Relation between Cerebral Small Vessel Function at 7T MRI and Small Vessel Disease Burden in a General Aging Population

Abstract

Introduction: There is a need for measures of early stages of cerebral small vessel diseases (cSVDs). Recently, using 7T MRI, abnormalities of small vessel function were reported in patients with clinically manifest cSVD. The question is if such abnormalities are also present in early, covert stages of cSVD. We, therefore, studied the relation between cerebral small vessel function measures on 7T MRI and the burden of covert cSVD in the general aging population.

Methods: Two hundred participants (mean age [years] ± SD: 71 ± 5, 43% women) without a history of stroke or dementia from the Rotterdam Study were included. Small vessel measures at 7T MRI, including perforating artery blood flow velocity and pulsatility and cerebrovascular reactivity (CVR) to carbon dioxide, were related to markers of cSVD burden at 1.5T MRI, including white matter hyperintensity (WMH) volume and microbleed, enlarged perivascular spaces, and lacune presence, using linear and logistic regression analyses. We also included cognitive performance as a clinical indicator of covert cSVD.

Results: Across the population, neither perforating artery flow measures nor CVR were significantly associated with cSVD lesion burden or cognition, with small point estimates and no consistent direction of effects. Yet, within individuals, CVR was lower inside WMHs compared to normal-appearing white matter (CVR_NAWM = 0.54 ± 0.48%; CVR_WMH = 0.24 ± 0.94%; p = 0.006).

Conclusion: Although these data confirm that vascular function is affected within WMH, we did not observe relations between small vessel function measures at 7T MRI and the burden of covert cSVD in this population-based sample. Apparently, these measures have limited sensitivity to early stages of cSVD.

Keywords: Covert cerebral small vessel diseases; MRI; Population cohort; Small vessel disease; White matter damage.

Fig. 1.

Small vessel function measures at 7T MRI. a Blood flow velocity measures of the perforatory arteries at the level of the semioval center (CSO) and the basal ganglia (BG) were performed with 2D phase contrast angiography. Vessels were automatically detected with an automated analysis tool. PI measures were obtained from the blood flow velocity time series over the cardiac cycle, representing vessel stiffness. Image modified from: https://www.istockphoto.com/nl/vector/brain-transverse-section-illustration-gm1389369649-446695497. b Cerebrovascular reactivity (CVR) to a hypercapnic stimulus was assessed at a whole-brain level during a CO₂ block stimulus (top plot) with blood-oxygenation level-dependent (BOLD) MRI. The amplitude of the time series of the BOLD-CVR response (bottom plot) to the hypercapnic stimulus represents the dilatory capacity of the vessel.

Fig. 2.

Small vessel function in relation to small vessel disease burden. Blood flow velocity in the perforating arteries of the semioval center (CSO; a) and the basal ganglia (BG; b), according to cSVD burden score group (0: blue; 1: red; ≥2: yellow). Pulsatility index (PI) of the perforating arteries of the CSO (c) and BG (d), according to cSVD burden score group. Blood-oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) in the cortical gray matter (e). BOLD-CVR in the NAWM (f). All data are unadjusted in box plots with medians and 25th and 75th percentiles and whiskers indicating the 95% confidence intervals. p values are shown for Tukey’s HSD post hoc tests after three-way ANOVA with correction for age and sex. Bonferroni correction was applied for multiple testing for each dependent variable across cSVD lesion burden groups (n = 3), and a p value ≈0.0167 was considered statistically significant. N.S., no significance.