Fibre microstructure and mechanics of atherosclerotic plaques

Atherosclerosis is characterised by the progressive growth of a plaque, where a fibrous cap covers a lipid-rich core. Rupture of this fibrous cap can lead to thrombosis and a heart attack or stroke. This dissertation considered the role of plaque microstructure in the mechanics and rupture risk of atherosclerotic plaques. Fibre structures in human atherosclerotic plaques were characterised through scanning electron microscopy, histology, and image processing. Local primary fibre orientation and the fibre dispersion were calculated. Plaque shoulder regions, where rupture is most frequent, had higher fibre dispersion and were more misaligned with the lumen wall. Comparative FE models were made from the plaque geometries and fibre structures found by image processing: one with evenly dispersed fibres (isotropic) and one with a preferred fibre orientation (anisotropic). The isotropic and anisotropic FE models predicted significantly different stresses. Stresses were often highest in the shoulder regions. Anisotropic stresses were calculated relative to fibres: axial stresses were highest, shear stresses were intermediate, and transverse stresses were low. Since the tissue is strongest in the fibre direction (axially), axial and shear failure modes should be considered. Material tests (uniaxial tension, trouser tear, and notched specimen) were used to characterise material properties in healthy porcine arteries. Fibre structures were evaluated by histology, multiphoton microscopy, and image processing. Samples were stiffer circumferentially and toughest against radial tears. Fractures progressed between fibres, rather than by breaking them. Material properties and fracture mechanisms were explained by fibre structures. In summary, atherosclerosis altered the fibre structure of the arteries, in ways that were mechanically significant and that explained clinical observations. Summary of Key Findings Factor Effect and Justification Source Triangle Potential for high stresses deeper into tissue Figures of Fibres Possible delamination plane (shearing) 2.1, 3.8, at Shoulder Seam closer to lumen may be higher risk 4.2, 4.5 Plaque Type Coronary smaller than carotid Tables on Stresses Some significantly different stresses 3.1, 4.4, Shoulders more at risk in coronary 4.5 Shoulders and fibrous cap similar risk in carotid Plaque Geometry more important for coronary Tables Geometry Coronary: sharp shoulder curvature (R2 ≈ 0.4) 4.8, 4.9 on Stresses Carotid: fibrous cap thickness (R2 ≈ 0.15) Fibre Coronary: fibre structure a limited factor Table Structure Carotid: fibre misalignment (R2 ≈ 0.2-0.3) 4.10 on Stresses Interactions and coupling with geometry Isotropic Explain about half (R2 ≈ 0.3-0.7) of variability Table FE Models in stresses from anisotropic FE models 4.11 Shear Probable failure mode: shear between fibres Figures Failure Shear stresses higher than transverse 2.2, 4.10, Fissures between fibres observed in SEM images 4.11, 5.9 Tearing ≈ 3× tougher across then between fibres Anisotropy Toughness probably decreases with anisotropy Figures on Tearing Anisotropy: stiffness and fibre structure 5.15, 5.16 Stretch on Fibres rearrange to direction of applied loads Figures Fibre Primary fibre orientation and dispersion change 6.5, 6.6, Structure May explain strain-stiffening of material 6.8, 6.9 Fibre Fibres recruited near and bridge over crack tips Figures Toughening Fibre cross-links fail, not fibres themselves 6.12-6.16 Mechanisms Mechanisms dependent on initial fibre structure