Search

The development of biophysical models for clinical applications is rapidly advancing in the research community, thanks to their predictive nature and their ability to assist the interpretation of clinical data. However, high-resolution and accurate multi-physics computational models are computationally expensive and their personalisation involves fine calibration of a large number of parameters, which may be space-dependent, challenging their clinical translation. In this work, we propose a new approach which relies on the combination of physics-informed neural networks (PINNs) with three-dimensional soft tissue nonlinear biomechanical models, capable of reconstructing displacement fields and estimating heterogeneous patient-specific biophysical properties. The proposed learning algorithm encodes information from a limited amount of displacement and, in some cases, strain data, that can be routinely acquired in the clinical setting, and combines it with the physics of the problem, represented by a mathematical model based on partial differential equations, to regularise the problem and improve its convergence properties. Several benchmarks are presented to show the accuracy and robustness of the proposed method and its great potential to enable the robust and effective identification of patient-specific, heterogeneous physical properties, s.a. tissue stiffness properties. In particular, we demonstrate the capability of the PINN to detect the presence, location and severity of scar tissue, which is beneficial to develop personalised simulation models for disease diagnosis, especially for cardiac applications., Comment: Accepted for publication in Computational Mechanics

Computational Fluid Dynamics (CFD) is used to assist in designing artificial valves and planning procedures, focusing on local flow features. However, assessing the impact on overall cardiovascular function or predicting longer-term outcomes may require more comprehensive whole heart CFD models. Fitting such models to patient data requires numerous computationally expensive simulations, and depends on specific clinical measurements to constrain model parameters, hampering clinical adoption. Surrogate models can help to accelerate the fitting process while accounting for the added uncertainty. We create a validated patient-specific four-chamber heart CFD model based on the Navier-Stokes-Brinkman (NSB) equations and test Gaussian Process Emulators (GPEs) as a surrogate model for performing a variance-based global sensitivity analysis (GSA). GSA identified preload as the dominant driver of flow in both the right and left side of the heart, respectively. Left-right differences were seen in terms of vascular outflow resistances, with pulmonary artery resistance having a much larger impact on flow than aortic resistance. Our results suggest that GPEs can be used to identify parameters in personalized whole heart CFD models, and highlight the importance of accurate preload measurements., Comment: 8 pages plus 15 pages supplement, 6 figures, 3 tables, submitted to IEEE Transactions on Biomedical Engineering

Fiber-reinforced soft biological tissues are typically modeled as hyperelastic, anisotropic, and nearly incompressible materials. To enforce incompressibility a multiplicative split of the deformation gradient into a volumetric and an isochoric part is a very common approach. However, due to the high stiffness of anisotropic materials in the preferred directions, the finite element analysis of such problems often suffers from severe locking effects and numerical instabilities. In this paper, we present novel methods to overcome locking phenomena for anisotropic materials using stabilized P1-P1 elements. We introduce different stabilization techniques and demonstrate the high robustness and computational efficiency of the chosen methods. In several benchmark problems we compare the approach to standard linear elements and show the accuracy and versatility of the methods to simulate anisotropic, nearly and fully incompressible materials. We are convinced that this numerical framework offers the possibility to accelerate accurate simulations of biological tissues, enabling patient-specfic parameterization studies, which require numerous forward simulations., Comment: This research has received funding from the European Union's Horizon 2020 research and innovation programme under the ERA-NET co-fund action No. 680969 (ERA-CVD SICVALVES) funded by the Austrian Science Fund (FWF), Grant I 4652-B

