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Modelling the impact of clot fragmentation on the microcirculation after thrombectomy.

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.

SUBMITTER: El-Bouri WK

PROVIDER: S-EPMC7990195 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeBoth intravenous thrombolysis (IVT) and intra-arterial endovascular thrombectomy (ET) improve the outcome of patients with acute ischaemic stroke, with endovascular thrombectomy being an option for those patients with large vessel occlusions. We sought to understand how organisation of services affects time to treatment for both intravenous thrombolysis and endovascular thrombectomy.MethodA multi-objective optimisation approach was used to explore the relationship between the number of intravenous thrombolysis and endovascular thrombectomy centres and times to treatment. The analysis is based on 238,887 emergency stroke admissions in England over 3 years (2013-2015).ResultsProviding hyper-acute care only in comprehensive stroke centres (CSC, providing both intravenous thrombolysis and endovascular thrombectomy, and performing >150 endovascular thrombectomy per year, maximum 40 centres) in England would lead to 15% of patients being more than 45 min away from care, and would create centres with up to 4300 stroke admissions/year. Mixing hyper-acute stroke units (providing intravenous thrombolysis only) with comprehensive stroke centres speeds time to intravenous thrombolysis and mitigates admission numbers to comprehensive stroke centres, but at the expense of increasing time to endovascular thrombectomy. With 24 comprehensive stroke centres and all remaining current acute stroke units as hyper-acute stroke units, redirecting patients directly to attend a comprehensive stroke centre by accepting a small delay (15-min maximum) in intravenous thrombolysis reduces time to endovascular thrombectomy: 25% of all patients would be redirected from hyper-acute stroke units to a comprehensive stroke centre, with an average delay in intravenous thrombolysis of 8 min, and an average improvement in time to endovascular thrombectomy of 80 min. The balance of comprehensive stroke centre:hyper-acute stroke unit admissions would change from 24:76 to 49:51.ConclusionPlanning of hyper-acute stroke services is best achieved when considering all forms of acute care and ambulance protocol together. Times to treatment need to be considered alongside manageable and sustainable admission numbers.

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Modelling the impact of clot fragmentation on the microcirculation after thrombectomy.

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