Development of a multi-physics and multi-scale model of thrombolysis for patient-specific appplications

Abstract

Thromboembolic diseases such as myocardial infarction and ischemic stroke are one of the main causes of death in the world. These pathologies occur when an abnormal blood clot develops in the human body and travels throughout the circulatory system as an embolus. If the occlusion takes place in the cerebral arteries, it can lead to acute ischemic stroke which, if not treated rapidly, will cause morbidity and death. One of the forms of treatment for ischemic stroke is thrombolytic therapy whereby a drug known as alteplase is provided intravenously to the patient so as to dissolve the occluding thrombus. This treatment, however, can provoke life-threatening side-effects such as intracerebral haemorrhage (ICH) and therefore is limited to only a subset of patients that are free of contraindications. Furthermore, thrombolytic therapy can sometimes be ineffective in treating certain types of occlusions. As such, there is considerable interest in the medical community in determining the scenarios where thrombolytic therapy can be ineffective and how existing treatment can be optimised.

To this end, a multi-physics and multi-scale computational model has been developed in an attempt to simulate the treatment of ischemic stroke with thrombolytic therapy. Blood flow and drug transport are described by partial differential equations that are solved with the aid of computational fluid dynamics (CFD) software. Fibrinolysis is described using a microscale model whereby changes in the clot microstructure give rise to changes in macroscopic properties of the clot such as clot resistance and composition. Arterial geometries include idealised models using CAD software and patient-specific models extracted from computed tomography angiography (CTA) images. Physiological flow boundary conditions are implemented by using 3 element Windkessel models while drug transport boundary conditions are determined with the aid of a compartmental model. Clots of different shapes, lengths and locations are studied and their dissolution patterns are examined under different thrombolysis regimens.

Predicted changes in the intra-arterial flowrate and pressure are consistent with data in the literature. The results show that under the assumption of homogeneous clot properties, clot lysis patterns are strongly dependent on clot position, whereas clot dissolution time is merely determined by clot length. Numerical simulations of different thrombolysis regimens indicate that treatment dose and duration can be personalised according to clot length and clot composition in order to lower the risk of ICH (intracerebral haemorrhage) and ensure successful vessel recanalization. It is demonstrated that the computational model developed in this study can be used to investigate clot dissolution in patient-specific geometries. Future work will attempt to test the use of this computational model in clinical settings and as an aid in the development of new therapies.