Single and bi-compartment poro-elastic model of perfused biological soft tissues: FEniCSx implementation and tutorial.

Soft biological tissues demonstrate strong time-dependent and strain-rate mechanical behavior, arising from their intrinsic visco-elasticity and fluid-solid interactions. The time-dependent mechanical properties of soft tissues influence their physiological functions and are related to several pathological processes. Poro-elastic modeling represents a promising approach because it allows the integration of multiscale/multiphysics data to probe biologically relevant phenomena at a smaller scale and embeds the relevant mechanisms at the larger scale. The implementation of multiphase flow poro-elastic models however is a complex undertaking, requiring extensive knowledge. The open-source software FEniCSx Project provides a novel tool for the automated solution of partial differential equations by the finite element method. This paper aims to provide the required tools to model the mixed formulation of poro-elasticity, from the theory to the implementation, within FEniCSx. Several benchmark cases are studied. A column under confined compression conditions is compared to the Terzaghi analytical solution, using the L2-norm. An implementation of poro-hyper-elasticity is proposed. A bi-compartment column is compared to previously published results (Cast3m implementation). For all cases, accurate results are obtained in terms of a normalized Root Mean Square Error (RMSE). Furthermore, the FEniCSx computation is found three times faster than the legacy FEniCS one. The benefits of parallel computation are also highlighted.

Global sensitivity study for irreversible electroporation: Towards treatment planning under uncertainty.

BACKGROUND: Electroporation-based cancer treatments are minimally invasive, nonthermal interventional techniques that leverage cell permeabilization to ablate the target tumor. However, the amount of permeabilization is susceptible to the numerous uncertainties during treatment, such as patient-specific variations in the tissue, type of the tumor, and the resolution of imaging equipment. These uncertainties can reduce the extent of ablation in the tissue, thereby affecting the effectiveness of the treatment. PURPOSE: The aim of this work is to understand the effect of these treatment uncertainties on the treatment outcome for irreversible electroporation (IRE) in the case of colorectal liver metastasis (CRLM). Understanding the nature and extent of these effects can help us identify the influential treatment parameters and build better models for predicting the treatment outcome. METHODS: This is an in silico study using a static computational model with a custom applicator design, spherical tissue, and tumor geometry. A nonlinear electrical conductivity, dependent on the local electric field, is considered. Morris analysis is used to identify the influential treatment parameters on the treatment outcome. Seven treatment parameters pertaining to the relative tumor location with respect to the applicator, the tumor growth pattern, and the electrical conductivity of tissue are analyzed. The treatment outcome is measured in terms of the relative tumor ablation with respect to the target ablation volume and total ablation volume. RESULTS: The Morris analysis was performed with 800 model evaluations, sampled from the seven dimensional input parameter space. Electrical properties of the tissue, especially the electrical conductivity of the tumor before ablation, were found to be the most influential parameter for relative tumor ablation and total ablation volume. This parameter was found to be about 4-15 times more influential than the least influential parameter, depending on the tumor size. The tumor border configuration was identified as the least important parameter for treatment effectiveness. The most desired treatment outcome is obtained by a combination of high healthy liver conductivity and low tumor conductivity. This information can be used to tackle worst-case scenarios in treatment planning. Finally, when the safety margins used in the clinical applications are accounted for, the effects of uncertainties in the treatment parameters reduce drastically. CONCLUSIONS: The results of this work can be used to create an efficient surrogate estimator for uncertainty quantification in the treatment outcome, that can be utilized in optimal real-time treatment planning solutions.

Global Sensitivity Analysis for Patient-Specific Aortic Simulations: The Role of Geometry, Boundary Condition and Large Eddy Simulation Modeling Parameters.

Numerical simulations for computational hemodynamics in clinical settings require a combination of many ingredients, mathematical models, solvers and patient-specific data. The sensitivity of the solutions to these factors may be critical, particularly when we have a partial or noisy knowledge of data. Uncertainty quantification is crucial to assess the reliability of the results. We present here an extensive sensitivity analysis in aortic flow simulations, to quantify the dependence of clinically relevant quantities to the patient-specific geometry and the inflow boundary conditions. Geometry and inflow conditions are generally believed to have a major impact on numerical simulations. We resort to a global sensitivity analysis, (i.e., not restricted to a linearization around a working point), based on polynomial chaos expansion (PCE) and the associated Sobol' indices. We regard the geometry and the inflow conditions as the realization of a parametric stochastic process. To construct a physically consistent stochastic process for the geometry, we use a set of longitudinal-in-time images of a patient with an abdominal aortic aneurysm (AAA) to parametrize geometrical variations. Aortic flow is highly disturbed during systole. This leads to high computational costs, even amplified in a sensitivity analysis -when many simulations are needed. To mitigate this, we consider here a large Eddy simulation (LES) model. Our model depends in particular on a user-defined parameter called filter radius. We borrowed the tools of the global sensitivity analysis to assess the sensitivity of the solution to this parameter too. The targeted quantities of interest (QoI) include: the total kinetic energy (TKE), the time-average wall shear stress (TAWSS), and the oscillatory shear index (OSI). The results show that these indexes are mostly sensitive to the geometry. Also, we find that the sensitivity may be different during different instants of the heartbeat and in different regions of the domain of interest. This analysis helps to assess the reliability of in silico tools for clinical applications.

