Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United Kingdom.
Liverpool Centre for Cardiovascular Science, Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom.
PLoS Comput Biol. 2021 Mar 12;17(3):e1008515. doi: 10.1371/journal.pcbi.1008515. eCollection 2021 Mar.
Many ischaemic stroke patients who have a mechanical removal of their clot (thrombectomy) do not get reperfusion of tissue despite the thrombus being removed. One hypothesis for this 'no-reperfusion' phenomenon is micro-emboli fragmenting off the large clot during thrombectomy and occluding smaller blood vessels downstream of the clot location. This is impossible to observe in-vivo and so we here develop an in-silico model based on in-vitro experiments to model the effect of micro-emboli on brain tissue. Through in-vitro experiments we obtain, under a variety of clot consistencies and thrombectomy techniques, micro-emboli distributions post-thrombectomy. Blood flow through the microcirculation is modelled for statistically accurate voxels of brain microvasculature including penetrating arterioles and capillary beds. A novel micro-emboli algorithm, informed by the experimental data, is used to simulate the impact of micro-emboli successively entering the penetrating arterioles and the capillary bed. Scaled-up blood flow parameters-permeability and coupling coefficients-are calculated under various conditions. We find that capillary beds are more susceptible to occlusions than the penetrating arterioles with a 4x greater drop in permeability per volume of vessel occluded. Individual microvascular geometries determine robustness to micro-emboli. Hard clot fragmentation leads to larger micro-emboli and larger drops in blood flow for a given number of micro-emboli. Thrombectomy technique has a large impact on clot fragmentation and hence occlusions in the microvasculature. As such, in-silico modelling of mechanical thrombectomy predicts that clot specific factors, interventional technique, and microvascular geometry strongly influence reperfusion of the brain. Micro-emboli are likely contributory to the phenomenon of no-reperfusion following successful removal of a major clot.
许多接受机械血栓清除术（血栓切除术）的缺血性脑卒中患者尽管血栓已被清除，但组织仍未再灌注。对于这种“无再灌注”现象的一个假设是，在血栓切除术中，大血栓上的微栓子碎裂并阻塞血栓位置下游的较小血管。这在体内是无法观察到的，因此我们在这里开发了一种基于体外实验的计算模型，以模拟微栓子对脑组织的影响。通过体外实验，我们在各种血栓一致性和血栓切除术技术下，获得血栓切除术后的微栓子分布。血流通过微血管系统进行建模，包括穿透性小动脉和毛细血管床，这些血管的统计准确体素。一种新的微栓子算法，根据实验数据进行模拟，用于模拟微栓子依次进入穿透性小动脉和毛细血管床的影响。在各种条件下计算放大的血流参数-通透性和耦合系数。我们发现，与穿透性小动脉相比，毛细血管床更容易发生阻塞，每阻塞单位血管的通透性下降 4 倍。个体微血管几何形状决定了对微栓子的鲁棒性。硬血栓碎裂会导致更大的微栓子和更大的血流下降，给定数量的微栓子。血栓切除术技术对血栓碎裂和微血管中的阻塞有很大影响。因此，机械血栓切除术的计算模型表明，血栓特定因素、介入技术和微血管几何形状强烈影响大脑的再灌注。微栓子可能是成功清除大血栓后出现无再灌注现象的原因之一。
