Wise S M, Lowengrub J S, Cristini V
Mathematics Department, University of Tennessee, Knoxville, TN 37996-1300, USA.
Math Comput Model. 2011 Jan 1;53(1-2):1-20. doi: 10.1016/j.mcm.2010.07.007.
In this paper we give the details of the numerical solution of a three-dimensional multispecies diffuse interface model of tumor growth, which was derived in (Wise et al., J. Theor. Biol. 253 (2008)) and used to study the development of glioma in (Frieboes et al., NeuroImage 37 (2007) and tumor invasion in (Bearer et al., Cancer Research, 69 (2009)) and (Frieboes et al., J. Theor. Biol. 264 (2010)). The model has a thermodynamic basis, is related to recently developed mixture models, and is capable of providing a detailed description of tumor progression. It utilizes a diffuse interface approach, whereby sharp tumor boundaries are replaced by narrow transition layers that arise due to differential adhesive forces among the cell-species. The model consists of fourth-order nonlinear advection-reaction-diffusion equations (of Cahn-Hilliard-type) for the cell-species coupled with reaction-diffusion equations for the substrate components. Numerical solution of the model is challenging because the equations are coupled, highly nonlinear, and numerically stiff. In this paper we describe a fully adaptive, nonlinear multigrid/finite difference method for efficiently solving the equations. We demonstrate the convergence of the algorithm and we present simulations of tumor growth in 2D and 3D that demonstrate the capabilities of the algorithm in accurately and efficiently simulating the progression of tumors with complex morphologies.
在本文中,我们详细给出了肿瘤生长三维多物种扩散界面模型的数值解,该模型在(怀斯等人,《理论生物学杂志》253卷(2008年))中被推导出来,并被用于(弗里博斯等人,《神经影像学》37卷(2007年))中研究神经胶质瘤的发展,以及在(贝尔等人,《癌症研究》,69卷(2009年))和(弗里博斯等人,《理论生物学杂志》264卷(2010年))中研究肿瘤侵袭。该模型具有热力学基础,与最近开发的混合模型相关,并且能够提供肿瘤进展的详细描述。它采用了扩散界面方法,即尖锐的肿瘤边界被由于细胞物种间的差异粘附力而产生的狭窄过渡层所取代。该模型由用于细胞物种的四阶非线性对流 - 反应 - 扩散方程(Cahn - Hilliard型)与用于底物成分的反应 - 扩散方程耦合而成。该模型的数值解具有挑战性,因为这些方程是耦合的、高度非线性的且数值刚性大。在本文中,我们描述了一种用于有效求解这些方程的完全自适应非线性多重网格/有限差分方法。我们证明了该算法的收敛性,并给出了二维和三维肿瘤生长的模拟结果,这些结果展示了该算法在准确且高效地模拟具有复杂形态的肿瘤进展方面的能力。