Simulating the spread of COVID-19 via a spatially-resolved susceptible-exposed-infected-recovered-deceased (SEIRD) model with heterogeneous diffusion.

We present an early version of a Susceptible-Exposed-Infected-Recovered-Deceased (SEIRD) mathematical model based on partial differential equations coupled with a heterogeneous diffusion model. The model describes the spatio-temporal spread of the COVID-19 pandemic, and aims to capture dynamics also based on human habits and geographical features. To test the model, we compare the outputs generated by a finite-element solver with measured data over the Italian region of Lombardy, which has been heavily impacted by this crisis between February and April 2020. Our results show a strong qualitative agreement between the simulated forecast of the spatio-temporal COVID-19 spread in Lombardy and epidemiological data collected at the municipality level. Additional simulations exploring alternative scenarios for the relaxation of lockdown restrictions suggest that reopening strategies should account for local population densities and the specific dynamics of the contagion. Thus, we argue that data-driven simulations of our model could ultimately inform health authorities to design effective pandemic-arresting measures and anticipate the geographical allocation of crucial medical resources.

Diffusion-reaction compartmental models formulated in a continuum mechanics framework: application to COVID-19, mathematical analysis, and numerical study.

The outbreak of COVID-19 in 2020 has led to a surge in interest in the research of the mathematical modeling of epidemics. Many of the introduced models are so-called compartmental models, in which the total quantities characterizing a certain system may be decomposed into two (or more) species that are distributed into two (or more) homogeneous units called compartments. We propose herein a formulation of compartmental models based on partial differential equations (PDEs) based on concepts familiar to continuum mechanics, interpreting such models in terms of fundamental equations of balance and compatibility, joined by a constitutive relation. We believe that such an interpretation may be useful to aid understanding and interdisciplinary collaboration. We then proceed to focus on a compartmental PDE model of COVID-19 within the newly-introduced framework, beginning with a detailed derivation and explanation. We then analyze the model mathematically, presenting several results concerning its stability and sensitivity to different parameters. We conclude with a series of numerical simulations to support our findings.

Coupled molecular-dynamics and finite-element-method simulations for the kinetics of particles subjected to field-mediated forces.

A computational approach that couples molecular-dynamics (MD) and the-finite-element-method (FEM) technique is here proposed for the theoretical study of the dynamics of particles subjected to electromechanical forces. The system consists of spherical particles (modeled as micrometric rigid bodies with proper densities and dielectric functions) suspended in a colloidal solution, which flows in a microfluidic channel in the presence of a generic nonuniform variable electric field generated by electrodes. The particles are subjected to external forces (e.g., drag or gravity) which satisfy a particlelike formulation that is typical of the MD approach, along with an electromechanical force that, in turn, requires the three-dimensional self-consistent solutions of correct continuum field equations during the integration of the equations of motion. In the MD-FEM method used in this work, the finite element method is applied to solve the continuum field equations while the MD technique is used for the stepwise explicit integration of the equations of motion. Our work shows the potential of coupled MD-FEM simulations for the study of electromechanical particles and opens a double perspective for implementing (a) MD away from the field of atomistic simulations and (b) the continuum-particle approach to cases where the conventional force evaluation used in MD is not applicable.

A Mass Conservative Kalman Filter Algorithm for Computational Thermo-Fluid Dynamics.

This paper studies Kalman filtering applied to Reynolds-Averaged Navier⁻Stokes (RANS) equations for turbulent flow. The integration of the Kalman estimator is extended to an implicit segregated method and to the thermodynamic analysis of turbulent flow, adding a sub-stepping procedure that ensures mass conservation at each time step and the compatibility among the unknowns involved. The accuracy of the algorithm is verified with respect to the heated lid-driven cavity benchmark, incorporating also temperature observations, comparing the augmented prediction of the Kalman filter with the Computational Fluid-Dynamic solution found on a fine grid.