Assessment of Small Vessel Function Using 7T MRI in Patients With Sporadic Cerebral Small Vessel Disease: The ZOOM@SVDs Study

Abstract

Background and objectives: Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia, but little is known about disease mechanisms at the level of the small vessels. 7T-MRI allows assessing small vessel function in vivo in different vessel populations. We hypothesized that multiple aspects of small vessel function are altered in patients with cSVD and that these abnormalities relate to disease burden.

Methods: Patients and controls participated in a prospective observational cohort study, the ZOOM@SVDs study. Small vessel function measures on 7T-MRI included perforating artery blood flow velocity and pulsatility index in the basal ganglia and centrum semiovale, vascular reactivity to visual stimulation in the occipital cortex, and reactivity to hypercapnia in the gray and white matter. Lesion load on 3T-MRI and cognitive function were used to assess disease burden.

Results: Forty-six patients with sporadic cSVD (mean age ± SD 65 ± 9 years) and 22 matched controls (64 ± 7 years) participated in the ZOOM@SVDs study. Compared with controls, patients had increased pulsatility index (mean difference 0.09, p = 0.01) but similar blood flow velocity in basal ganglia perforating arteries and similar flow velocity and pulsatility index in centrum semiovale perforating arteries. The duration of the vascular response to brief visual stimulation in the occipital cortex was shorter in patients than in controls (mean difference -0.63 seconds, p = 0.02), whereas reactivity to hypercapnia was not significantly affected in the gray and total white matter. Among patients, reactivity to hypercapnia was lower in white matter hyperintensities compared with normal-appearing white matter (blood-oxygen-level dependent mean difference 0.35%, p = 0.001). Blood flow velocity and pulsatility index in basal ganglia perforating arteries and reactivity to brief visual stimulation correlated with disease burden.

Discussion: We observed abnormalities in several aspects of small vessel function in patients with cSVD indicative of regionally increased arteriolar stiffness and decreased reactivity. Worse small vessel function also correlated with increased disease burden. These functional measures provide new mechanistic markers of sporadic cSVD.

Figure 1. Flowchart of Participant Inclusions and Exclusions

Reasons for screen failures are no lacune lesion on study MRI for 3 patients recruited because of a clinical diagnosis lacunar infarct, objective cognitive deficits for one control, an occlusion of the internal carotid on study MRI for one control, and 2 controls who had signs of cSVD on study MRI. Reasons for not acquired 7T-MRIs are scanning was too much a burden for 4 patients and one patient and 2 controls were claustrophobic in the 7T-MRI.

Figure 2. Flowchart Showing Reasons for Excluded Scans per Small Vessel Function Measure

Reasons for not acquired measurements are the participant could not continue the scanning session for the 2D-Qflow scan (1); glasses that would not fit in the head coil (3), very bad vision of the participant (2), or unable to finish the sequence (1) for the BOLD short visual stimulus scan; and equipment not yet available (5) or participants unwilling or unable to do or finish the hypercapnia challenge (4) for the BOLD hypercapnia scan.

Figure 3. Mean and Individual Participants Blood Flow Velocity Traces

The mean blood flow velocity (solid lines) and standard errors of the mean (shaded lines) in perforating arteries in the centrum semiovale (A) and basal ganglia (C) for patients with sporadic cSVD and controls. Individual blood flow velocity traces in perforating arteries in the centrum semiovale (B) and basal ganglia (D) for sporadic cSVD in red and controls in blue.

Figure 4. Hemodynamic Response Functions After Visual Stimulation

(A) Shown are the average hemodynamic response function estimates (solid lines) and standard errors of the mean (shaded areas) after 500 ms visual stimulation (black bar) for patients with sporadic cSVD (red) and controls (blue). The horizontal dotted lines indicate the full width at half maximum which was significantly shorter in patients (mean ± SD: 3.37 ± 0.97) than in controls (4.00 ± 0.80, p = 0.02). (B) Individual BOLD hemodynamic response function estimates after 500 ms visual stimulation for all patients with sporadic cSVD and controls.