Purpose-Coronary artery stenosis, or abnormal narrowing, is a widespread and potentially fatal cardiac disease. After treatment by balloon angioplasty and stenting, restenosis may occur inside the stent due to excessive neointima formation. Simulations of in-stent restenosis can provide new insight into this process. However, uncertainties due to variability in patient-specific parameters must be taken into account. Methods-We performed an uncertainty quantification (UQ) study on a complex two-dimensional in-stent restenosis model. We used a quasi-Monte Carlo method for UQ of the neointimal area, and the Sobol sensitivity analysis (SA) to estimate the proportions of aleatory and epistemic uncertainties and to determine the most important input parameters. Results-We observe approximately 30% uncertainty in the mean neointimal area as simulated by the model. Depending on whether a fast initial endothelium recovery occurs, the proportion of the model variance due to natural variability ranges from 15 to 35%. The endothelium regeneration time is identified as the most influential model parameter. Conclusion-The model output contains a moderate quantity of uncertainty, and the model precision can be increased by obtaining a more certain value on the endothelium regeneration time. We conclude that the quasi-Monte Carlo UQ and the Sobol SA are reliable methods for estimating uncertainties in the response of complicated multiscale cardiovascular models.

Multiscale simulations are an essential computational method in a range of research disciplines, and provide unprecedented levels of scientific insight at a tractable cost in terms of effort and compute resources. To provide this, we need such simulations to produce results that are both robust and actionable. The VECMA toolkit (VEC-MAtk), which is officially released in conjunction with the present paper, establishes a platform to achieve this by exposing patterns for verification, validation and uncertainty quantification (VVUQ). These patterns can be combined to capture complex scenarios, applied to applications in disparate domains, and used to run multiscale simulations on any desktop, cluster or supercomputing platform.

We explore the efficiency of a semi-intrusive uncertainty quantification (UQ) method for multiscale models as proposed by us in an earlier publication. We applied the multiscale metamodelling UQ method to a two-dimensional multiscale model for the wound healing response in a coronary artery after stenting (in-stent restenosis). The results obtained by the semi-intrusive method show a good match to those obtained by a black-box quasi-Monte Carlo method. Moreover, we significantly reduce the computational cost of the UQ. We conclude that the semi-intrusive metamodelling method is reliable and efficient, and can be applied to such complex models as the in-stent restenosis ISR2D model. This article is part of the theme issue ‘Multiscale modelling, simulation and computing: from the desktop to the exascale’.

A family of semi-intrusive Uncertainty Quantification (UQ) methods for multiscale models is introduced. The methods are semi-intrusive in the sense that inspection of the model is limited up to the level of the single scale systems, and viewing these single scale components as black-boxes. The goal is to estimate uncertainty in the result of multiscale models at a reduced amount of time as compared to black-box Monte Carlo (MC). In the resulting semi-intrusive MC method, the required number of samples of an expensive single scale model is minimized in order to reduce the execution time for the overall UQ. In the metamodeling approach the expensive model component is replaced completely by a computationally much cheaper surrogate model. These semi-intrusive algorithms have been tested on two case studies based on reaction-diffusion dynamics. The results demonstrate that the proposed semiintrusive methods can result in a significant reduction of the computational time for multiscale UQ, while still computing accurately the estimates of uncertainties. The semi-intrusive methods can therefore be a valid alternative, when uncertainties of a multiscale model cannot be estimated by the blackbox MC methods in a feasible amount of time.

We present the VECMA toolkit (VECMAtk), a flexible software environment for single and multiscale simulations that introduces directly applicable and reusable procedures for verification, validation (V&V), sensitivity analysis (SA) and uncertainty quantication (UQ). It enables users to verify key aspects of their applications, systematically compare and validate the simulation outputs against observational or benchmark data, and run simulations conveniently on any platform from the desktop to current multi-petascale computers. In this sequel to our paper on VECMAtk which we presented last year [ 1 ] we focus on a range of functional and performance improvements that we have introduced, cover newly introduced components, and applications examples from seven different domains such as conflict modelling and environmental sciences. We also present several implemented patterns for UQ/SA and V&V, and guide the reader through one example concerning COVID-19 modelling in detail. This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantification in silico ’.