Thrombus analogue material: Mechanical characterisation and use in in-vitro modelling of acute ischemic stroke treatment
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Acute ischemic stroke (AIS), which accounts for approximately 85% of all strokes globally, is among the leading causes of death and long-term disability. It occurs when a blood clot causes an occlusion in a blood vessel, resulting in reduced blood flow to an area of the brain. Mechanical thrombectomy (MT), where the clot is removed from the occluded vessel, has become the new standard of care in stroke treatment. In-vitro thrombus analogs are very useful in the pre-clinical testing of devices intended for use in thrombectomy, where amongst other things they can be used to evaluate the number of attempts required to remove the thrombus and the associated risk of embolisation. Some key determinants for success of the thrombectomy procedure are the mechanical properties and composition of the occluding thrombus. In this thesis, a range of clot analogues with varying compositions and mechanical behaviour are developed. A repeatable test method, that can be used to test a broad range of clot types, is presented and for the first time, an investigation of the mechanical behaviour of clot analogues, as a function of composition, is reported. The effect of platelet-driven contraction on the mechanical properties and microstructure of the clot analogues is also investigated. An appropriate hyper-viscoelastic constitutive model is identified and fitted to the experimental results. The clot analogues were then used in the development of an appropriate in-vitro model of AIS. This model was used to compare the effectiveness of various MT techniques on clots with varying mechanical properties. Finally, the in-vitro model was used to investigate the effect of clot mechanical properties and composition on the occlusion dynamics and deformation of an occluding clot under physiological conditions of pressure and flow, using the previously characterised clot analogues. The compression test set-up was found to be robust enough to test a broad range of clots, and the clot analogues were found to have similar mechanical behaviour to the human thromboemboli. Clot analogue composition was found to strongly affect the observed mechanical behaviour. Similarly, platelet-contraction was found to significantly affect clot volume and microstructure, and in turn, clot stiffness. The proposed hyper-viscoelastic constitutive model was found to successfully capture the material test data. The feasibility of the in-vitro AIS mode was demonstrated and a limited evaluation of different MT approaches was performed. Although a more comprehensive analysis is required to draw definitive conclusions when comparing techniques, the clot mechanical behaviour was found to impact the effectiveness of various MT techniques. Similarly, the clot mechanical behaviour and composition was also found to affect the clot behaviour and angiographic appearance when lodged in the in-vitro model under physiological conditions. This behaviour may be useful in the identification of particular clot types prior to treatment, and could assist the physician in selecting the most appropriate treatment method to administer or on what MT technique to use, to ensure a greater success rate in each case. In conclusion, the work performed in this thesis has led to an enhanced understanding of the mechanical behaviour of thrombus material. The mechanical characterisation and modelling presented are of key importance and offer a framework that could be used as an aid in the future development of treatment devices and procedures for AIS.
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