Department of Neuroradiology, University Hospital Munich, Munich, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Linn
authors.affiliation: Department of Medicine, Division of Brain Sciences, Imperial College London, London, UK.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Matthews
authors.affiliation: CNRS-CEA UMR5296, University of Bordeaux, Bordeaux, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Mazoyer
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mok
authors.affiliation: Department of Clinical Sciences, Neurology, Lund University, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Norrving
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
authors.affiliation: Neurofarba Department, University of Florence, Florence, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pantoni
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ropele
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Perminder
authors.initials: P
authors.lastname: Sachdev
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Smith
authors.affiliation: Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada.
authors.forename: Luciano A
authors.initials: LA
authors.lastname: Sposato
authors.affiliation: Institute of Health and Society, Newcastle University Institute of Ageing, Newcastle University, Newcastle, UK.
authors.forename: Blossom
authors.initials: B
authors.lastname: Stephan
authors.affiliation: Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Swartz
authors.affiliation: Inserm UMR897, University of Bordeaux, Bordeaux, France
authors.forename: Christophe
authors.initials: C
authors.lastname: Tzourio
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: van Buchem
authors.affiliation: Department of Radiology and Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.affiliation: Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: van Oostenbrugge
authors.affiliation: Department of Radiology and Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
authors.affiliation: Department of Neurology, J. Philip Kistler Stroke Research Center, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Viswanathan
authors.affiliation: Department of Brain Repair and Rehabilitation, Stroke Research Group, UCL, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Werring
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilian-University (LMU), Munich, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Wollenweber
authors.affiliation: Department of Neuroimaging Sciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK  Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), University of Edinburgh, Edinburgh, UK.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
authors.affiliation: University Paris Diderot, Sorbonne Paris Cité, UMRS 1161 INSERM, Paris, France DHU NeuroVasc, Sorbonne Paris Cité, Paris, France Department of Neurology, AP-HP, Lariboisière Hospital, Paris, France hugues.chabriat@aphp.fr.
authors.forename: Hugues
authors.initials: H
authors.lastname: Chabriat
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging*; D059345:Cerebral Small Vessel Diseases / Q000000981:diagnostic imaging*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D055806:Microvessels / Q000000981:diagnostic imaging*; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers
keywords: Magnetic resonance imaging; atrophy; brain volume; cerebral small vessel disease; lacunes; marker; microbleeds; perivascular spaces; repeatability; reproducibility; variability; white matter hyperintensities