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.

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.

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 objective: Although the association of wall shear stress (WSS) with coronary artery disease has been well studied, that of mechanical wall stress (MWS) is mainly overlooked. In this study, we performed in-silico artery-specific modeling to investigate the involvement of both MWS and WSS in coronary artery disease. Methods: Fifteen coronary arteries from five adult familial hypercholesterolemic pigs were imaged by coronary computed tomography angiography, intravascular ultrasound, and optical coherence tomography at three time points (3, 9, and 12 months). Local WSS and MWS in 3 mm/45° sectors were determined using artery-specific computational models. The relationship of WSS and MWS with wall thickness change (ΔWT) over time was statistically analyzed using Generalized Linear Mixed models. Results: A positive ΔWT was measured in all sectors, where plaque sectors presented a greater ΔWT rate compared to plaque-free sectors. In plaque-free sectors, low WSS was associated with a higher ΔWT rate (p < 0.001). In plaque sectors, high MWS was associated with a higher ΔWT rate (p < 0.05), where ΔWT rate was, although slightly, even greater in the plaque sectors with lipid-rich necrotic core (p < 0.05). Conclusions: Our results from in-silico coronary-specific models suggest that WSS and MWS may play a dominant role at different stages of coronary artery disease. WSS may be more critical in the early stages of plaque formation while MWS might have greater significance in the progression of existing plaques.

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.