Rationale and Objectives: While calcification is a highly prevalent component in atherosclerotic extracranial carotid arteries and is known to impact plaque stability, the link between carotid calcification and ischemic events is yet to be identified. We aimed to investigate the associations of geometric features of carotid calcifications, and their temporal changes, with ischemic events. Materials and Methods: We retrospectively analyzed 128 mildly stenotic carotid arteries (Plaque At Risk study) from 64 patients with recent ischemic event, using multi-detector computed tomography angiography data at baseline and after 2 years. The 3D artery and calcification geometries were reconstructed with a semi-automatic pipeline, and an in-depth calcification morphometric assessment was performed. We examined the distribution of the calcification morphometrics and their temporal changes and investigated their associations with ischemic events at the time of inclusion, using generalized linear mixed models. Results: At baseline, compared to contralateral asymptomatic arteries, symptomatic carotids had more calcification bodies (mean [95%CI]: 1.9 [1.4–2.6] vs. 1.6 [1.2–2.2]). These calcifications were smaller (mean area [95%CI]: 3.7 mm² [2.9–5.1] vs. 4.5 mm² [3.5–5.8]) and narrower (mean width [95%CI]: 2.7 mm [2.3–3.4] vs. 3.1 mm [2.5–3.6]). At 2-year follow-up, adjusting for baseline measurements, these calcifications were smaller (mean width [95%CI]: 2.9 mm [2.5–3.5] vs. 3.3 mm [2.7–3.7]) and longer (mean [95%CI]: 8.6 mm [7.1–10.5] vs. 7.5 mm [6.3–9.5]) compared to asymptomatic side. Conclusion: Symptomatic carotid arteries presented more and smaller calcifications with a tendency to grow more in the longitudinal artery direction, providing insights into the role of carotid calcifications in ischemic events.

Background: Intracranial artery calcification detected on CT imaging is a recognized risk factor for ischemic cerebrovascular diseases, but the underlying etiology of this association remains unclear. Differences in objective morphometric characteristics of these calcifications may partially explain this association, yet these measurements are largely absent in the literature. We investigated intracranial artery calcification morphometry in patients with recent anterior ischemic stroke or TIA, assessing potential differences between calcifications in both intracranial carotid arteries (ICAs) located ipsilateral and contralateral to the cerebral ischemia. Methods: Among 100 patients (mean age 69.6 (SD 8.8) years) presenting to academic neurology departments, 3D reconstructions of both ICAs were based on clinical CT-angiography images. On these reconstructions, a luminal centerline and cross-sections perpendicular to this centerline were created, facilitating the assessment of calcification morphometry, spatial orientation and stenosis severity. Differences in calcification characteristics between ICAs were assessed using two-sided Wilcoxon signed-rank and χ² tests. Results: Among 200 arteries, a median of four (IQR 2–6) individual calcifications were counted, with a mean area of 1.8 (IQR 1.2–2.7) mm², a mean arc width of 43.5 (IQR 32.3–53.2) degrees, and median longitudinal extent of 15.4 (IQR 5.9–27.0) mm. Calcifications were most often present in the anatomical C4 section (56.0%), with predominantly posterosuperior orientation (38.5%) and 42.0% had a local stenosis severity > 70%. None of these aspects significantly differed between ICAs, and this remained after restricting analyses to patients with undetermined etiology. Conclusions: We found no differences in morphometrical or spatial aspects of calcifications between ICAs ipsilateral and contralateral to the cerebral ischemia.

Background and aims: Local biomechanical factors are known to influence atherosclerosis in extracranial carotid arteries. While the role of some flow-driven biomechanical factors has been investigated, the influence of pressure-driven mechanical wall stress (MWS) has received limited attention. In this study, the association of the pressure-driven and flow-driven biomechanical factors with carotid atherosclerosis was examined. Methods: Carotid arteries (n = 150) with mild-to-moderate stenosis from 75 symptomatic patients (Plaque-At-Risk study) were imaged using multi-detector computed tomography angiography (MDCTA) at the time of inclusion and after 2 years. Structural changes in carotid wall and calcifications were quantified from MDCTA data while the local baseline biomechanical factors in the carotids were determined using fluid-structure interaction (FSI) computational models. The associations of the local pressure-driven and flow-driven biomechanical factors with the carotid wall and calcification changes were studied using Generalized Linear Mixed models. Results: Over two years, plaque sectors, with calcified and non-calcified sectors combined, exhibited minimal change in wall thickness, likely due to medical treatment. High MWS was associated (p < 0.001) with a reduction in plaque thickness. In calcified plaque sectors, high MWS and low oscillatory shear index (OSI) were associated (p < 0.001) with greater calcification thickness increase. The distance between the lumen and calcification decreased over time, especially in the sectors exposed to high time-averaged wall shear stress (TAWSS) and high MWS. Conclusions: Our results suggest that the pressure-driven local MWS and flow-driven OSI and TAWSS significantly correlate with the development of calcified and non-calcified plaques in carotid arteries. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01208025.

Introduction: Ischemic stroke incidence varies significantly with respect to sex and cardiovascular risk factors (CVRFs), a relationship that it is not well understood. Calcification in carotid atherosclerosis is known to impact plaque stability, potentially linked to ischemic stroke. The objective was to assess the in-depth calcification morphometrics within extracranial carotid atherosclerosis, their temporal changes, and associations with sex and CVRFs. Methods: Carotid arteries (n = 144) with confirmed atherosclerosis and mild-to-moderate stenosis from 72 symptomatic patients (Plaque-At-Risk study) with recent ischemic event due to ischemia in the territory of a carotid artery were imaged using multidetector computed tomography angiography (MDCTA) at baseline and after 2 years. The lumen, vessel wall, and calcifications were segmented semiautomatically, and the carotid geometries were 3D reconstructed. A comprehensive morphometric assessment of carotid calcifications was performed on the baseline and followup scans. We investigated distributions of these metrics and their associations with sex and CVRFs using generalized linear mixed models. Results: Our findings suggest that women have larger (4.5 mm2 [95% CI: 3.2-6.2] vs. 3.2 mm2 [95% CI: 2.4-4.2]) calcifications, located closer to the lumen (0.6 mm [95% CI: 0.4-0.8] vs. 0.9 mm [95% CI: 0.7-1.2]) in contrast to men at baseline and follow-up, adjusted for baseline measurements. At the baseline, nonsmokers had larger (5.3 mm2 [95% CI: 3.7-7.5] vs. 3.2 mm2 [95% CI: 2.3-4.4]) and longer (5.7 mm [95% CI: 4.1-7.3] vs. 2.4 mm [95% CI: 1.6-3.6]) calcifications than the current smokers. Diabetic patients had thicker (1.1 mm [95% CI: 0.8-1.3] vs. 0.8 mm [95% CI: 0.7-0.9]) carotid calcifications at baseline. Conclusion: Our in-depth analyses exposed several geometric features of carotid calcifications associated with sex and CVRFs and provided further insight into the pathophysiology of carotid atherosclerosis.