Instrumental validation of free water, peak-width of skeletonized mean diffusivity, and white matter hyperintensities: MarkVCID neuroimaging kits

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5 Scopus citations


Introduction: To describe the protocol and findings of the instrumental validation of three imaging-based biomarker kits selected by the MarkVCID consortium: free water (FW) and peak width of skeletonized mean diffusivity (PSMD), both derived from diffusion tensor imaging (DTI), and white matter hyperintensity (WMH) volume derived from fluid attenuation inversion recovery and T1-weighted imaging. Methods: The instrumental validation of imaging-based biomarker kits included inter-rater reliability among participating sites, test–retest repeatability, and inter-scanner reproducibility across three types of magnetic resonance imaging (MRI) scanners using intra-class correlation coefficients (ICC). Results: The three biomarkers demonstrated excellent inter-rater reliability (ICC >0.94, P-values <.001), very high agreement between test and retest sessions (ICC >0.98, P-values <.001), and were extremely consistent across the three scanners (ICC >0.98, P-values <.001). Discussion: The three biomarker kits demonstrated very high inter-rater reliability, test–retest repeatability, and inter-scanner reproducibility, offering robust biomarkers suitable for future multi-site observational studies and clinical trials in the context of vascular cognitive impairment and dementia (VCID).

Original languageEnglish
Article numbere12261
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Issue number1
StatePublished - 2022

Bibliographical note

Funding Information:
U24NS100591; UH3NS100599; UH3NS100588; UH3NS100608; UH3NS100605; UH3NS100606; UH3NS100598; UH3NS100614; P30 AG 010129; 5UH2NS100614-02. The authors thank: Bruce Fischl, Department of Radiology, Massachusetts General Hospital; Arnold M. Evia, Rush Alzheimer's Disease Center, Rush University Medical Center and Nazanin Makkinejad, Department of Biomedical Engineering, Illinois Institute of Technology; Xin Li and Yang Li, Department of Radiology, Johns Hopkins University School of Medicine; Samantha Ma, Departments of Neurology and Radiology, Keck School of Medicine, University of Southern California; Elyas Fadaee, Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health San Antonio; Andrew Warren, Mitchell Horn, and Vanessa Gonzalez, Department of Neurology, Massachusetts General Hospital; and Linda McGavern from NIH/NINDS.

Publisher Copyright:
© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.


  • VCID
  • biomarker
  • diffusion tensor imaging
  • free water
  • magnetic resonance imaging
  • peak-width skeletonized mean diffusivity
  • small vessel disease
  • vascular contributions to cognitive impairment and dementia
  • white matter hyperintensity
  • white matter injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health


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