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Objective: Cerebral small vessel diseases (cSVDs) are a major cause of stroke and dementia. We used cutting‐edge 7T‐MRI techniques in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), to establish which aspects of cerebral small vessel function are affected by this monogenic form of cSVD. Methods: We recruited 23 CADASIL patients (age 51.1 ± 10.1 years, 52% women) and 13 age‐ and sex‐matched controls (46.1 ± 12.6, 46% women). Small vessel function measures included: basal ganglia and centrum semiovale perforating artery blood flow velocity and pulsatility, vascular reactivity to a visual stimulus in the occipital cortex and reactivity to hypercapnia in the cortex, subcortical gray matter, white matter, and white matter hyperintensities. Results: Compared with controls, CADASIL patients showed lower blood flow velocity and higher pulsatility index within perforating arteries of the centrum semiovale (mean difference − 0.09 cm/s, p = 0.03 and 0.20, p = 0.009) and basal ganglia (mean difference − 0.98 cm/s, p = 0.003 and 0.17, p = 0.06). Small vessel reactivity to a short visual stimulus was decreased (blood‐oxygen‐level dependent [BOLD] mean difference −0.21%, p = 0.04) in patients, while reactivity to hypercapnia was preserved in the cortex, subcortical gray matter, and normal appearing white matter. Among patients, reactivity to hypercapnia was decreased in white matter hyperintensities compared to normal appearing white matter (BOLD mean difference −0.29%, p = 0.02). Interpretation: Multiple aspects of cerebral small vessel function on 7T‐MRI were abnormal in CADASIL patients, indicative of increased arteriolar stiffness and regional abnormalities in reactivity, locally also in relation to white matter injury. These observations provide novel markers of cSVD for mechanistic and intervention studies. ANN NEUROL 2023;93:29–39 [ABSTRACT FROM AUTHOR]

Background: Blood flow velocity and pulsatility of small cerebral perforating arteries can be measured using 7T quantitative 2D phase contrast (PC) MRI. However, ghosting artifacts arising from subject movement and pulsating large arteries cause false positives when applying a previously published perforator detection method. Purpose: To develop a robust, automated method to exclude perforators located in ghosting artifacts. Study Type: Retrospective. Subjects: Fifteen patients with vascular cognitive impairment or carotid occlusive disease and 10 healthy controls. Field Strength/Sequence: 7T/cardiac‐gated 2D PC MRI. Assessment: Perforators were automatically excluded from ghosting regions, which were defined as bands in the phase‐encoding direction of large arteries. As reference, perforators were manually excluded by two raters (T.A., J.J.M.Z.), based on perforator location with respect to visible ghosting artifacts. The performance of both censoring methods was assessed for the number of (Nincluded), mean velocity (Vmean), and pulsatility index (PI) of the included perforators. Statistical Tests: For within‐method comparisons, inter‐ and intrarater reliability were assessed for the manual method, and test–retest reliability was assessed for both methods from repeated 2D PC scans (without repositioning). Intraclass correlation coefficients (ICCs) and their 95% confidence intervals (CIs) were determined for Nincluded, Vmean, and PI for all within‐method comparisons. The ICC to compare between the two methods was determined with the use of both (test–retest) scans using a multilevel nonlinear mixed model. Results: The automated censoring method showed a moderate to good ICC (95% CI) vs. manual censoring for Nincluded (0.73 [0.58–0.87]) and Vmean (0.90 [0.84–0.96]), and a moderate ICC for PI (0.57 [0.37–0.76]). The test–retest reliability of the manual censoring method was considerably lower than the interrater and intrarater reliability, indicating that scanner noise dominates the uncertainty of the analysis. Data Conclusion: The proposed automated censoring method can reliably exclude small perforators affected by ghosting artifacts. Level of Evidence: 3. Technical Efficacy Stage: 1. [ABSTRACT FROM AUTHOR]

Background: Net cerebrospinal fluid (CSF) flow through the cerebral aqueduct may serve as a marker of CSF production in the lateral ventricles, and changes that occur with aging and in disease.Purpose: To investigate the confounding influence of the respiratory cycle on net CSF flow and stroke volume measurements.Study Type: Cross-sectional study.Subjects: Twelve young, healthy subjects (seven male, age range 19-39 years, average age 28.3 years).Field Strength/sequence: Phase contrast MRI (PC-MRI) measurements were performed at 7T, with and without respiratory gating on expiration and on inspiration. All measurements were repeated.Assessment: Net CSF flow and stroke volume in the aqueduct, over the cardiac cycle, was determined.Statistical Tests: Repeatability was determined using the intraclass correlation coefficient (ICC) and linear regression analysis between the repeated measurements. Repeated measures analysis of variance (ANOVA) was performed to compare the measurements during inspiration/expiration/no gating. Linear regression analysis was performed between the net CSF flow difference (inspiration minus expiration) and stroke volume.Results: Net CSF flow (average ± standard deviation) was 0.64 ± 0.32 mL/min (caudal) during expiration, 0.12 ± 0.49 mL/min (cranial) during inspiration, and 0.31 ± 0.18 mL/min (caudal) without respiratory gating. Respiratory gating did not affect stroke volume measurements (41 ± 18, 42 ± 19, 42 ± 19 μL/cycle for expiration, no respiratory gating and inspiration, respectively). Repeatability was best during inspiration (ICC = 0.88/0.56/-0.31 for gating on inspiration/expiration/no gating). A positive association was found between average stroke volume and net flow difference between inspiration and expiration (R = 0.678/0.605, P = 0.015/0.037 for the first/second repeated measurement).Data Conclusion: Measured net CSF flow is confounded by respiration effects. Therefore, net CSF flow measurements with PC-MRI cannot in isolation be directly linked to CSF production.Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:433-444. [ABSTRACT FROM AUTHOR]