A Method to Study the Correlation Between Local Collagen Structure and Mechanical Properties of Atherosclerotic Plaque Fibrous Tissue

Abstract

The rupture of atherosclerotic plaques in coronary and carotid arteries is the primary cause of fatal cardiovascular events. However, the rupture mechanics of the heterogeneous, highly collagenous plaque tissue, and how this is related to the tissue's fibrous structure, are not known yet. Existing pipelines to study plaque mechanics are limited to obtaining only gross mechanical characteristics of the plaque tissue, based on the assumption of structural homogeneity of the tissue. However, fibrous plaque tissue is structurally heterogeneous, arguably mainly due to local variation in the collagen fiber architecture.The mechano-imaging pipeline described here has been developed to study the heterogeneous structural and mechanical plaque properties. In this pipeline, the tissue's local collagen architecture is characterized using multiphoton microscopy (MPM) with second-harmonic generation (SHG), and the tissue's failure behavior is characterized under uniaxial tensile testing conditions using digital image correlation (DIC) analysis. This experimental pipeline enables correlation of the local predominant angle and dispersion of collagen fiber orientation, the rupture behavior, and the strain fingerprints of the fibrous plaque tissue. The obtained knowledge is key to better understand, predict, and prevent atherosclerotic plaque rupture events.

The interplay of collagen, macrophages, and microcalcification in atherosclerotic plaque cap rupture mechanics

“…Regarding collagen, emerging studies focus on the mechanical properties of collagen using a bottom-up approach studying nanoscale collagen mechanics [ 80 ], to be able to link this to mesoscale. In addition, increasing attention is being paid to the differences in global and local mechanical behavior [ 57 , 241 ]. With respect to microcalcification, in-depth histological or micro-CT analyses of patient material, assessing microcalcification clustering, particle shape and density, are lacking.…”

A tissue-engineered model of the atherosclerotic plaque cap: Toward understanding the role of microcalcifications in plaque rupture

“…Before testing, samples were rinsed in PBS and imaged with a high frequency, high spatial resolution ultrasound system (VEVO 3100, FUJIFILM VisualSonics, Canada) using a linear transducer (MX550) to assess the dimensions of the central region of the sample. For uniaxial tensile testing, a custom-designed set-up 46,47 equipped with a 20 N load cell (LCMFD-20N, Omega Engineering, USA) was used. The samples were placed, in the uniaxial tensile tester using the Velcro constraints, and the tests were performed while the samples were submerged in PBS at 37 °C.…”