Internal carotid artery (ICA) stenoses are one of the major sources of ischemic stroke [
1]. They are attributed to traditional cardiovascular risk factors acting on the arterial wall over decades. However, ICA stenoses often develop asymmetrically [
2], suggesting that additional parameters such as carotid geometry and the specific distribution of wall shear stress (WSS) may be responsible for the development and progression of atherosclerosis [
3]. This is further supported by the observation that atherosclerosis is particularly concentrated at the outlet of arteries such as the carotid bulb while straight segments such as the common carotid artery or abdominal aorta are far less affected [
4‐
6]. This suggests that hemodynamic, geometric or genetic factors play an important role at arterial bifurcations or curvatures while cardiovascular risk factors are the dominant factor in straight vessels [
7]. Previous studies have shown that individual geometry, low WSS and high oscillatory shear index (OSI) at the carotid bifurcation could play a role in the development of atherosclerotic lesions [
7‐
9]. Studies in healthy subjects using computational fluid dynamics (CFD) and 4D flow cardiovascular magnetic resonance (CMR) demonstrated that these potentially atherogenic flow conditions predominantly occur at the posterior wall of the proximal ICA (bulb) [
4,
8,
10]. Interestingly, this coincides with the area where atherosclerotic plaques and stenoses typically occur [
7,
8,
10]. Furthermore, animal models revealed that WSS correlated with plaque composition, leading to unstable “high-risk” plaques in zones with low WSS [
11,
12]. Low WSS and high OSI obviously initiate atherosclerosis through endothelial damage resulting in increased susceptibility to wall injury and inflammation. Accordingly, this facilitates lipids to migrate into the vessel wall. By contrast, there is emerging evidence that high WSS possibly promotes intra-plaque hemorrhage, thinning of the fibrous cap and ultimately leads to plaque rupture [
3,
7,
13,
14].
Bifurcation geometry was proposed as an important factor for these hemodynamic conditions and considered as a potential surrogate parameter for atherosclerotic risk prediction. The analysis of computed tomography angiography (CTA) in 178 patients by Phan et al. [
15] underlined that geometry and anatomy enhance the risk of carotid stenosis independent of traditional vascular risk factors. This was confirmed by Bijari et al. [
16], who studied bifurcation geometry and wall thickness using CMR in > 1000 patients. However, three-dimensional (3D) blood flow, WSS and OSI were not investigated in either study. In turn, a study of 14 subjects, in which WSS was measured by CFD and 4D flow CMR, revealed that wall thickness at the bifurcation increased with decreasing WSS [
17]. However, the number of subjects was small and individual carotid geometry was not considered. Thus, to date there is no larger study that has investigated patients with carotid plaques by measuring the impact of both carotid geometry and WSS on carotid wall thickness.
Therefore, to study this fluid-structure interaction, we applied a comprehensive 3D-multi-contrast CMR protocol in a larger cohort of high-risk patients with carotid atherosclerosis and fused information on individual carotid geometry, WSS and OSI with wall thickness data at the ICA bulb. To study patients with atherosclerosis of various degrees we included small plaques up to 50% ICA stenosis and applied a plane- and segment-wise analysis strategy which is well suited for carotid wall thickness measurement and which was used as one outcome variable in the present study. We intended to identify independent risk factors for carotid atherosclerosis beyond traditional cardiovascular risk factors that can be used to detect high-risk patients for carotid artery atherosclerosis and to optimize their therapy in the future.