Computer models of cardiac electro-mechanics (EM) show promise as an effective means for quantitative analysis of clinical data and, potentially, for predicting therapeutic responses.realize such advanced applications methodological key challenges must be addressed. Enhanced computational efficiency and robustness is crucial to facilitate, within tractable time frames, model personalization, the simulation of prolonged observation periods under a broad range of conditions, and physiological completeness encompassing therapy-relevant mechanisms is needed to endow models with predictive capabilities beyond the mere replication of observations. Here, we introduce a universal feature-complete cardiac EM modeling framework that builds on a flexible method for coupling a 3D model of bi-ventricular EM to the physiologically comprehensive 0D CircAdapt model representing atrial mechanics and closed-loop circulation. A detailed mathematical description is given and efficiency, robustness, and accuracy of numerical scheme and solver implementation are evaluated. After parameterization and stabilization of the coupled 3D-0D model to a limit cycle under baseline conditions, the model's ability to replicate physiological behaviors is demonstrated, by simulating the transient response to alterations in loading conditions and contractility, as induced by experimental protocols used for assessing systolic and diastolic ventricular properties. Mechanistic completeness and computational efficiency of this novel model render advanced applications geared towards predicting acute outcomes of EM therapies feasible., Comment: This project has received funding from the EU's H2020 programme under the Marie Sklodowska-Curie Action InsiliCardio, GA No. 750835 and under the ERA-NET co-fund action No. 680969 (ERA-CVD SICVALVES) funded by the Austrian Science Fund (FWF), GA I 4652-B to CMA. The research was supported by the Grants F3210-N18 and I2760-B30 from the FWF and a BioTechMed Graz flagship award ILearnHeart to GP

Simulating the interaction of fluids with immersed moving solids is playing an important role for gaining a better quantitative understanding of how fluid dynamics is altered by the presence of obstacles and which forces are exerted on the solids by the moving fluid. Such problems appear in various contexts, ranging from numerous technical applications such as turbines to medical problems such as the regulation of hemodyamics by valves. Typically, the numerical treatment of such problems is posed within a fluid structure interaction (FSI) framework. General FSI models are able to capture bidirectional interactions, but are challenging to solve and computationally expensive. Simplified methods offer a possible remedy by achieving better computational efficiency to broaden the scope to demanding application problems with focus on understanding the effect of solids on altering fluid dynamics. In this study we report on the development of a novel method for such applications. In our method rigid moving obstacles are incorporated in a fluid dynamics context using concepts from porous media theory. Based on the Navier-Stokes-Brinkman equations which augments the Navier-Stokes equation with a Darcy drag term our method represents solid obstacles as time-varying regions containing a porous medium of vanishing permeability. Numerical stabilization and turbulence modeling is dealt with by using a residual based variational multiscale formulation. The key advantages of our approach -- computational efficiency and ease of implementation -- are demonstrated by solving a standard benchmark problem of a rotating blood pump posed by the Food and Drug Administration Agency (FDA). Validity is demonstrated by conducting a mesh convergence study and by comparison against the extensive set of experimental data provided for this benchmark.

Computational formulations for large strain, polyconvex, nearly incompressible elasticity have been extensively studied, but research on enhancing solution schemes that offer better tradeoffs between accuracy, robustness, and computational efficiency remains to be highly relevant. In this paper, we present two methods to overcome locking phenomena, one based on a displacement-pressure formulation using a stable finite element pairing with bubble functions, and another one using a simple pressure-projection stabilized P1-P1 finite element pair. A key advantage is the versatility of the proposed methods: with minor adjustments they are applicable to all kinds of finite elements and generalize easily to transient dynamics. The proposed methods are compared to and verified with standard benchmarks previously reported in the literature. Benchmark results demonstrate that both approaches provide a robust and computationally efficient way of simulating nearly and fully incompressible materials., Comment: This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Action H2020-MSCA-IF-2016 InsiliCardio, GA No. 750835 to CMA. Additionally, the research was supported by the Grants F3210-N18 and I2760-B30 from the Austrian Science Fund (FWF) and BioTechMed-Graz (Grant No. Flagship Project: ILearnHeart)

