Development of a protocol to assess within-subject, regional white matter hyperintensity changes in aging and dementia.

Journal Article (Journal Article)


White matter hyperintensities (WMH), associated with both dementia risk and progression, can individually progress, remain stable, or even regress influencing cognitive decline related to specific cerebrovascular-risks. This study details the development and validation of a registration protocol to assess regional, within-subject, longitudinal WMH changes (ΔWMH) that is currently lacking in the field.

New method

3D-FLAIR images (baseline and one-year-visit) were used for protocol development and validation. The method was validated by assessing the correlation between forward and reverse longitudinal registration, and between summated regional progression-regression volumes and Global ΔWMH. The clinical relevance of growth-regression ΔWMH were explored in relation to an executive function test.


MRI scans for 79 participants (73.5 ± 8.8 years) were used in this study. Global ΔWMH vs. summated regional progression-regression volumes were highly associated (r2 = 0.90; p-value < 0.001). Bi-directional registration validated the registration method (r2 = 0.999; p-value < 0.001). Growth and regression, but not overall ΔWMH, were associated with one-year declines in performance on Trial-Making-Test-B.

Comparison with existing method(s)

This method presents a unique registration protocol for maximum tissue alignment, demonstrating three distinct patterns of longitudinal within-subject ΔWMH (stable, growth and regression).


These data detail the development and validation of a registration protocol for use in assessing within-subject, voxel-level alterations in WMH volume. The methods developed for registration and intensity correction of longitudinal within-subject FLAIR images allow regional and within-lesion characterization of longitudinal ΔWMH. Assessing the impact of associated cerebrovascular-risks and longitudinal clinical changes in relation to dynamic regional ΔWMH is needed in future studies.

Full Text

Duke Authors

Cited Authors

  • Bahrani, AA; Smith, CD; Barber, JM; Al-Janabi, OM; Powell, DK; Andersen, AH; Ramey, BD; Abner, EL; Goldstein, LB; Winder, Z; Gold, BT; Van Eldik, L; Wilcock, DM; Jicha, GA

Published Date

  • August 2021

Published In

Volume / Issue

  • 360 /

Start / End Page

  • 109270 -

PubMed ID

  • 34171312

Pubmed Central ID

  • PMC8513808

Electronic International Standard Serial Number (EISSN)

  • 1872-678X

International Standard Serial Number (ISSN)

  • 0165-0270

Digital Object Identifier (DOI)

  • 10.1016/j.jneumeth.2021.109270


  • eng