Lattice boltzmann based simulation of blood vessel normalization in tumors

肿瘤血管以混乱的方式生长。这会损害化疗药物的输送。肿瘤血管的正常化已被证明是提高随后施用的化疗药物的效率的有希望的方式。抗VEGF疗法的主要作用是降低血管渗漏（水力传导率）、降低血管直径和修剪未成熟血管网络。据认为，这些因素中的每一个都可能影响血管网络的功能。 不幸的是，抗VEGF疗法影响血管结构和渗漏。这些变化是动态的并且在时间上重叠，并且很难确定药物递送最佳的一致和可预测的正常化。这在很大程度上是由于系统的非线性，以及在临床试验或动物研究中无法区分血管渗漏减少的影响和由于结构网络变化引起的影响。为了解决这个问题，我们将开发数学模型来解耦血管渗漏和网络结构变化。这将允许确定在抗血管生成治疗期间每个因素如何影响流动模式、氧气分布和药物递送。了解水力传导性和网络结构如何增强化疗药物的递送，将允许合理使用现有药物，或设计新的药物，以改善化疗。对于血管重塑过程的模拟，我们提出了一种基于格子Boltzmann的模拟。该模拟应能够在实际3D网络上求解血管网络的完整血液动力学。此外，它必须能够基于红细胞的分布来计算系统中的氧气分布。由此，可以计算生长因子（即VEGF）的分布，然后基于局部剪切应力和VEGF浓度实现血管结构的局部重塑。

Tumor blood vessels grow in a chaotic manner. This compromises the delivery of chemo therapeutics. Normalization of tumor blood vessels has shown to be a promising way to improve the efficiency of subsequently administered chemotherapeutics. The predominant effects of anti-VEGF therapies are decreased vessel leakiness hydraulic conductivity), decreased vessel diameters and pruning of the immature vessel network. It is thought that each of these can influence the functionality of the vessel network. Unfortunately, anti-VEGF therapies affect vessel structure and leakiness. These changes are dynamic and overlapping in time, and it has been difficult to identify a consistent and predictable normalization during which drug delivery is optimal. This is largely due to the non-linearity in the system, and the inability to distinguish the effects of decreased vessel leakiness from those due to structural network changes in clinical trials or animal studies.To address this problem, we will develop mathematical model to decouple vascular leakiness and network structural changes. This will allow determination of how each factor influences flow patterns, oxygen distribution, and drug delivery during anti-angiogenic therapy. An understanding of how hydraulic conductivity and network architecture act to enhance delivery of chemotherapeutics, will allow rational use of existing drugs, or the design of new ones, to improve chemotherapy.For the simulation of the vascular remodeling process we propose a lattice Boltzmann based simulation. This simulation should be able to solve the full hemodynamic of the vessel network on an actual 3D network. Further it has to be able to calculate the oxygen distribution in of the system based the distribution of red blood cells. From this the distribution of growth factors (i.e. VEGF) can be calculated which then enables an local remodeling of the vessel structure based on the local shear stress and VEGF concentration.