Computational fluid dynamics (CFD) models of blood flow in the left ventricle (LV) and aorta are important tools for analyzing the mechanistic links between myocardial deformation and flow patterns. Typically, the use of image-based kinematic CFD models prevails in applications such as predicting the acute response to interventions which alter LV afterload conditions. However, such models are limited in their ability to analyze any impacts upon LV load or key biomarkers known to be implicated in driving remodeling processes as LV function is not accounted for in a mechanistic sense. This study addresses these limitations by reporting on progress made towards a novel electro-mechano-fluidic (EMF) model that represents the entire physics of LV electromechanics (EM) based on first principles. A biophysically detailed finite element (FE) model of LV EM was coupled with a FE-based CFD solver for moving domains using an arbitrary Eulerian-Lagrangian (ALE) formulation. Two clinical cases of patients suffering from aortic coarctations (CoA) were built and parameterized based on clinical data under pre-treatment conditions. For one patient case simulations under post-treatment conditions after geometric repair of CoA by a virtual stenting procedure were compared against pre-treatment results. Numerical stability of the approach was demonstrated by analyzing mesh quality and solver performance under the significantly large deformations of the LV blood pool. Further, computational tractability and compatibility with clinical time scales were investigated by performing strong scaling benchmarks up to 1536 compute cores. The overall cost of the entire workflow for building, fitting and executing EMF simulations was comparable to those reported for image-based kinematic models, suggesting that EMF models show potential of evolving into a viable clinical research tool., Comment: This research was supported by the grants F3210-N18 and I2760-B30 from the Austrian Science Fund (FWF), the EU grant CardioProof agreement 611232 and a BioTechMed award to GP. Additionally, this project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Action H2020-MSCA-IF-2016 InsiliCardio, GA No. 750835

Introduction: Stenotic aortic valve disease (AS) causes pressure overload of the left ventricle (LV) that may trigger adverse remodeling and precipitate progression towards heart failure (HF). As myocardial energetics can be impaired during AS, LV wall stresses and biomechanical power provide a complementary view of LV performance that may aide in better assessing the state of disease. Objectives: Using a high-resolution electro-mechanical (EM) in silico model of the LV as a reference, we evaluated clinically feasible Laplace-based methods for assessing global LV wall stresses and biomechanical power. Methods: We used N = 4 in silico finite element (FE) EM models of LV and aorta of patients suffering from AS. All models were personalized with clinical data under pre-treatment conditions. LV wall stresses and biomechanical power were computed accurately from FE kinematic data and compared to Laplace-based estimation methods which were applied to the same FE model data. Results and Conclusion: Laplace estimates of LV wall stress are able to provide a rough approximation of global mean stress in the circumferential-longitudinal plane of the LV. However, according to FE results spatial heterogeneity of stresses in the LV wall is significant, leading to major discrepancies between local stresses and global mean stress. Assessment of mechanical power with Laplace methods is feasible, but these are inferior in accuracy compared to FE models. The accurate assessment of stress and power density distribution in the LV wall is only feasible based on patient-specific FE modeling., Comment: This research was supported by the grants F3210-N18 and I2760-B30 from the Austrian Science Fund (FWF), the EU grant CardioProof agreement 611232 and a BioTechMed award to GP. Additionally, this project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-Curie Action H2020-MSCA-IF-2016 InsiliCardio, GA No. 750835

In this paper we present a discontinuous Galerkin finite element method for the solution of the transient Stokes equations on moving domains. For the discretization we use an interior penalty Galerkin approach in space, and an upwind technique in time. The method is based on a decomposition of the space-time cylinder into finite elements. Our focus lies on three-dimensional moving geometries, thus we need to triangulate four dimensional objects. For this we will present an algorithm to generate $d+1$-dimensional simplex space-time meshes and we show under natural assumptions that the resulting space-time meshes are admissible. Further we will show how one can generate a four-dimensional object resolving the domain movement. First numerical results for the transient Stokes equations on triangulations generated with the newly developed meshing algorithm are presented.