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Towards the development of guidelines for the endovascular treatment of peripheral artery disease: a tissue characterisation approach

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dc.contributor.advisor Walsh, Michael T. Cunnane, Eoghan M. 2015-12-16T17:14:49Z 2015-12-16T17:14:49Z 2015
dc.description peer-reviewed en_US
dc.description.abstract The femoral arteries are one of the most susceptible vascular locations for the development of atherosclerosis. The occurrence of this disease process in these vessels is the leading cause of lifestyle-limiting claudication and ischemic rest pain. Common femoral endarterectomy has been the standard treatment for focal occlusive disease of the femoral arteries for over 50 years. However, morbidity rates remain high due to its invasive nature and certain groups of patients are considered high risk for surgery. The use of Percutaneous Transluminal Angioplasty (PTA) has been advocated as a treatment alternative for patients at higher risk of surgical morbidity and mortality. Despite this, the long term results for PTA in the femoral arteries are disappointing due to uncontrolled dissections in complex lesions, inadequate luminal expansion in rigid strictures and recurrent stenosis in the dilated segment. PTA therefore requires procedural, technological, and suitable patient selection enhancements to function effectively as a treatment modality. Cutting Balloon Angioplasty (CBA) is an additional treatment alternative that employs a non-compliant balloon with radially positioned microblades to incise the plaque and propagate a controlled crack thereby reducing elastic recoil, vessel dilation, vessel injury, and subsequent restenosis. Preliminary reports have highlighted the possibility of CBA application in the peripheral arteries. However, various complications have also been reported including arterial rupture, delayed perforation and fracture of microsurgical blades. Arterial injury response to endovascular treatment varies significantly with plaque composition and it has been previously stated that the mechanisms of CBA affected by plaque composition need to be clarified. Therefore, a need exists to characterise the fracture behaviour of atherosclerotic femoral tissue and relate it to plaque biological content and structural morphology. Consequently, the research objective of this thesis is to enhance the implementation of endovascular treatments of the femoral arteries by presenting novel information regarding the characteristics of the target lesion. To achieve this, the mechanical properties and fracture behaviour of human atherosclerotic femoral tissue is characterised and related to plaque biological content and structural morphology. This will facilitate for more informed patient stratification, treatment approaches, and device design. A standardised uniaxial extension protocol is proposed and employed to characterise the mechanical behaviour of 20 endarterectomised femoral plaque samples in order to determine the tissue’s response to large circumferential deformation, the conditions induced during endovascular treatment. Guillotine testing is also employed to determine the Mode I fracture toughness of 30 sections from 5 endarterectomised femoral plaque samples to examine the tissue’s ability to resist crack propagation, the conditions induced specifically during CBA. This mechanical behaviour and fracture toughness are related to plaque biological content using Fourier transform infrared and structural morphology using scanning electron microscopy in order to determine the effect of plaque content and morphology on the mechanical response to large deformation and cut propagation. This information is then utilised to develop predictive tools and guidelines for the endovascular treatment of peripheral artery disease. Such tools can be employed to stratify patients, treatments, and devices in order to avoid endovascular treatment of lesions that are vulnerable to mechanically induced failure during PTA or that are resistant to cut propagation during CBA. Material models based on this novel mechanical and biological characterisation are also developed to better represent diseased femoral vessels numerically. Such vessel appropriate material models may lead to the production of endovascular devices and treatments that are more suited to treating atherosclerotic lesions of the femoral vessels. The characterisation of 20 human femoral atherosclerotic plaque samples revealed the identification of three plaque classifications that exhibit distinct mechanical and biological characteristics. The mechanical behaviour of the heavily calcified femoral plaque group identified suggests that femoral plaques exhibiting a ratio of calcified tissue to lipid content exceeding 2 may be vulnerable to failure during endovascular device deployment as these plaques undergo mechanically induced failure at a reduced stress and stretch. Compiling the characteristics of these 20 human femoral atherosclerotic plaque samples, with the results obtained from testing 24 carotid plaque samples in an identical manner, revealed significant differences in mechanical responses to large deformation that may aid in explaining the contrasting restenotic responses demonstrated by these vascular locations. Furthermore, the significant correlations between the biological content and the mechanical responses of both plaque groups highlights the potential to develop a tool to stratify patients based on predicted plaque mechanical response. Such a tool could stratify patients into those suitable for endovascular intervention and those that should receive open surgery or a monitoring protocol. The fracture toughness of 30 sections from 5 human femoral atherosclerotic plaque samples was characterised and related to biological content and structural morphology. A large degree of inter and intra sample variance was identified, with toughness values ranging far above and below those established for healthy arterial tissue. These results demonstrate the difficulty in effectively implementing CBA in complex atherosclerotic femoral lesions. However, the biological parameter depicting plaque calcified content correlates significantly with sample toughness. This highlights the potential to utilise this parameter as a preoperative tool for predicting the fracture response of a target lesion to CBA. Such a tool may lead to a reduction in clinically observed complications, an improvement in trial results, and an increased adoption of the CBA technique to reduce vessel trauma and further endovascular treatment uptake. Novel vessel appropriate material models are developed from the previously characterised mechanical behaviour of 20 femoral plaque samples. Comparing these material models to those currently employed in literature highlights the large discrepancies introduced by numerically representing femoral plaque tissue using material models based on atherosclerotic aortic plaque data. Future studies seeking to simulate endovascular treatments or device design should employ vessel-appropriate material models to represent the response of diseased femoral tissue in order to obtain more accurate numerical results. en_US
dc.language.iso eng en_US
dc.publisher University of Limerick en_US
dc.subject peripheral artery disease en_US
dc.subject plaque en_US
dc.title Towards the development of guidelines for the endovascular treatment of peripheral artery disease: a tissue characterisation approach en_US
dc.type info:eu-repo/semantics/doctoralThesis en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.type.supercollection ul_theses_dissertations en_US
dc.contributor.sponsor Irish Government’s Programme for Research in Third Level Institutions Cycle 5 en_US
dc.contributor.sponsor IRC en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US

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