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.
Neumann boundary conditions prescribing the total momentum flux at inflow boundaries of biomechanical problems are proposed in this study. This approach enables the simultaneous application of velocity/flow rate and pressure curves at inflow boundaries. As the basic numerical method, a residual-based variational multiscale (or stabilized) finite element method is presented. The focus of the numerical examples in this work is on respiratory flows with complete flow reversals. However, the proposed formulation is just as well suited for cardiovascular flow problems with partial retrograde flow. Instabilities, which were reported for such problems in the literature, are resolved by the present approach without requiring the additional consideration of a Lagrange multiplier technique. The suitability of the approach is demonstrated for two respiratory flow examples, a rather simple tube and complex tracheobronchial airways (up to the fourth generation, segmented from end-expiratory CT images). For the latter example, the boundary conditions are generated from mechanical ventilation data obtained from an intensive care unit patient suffering from acute lung injury. For the tube, analytical pressure profiles can be replicated, and for the tracheobronchial airways, a correct distribution of the prescribed total momentum flux at the inflow boundary into velocity and pressure part is observed.
In this article, we propose a comprehensive computational model of the entire respiratory system, which allows simulating patient-specific lungs under different ventilation scenarios and provides a deeper insight into local straining and stressing of pulmonary acini. We include novel 0D inter-acinar linker elements to respect the interplay between neighboring alveoli, an essential feature especially in heterogeneously distended lungs. The model is applicable to healthy and diseased patient-specific lung geometries. Presented computations in this work are based on a patient-specific lung geometry obtained from computed tomography data and composed of 60,143 conducting airways, 30,072 acini, and 140,135 inter-acinar linkers. The conducting airways start at the trachea and end before the respiratory bronchioles. The acini are connected to the conducting airways via terminal airways and to each other via inter-acinar linkers forming a fully coupled anatomically based respiratory model. Presented numerical examples include simulation of breathing during a spirometry-like test, measurement of a quasi-static pressure-volume curve using a supersyringe maneuver, and volume-controlled mechanical ventilation. The simulations show that our model incorporating inter-acinar dependencies successfully reproduces physiological results in healthy and diseased states. Moreover, within these scenarios, a deeper insight into local pressure, volume, and flow rate distribution in the human lung is investigated and discussed. Copyright © 2016 John Wiley & Sons, Ltd.
In this article, a novel approach is presented for combining standard fluid-structure interaction with additional volumetric constraints to model fluid flow into and from homogenised solid domains. The proposed algorithm is particularly interesting for investigations in the field of respiratory mechanics as it enables the mutual coupling of airflow in the conducting part and local tissue deformation in the respiratory part of the lung by means of a volume constraint. In combination with a classical monolithic fluid-structure interaction approach, a comprehensive model of the human lung can be established that will be useful to gain new insights into respiratory mechanics in health and disease. To illustrate the validity and versatility of the novel approach, three numerical examples including a patient-specific lung model are presented. The proposed algorithm proves its capability of computing clinically relevant airflow distribution and tissue strain data at a level of detail that is not yet achievable, neither with current imaging techniques nor with existing computational models. Copyright © 2016 John Wiley & Sons, Ltd.
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