Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease

François De Guio, Eric Jouvent, Geert Jan Biessels, Sandra E. Black, Carol Brayne, Christopher Chen, Charlotte Cordonnier, Frank Eric De Leeuw, Martin Dichgans, Fergus Doubal, Marco Duering, Carole Dufouil, Emrah Duzel, Franz Fazekas, Vladimir Hachinski, M. Arfan Ikram, Jennifer Linn, Paul M. Matthews, Bernard Mazoyer, Vincent MokBo Norrving, John T. O'Brien, Leonardo Pantoni, Stefan Ropele, Perminder Sachdev, Reinhold Schmidt, Sudha Seshadri, Eric E. Smith, Luciano A. Sposato, Blossom Stephan, Richard H. Swartz, Christophe Tzourio, Mark Van Buchem, Aad Van Der Lugt, Robert Van Oostenbrugge, Meike W. Vernooij, Anand Viswanathan, David Werring, Frank Wollenweber, Joanna M. Wardlaw, Hugues Chabriat

Research output: Contribution to journalReview articlepeer-review

76 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1319-1337
Number of pages19
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number8
StatePublished - Aug 1 2016
Externally publishedYes


  • Magnetic resonance imaging
  • atrophy
  • brain volume
  • cerebral small vessel disease
  • lacunes
  • marker
  • microbleeds
  • perivascular spaces
  • repeatability
  • reproducibility
  • variability
  • white matter hyperintensities

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Cardiology and Cardiovascular Medicine


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