A computational and experimental investigation of the in-vivo biomechanics of the human aorta
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The overall objective of this thesis is to provide a new understanding of the degree of biomechanical heterogeneity that exists along the human aorta, against the backdrop of clinical literature reporting that patient outcomes depend on the distance of aortic repair from the heart. Spatial variance in human aortic bioarchitecture responsible for the elasticity of the vessel is poorly understood. We present a quantification of the constituents responsible for aortic compliance, namely, elastin, collagen and smooth muscle cells, using histological and stereological techniques along the vessel length. Using donated cadaveric tissue, a series of samples were excised between the proximal ascending aorta and the distal abdominal aorta, for five cadavers, each of which underwent various staining procedures to enhance specific constituents of the wall. Using polarised light microscopy techniques, the orientation of collagen fibres was studied for each location and each tunical layer of the aorta. Significant transmural and longitudinal heterogeneity in collagen fibre orientations were uncovered throughout the vessel. It is shown that a von Mises mixture model is required accurately to fit the complex collagen fibre distributions that exist along the aorta. Additionally, collagen and smooth muscle cell density was observed to increase with increasing distance from the heart, whereas elastin density decreased. Evidence clearly demonstrates that the aorta is highly heterogeneous in terms of bioarchitecture along its length, providing a microstructural basis for varying biomechanical properties spatially. Several limitations exist with the ex-vivo approach to aortic mechanical property characterization including; (i) sample dimensions are generally small, presenting difficulty in terms of tensile testing, (ii) medical legislation prevents extension of the operative field for the purposes of obtaining ‘healthy’ samples, essentially rendering all tissue excised surgically to be either diseased or dead, and (iii) samples are generally from isolated segments of the aorta which cannot be taken to represent the properties of the entire vessel. As an alternative, we adopt an in-vivo approach to investigate the spatial variance in biomechanics of the healthy human aorta. Accurate measurement of the kinematics and haemodynamics of the aorta however, presents a considerable challenge. We present a dual-VENC 4D Flow MRI protocol capable of capturing the unsteady non-uniform blood flow throughout the entire vessel and cardiac cycle, in addition to measurement of the dynamically changing geometry of the aortic wall. Cross sectional area change, volumetric flow rate, and compliance are observed to decrease with increasing distance from the heart, while pulse wave velocity is observed to increase. A non-linear aortic lumen pressure-area relationship is observed throughout the aorta, such that a high vessel compliance occurs at low pressures, and a low vessel compliance occurs at high pressures. Results show that the biomechanical behaviour of the aorta is highly dependent on the time-point of the cardiac cycle and on the spatial location relative to the heart. We then turn our focus to characterizing the spatially varying non-linear compliance of the aorta in-vivo using a combined MRI/FEA framework and a novel physically motivated constitutive law. It is shown that in order to accurately capture the biomechanics of the aorta, the contractile elements of the vessel wall must be incorporated in the material model. The pre-stretch of elastin and the contraction of smooth muscle cells (SMCs) are applied, resulting in a reduction in the reference lumen area to a new equilibrium area. The novel constitutive law is also demonstrated to capture the key features of both elastin and SMC knockout experiments. A subject-specific FE model is generated directly from the MRI data presented in Chapter 5, and the volume fractions of the constituent components of the aortic material model (i.e. non-linear elastic collagen, pre-stretched elastin, and contractile SMCs) were computed so that the in-silico pressure-area curves accurately predict the corresponding MRI data at each location. This leads to the prediction that collagen and smooth muscle volume fractions increase distally, while elastin volume fraction decreases distally. This finding is supported by the histological analyses presented in Chapter 4. The current study validates the inaccuracy in the assumption that the aorta exhibits a spatially uniform compliance along its length and a temporally uniform stiffness throughout the cardiac cycle. The effect of repair techniques on the biomechanics of the human aorta has not been rigorously investigated to date, resulting in significant levels of postoperative complications for patients worldwide. Furthermore, several studies show that cardiac death is dependent on the location of the aortic repair. We show using our combined MRI/FEA framework, that both endovascular aortic repair (EVAR) and open surgical repair (OSR) significantly alter the biomechanics of the human aorta. Following an EVAR, the aorta reaches a new equilibrium configuration due to the outward force of the implant being balanced by increased tension in the vessel wall. This additional strain being imparted on the aortic wall results in the material transition from the high compliance regime (HCR) into the low compliance regime (LCR). The stent-graft unloads from the crimped configuration during deployment and operates along the unloading plateau between diastole and systole. The direct effective stiffness of the implant is negligible compared to the high-stiffness of the artery wall in the LCR. As a result, the pressure-area relationship post-stenting between diastole and systole follows that of the local LCR slope of the aorta. The stented section follows the local LCR slope for the entire cardiac cycle, and as a result the effective change in diastole is more pronounced proximally versus distally where the bi-linearity of the pressure-area curve is more pronounced. Finally, we also show that OSR results in a profound change in both the HCR and LCR slope, where a near zero compliance is observed throughout the entire cardiac cycle. The link between aortic heterogeneity and compliance mismatch uncovered may significantly advance the current understanding of the efficacy of aortic devices and their impact on the cardiovascular system.
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