Modelling the impact of clot fragmentation on the microcirculation after thrombectomy

• Published in: PLoS computational biology Vol. 17; no. 3; p. e1008515
• Main Authors: El-Bouri, Wahbi K, MacGowan, Andrew, Józsa, Tamás I, Gounis, Matthew J, Payne, Stephen J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.03.2021; Public Library of Science (PLoS)
• Subjects: Aging; Analysis; Biology and Life Sciences; Blood clotting; Blood coagulation; Blood flow; Blood vessels; Blood-brain barrier; Brain Ischemia - pathology; Brain Ischemia - therapy; Brain research; Care and treatment; Catheters; Cerebral blood flow; Cerebral embolism and thrombosis; Clinical outcomes; Clotting; Data collection; Diagnosis; Experiments; Humans; Hypotheses; Inflammation; Ischemia; Leukocytes; Medical instruments; Medicine and Health Sciences; Microcirculation; Microvasculature; Occlusion; Oxidative stress; Patients; Permeability; Physical Sciences; Research and Analysis Methods; Stalling; Stroke; Surgery; Thrombectomy; Thrombosis - pathology; Treatment Outcome; Ultrastructure; Vasoconstriction; Veins & arteries; United Kingdom
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1008515

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.