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Modelling the impact of clot fragmentation on the microcirculation after thrombectomy

El-Bouri, Wahbi K.
MacGowan, Andrew
Jozsa, Tamas I.
Gounis, Matthew J
Payne, Stephen J.
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Abstract

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.

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El-Bouri WK, MacGowan A, Józsa TI, Gounis MJ, Payne SJ. Modelling the impact of clot fragmentation on the microcirculation after thrombectomy. PLoS Comput Biol. 2021 Mar 12;17(3):e1008515. doi: 10.1371/journal.pcbi.1008515. PMID: 33711015; PMCID: PMC7990195. Link to article on publisher's site

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DOI
10.1371/journal.pcbi.1008515
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33711015
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This article is based on a previously available preprint on bioRxiv that is also available in eScholarship@UMMS.

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Copyright: © 2021 El-Bouri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.