A fully coupled computational fluid dynamics - agent-based model of atherosclerotic plaque development: Multiscale modeling framework and parameter sensitivity analysis.
Agent-based model
Atherosclerosis
Computer modeling
ECM
Hemodynamics
Lipid plaque
Multiscale model
Remodeling
SMC
Wall shear stress
Journal
Computers in biology and medicine
ISSN: 1879-0534
Titre abrégé: Comput Biol Med
Pays: United States
ID NLM: 1250250
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
07
11
2019
revised:
13
01
2020
accepted:
13
01
2020
pubmed:
31
1
2020
medline:
22
6
2021
entrez:
31
1
2020
Statut:
ppublish
Résumé
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. 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. 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. The fully coupled CFD-ABM framework described atherosclerotic morphological and compositional changes triggered by a disturbed hemodynamics.
Sections du résumé
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.
Identifiants
pubmed: 31999550
pii: S0010-4825(20)30022-6
doi: 10.1016/j.compbiomed.2020.103623
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
103623Subventions
Organisme : NHLBI NIH HHS
ID : U01 HL119178
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflicts of interest.