Shear-induced platelet activation and its relationship with blood flow topology in a numerical model of stenosed carotid bifurcation
Highlights
Study of the local hemodynamics in a realistic image-based model of stenosed carotid artery. ► Influence of the stenotic disturbed flow on transport and activation of platelets. ► Flow-induced level of platelet activation predicted by adopting a cumulative blood damage model. ► Stenosis enhances the risk for flow-induced activation of platelet. ► Helical flow patterns act as protective factors against platelet activation.
Introduction
Artery disease is one of the most common healthcare problems in the Western world [1]. In particular, vascular pathologies responsible for the narrowing of arterial lumen could lead to the development of atherosclerotic plaques on vessel walls and/or formation of thrombus, ultimately provoking thromboembolic events or vessel occlusion. One of the mechanisms involved in these phenomena is platelet activation. It is well known that fluid forces and local flow features, as well as concentrations of coagulation factors and platelet agonists, regulate the function of platelets, and abnormal levels of these species may lead to platelet activation, aggregation and adhesion to the vessel wall [2].
Regarding flow-induced mechanical stimulation of platelets, numerous studies [3], [4], [5], [6], [7], [8] have demonstrated that (1) high rates of shear, and (2) abnormal flow patterns, such as flow stagnation or recirculation characterized by low shear and longer retention time, can enhance hemodynamic platelet activation locally. In stenosed arteries the fact that the flow accelerates in the proximal region, and reaches a maximum velocity at the throat before decelerating in the poststenotic region, leads to further flow disturbance and to an appreciable reduction of blood transport to the region beyond the narrowing.
This local hemodynamic feature of stenosed arteries leads to serious circulatory disorders which influence further development of the disease [9], [10], [11]: in the presence of stenosis, varying and abnormal shear stress levels are present at the arterial wall and within the bulk, with high shear stress values in the region proximal to the stenosis and low and oscillatory shear stress values in the distal region [5], [6], [12], [13], [14]. While regions of low and/or oscillating wall shear stress (WSS) are vulnerable to development of endothelium damage, atherosclerosis, intimal thickening, and hyperplasia, sites exposed to shear values higher than the physiological ones might be predisposed to mechanically induced blood trauma, with consequences on platelet activation, aggregation, or lytic processes [5], [6], [15], [16].
In this context, it is clear that the study of the dynamics of blood flow and platelet transport in pathological vessels is crucial to gain insight into the role of abnormal flow in the development of the disease [7]. Several works focused on the flow-induced mechanisms leading to platelet activation in models of stenosed vessels. Among them, Bluestein and co-workers [5], [6] analyzed the mechanisms involved in platelet kinetics within simplified models of stenosed coronary vessels, aiming to determine whether platelets were brought beyond the activation threshold as a consequence of their exposition to shear forces.
In view of the above considerations, in the present study we report for the first time a comprehensive analysis of the local hemodynamics within a realistic, image-based model of stenosed carotid artery bifurcation, focused not only on the abnormal flow caused by the stenosis, but also on its influence on platelet transport. The flow field within a model of stenosed carotid bifurcation, reconstructed from medical images, was resolved using computational fluid dynamics (CFD), and the local hemodynamics was investigated by calculating (1) one well consolidated WSS-based hemodynamic descriptor, which gives quantitative measure of the interaction between blood and vessel wall, and (2) a prediction of the flow-induced activation of transported platelets, evaluated using an experimentally tuned and validated Lagrangian-based model of mechanically-induced blood damage (proposed by Grigioni and colleagues [17], and adapted by Nobili et al. [18] by correlating the model predictions with in vitro platelet activation measurements). To complete the study, motivated by considerations on bulk flow structures primarily responsible for transport and mixing in fluids, and by recent findings on the reduction of platelet adhesion due to intentionally induced helical flow in a glass tube [19], we investigated if the onset and the evolution of helical patterns in the bulk flow might be instrumental in moderating/enhancing the burden of shear-induced activation of platelets in stenosed carotid bifurcations. To do it, a bulk flow-descriptor, which is capable of reducing the inherent complexity associated with four-dimensional (4D) flow fields in arteries, was used [17], [20], [21], [22], [23]. The proposed comprehensive approach may be helpful in acquiring more knowledge about the role played by platelet transport in diseased arteries.
Section snippets
Computational model
An image-based model of the left carotid bifurcation of a 74 year old male, presenting a 51% stenosed proximal internal carotid artery (ICA), was reconstructed from magnetic resonance (MR) images (Fig. 1(A)) [24]. In detail, using a 1.5T MR scanner (Siemens Sonata), transaxial T1-weighted fast spin echo (FSE) images were acquired. In correspondence of plaque location, additional higher resolution T1 and T2-weighted images were also acquired. The lumen was segmented based on the region-growing
Abnormal flow at the lumen surface
The mean and maximum absolute TAWSS values over the plaque surface were 1.61 and 4.11 Pa respectively, compared with 3.21 and 9.00 Pa for the whole geometry [24]. In order to point out the differences of TAWSS values over the plaque, Fig. 2(A) shows TAWSS distributions with TAWSS color-scale terminating at highest value found over the plaque area. As expected, low TAWSS values were found at the proximal ICA, where the plaque is located, and also at the opposite side (proximal ECA). In detail,
Discussion
Abnormal flow plays a primary role in the onset of vascular pathologies not only as a consequence of the action of non-physiological friction forces exerted at the luminal surface (3D phenomenon), but also because of the alterations in the transport of atherogenic particles [28], such as platelets (4D phenomenon). In particular, the hemodynamics within a stenosed carotid bifurcation is a 4D process that involves interaction, reconnection and continuous re-organization of structures in the
Acknowledgments
The authors are greatly thankful to Dr. Raffaele Ponzini for his support in movie creation.
Diana Massai is a Postdoctoral Fellow at the Industrial Bioengineering Group of the Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Italy.
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Diana Massai is a Postdoctoral Fellow at the Industrial Bioengineering Group of the Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Italy.
Giulia Soloperto is a Postdoctoral Fellow at the National Research Council Bioengineering Division, Institute of Clinical Physiology, Lecce, Italy.
Diego Gallo is a Postdoctoral Fellow at the Industrial Bioengineering Group of the Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Italy.
Xiao Yun Xu is Professor of Biofluid Mechanics and Director of Postgraduate Studies, Department of Chemical Engineering, Imperial College London, United Kingdom.
Umberto Morbiducci is Adjunct Professor of Cardiovascular Biomechanics at the Politecnico di Torino, and works in the Industrial Bioengineering Group of the Department of Mechanical and Aerospace Engineering at Politecnico di Torino, Italy.