Global and local analysis of the mechanical and structural characteristics of carotid atherosclerotic plaques for rupture risk assessment

Abstract

The rupture of atherosclerotic plaques present in vital arteries is the main trigger of fatal cardiovascular events, such as heart attacks and strokes. Plaque rupture is a mechanical failure of the fibrous plaque tissue that ensues upon large deformations of the tissue, induced by the blood pressure. Current knowledge on the rupture characteristics of plaque tissue is, however, scarce and limited to global, aggregate tissue properties, although plaque rupture is a local phenomenon. Hence, local mechanical and structural evaluations of the heterogeneous, highly collagenous plaque tissue are required for better understanding the plaque rupture.

To achieve this, a combination of mechanical and structural analyses was performed in this study. The collagen structure of human carotid plaques was imaged by means of Multiphoton microscopy using Second-Harmonic Generation signals (MPM-SHG), and it was characterized in terms of fiber orientation and dispersion. Subsequently, the imaged plaques were subjected to uniaxial tensile tests until rupture to characterize their mechanical response. Apart from the traditional global analysis, the local mechanical response was analyzed through Digital Image Correlation (DIC). This way, the structural heterogeneity of the plaque tissue was assessed and the role of collagen fiber organization in plaque mechanics was investigated locally.

The structural analysis of the plaque tissue samples demonstrated a predominant overall fiber orientation along the circumferential direction of the artery. Yet, high local variability in collagen orientation and dispersion was measured. The global, average mechanical response of the plaques showed a non-linear behavior, typical to many soft biological tissues and the local mechanical analysis demonstrated highly heterogeneous strain distributions in the plaques. Furthermore, regions that were about to rupture, showed higher tensile strains compared to the overall plaque strain, implying the possibility of establishing strain as a predictive metric for rupture. Whereas the global analysis did not yield any important correlation between the overall collagen structural parameters and the global mechanical tissue response, the local analyses indicated that the regional predominant fiber angle might influence the regional strain, and probably the plaque rupture risk.