Speakers - 2026

Title: Understanding how microstructural measures from Diffusion Tensor Imaging (DTI) relate to Small Vessel Disease in White Matter Lesions (WMLs)

Abstract

Background:

Cerebral small vessel disease (SVD) is a major cause of stroke and dementia. Its primary MRI manifestation, white matter lesions (WMLs), reflects advanced pathology and incompletely characterizes underlying tissue injury. Diffusion tensor imaging (DTI) can quantify early microstructural white matter injury not visible on conventional MRI, but the extent to which DTI metrics explain or relate to WMLs of presumed vascular origin remains unclear.

Methods:

A targeted review of MEDLINE and EMBASE was conducted to identify studies examining the relationship between common DTI metrics: fractional anisotropy (FA) and mean diffusivity (MD) and WMLs in SVD. The results of the search were reviewed for relevance, summarised, and critically appraised.

Results:

The relationship between DTI metrics and WMLs is highly context dependent, varying fundamentally by disease state. In both normal aging and Alzheimer’s disease, higher WML burden is consistently associated with lower FA and higher MD. In aging, this lesion burden strongly mediates age associated diffusion abnormalities. In AD, microstructural disruption is also reported to be largely confined to WMLs. A distinct contrast emerges in Parkinson’s disease, where widespread abnormalities in normal appearing white matter (NAWM) are detected early and progress independently of WML volume. In stroke, NAWM diffusion metrics themselves serve as strong independent predictors of functional outcomes. Across conditions, DTI reveals that microstructural changes in NAWM can precede visible lesion formation. However, the prognostic primacy of WML volume versus diffusion metrics varies by disease. The association pattern is further modulated by lesion location and differs between FA and MD, which frequently provide dissociated information

Conclusion:

DTI reveals that microstructural injury in SVD extends beyond visible WMLs, but the relationship between the two is not uniform. DTI metrics and WML volume capture distinct, complementary, and sometimes decoupled aspects of white matter pathology across different diseases. This indicates that DTI abnormalities are not universally explained by WMLs and are influenced by disease specific mechanisms. Integrating these measures requires a nuanced, disease aware framework rather than a single explanatory model.