Key influencers in an aneurysmal thrombosis model: A sensitivity analysis and validation study

Thrombosis is a biological response closely related to intracranial aneurysms, and the formation of thrombi inside the aneurysm is an important determinant of outcome after endovascular therapy. As the regulation of thrombosis is immensely complicated and the mechanisms governing thrombus formation are not fully understood, mathematical and computational modeling has been increasingly used to gain insight into thrombosis over the last 30 years. To have a robust computational thrombosis model for possible clinical use in the future, it is essential to assess the model's reliability through comprehensive sensitivity analysis of model parameters and validation studies based on clinical information of real patients. Here, we conduct a global sensitivity analysis on a previously developed thrombosis model, utilizing thrombus composition, the flow-induced platelet index, and the bound platelet concentration as output metrics. These metrics are selected for their relevance to thrombus stability. The flow-induced platelet index quantifies the effect of blood flow on the transport of platelets to and from the site of thrombus formation and thus on the final platelet content of the formed thrombus. The sensitivity analysis of the thrombus composition indicates that the concentration of resting platelets most influences the final thrombus composition. Then, for the first time, we validate the thrombosis model based on a real patient case using patient-specific resting platelet concentration and two previously calibrated trigger thresholds for thrombosis initiation. We show that our thrombosis model is capable of predicting thrombus formation both before and after endovascular treatment.