模拟血管状态对热疗后肿瘤演变和结局的影响
Modelling the effect of vascular status on tumour evolution and outcome after thermal therapy
摘要：
微尺度氧合在肿瘤进展中起着重要作用。肿瘤微环境中氧分布的时空变异性有助于细胞异质性和常氧和缺氧群体的出现。局部氧水平强烈影响肿瘤对不同治疗方式的施用的反应，并且更普遍地影响对治疗的抗性现象。已经提出了几种干预措施来改善肿瘤氧合，其中提高局部温度（高热）是一种重要的干预措施。虽然必须考虑其他因素，如代谢活动，但肿瘤血管系统的熟练程度是组织氧合及其温度图的关键因素。因此，从数学建模的角度来看，这些因素的相互作用引起了相当大的关注。在这里，我们提出了一个基于运输的偏微分方程系统，旨在描述健康和肿瘤细胞亚群的动态在微尺度上放置在两个血管之间的区域。通过使用该模型与不同的流动条件下，我们分析了在不同的情况下出现的血管状态，无论是在自由的进展和热治疗下的氧气和温度曲线。我们发现，低氧水平与优先由缺氧细胞填充的位置中的温度升高相关，并且高度依赖于血流的高血压诱导的细胞死亡仅会出现在局部脉管系统高度破坏的条件下。这导致热对缺氧细胞的显著影响。此外，当发生明显的细胞死亡时，随之而来的是氧水平的显着增加。
英文摘要：
Microscale oxygenation plays a prominent role in tumour progression. Spatiotemporal variability of oxygen distribution in the tumour microenvironment contributes to cellular heterogeneity and to the emergence of normoxic and hypoxic populations. Local levels of oxygen strongly affect the response of tumours to the administration of different therapeutic modalities and, more generally, to the phenomenon of resistance to treatments. Several interventions have been proposed to improve tumour oxygenation, being the elevation of the local temperature (hyperthermia) an important one. While other factors such as the metabolic activity have to be considered, the proficiency of the tumour vascular system is a key factor both for the tissue oxygenation and for its temperature maps. Consequently, the interplay of these factors has attracted considerable attention from the mathematical modelling perspective. Here we put forward a transport-based system of partial differential equations aimed at describing the dynamics of healthy and tumour cell subpopulations at the microscale in a region placed between two blood vessels. By using this model with diverse flow conditions, we analyse the oxygen and temperature profiles that arise in different scenarios of vascular status, both during free progression and under thermal therapy. We find that low oxygen levels are associated to elevations of temperature in locations preferentially populated by hypoxic cells, and hyperthermia-induced cell death, being strongly dependent on blood flow, would only appear under highly disrupted conditions of the local vasculature. This results in a noticeable effect of heat on hypoxic cells. Additionally, when pronounced cell death occurs, it is followed by a significant increase in the oxygen levels.
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