Global sensitivity analysis of a homogenized constrained mixture model of arterial growth and remodeling

Growth and remodeling in arterial tissue have attracted considerable attention over the last decade. Mathematical models have been proposed, and computational studies with these have helped to understand the role of the different model parameters. So far it remains, however, poorly understood how much of the model output variability can be attributed to the individual input parameters and their interactions. To clarify this, we propose herein a global sensitivity analysis, based on Sobol indices, for a homogenized constrained mixture model of aortic growth and remodeling. In two representative examples, we found that 54–80% of the long term output variability resulted from only three model parameters. In our study, the two most influential parameters were the one characterizing the ability of the tissue to increase collagen production under increased stress and the one characterizing the collagen half-life time. The third most influential parameter was the one characterizing the strain-stiffening of collagen under large deformation. Our results suggest that in future computational studies it may - at least in scenarios similar to the ones studied herein - suffice to use population average values for the other parameters. Moreover, our results suggest that developing methods to measure the said three most influential parameters may be an important step towards reliable patient-specific predictions of the enlargement of abdominal aortic aneurysms in clinical practice.

Subjects

Abdominal aortic aneurysm

Global sensitivity analysis

Growth and remodeling

Homogenized constrained mixture

DDC Class

570: Biowissenschaften, Biologie

600: Technik

610: Medizin

620: Ingenieurwissenschaften

Funding Organisations

Deutsche Forschungsgemeinschaft (DFG)

International Graduate School of Science and Engineering (IGSSE)

More Funding Information

Open Access funding enabled and organized by Projekt DEAL.

Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - Projektnummer 257981274, Projektnummer
386349077. The authors also gratefully acknowledge financial support by the International Graduate School of Science and Engineering (IGSSE) of Technical University of Munich, Germany.

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Brandstaeter2021_Article_GlobalSensitivityAnalysisOfAHo.pdf

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Global sensitivity analysis of a homogenized constrained mixture model of arterial growth and remodeling