A Methodology to Analyze Changes in Lipid Core and Calcification Onto Fibrous Cap Vulnerability: The Human Atherosclerotic Carotid Bifurcation as an Illustratory Example

Abstract

A lipid core that occupies a high proportion of the plaque volume in addition to a thin fibrous cap is a predominant indicator of plaque vulnerability. Nowadays, noninvasive imaging modalities can identify such structural components, however, morphological criteria alone cannot reliably identify high-risk plaques. Information, such as stresses in the lesion's components, seems to be essential. This work presents a methodology able to analyze the effect of changes in the lipid core and calcification on the wall stresses, in particular, on the fibrous cap vulnerability. Using high-resolution magnetic resonance imaging and histology of an ex vivo human atherosclerotic carotid bifurcation, a patient-specific three-dimensional geometric model, consisting of four tissue components, is generated. The adopted constitutive model accounts for the nonlinear and anisotropic tissue behavior incorporating the collagen fiber orientation by means of a novel and robust algorithm. The material parameters are identified from experimental data. A novel stress-based computational cap vulnerability index is proposed to assess quantitatively the rupture-risk of fibrous caps. Nonlinear finite element analyses identify that the highest stress regions are located at the vicinity of the shoulders of the fibrous cap and in the stiff calcified tissue. A parametric analysis reveals a positive correlation between the increase in lipid core portion and the mechanical stress in the fibrous cap and, hence, the risk for cap rupture. The highest values of the vulnerability index, which correlate to more vulnerable caps, are obtained for morphologies for which the lipid cores were severe; heavily loaded fibrous caps were thus detected. The proposed multidisciplinary methodology is able to investigate quantitatively the mechanical behavior of atherosclerotic plaques in patient-specific stenoses. The introduced vulnerability index may serve as a more quantitative tool for diagnosis, treatment and prevention.

Prediction of fibre architecture and adaptation in diseased carotid bifurcations

“…Maximum stresses in the plaque have been found at the shoulders by several investigators (Li et al 2006;Gao et al 2009;Kiousis et al 2009;Creane et al 2010); here, we see that changing the fibre configuration within the healthy arterial wall significantly alters the stress in these critical locations of the plaque (see Fig. 7).…”

“…The identification of plaques vulnerable to rupture prior to the onset of symptoms would have major clinical advantages. Several studies have attempted to correlate the stresses within the plaque to its vulnerability using patient-specific finite element (FE) analyses (Li et al 2006;Tang et al 2008;Gao et al 2009;Kiousis et al 2009;Creane et al 2010). A significant limitation of many of these studies (Li et al 2006;Tang et al 2008;Gao et al 2009;Creane et al 2010) is the use of an isotropic material model given that it is known that the arterial wall behaves anisotropically (Rhodin 1980;Patel et al 1969;Holzapfel et al 2002) and since this may significantly alter the predicted stresses (Rodriguez et al 2008).…”

“…Hariton et al (2007b) and Alastrue et al (2010) calculated the principal stress directions from an isotropic analysis, setting fibre directions at an angle between the first and second principal directions of stress. Kiousis et al (2009) and Mortier et al (2010) used geometric systems for defining fibre directions with a local basis created in each element of the FE mesh and the fibre directions set at an angle between the circumferential and axial directions.…”

Constitutive modelling of arteries

“…It turns out that the resulting distributions of the wall stresses are strongly dependent on the stent design, and it was shown how a stent design should be modified to reduce the maximum wall stresses. In addition, Kiousis et al (2009) proposed a computational methodology to analyse the effect of changes in the lipid pool and calcification on wall stresses and on the collagenous cap vulnerability in a human carotid bifurcation. They found a positive correlation between the increase of lipid pool and the mechanical stress in the collagenous cap, and hence an increased risk of cap rupture.…”

Cholesterol Is Associated with the Presence of a Lipid Core in Carotid Plaque of Asymptomatic, Young-to-Middle-Aged African Americans with and without HIV Infection and Cocaine Use Residing in Inner-City Baltimore, Md., USA

“…Carotid plaque vulnerability to rupture has been reported to be associated with stroke and other cerebrovascular events [11,12,13] and a lipid core with a thin fibrous cap that occupies a high proportion of the plaque volume is a predominant indicator of plaque vulnerability [14]. It has been reported that cerebral events can be precipitated by plaque rupture resulting from fibrous cap foam cell infiltration and cap thinning, similar to the mechanism of coronary plaque rupture leading to myocardial events [15].…”