BACKGROUND AND PURPOSE: Carotid webs are increasingly recognized as an important cause of (recurrent) ischemic stroke in patients without other cardiovascular risk factors. Hemodynamic flow patterns induced by these lesions might be associated with thrombus formation. The aim of our study was to evaluate flow patterns of carotid webs using computational fluid dynamics. MATERIALS AND METHODS: Patients with a carotid web in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) were selected for hemodynamic evaluation with computational fluid dynamics models based on lumen segmentations obtained from CT angiography scans. Hemodynamic parameters, including the area of recirculation zone, time-averaged wall shear stress, transverse wall shear stress, and the oscillatory shear index, were assessed and compared with the contralateral carotid bifurcation. RESULTS: In our study, 9 patients were evaluated. Distal to the carotid webs, recirculation zones were significantly larger compared with the contralateral bifurcation (63 versus 43 mm 2 , P ϭ .02). In the recirculation zones of the carotid webs and the contralateral carotid bifurcation, time-averaged wall shear stress values were comparable (both: median, 0.27 Pa; P ϭ .30), while transverse wall shear stress and oscillatory shear index values were significantly higher in the recirculation zone of carotid webs (median, 0.25 versus 0.21 Pa; P ϭ .02 and 0.39 versus 0.30 Pa; P ϭ .04). At the minimal lumen area, simulations showed a significantly higher time-averaged wall shear stress in the web compared with the contralateral bifurcation (median, 0.58 versus 0.45 Pa; P ϭ .01). CONCLUSIONS: Carotid webs are associated with increased recirculation zones and regional increased wall shear stress metrics that are associated with disturbed flow. These findings suggest that a carotid web might stimulate thrombus formation, which increases the risk of acute ischemic stroke. ABBREVIATIONS: CFD ϭ computational fluid dynamics; IQR ϭ interquartile range; OSI ϭ oscillatory shear index; TAWSS ϭ time-averaged wall shear stress; TransWSS ϭ transverse wall shear stress; WSS ϭ wall shear stress

Background and Purpose: Incidence of ischemic stroke differs between men and women, with substantially higher rates in men. The underlying mechanism of this difference remains poorly understood but may be because of differences in carotid atherosclerosis. Using an in-depth imaging-based approach, we investigated differences between carotid plaque composition and morphology in male and female patients with stroke, taking into account differences in total plaque burden. Additionally, we investigated all possible within-artery combinations of plaque characteristics to explore differences between various plaque phenotypes. Methods: We included 156 men and 68 women from the PARISK (Plaque At Risk) study, a prospective cohort study of patients with recent ischemic cerebrovascular symptoms and <70% ipsilateral carotid stenosis. Plaque characteristics (intraplaque hemorrhage [IPH], lipid-rich necrotic core [LRNC], calcifications, thin-or-ruptured fibrous cap, ulcerations, total plaque volume) were assessed with magnetic resonance imaging and multidetector-row computed tomography angiography. We used multivariable logistic and linear regression analyses to assess sex differences in plaque characteristics. Results: We found significant difference in total plaque volume between men and women (β=22.9 mm 3 [95% CI, 15.4–30.5]; mean volume in men 1399±425 mm 3 , in women 1011±242 mm 3 ). Additionally, men were more likely to have IPH (odds ratio [OR]=2.8 [95% CI, 1.3–6.3]; IPH proportion in men 49%, in women 16%) and LRNC (OR=2.4 [95% CI, 1.2–4.7]; LRNC proportion in men 73%, in women 41%) even after adjustment for total plaque volume. We found no sex-specific differences in plaque volume-corrected volumes of IPH, LRNC, and calcifications. In terms of coexistence of plaque characteristics, we found that men had more often a plaque with coexistence of calcifications, LRNC, and IPH (OR=2.7 [95% CI, 1.2–7.0]), with coexistence of thin-or-ruptured fibrous cap/ulcerations, LRNC, and IPH (OR=2.4 [95% CI, 1.1–5.9]), and with coexistence of all plaque characteristics (OR=3.0 [95% CI, 1.2–8.6]). Conclusions: In symptomatic patients with mild-to-moderate carotid stenosis, men are more likely to have a high-risk carotid plaque with IPH and LRNC than women, regardless of total plaque burden. Men also have more often a plaque with multiple vulnerable plaque components, which could comprise an even higher stroke risk. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01208025.

The role of wall shear stress (WSS) in atherosclerotic plaque development is evident, but the relation between WSS and plaque composition in advanced atherosclerosis, potentially resulting in plaque destabilization, is a topic of discussion. Using our previously developed image registration pipeline, we investigated the relation between two WSS metrics, time-averaged WSS (TAWSS) and the oscillatory shear index (OSI), and the local histologically determined plaque composition in a set of advanced human carotid plaques. Our dataset of 11 carotid endarterectomy samples yielded 87 histological cross-sections, which yielded 511 radial bins for analysis. Both TAWSS and OSI values were subdivided into patient-specific low, mid, and high tertiles. This cross-sectional study shows that necrotic core (NC) size and macrophage area are significantly larger in areas exposed to high TAWSS or low OSI. Local TAWSS and OSI tertile values were generally inversely related, as described in the literature, but other combinations were also found. Investigating the relation between plaque vulnerability features and different combinations of TAWSS and OSI tertile values revealed a significantly larger cap thickness in areas exposed to both low TAWSS and low OSI. In conclusion, our study confirmed previous findings, correlating high TAWSS to larger macrophage areas and necrotic core sizes. In addition, our study demonstrated new relations, correlating low OSI to larger macrophage areas, and a combination of low TAWSS and low OSI to larger cap thickness.

Wall shear stress (WSS), the frictional force exerted on endothelial cells by blood flow, is hypothesised to influence atherosclerotic plaque growth and composition. We developed a methodology for image registration of MR and histology images of advanced human carotid plaques and corresponding WSS data, obtained by MRI and computational fluid dynamics. The image registration method requires four types of input images, in vivo MRI, ex vivo MRI, photographs of transversally sectioned plaque tissue and histology images. These images are transformed to a shared 3D image domain by applying a combination of rigid and non-rigid registration algorithms. Transformation matrices obtained from registration of these images are used to transform subject-specific WSS data to the shared 3D image domain as well. WSS values originating from the 3D WSS map are visualised in 2D on the corresponding lumen locations in the histological sections and divided into eight radial segments. In each radial segment, the correlation between WSS values and plaque composition based on histological parameters can be assessed. The registration method was successfully applied to two carotid endarterectomy specimens. The resulting matched contours from the imaging modalities had Hausdorff distances between 0.57 and 0.70 mm, which is in the order of magnitude of the in vivo MRI resolution. We simulated the effect of a mismatch in the rigid registration of imaging modalities on WSS results by relocating the WSS data with respect to the stack of histology images. A 0.6 mm relocation altered the mean WSS values projected on radial bins on average by 0.59 Pa, compared to the output of original registration. This mismatch of one image slice did not change the correlation between WSS and plaque thickness. In conclusion, we created a method to investigate correlations between WSS and plaque composition.