Nonlinear multiscale analysis of coronary atherosclerotic vulnerable plaque artery: fluid-structural modeling with micromechanics.

A unique three-dimensional (3D) computational multiscale modeling approach is proposed to investigate the influence of presence of microcalcification particles on the stress field distribution in the thin cap layer of a coronary atherosclerotic vulnerable plaque system. A nested 3D modeling analysis framework spanning the multiscale nature of a coronary atherosclerotic vulnerable plaque is presented. At the microscale level, a micromechanical modeling approach, which is based on computational finite-element (FE) representative unit cell, is applied to obtain the homogenized nonlinear response of the calcified tissue. This equivalent response effectively allows the integration of extremely small microcalcification inclusions in a global biomechanical FE model. Next, at the macroscale level, a 3D patient-based fluid-structure interaction FE model, reconstructing a refined coronary artery geometry with calcified plaque lesion, is generated to study the mechanical behavior of such multi-component biomechanical system. It is shown that the proposed multiscale modeling approach can generate a higher resolution of stress and strain field distributions within the coronary atherosclerotic vulnerable plaque system and allow the assessment of the local concentration stress around the microcalcifications in plaque cap layers. A comparison of stress field distributions within cap layers with and without inclusion of microcalcifications is also presented.

Controlling cardiac transport and plaque formation.

Macro-particles transported in the bloodstream, such as LDL particles and macrophages, are considered to be one of the initiating factors of atherosclerotic plaque development. LDL infiltration from the bloodstream into a blood vessel's wall, whether the coronary, peripheral, or carotid arteries, is considered a major inflammatory factor, recruiting macrophages from the blood flow and leading to the formation of vulnerable atherosclerotic plaques. Infiltration sites are influenced by patterns of blood flow, as regions of lower shear stresses and high oscillations may give rise to higher infiltration rates through the endothelium, exacerbating the growth of a plaque and its tendency to rupture. Previous studies demonstrated a high prevalence of rupture sites proximal to the minimum lumen area, which raised the question of whether the existence of two distinct adjacent plaques, in which the distal plaque is more severe, can give rise to hemodynamic forces that can push the non-stenotic plaque to rupture. Models of the coronary arteries with one and two eccentric and concentric stenotic narrowings were built into a closed flow loop. The single stenosis model had a 75% area reduction narrowing (representing the vunerable atherosclerotic plaque) with relevant elastic properties. The double stenosis model included an additional distal 84% area reduction narrowing. The flow in the area between the two stenoses was recorded and analyzed using continuous doppler particle image velocimetry (CDPIV), together with the hydrostatic pressure acting on the proximal plaque. Results indicated that the combined shear rates and pressure effects in a model with a significant distal stenosis can contribute to the increase in plaque instability by LDL and enhanced macrophage uptake. The highly oscillatory nature of the disturbed flow near the shoulder of the vulnerable atherosclerotic plaque enriches its lipid soft core, and the high hydrostatic pressures acting on the same lesion in this geometry induce high internal maximal stresses that can trigger the rupture of the plaque.