Chen Ying, Wise Steven M, Shenoy Vivek B, Lowengrub John S
Department of Mathematics, University of California, Irvine, CA, USA.
Int J Numer Method Biomed Eng. 2014 Jul;30(7):726-54. doi: 10.1002/cnm.2624. Epub 2014 Jan 17.
In this paper, we extend the 3D multispecies diffuse-interface model of the tumor growth, which was derived in Wise et al. (Three-dimensional multispecies nonlinear tumor growth-I: model and numerical method, J. Theor. Biol. 253 (2008) 524-543), and incorporate the effect of a stiff membrane to model tumor growth in a confined microenvironment. We then develop accurate and efficient numerical methods to solve the model. When the membrane is endowed with a surface energy, the model is variational, and the numerical scheme, which involves adaptive mesh refinement and a nonlinear multigrid finite difference method, is demonstrably shown to be energy stable. Namely, in the absence of cell proliferation and death, the discrete energy is a nonincreasing function of time for any time and space steps. When a simplified model of membrane elastic energy is used, the resulting model is derived analogously to the surface energy case. However, the elastic energy model is actually nonvariational because certain coupling terms are neglected. Nevertheless, a very stable numerical scheme is developed following the strategy used in the surface energy case. 2D and 3D simulations are performed that demonstrate the accuracy of the algorithm and illustrate the shape instabilities and nonlinear effects of membrane elastic forces that may resist or enhance growth of the tumor. Compared with the standard Crank-Nicholson method, the time step can be up to 25 times larger using the new approach.
在本文中,我们扩展了肿瘤生长的三维多物种扩散界面模型,该模型由怀斯等人(《三维多物种非线性肿瘤生长 - I:模型与数值方法》,《理论生物学杂志》253卷(2008年)524 - 543页)推导得出,并纳入了刚性膜的影响,以模拟在受限微环境中的肿瘤生长。然后,我们开发了精确且高效的数值方法来求解该模型。当膜具有表面能时,该模型是变分的,并且涉及自适应网格细化和非线性多重网格有限差分法的数值格式被证明是能量稳定的。也就是说,在没有细胞增殖和死亡的情况下,对于任何时间和空间步长,离散能量是时间的非增函数。当使用膜弹性能的简化模型时,所得模型的推导类似于表面能情况。然而,弹性能模型实际上是非变分的,因为某些耦合项被忽略了。尽管如此,遵循表面能情况中使用的策略开发了一种非常稳定的数值格式。进行了二维和三维模拟,展示了算法的准确性,并说明了可能抵抗或促进肿瘤生长的膜弹力的形状不稳定性和非线性效应。与标准的克兰克 - 尼科尔森方法相比,使用新方法时时间步长可以增大到25倍。