Objective

To investigate cerebrovascular reactivity (CVR), blood flow, vascular and cerebrospinal fluid (CSF) pulsatility, and their independent relationship to cerebral small vessel disease (SVD) features, in patients with minor ischaemic stroke and MRI evidence of SVD.

Methods

We recruited patients with minor ischaemic stroke and assessed CVR using Blood Oxygen Level Dependent (BOLD) MRI during a hypercapnic challenge, cerebral blood flow, vascular and CSF pulsatility using phase contrast MRI, and structural MR brain imaging to quantify white matter hyperintensities (WMH) and perivascular spaces (PVS). We used multiple regression to identify parameters associated with SVD features, controlling for patient characteristics.

Results

53 of 60 patients completed the study with a full dataset (age 68.0±8.8, 74% male, 75% hypertensive). After controlling for age, gender and systolic BP, lower white matter CVR was associated with higher WMH volume (-0.01%/mmHg per log10 increase in WMH volume, p=0.02), basal ganglia PVS (-0.01%/mmHg per point increase in PVS score, p=0.02) and higher venous pulsatility (superior sagittal sinus -0.03%/mmHg, p=0.02, per unit increase in pulsatility index) but not with cerebral blood flow (p=0.58). Lower foramen magnum CSF stroke volume was associated with worse white matter CVR (0.04%/mmHg per ml increase in stroke volume, p=0.04) and more severe basal ganglia PVS (p=0.09).

Conclusions

Lower CVR, higher venous pulsatility and lower foramen magnum CSF stroke volume indicate that dynamic vascular dysfunctions underpin PVS dysfunction and WMH development. Further exploration of microvascular dysfunction and CSF dynamics may uncover new mechanisms and intervention targets to reduce SVD lesion development, cognitive decline and stroke.