This paper presents a subject-specific in-silico framework in which we uncover the relationship between the spatially varying constituents of the aorta and the non-linear compliance of the vessel during the cardiac cycle uncovered through our MRI investigations. A microstructurally motivated constitutive model is developed, and simulations reveal that internal vessel contractility, due to pre-stretched elastin and actively generated smooth muscle cell stress, must be incorporated, along with collagen strain stiffening, in order to accurately predict the non-linear pressure-area relationship observed in-vivo. Modelling of elastin and smooth muscle cell contractility allows for the identification of the reference vessel configuration at zero-lumen pressure, in addition to accurately predicting high- and low-compliance regimes under a physiological range of pressures. This modelling approach is also shown to capture the key features of elastin digestion and SMC activation experiments. The volume fractions of the constituent components of the aortic material model were computed so that the in-silico pressure-area curves accurately predict the corresponding MRI data at each location. Simulations reveal that collagen and smooth muscle volume fractions increase distally, while elastin volume fraction decreases distally, consistent with reported histological data. Furthermore, the strain at which collagen transitions from low to high stiffness is lower in the abdominal aorta, again supporting the histological finding that collagen waviness is lower distally. The analyses presented in this paper provide new insights into the heterogeneous structure-function relationship that underlies aortic biomechanics. Furthermore, this subject-specific MRI/FEA methodology provides a foundation for personalised in-silico clinical analysis and tailored aortic device development. STATEMENT OF SIGNIFICANCE: This study provides a significant advance in in-silico medicine by capturing the structure/function relationship of the subject-specific human aorta presented in our previous MRI analyses. A physiologically based aortic constitutive model is developed, and simulations reveal that internal vessel contractility must be incorporated, along with collagen strain stiffening, to accurately predict the in-vivo non-linear pressure-area relationship. Furthermore, this is the first subject-specific model to predict spatial variation in the volume fractions of aortic wall constituents. Previous studies perform phenomenological hyperelastic curve fits to medical imaging data and ignore the prestress contribution of elastin, collagen, and SMCs and the associated zero-pressure reference state of the vessel. This novel MRI/FEA framework can be used as an in-silico diagnostic tool for the early stage detection of aortic pathologies.
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http://dx.doi.org/10.1016/j.actbio.2021.02.027 | DOI Listing |
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