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

Matthew J Gounis,Stephen J Payne,Tamás I Józsa,Andrew Macgowan,Wahbi K El-Bouri

doi:10.1371/journal.pcbi.1008515

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.

Highlights

Stroke is the second largest cause of mortality and of adult disability globally [1]
After an ischaemic stroke—one where a clot blocks a major artery in the brain—patients can undergo a procedure where the clot is removed mechanically via a catheter—a
This paper seeks to answer, through modelling informed by in-vitro experiments, the following questions: To what extent is clot fragmentation responsible for the post-thrombectomy no-reflow phenomenon? Can the changes in the blood flow modelling parameters due to micro-emboli showers be accurately quantified such that they can be used in the full organ models? What impact do thrombectomy technique and clot consistency have on downstream blood flow post-thrombectomy?

Summary

Introduction

Stroke is the second largest cause of mortality and of adult disability globally [1]. Many patients do not recover full perfusion in their tissue downstream of the recanalized vessel [6] This observation, commonly known as the “no-reflow” or “no-reperfusion” phenomenon, has been documented in numerous studies involving both animals and humans [7,8,9,10,11,12]. Hypotheses for this phenomenon include: changes in the ultrastructure of the microvasculature and spontaneous blood clotting [7], capillary stalling and leukocyte adhesion [10, 13,14,15], breakdown of the blood-brain barrier leading to tissue swelling and vessel collapse [12, 16, 17], vasoconstriction of the capillary vessels due to pericyte death [10, 18, 19], oxidative stress and inflammatory responses [11], and micro-emboli fragments post-recanalization blocking micro-vessels downstream of the clot [8, 20]

Methods

Results

Conclusion