Theoretical simulation of tumour oxygenation and results from acute and chronic hypoxia
Theoretical simulation of tumour oxygenation and results from acute and chronic hypoxia
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DOI：
10.1088/0031-9155/48/17/307
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发表时间：
2003-09-07
影响因子：
3.5
通讯作者：
Karlsson, M
中科院分区：
文献类型：
--
作者：
Dasu, A;Toma-Dasu, I;Karlsson, M
肿瘤微环境被认为对癌症治疗的结果负责，因此表征和量化它是极其重要的。不幸的是，目前可用的大多数实验技术都是侵入性的，通常不知道这如何影响结果。另一方面，非侵入性方法具有几何分辨率，并不总是适合于肿瘤反应的建模。微环境的理论模拟可能是一种替代方法，可以为准确描述肿瘤组织提供定量数据。本文提出了一个计算机模型，允许模拟肿瘤氧合。该模型以二维几何形式模拟氧气扩散和消耗的基本物理过程，以研究描述组织几何形状的不同参数的影响。本文还提出了一种新的方法来模拟扩散受限（慢性）缺氧和灌注受限（急性）缺氧的影响。结果表明，所有描述组织脉管系统的参数都是描述组织氧合的重要参数。假设血管结构是通过血管间距离的分布来描述的，那么为了充分表征组织氧合，就需要分布的平均值和宽度。不完整的数据，如在组织的非代表性区域测量的分布，可能无法给出相关的组织氧合。肿瘤氧合的理论模型也允许区分急性和慢性缺氧细胞，这一区别在其他方法中并不总是能看到。我们观察到，急性缺氧细胞的比例不仅取决于在任何特定时刻塌陷的血管的比例，而且还取决于血管在空间上的分布。这些都表明，从基本原理出发的组织氧合理论建模是一种稳健的方法，可以用来量化组织氧合，并为其他模拟提供输入参数。
The tumour microenvironment is considered to be responsible for the outcome of cancer treatment and therefore it is extremely important to characterize and quantify it. Unfortunately, most of the experimental techniques available now are invasive and generally it is not known how this influences the results. Non-invasive methods on the other hand have a geometrical resolution that is not always suited for the modelling of the tumour response. Theoretical simulation of the microenvironment may be an alternative method that can provide quantitative data for accurately describing tumour tissues.This paper presents a computerized model that allows the simulation of the tumour oxygenation. The model simulates numerically the fundamental physical processes of oxygen diffusion and consumption in a two-dimensional geometry in order to study the influence of the different parameters describing the tissue geometry. The paper also presents a novel method to simulate the effects of diffusion-limited (chronic) hypoxia and perfusion-limited (acute) hypoxia.The results show that all the parameters describing tissue vasculature are important for describing tissue oxygenation. Assuming that vascular structure is described by a distribution of inter-vessel distances, both the average and the width of the distribution are needed in order to fully characterize the tissue oxygenation. Incomplete data, such as distributions measured in a nonrepresentative region of the tissue, may not give relevant tissue oxygenation.Theoretical modelling of tumour oxygenation also allows the separation between acutely and chronically hypoxic cells, a distinction that cannot always be seen with other methods. It was observed that the fraction of acutely hypoxic cells depends not only on the fraction of collapsed blood vessels at any particular moment, but also on the distribution of vessels in space as well.All these suggest that theoretical modelling of tissue oxygenation starting from the basic principles is a robust method that can be used to quantify the tissue oxygenation and to provide input parameters for other simulations.