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胶质瘤沿白质束生长:基于多尺度扩散张量成像的模型

Glioma follow white matter tracts: a multiscale DTI-based model.

作者信息

Engwer Christian, Hillen Thomas, Knappitsch Markus, Surulescu Christina

机构信息

Institut für Numerische und Angewandte Mathematik, WWU Münster, Münster, Germany,

出版信息

J Math Biol. 2015 Sep;71(3):551-82. doi: 10.1007/s00285-014-0822-7. Epub 2014 Sep 12.

Abstract

Gliomas are a class of rarely curable tumors arising from abnormal glia cells in the human brain. The understanding of glioma spreading patterns is essential for both radiological therapy as well as surgical treatment. Diffusion tensor imaging (DTI) allows to infer the white matter fibre structure of the brain in a noninvasive way. Painter and Hillen (J Theor Biol 323:25-39, 2013) used a kinetic partial differential equation to include DTI data into a class of anisotropic diffusion models for glioma spread. Here we extend this model to explicitly include adhesion mechanisms between glioma cells and the extracellular matrix components which are associated to white matter tracts. The mathematical modelling follows the multiscale approach proposed by Kelkel and Surulescu (Math Models Methods Appl Sci 23(3), 2012). We use scaling arguments to deduce a macroscopic advection-diffusion model for this process. The tumor diffusion tensor and the tumor drift velocity depend on both, the directions of the white matter tracts as well as the binding dynamics of the adhesion molecules. The advanced computational platform DUNE enables us to accurately solve our macroscopic model. It turns out that the inclusion of cell binding dynamics on the microlevel is an important factor to explain finger-like spread of glioma.

摘要

神经胶质瘤是一类源于人类大脑中异常神经胶质细胞的难以治愈的肿瘤。了解神经胶质瘤的扩散模式对于放射治疗和手术治疗都至关重要。扩散张量成像(DTI)能够以非侵入性方式推断大脑的白质纤维结构。佩因特和希伦(《理论生物学杂志》323:25 - 39,2013年)使用动力学偏微分方程将DTI数据纳入一类用于神经胶质瘤扩散的各向异性扩散模型。在此,我们扩展该模型以明确纳入神经胶质瘤细胞与细胞外基质成分之间的粘附机制,这些成分与白质束相关。数学建模遵循凯尔凯尔和苏勒雷斯库(《数学模型与方法应用科学》23(3),2012年)提出的多尺度方法。我们使用尺度论证来推导此过程的宏观平流 - 扩散模型。肿瘤扩散张量和肿瘤漂移速度既取决于白质束的方向,也取决于粘附分子的结合动力学。先进的计算平台DUNE使我们能够精确求解我们的宏观模型。结果表明,在微观层面纳入细胞结合动力学是解释神经胶质瘤指状扩散的一个重要因素。

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