Fundamental insights into the biomechanics of atherosclerotic plaque tissue: Determining possible new diagnostic measures of plaque vulnerability
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Johnston, Robert Daniel, Fundamental insights into the biomechanics of atherosclerotic plaque tissue: Determining possible new diagnostic measures of plaque vulnerability, Trinity College Dublin.School of Engineering, 2022Download Item:
Abstract:
Carotid atherosclerotic plaque rupture is known to be a major contributor to ischaemic stroke cases. The development of atherosclerotic plaques within the vessel wall alters both the geometry and mechanical environment of the tissue. However, current diagnostic measures only focus on this change of geometry and not the mechanics of the tissue. Rupture can be observed as a purely mechanical event, whereby the forces exerted on the tissue exceeds its mechanical strength. Therefore, it is of utmost importance to establish a mechanically sensitive indicator that can establish atherosclerotic plaques which are more vulnerable to rupture. The aim of this thesis is to establish possible new diagnostic measures of plaque rupture vulnerability using experimental and computational methods.
In the literature, characterizing the location of high stress in the vessel wall has often been proposed as a potential indicator of structural weakness. This work shows that without consideration of the zero-pressure configuration, residual stress and patient specific material parameter there would be an overestimation in the stress calculated. These factors must therefore be included for accurate computational analysis. To understand the mechanics of atherosclerotic plaque tissue and the role collagen has in its mechanical behaviour, atherosclerotic plaque cap samples were pre-screened using small angle light scattering (SALS) to establish the predominant collagen fibre orientation and subsequently uniaxial tensile tests to failure were performed. These results show that when collagen fibres are in the predominantly axial direction they fail at lower stress, higher strain and have lower stiffness while the opposite is observed for tissue with fibres in the predominantly circumferential direction. This is important to note as being able to characterize the strain or establish the collagen fibre orientation, using in-vivo imaging techniques, could potentially aid in determining the overall mechanical strength of the tissue. From this mechanical knowledge, patient specific finite element models were created from in-vivo MRI images for both healthy volunteers and patients. In order to establish the dominant fibre orientation within these atherosclerotic plaques, ex-vivo diffusion tensor imaging (DTI) was performed to give the helical angle which was used to inform the FE models. A novel remodelling metric (RM), dependent on the change of the collagen fibre orientation and the evolution of internal variables that captures the softening that is associated with how far the fibres are from their optimal configuration when the arterial vessel is subjected to load was used to assess the possible vulnerability of atherosclerotic plaques. Overall, this preliminary work has demonstrated the capability of using the RM to possibly characterize plaque vulnerability when being informed with patient specific fibre angles from ex-vivo DTI. This is because the remodelling metric observed is higher when the fibres are not in the load bearing configuration. The last aim of this work involved characterizing the strain environment across atherosclerotic plaques using in-vivo MRI to establish a sensitive imaging indicator that could possibly aid in determining which plaques are more vulnerable to rupture and verifying these results using patient specific finite element models. Acquiring images at two cardiac phases using triggering, the circumferential strain and its variability across healthy and diseased carotid bifurcation was calculated. Furthermore, patient specific computational models were created, and the circumferential strain and its variability was again calculated and subsequently compared to the imaging data. Importantly, this study shows that in healthy vessels there is a consistent strain across the bifurcation with small variability however, when plaques are present, higher strains can occur at locations proximal and distal to location of highest stenosis. High strains could suggest that collagen fibres at these locations are disorganized and orientated more axially then in the load bearing circumferential direction. Overall, this study shows that characterizing the strain environment of atherosclerotic plaques in-vivo can offer a key mechanical insight into the mechanical integrity of the tissue and that patient specific finite element models can verify the results obtained and allow for further characterization of the vulnerability of atherosclerotic plaques to rupture.
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https://tcdlocalportal.tcd.ie/pls/EnterApex/f?p=800:71:0::::P71_USERNAME:JOHNSTRODescription:
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Author: Johnston, Robert Daniel
Advisor:
Lally, CaitrionaPublisher:
Trinity College Dublin. School of Engineering. Discipline of Mechanical & Manuf. EngType of material:
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