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

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. 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. 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. Tracking dynamic changes in white matter hyperintensities (WMH) is critical for the assessment of longitudinal degenerative and vascular disease related injury. WMHs have been shown to progress, remain stable, or even regress over time. The present study sought to develop and validate a registration protocol that will allow the assessment of regional, within-subject, longitudinal WMH changes over periods as short as one-year, necessary for use in future clinical trials of disease modifying therapies that hope to limit, stabilize, or even reverse deleterious WMH injury. [Display omitted] • Midpoint co-registration of FLAIR images can be used to assess longitudinal WMH changes. • Image intensity z-score corrections minimize co-registration T2 signal artifacts. • Dynamic intra-subject WMH volume changes include a mix of both progression and regression. • WMH progression is associated with a decline in executive function. • This standardized protocol can accurately detect such changes over a short one-year interval. [ABSTRACT FROM AUTHOR]