Intracranial hemodynamic relationships in patients with cerebral small vessel disease

Abstract

ObjectiveTo 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.MethodsWe 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.ResultsFifty-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).ConclusionsLower 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.

A Comparison of CVR Magnitude and Delay Assessed at 1.5 and 3T in Patients With Cerebral Small Vessel Disease

“…Although CVR magnitude tended to be lower in patients who were older, male, and had higher blood pressure at both 1.5T and 3T, none of the associations reached conventional statistical significance, likely due to lack of power in this subset of the main study. Nevertheless the direction of effect was broadly consistent with previous work showing lower CVR in older patients (Hund-Georgiadis et al, 2003;Conijn et al, 2012;Gauthier et al, 2015;Blair et al, 2020), males than females (Kastrup et al, 1997;Cupini et al, 2001;Tallon et al, 2020), and in patients with higher blood pressure (Conijn et al, 2012;Haight et al, 2015). We found that subcortical GM and WM CVR tended to be lower in patients with higher WMH volume, Fazekas (deep, periventricular, and total), and SVD score at both 3T and 1.5T, replicating previously published findings in a larger cohort (of which these patients formed a subgroup) scanned at 1.5T (Blair et al, 2020).…”

“…An experienced neuroradiologist assessed SVD features of WMH, lacunes, microbleeds, visible PVS, and brain atrophy, using visual ratings on the 1.5T scans, including Fazekas score for WMH, PVS and atrophy scores, and counts of lacunes and microbleeds, which were used to calculate the SVD score (Staals et al, 2014;Blair et al, 2020). We converted the DICOM files through SPM8 (Wellcome Department of Imaging Neuroscience, London, United Kingdom) (Friston, 2007).…”

Cerebrovascular Reactivity Measurement Using Magnetic Resonance Imaging: A Systematic Review

“…Statistical analyses should account for such key covariates, which requires larger sample sizes or matched study design. CVR is also associated with vascular risk factors including hypertension, diabetes, hypercholesterolemia and smoking (Haight et al, 2015;Tchistiakova et al, 2015;Sam et al, 2016b;Blair et al, 2020).…”

Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3

“…We assess CVR using a blood oxygenation level dependent (BOLD) MRI sequence, during which participants inhale air with intermittent-added CO 2 (12-min paradigm alternating 2 min air and 3 min 6% CO 2 ) through a tightfitting facemask, described previously. 13,44 Arterial, venous and CSF pulsatility are measured using phase contrast MRI sequences. 14,44 We measure CBF using major arterial phase contrast flow measures obtained during pulsatility measurements (and arterial spin labelling where feasible).…”

“…6 Recent advances in neuroimaging have uncovered candidate mechanisms for underlying pathophysiological processes. Furthermore, SVD appears to be more dynamic and global than previously thought, since recent studies show: (a) WMH can regress as well as progress; [7][8][9][10] (b) SVD is associated with cerebrovascular dysfunction including diffuse blood-brain barrier (BBB) failure; 11 (c) with some evidence for other vascular dysfunctions including reduced cerebrovascular reactivity (CVR) and increased intracranial pulsatility [12][13][14] and (d) acute, apparently 'silent', lesions on diffusion weighted imaging (DWI) may be more frequent than previously thought. [15][16][17] Most SVD lesions are thought to develop 'silently'.…”