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Modelling the effects of cerebral microthrombi on tissue oxygenation and cell death
bioRxiv - Neuroscience Pub Date : 2021-01-18 , DOI: 10.1101/2021.01.16.426717
Yidan Xue , Wahbi K. El-Bouri , Tamás I. Józsa , Stephen J. Payne

Thrombectomy, the mechanical removal of a clot, is the most common way to treat ischaemic stroke with large vessel occlusions. However, perfusion cannot always be restored after such an intervention. It has been hypothesised that the absence of reperfusion is due to the clot fragments that block the downstream vessels. In this paper, we present a new way of quantifying the effects of cerebral microthrombi on oxygen transport to tissue in terms of hypoxia and ischaemia. The oxygen transport was simulated with the Green's function method on physiologically accurate microvascular cubes, which was found independent of both microvascular geometry and length scale. The microthrombi occlusions were then simulated in the microvasculature, which were extravasated over time with a new vessel extravasation model. The tissue hypoxic fraction was fitted as a sigmoidal function of vessel blockage fraction, which was then taken to be a function of time after the formation of microthrombi occlusions. A novel hypoxia-based 3-state cell death model was finally proposed to simulate the hypoxic tissue damage over time. Using the cell death model, the impact of a certain degree of microthrombi occlusions on tissue viability and microinfarct volume can be predicted over time. Quantifying the impact of microthrombi on oxygen transport and tissue death will play an important role in full brain models of ischaemic stroke and thrombectomy.

中文翻译:

模拟脑微血栓对组织氧合和细胞死亡的影响

血栓切除术是一种机械清除血栓的方法,是治疗大血管闭塞性缺血性卒中的最常见方法。然而,在这样的干预之后不能总是恢复灌注。假设没有再灌注是由于阻塞下游血管的凝块碎片所致。在本文中,我们提出了一种新的量化缺氧和局部缺血方面脑微血栓对氧向组织运输的作用的新方法。使用格林函数方法在生理上精确的微血管立方体上模拟了氧气的运输,发现该过程与微血管的几何形状和长度尺度无关。然后在微脉管系统中模拟微血栓闭塞,并随时间用新的血管渗出模型进行渗出。将组织缺氧分数拟合为血管阻塞分数的S形函数,然后将其视为微血栓闭塞形成后时间的函数。最终提出了一种新型的基于缺氧的三态细胞死亡模型,以模拟随时间变化的缺氧组织损伤。使用细胞死亡模型,可以预测一段时间内一定程度的微血栓闭塞对组织活力和微梗塞体积的影响。量化微血栓对氧传输和组织死亡的影响将在缺血性中风和血栓切除的全脑模型中发挥重要作用。最终提出了一种新型的基于缺氧的三态细胞死亡模型,以模拟随时间变化的缺氧组织损伤。使用细胞死亡模型,可以预测一段时间内一定程度的微血栓闭塞对组织活力和微梗塞体积的影响。量化微血栓对氧传输和组织死亡的影响将在缺血性中风和血栓切除的全脑模型中发挥重要作用。最终提出了一种新型的基于缺氧的三态细胞死亡模型,以模拟随时间变化的缺氧组织损伤。使用细胞死亡模型,可以预测一段时间内一定程度的微血栓闭塞对组织活力和微梗塞体积的影响。量化微血栓对氧传输和组织死亡的影响将在缺血性中风和血栓切除的全脑模型中发挥重要作用。
更新日期:2021-01-19
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