Intracranial hemodynamic relationships in patients with cerebral small vessel disease

Abstract

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

Methods: We recruited patients with minor ischemic stroke and assessed CVR using blood oxygen level-dependent MRI during a hypercapnic challenge, cerebral blood flow (CBF), vascular and CSF pulsatility using phase-contrast MRI, and structural magnetic resonance brain imaging to quantify white matter hyperintensities (WMHs) and perivascular spaces (PVSs). We used multiple regression to identify parameters associated with SVD features, controlling for patient characteristics.

Results: Fifty-three of 60 patients completed the study with a full data set (age 68.0% ± 8.8 years, 74% male, 75% hypertensive). After controlling for age, sex, and systolic blood pressure, lower white matter CVR was associated with higher WMH volume (-0.01%/mm Hg per log10 increase in WMH volume, p = 0.02), basal ganglia PVS (-0.01%/mm Hg per point increase in the PVS score, p = 0.02), and higher venous pulsatility (superior sagittal sinus -0.03%/mm Hg, p = 0.02, per unit increase in the pulsatility index) but not with CBF (p = 0.58). Lower foramen magnum CSF stroke volume was associated with worse white matter CVR (0.04%/mm Hg 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.

Figure 1. White matter CVR and WMH volume, WMH Fazekas score, and PVS scores

(A) White matter CVR and WMH volume β = −0.013 (95% CI −0.020 to −0.005). (B) White matter CVR and periventricular Fazekas score β = −0.015 (95% CI −0.024 to −0.007). (C) White matter CVR and deep Fazekas score β = −0.008 (95% CI −0.017 to 0.001). (D) White matter CVR and basal ganglia PVS score β = −0.012 (95% CI −0.020 to −0.005). (E) White matter CVR and centrum semiovale PVS score β = −0.009 (95% CI −0.016 to −0.001). CI = confidence interval; CVR = cerebrovascular reactivity; PVS = perivascular space; WMH = white matter hyperintensity.

Figure 2. Relationship of white matter CVR, foramen magnum CSF stroke volume, and superior sagittal sinus pulsatility index

(A) White matter CVR and foramen magnum CSF stroke volume β = 0.033 (95% CI −0.004 to 0.070). (B) White matter CVR and superior sagittal sinus PI β = −0.044 (95% CI −0.073 to −0.014). (C) Foramen magnum CSF stroke volume and superior sagittal sinus PI β = −0.249 (95% CI −0.477 to −0.020). CI = confidence interval; CVR = cerebrovascular reactivity; PI = pulsatility index.