Changes in microvessel density in normal-appearing white matter in relation to cerebral small vessel disease: A cohort study

Abstract

Background and purpose

White matter hyperintensities (WMH) of presumed vascular origin describe structural alterations of cerebral white matter, thought to result from cerebral small vessel disease. However, the in vivo effects of WMH on normal-appearing white matter microvasculature remain elusive. Therefore, we conducted an exploratory investigation of microvascular density in normal-appearing and pathological white matter in patients with WMH.

Methods

Using magnetic resonance imaging-based vessel size imaging we investigated an index of microvessel density in vivo in two clinical cohorts with ischaemic events (cohort_A, N = 88, mean age = 77.18) and intracranial neoplasms (cohort_B, N = 58, mean age = 65.45). For analysis, regions of interest were created for the whole normal-appearing white matter, the normal-appearing centrum semiovale, the WMH, the WMH penumbra, and the normal-appearing striatum. The severity of WMH-burden was quantified using the Wahlund score.

Results

In both cohorts, the index of microvessel density in the striatum was significantly higher than in normal-appearing white matter. There was no significant difference between WMH and WMH penumbra. However, both WMH and WMH penumbra had a significantly lower index of microvessel density than normal-appearing white matter in the subgroup of patients with high Wahlund scores. Lastly, the index of microvessel density in the normal-appearing centrum semiovale was higher in patients with high compared to low Wahlund scores in both cohorts. This comparison was not significant after adjusting for age.

Conclusions

Our results suggest a complex relationship between cerebral small vessel disease-related WMH and microvascular changes in the normal-appearing white matter, potentially indicative of WMH-related angiogenesis.