A twofold usage of an agent-based model of vascular adaptation to design clinical experiments

Casarin, Stefano; Berceli, Scott A.; Garbey, Marc

doi:10.1016/j.jocs.2018.09.013

Cited by 6 publications

(5 citation statements)

References 23 publications

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“…Moreover, in a future perspective, the combination of sensitivity analysis and inverse problem solution proposed by Casarin et al [53,54] can be a valuable tool to further narrow the range of optimal setting of the ABM model coefficients.…”

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confidence: 99%

A fully coupled computational fluid dynamics – agent-based model of atherosclerotic plaque development: Multiscale modeling framework and parameter sensitivity analysis

Corti¹,

Chiastra²,

Colombo³

et al. 2020

Computers in Biology and Medicine

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Background. Peripheral artery disease (PAD) is an atherosclerotic disorder that leads to unpaired 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.

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confidence: 99%

A fully coupled computational fluid dynamics – agent-based model of atherosclerotic plaque development: Multiscale modeling framework and parameter sensitivity analysis

Corti¹,

Chiastra²,

Colombo³

et al. 2020

Computers in Biology and Medicine

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“…With an escalating complexity, we will assist to an increased computational burden that will translate in a dilation of the time needed for a single simulation. To shorten the required computational time, the Matlab® code will be translated in an executable C-code (via Matlab® "coder" Toolbox) and parallel computing techniques will be applied as previously reported [25].…”

Section: Discussionmentioning

confidence: 99%

An agent-based model of prostate Cancer bone metastasis progression and response to Radium223

Casarin

Dondossola²

2020

BMC Cancer

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Background Bone metastasis is the most frequent complication in prostate cancer patients and associated outcome remains fatal. Radium223 (Rad223), a bone targeting radioisotope improves overall survival in patients (3.6 months vs. placebo). However, clinical response is often followed by relapse and disease progression, and associated mechanisms of efficacy and resistance are poorly understood. Research efforts to overcome this gap require a substantial investment of time and resources. Computational models, integrated with experimental data, can overcome this limitation and drive research in a more effective fashion. Methods Accordingly, we developed a predictive agent-based model of prostate cancer bone metastasis progression and response to Rad223 as an agile platform to maximize its efficacy. The driving coefficients were calibrated on ad hoc experimental observations retrieved from intravital microscopy and the outcome further validated, in vivo. Results In this work we offered a detailed description of our data-integrated computational infrastructure, tested its accuracy and robustness, quantified the uncertainty of its driving coefficients, and showed the role of tumor size and distance from bone on Rad223 efficacy. In silico tumor growth, which is strongly driven by its mitotic character as identified by sensitivity analysis, matched in vivo trend with 98.3% confidence. Tumor size determined efficacy of Rad223, with larger lesions insensitive to therapy, while medium- and micro-sized tumors displayed up to 5.02 and 152.28-fold size decrease compared to control-treated tumors, respectively. Eradication events occurred in 65 ± 2% of cases in micro-tumors only. In addition, Rad223 lost any therapeutic effect, also on micro-tumors, for distances bigger than 400 μm from the bone interface. Conclusions This model has the potential to be further developed to test additional bone targeting agents such as other radiopharmaceuticals or bisphosphonates.

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“…The ratio of VSMC/ECM was 1. The initial cellular pattern in a vessel cross-section was random according to the published literature (Hwang et al, 2013;Garbey et al, 2015;Casarin et al, 2018). Figure 3 shows the vessel cross-section after geometry initialization.…”

Section: Agent-based Modelmentioning

confidence: 99%

Multiscale Modeling of Vascular Remodeling Induced by Wall Shear Stress

et al. 2022

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ObjectiveHemodynamics-induced low wall shear stress (WSS) is one of the critical reasons leading to vascular remodeling. However, the coupling effects of WSS and cellular kinetics have not been clearly modeled. The aim of this study was to establish a multiscale modeling approach to reveal the vascular remodeling behavior under the interaction between the macroscale of WSS loading and the microscale of cell evolution.MethodsComputational fluid dynamics (CFD) method and agent-based model (ABM), which have significantly different characteristics in temporal and spatial scales, were adopted to establish the multiscale model. The CFD method is for the second/organ scale, and the ABM is for the month/cell scale. The CFD method was used to simulate blood flow in a vessel and obtain the WSS in a vessel cross-section. The simulations of the smooth muscle cell (SMC) proliferation/apoptosis and extracellular matrix (ECM) generation/degradation in a vessel cross-section were performed by using ABM. During the simulation of the vascular remodeling procedure, the damage index of the SMC and ECM was defined as deviation from the obtained WSS. The damage index decreased gradually to mimic the recovery of WSS-induced vessel damage.Results(1) The significant wall thickening region was consistent with the low WSS region. (2) There was no evident change of wall thickness in the normal WSS region. (3) When the damage index approached to 0, the amount and distribution of SMCs and ECM achieved a stable state, and the vessel reached vascular homeostasis.ConclusionThe established multiscale model can be used to simulate the vascular remodeling behavior over time under various WSS conditions.

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A twofold usage of an agent-based model of vascular adaptation to design clinical experiments

Cited by 6 publications

References 23 publications

A fully coupled computational fluid dynamics – agent-based model of atherosclerotic plaque development: Multiscale modeling framework and parameter sensitivity analysis

A fully coupled computational fluid dynamics – agent-based model of atherosclerotic plaque development: Multiscale modeling framework and parameter sensitivity analysis

An agent-based model of prostate Cancer bone metastasis progression and response to Radium223

Multiscale Modeling of Vascular Remodeling Induced by Wall Shear Stress

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