Cerebral haemodynamics and white matter hyperintensities: findings using non-invasive brain imaging

Utilizing non-invasive neuroimaging for characterization of blood brain barrier (BBB) changes and perfusion deficits underlying small vessel disease pathobiology including white matter hyperintensities (WMH) remains largely unexplored.

We examined the underlying haemodynamics of WMH by assessing complex relationships between cerebral blood flow, BBB permeability and WMH burden.

Cross-sectional data from study participants belonging to the community-based Biomarker and Cognition Cohort Study, Singapore was obtained.

Brain structural and novel non-invasive multi-echo Arterial Spin Labeling data was obtained from 128 participants to derive cerebral blood flow (CBF), arterial transit time (ATT) and BBB time of exchange (T_ex).

Neurovascular measures from BBB imaging comprising lower CBF (β=-0.005; p = 0.0139), longer ATT (β=0.644; p = 0.0132) and shorter BBB T_ex (β=-0.002; p = 0.0023) were independently associated with higher WMH and higher age-at-visit. Model fit statistics indicated good fit for the structural equation model with a comparative fit index of 0.975 and Standardized Root Mean Square Residual of 0.074. Structural equation modelling revealed CBF (β=0.533; p < 0.001) and ATT (β=-0.254; p = 0.001) as predictors of BBB permeability. Subsequently higher BBB permeability predicted higher WMH burden (β=-0.387; p < 0.001). Additionally, vascular risk factors comprising higher blood pressure and haemoglobinA1C related to lower CBF and shorter BBB T_ex.

Our study highlights that CBF and ATT contribute to BBB permeability, which in turn impacts WMH burden. Vascular risk factors also impact neurovascular measures. These findings add to the growing evidence on the potential role of BBB and perfusion deficits underlying small vessel disease burden.