Anna Corti1, Claudio Chiastra2, Monika Colombo1, Marc Garbey3, Francesco Migliavacca1, Stefano Casarin4. 1. Laboratory of Biological Structure Mechanics (LaBS), Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Milan, Italy. 2. Laboratory of Biological Structure Mechanics (LaBS), Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Milan, Italy; PoliTo(BIO)Med Lab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy. Electronic address: claudio.chiastra@polito.it. 3. Center for Computational Surgery, Houston Methodist Research Institute, Houston, TX, USA; Department of Surgery, Houston Methodist Hospital, Houston TX, USA; LASIE UMR 7356 CNRS, University of La Rochelle, La Rochelle, France. 4. Center for Computational Surgery, Houston Methodist Research Institute, Houston, TX, USA; Department of Surgery, Houston Methodist Hospital, Houston TX, USA; Houston Methodist Academic Institute (HMAI), Houston, TX, USA.
Abstract
BACKGROUND: Peripheral Artery Disease (PAD) is an atherosclerotic disorder that leads to impaired lumen patency through intimal hyperplasia and the build-up of plaques, mainly localized in areas of disturbed flow. Computational models can provide valuable insights in the pathogenesis of atherosclerosis and act as a predictive tool to optimize current interventional techniques. Our hypothesis is that a reliable predictive model must include the atherosclerosis development history. Accordingly, we developed a multiscale modeling framework of atherosclerosis that replicates the hemodynamic-driven arterial wall remodeling and plaque formation. METHODS: The framework was based on the coupling of Computational Fluid Dynamics (CFD) simulations with an Agent-Based Model (ABM). The CFD simulation computed the hemodynamics in a 3D artery model, while 2D ABMs simulated cell, Extracellular Matrix (ECM) and lipid dynamics in multiple vessel cross-sections. A sensitivity analysis was also performed to evaluate the oscillation of the ABM output to variations in the inputs and to identify the most influencing ABM parameters. RESULTS: Our multiscale model qualitatively replicated both the physiologic and pathologic arterial configuration, capturing histological-like features. The ABM outputs were mostly driven by cell and ECM dynamics, largely affecting the lumen area. A subset of parameters was found to affect the final lipid core size, without influencing cell/ECM or lumen area trends. CONCLUSION: The fully coupled CFD-ABM framework described atherosclerotic morphological and compositional changes triggered by a disturbed hemodynamics.
BACKGROUND: Peripheral Artery Disease (PAD) is an atherosclerotic disorder that leads to impaired lumen patency through intimal hyperplasia and the build-up of plaques, mainly localized in areas of disturbed flow. Computational models can provide valuable insights in the pathogenesis of atherosclerosis and act as a predictive tool to optimize current interventional techniques. Our hypothesis is that a reliable predictive model must include the atherosclerosis development history. Accordingly, we developed a multiscale modeling framework of atherosclerosis that replicates the hemodynamic-driven arterial wall remodeling and plaque formation. METHODS: The framework was based on the coupling of Computational Fluid Dynamics (CFD) simulations with an Agent-Based Model (ABM). The CFD simulation computed the hemodynamics in a 3D artery model, while 2D ABMs simulated cell, Extracellular Matrix (ECM) and lipid dynamics in multiple vessel cross-sections. A sensitivity analysis was also performed to evaluate the oscillation of the ABM output to variations in the inputs and to identify the most influencing ABM parameters. RESULTS: Our multiscale model qualitatively replicated both the physiologic and pathologic arterial configuration, capturing histological-like features. The ABM outputs were mostly driven by cell and ECM dynamics, largely affecting the lumen area. A subset of parameters was found to affect the final lipid core size, without influencing cell/ECM or lumen area trends. CONCLUSION: The fully coupled CFD-ABM framework described atherosclerotic morphological and compositional changes triggered by a disturbed hemodynamics.
Authors: Anna Corti; Monika Colombo; Jared M Rozowsky; Stefano Casarin; Yong He; Dario Carbonaro; Francesco Migliavacca; Jose F Rodriguez Matas; Scott A Berceli; Claudio Chiastra Journal: J R Soc Interface Date: 2022-03-30 Impact factor: 4.118