Multiscale Dynamics of Blood Flow and Associated Cycling Hypoxia in Vascular Tumours

血管肿瘤血流的多尺度动力学和相关的循环缺氧

• 批准号: EP/X023869/1
• 负责人: Yaron Ben-Ami
• 金额: $ 26万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX023869%2F1
• 关键词: Multiscale; Dynamics; Blood; Flow; Associated

It has long been hypothesised that the abnormal and heterogeneous architecture of tumour vascular networks promotes irregular spatio-temporal variations in blood flow rates, haematocrit distribution, and consequent oxygen delivery. These irregularities can cause the formation of cyclic hypoxic areas - regions experiencing transient periods of oxygen deprivation and reoxygenation. Exposure to such fluctuating oxygen levels is assumed to select and promote metastatic spread and resistance to radio- and chemo-therapy. Consequently, understanding the microstructural and fluid-dynamic mechanisms that promote macroscopic oxygenation oscillations and how they may be clinically altered is of great importance.The goal of this project is to develop a multiscale mathematical framework to model blood flow and oxygen transport within vascular tumours, in order to shed light on the links between microscopic haemodynamic mechanisms and the emergence of cycling hypoxia at the macroscale. The methodology will be based on multiple-scale homogenisation - a formal mathematical approach used to derive systems of continuum equations, by upscaling descriptions of transport phenomena from the single capillary scale to the macroscopic scale of the tumour. Using this method, I will establish how microstructural vascular heterogeneities, together with flow-nonlinearities induced by haematocrit-dependent blood viscosity and biased haematocrit partitioning at vessel branch-points, can lead to macroscopic flow-oscillations and consequent unsteady tissue oxygenation. The mathematical framework thus developed could be used, in the longer term, to identify tumour structures that will benefit from transient vascular normalisation treatments, to predict the consequent effect of such protocols on diminishing hypoxia, and thereby improve and personalise tumour responses to existing treatments.

长期以来，人们一直假设肿瘤血管网络的异常和异质结构会促进血流速率、血细胞比容分布和随后的氧气输送的不规则时空变化。这些不规则性会导致周期性缺氧区域的形成，即经历短暂缺氧和复氧的区域。暴露于这种波动的氧气水平被认为会选择和促进转移扩散以及对放疗和化疗的抵抗。因此，了解促进宏观氧合振荡的微观结构和流体动力学机制以及如何在临床上改变它们非常重要。该项目的目标是开发一个多尺度数学框架来模拟血管肿瘤内的血流和氧运输，以阐明微观血流动力学机制与循环缺氧的出现之间的联系。 宏观尺度。该方法将基于多尺度均质化——一种用于推导连续方程组的正式数学方法，通过将传输现象的描述从单一毛细管尺度升级到肿瘤的宏观尺度。使用这种方法，我将确定微结构血管异质性以及由血细胞比容依赖性血液粘度和血管分支点处的血细胞比容分配偏差引起的血流非线性如何导致宏观血流振荡和随后的不稳定组织氧合。从长远来看，由此开发的数学框架可用于识别将受益于短暂血管正常化治疗的肿瘤结构，预测此类方案对减少缺氧的后续影响，从而改善和个性化肿瘤对现有治疗的反应。