Alamer Moath, Yun Xu Xiao
Department of Chemical Engineering Imperial College London, South Kensington Campus, London, United Kingdom.
Biophys Rep. 2021 Feb 28;7(1):35-54. doi: 10.52601/bpr.2021.200041.
Tumour vasculature is known to be aberrant, tortuous and erratic which can have significant implications for fluid flow. Fluid dynamics in tumour tissue plays an important part in tumour growth, metastasis and the delivery of therapeutics. Mathematical models are increasingly employed to elucidate the complex interplay between various aspects of the tumour vasculature and fluid flow. Previous models usually assume a uniformly distributed vasculature without explicitly describing its architecture or incorporate the distribution of vasculature without accounting for real geometric features of the network. In this study, an integrated computational model is developed by resolving fluid flow at the single capillary level across the whole tumour vascular network. It consists of an angiogenesis model and a fluid flow model which resolves flow as a function of the explicit vasculature by coupling intravascular flow and interstitial flow in tumour tissue. The integrated model has been used to examine the influence of microvascular distribution, necrosis and vessel pruning on fluid flow, as well as the effect of heterogeneous vessel permeability. Our results reveal the level of nonuniformity in tumour interstitial fluid pressure (IFP), with large variations in IFP profile between necrotic and non-necrotic tumours. Changes in microscopic features of the vascular network can significantly influence fluid flow in the tumour where removal of vessel blind ends has been found to reduce IFP and promote interstitial fluid flow. Our results demonstrate the importance of incorporating microscopic properties of the tumour vasculature and intravascular flow when predicting fluid flow in tumour tissue.
已知肿瘤血管系统异常、曲折且不规则，这可能对流体流动产生重大影响。肿瘤组织中的流体动力学在肿瘤生长、转移和治疗药物递送中起着重要作用。越来越多的数学模型被用于阐明肿瘤血管系统各个方面与流体流动之间的复杂相互作用。先前的模型通常假设血管系统分布均匀，而没有明确描述其结构，或者在不考虑网络实际几何特征的情况下纳入血管分布。在本研究中，通过解析整个肿瘤血管网络中单个毛细血管水平的流体流动，开发了一个综合计算模型。它由一个血管生成模型和一个流体流动模型组成，该流体流动模型通过耦合肿瘤组织中的血管内流动和间质流动，将流动解析为明确血管系统的函数。该综合模型已被用于研究微血管分布、坏死和血管修剪对流体流动的影响，以及血管通透性异质性的影响。我们的结果揭示了肿瘤间质液压力（IFP）的不均匀程度，坏死肿瘤和非坏死肿瘤之间的IFP分布存在很大差异。血管网络微观特征的变化可显著影响肿瘤中的流体流动，已发现去除血管盲端可降低IFP并促进间质液流动。我们的结果证明了在预测肿瘤组织中的流体流动时，纳入肿瘤血管系统的微观特性和血管内流动的重要性。
