P7 - Modeling of function-perfusion-deformation interaction on liver lobulus and cellular scale based on a bi-scale continuum FEM model

该项目是“复杂切除中肝灌注-功能关系的量化-系统医学方法”（QuaLiPerF）研究小组的一部分。在本研究单元中，本项目旨在数值模拟小叶水平上机械和生物耦合的灌注功能过程。肝小叶层是连接下一个较大的（器官血管系统）和下一个较小的（细胞系统）的层。这允许模拟二维和三维（2D/3D）肝小叶组（最多20个）。我们将研究脂肪堆积过程中血液灌注的变化，并计算脂肪在肝小叶堆积的瞬时空间分布。该模型将提供通过门静脉结扎（PVL）和肝脏切除（(e)PHx）引起的脂肪堆积引起的灌注变化信息。我们将扩展该模型来模拟肝脏再生过程中的组织生长和结构变化。一个时间依赖的正弦波的重新定向方法将被纳入。变形、流动和运输过程将使用耦合偏微分方程（PDE）系统进行建模，而代谢过程和脂肪积累将使用系统生物学方法使用常微分方程（PDE- ode耦合）系统进行描述。高分辨率、超弹性和多孔小叶模型是在热力学一致的连续介质力学多相和多尺度方法中开发和验证的。该模型直接建立在力学第一原理的基础上，并以多孔介质扩展理论为基础。此外，小叶模型在器官水平上通过耦合边界值与大血管系统相联系。在脂肪积累、PVL、(e)PHx和再生过程中，肝脏小叶的血液灌注变化和异质性被转移到器官多尺度模型中。我们将通过模型简化的方法来提高计算速度和效率。方法为离散经验插值法（DEIM），适当正交分解（POD）或两者的组合。人工神经网络（ANN）将被用作高保真多相和多尺度模型的替代模型。最后，我们将为研究单位的长期愿景奠定基础，以建立临床应用的3D建模计算机工具，使基于功能的手术计划和风险评估成为可能。作为一项概念验证研究，我们将使用商业程序可视化临床和模拟数据，以创建预定切除后器官和小叶水平功能受损和灌注的首次演示。

The project is part of the research group "Quantification of the liver perfusion-function relationship in complex resection - a systems medicine approach" (QuaLiPerF). Within this research unit, this project aims to numerically simulate the mechanically and biologically coupled perfusion-function processes on the lobular level. The hepatic lobular level is the connection between the next larger (organ vascular system) and the next smaller (cell system) level. This allows the simulation of two- and three-dimensional (2D/3D) liver lobule groups (up to 20). We will study the changes in blood perfusion during fat accumulation and calculate the transient spatial distribution of fat accumulation in the liver lobules. The model will provide information on perfusion changes induced by fat accumulation via portal vein ligation (PVL) and liver resection ((e)PHx). We will extend the model to simulate tissue growth and structural changes during liver regeneration. A time-dependent reorientation approach of the sinusoids will be incorporated. The deformation, flow and transport processes will be modelled using a system of coupled partial differential equations (PDE), while the metabolic processes and fat accumulation will be described using a systems biology approach using a system of ordinary differential equations (PDE-ODE coupling). The high-resolution, hyperelastic and porous lobular model is developed and verified within a thermodynamically consistent continuum mechanical multiphase and multi-scale approach. The model is directly founded on first principles of mechanics and based on the extended theory of porous media (eTPM). In addition, the lobular model is linked to the macro-vessel system at the organ level via coupled boundary values. The variations in blood perfusion and heterogeneity in the liver lobules are transferred to the organ multi-scale model during fat accumulation, after PVL, after (e)PHx and during regeneration. We will increase computational speed and efficiency by approaches to model reduction. Methods for this are the discrete empirical interpolation method (DEIM), proper orthogonal decomposition (POD) or a combination of both. Artificial neural networks (ANN) are to be used as a surrogate model for the high-fidelity multi-phase and multi-scale models.Finally, we will lay the foundation for the long-term vision of the research unit to build a clinically applicable 3D modelling computer tool that enables function-based surgical planning and risk assessment. As a proof-of-concept study, we will visualize clinical and simulation data using a commercial program to create a first demonstration of impaired function and perfusion at organ and lobular level after a predetermined resection.