An approach for vascular tumor growth based on a hybrid embedded/homogenized treatment of the vasculature within a multiphase porous medium model.

The aim of this work is to develop a novel computational approach to facilitate the modeling of angiogenesis during tumor growth. The preexisting vasculature is modeled as a 1D inclusion and embedded into the 3D tissue through a suitable coupling method, which allows for nonmatching meshes in 1D and 3D domain. The neovasculature, which is formed during angiogenesis, is represented in a homogenized way as a phase in our multiphase porous medium system. This splitting of models is motivated by the highly complex morphology, physiology, and flow patterns in the neovasculature, which are challenging and computationally expensive to resolve with a discrete, 1D angiogenesis and blood flow model. Moreover, it is questionable if a discrete representation generates any useful additional insight. By contrast, our model may be classified as a hybrid vascular multiphase tumor growth model in the sense that a discrete, 1D representation of the preexisting vasculature is coupled with a continuum model describing angiogenesis. It is based on an originally avascular model which has been derived via the thermodynamically constrained averaging theory. The new model enables us to study mass transport from the preexisting vasculature into the neovasculature and tumor tissue. We show by means of several illustrative examples that it is indeed capable of reproducing important aspects of vascular tumor growth phenomenologically.

A coupled approach for fluid saturated poroelastic media and immersed solids for modeling cell-tissue interactions.

In this paper, we propose a finite element-based immersed method to treat the mechanical coupling between a deformable porous medium model (PM) and an immersed solid model (ISM). The PM is formulated as a homogenized, volume-coupled two-field model, comprising a nearly incompressible solid phase that interacts with an incompressible Darcy-Brinkman flow. The fluid phase is formulated with respect to the Lagrangian finite element mesh, following the solid phase deformation. The ISM is discretized with an independent Lagrangian mesh and may behave arbitrarily complex (it may, eg, be compressible, grow, and perform active deformations). We model two distinct types of interactions, namely, (1) the immersed fluid-structure interaction (FSI) between the ISM and the fluid phase in the PM and (2) the immersed structure-structure interaction (SSI) between the ISM and the solid phase in the PM. Within each time step, we solve both FSI and SSI, employing strongly coupled partitioned schemes. This novel finite element method establishes a main building block of an evolving computational framework for modeling and simulating complex biomechanical problems, with focus on key phenomena during cell migration. Cell movement is strongly influenced by mechanical interactions between the cell body and the surrounding tissue, ie, the extracellular matrix (ECM). In this context, the PM represents the ECM, ie, a fibrous scaffold of structural proteins interacting with interstitial flow, and the ISM represents the cell body. The FSI models the influence of fluid drag, and the SSI models the force transmission between cell and ECM at adhesions sites.

A monolithic multiphase porous medium framework for (a-)vascular tumor growth.

We present a dynamic vascular tumor model combining a multiphase porous medium framework for avascular tumor growth in a consistent Arbitrary Lagrangian Eulerian formulation and a novel approach to incorporate angiogenesis. The multiphase model is based on Thermodynamically Constrained Averaging Theory and comprises the extracellular matrix as a porous solid phase and three fluid phases: (living and necrotic) tumor cells, host cells and the interstitial fluid. Angiogenesis is modeled by treating the neovasculature as a proper additional phase with volume fraction or blood vessel density. This allows us to define consistent inter-phase exchange terms between the neovasculature and the interstitial fluid. As a consequence, transcapillary leakage and lymphatic drainage can be modeled. By including these important processes we are able to reproduce the increased interstitial pressure in tumors which is a crucial factor in drug delivery and, thus, therapeutic outcome. Different coupling schemes to solve the resulting five-phase problem are realized and compared with respect to robustness and computational efficiency. We find that a fully monolithic approach is superior to both the standard partitioned and a hybrid monolithic-partitioned scheme for a wide range of parameters. The flexible implementation of the novel model makes further extensions (e.g., inclusion of additional phases and species) straightforward.