Notice and Invitation Oral Defense of Doctoral Dissertation The Volgenau School of Engineering, George Mason University Felicitas Josephine Detmer Bachelor of Science, Karlsruhe Institute of Technology, 2014 Master of Science, Otto von Guericke University Magdeburg, 2016 Aneurysm Rupture Risk Analysis and Risk Prediction Modeling Based on CFD Simulations and Statistical Learning Monday, September 23, 2019, 9:30am - 11:30am Krasnow, Room 229 All are invited to attend. Committee Dr. Juan R. Cebral, Chair Dr. Parag Chitnis Dr. Fernando Mut Dr. Martin Slawski Abstract Cerebral aneurysms are a common vascular disease occurring in about 2-3% of the general population. While most aneurysms remain asymptomatic and never rupture during a patient's lifetime, aneurysm rupture leads to subarachnoid hemorrhage, a subtype of stroke, which is associated with high mortality, morbidity, and substantial economic burden. Today, an increasing number of unruptured aneurysms are diagnosed as incidental findings. Since the risks related to treatment and post-treatment complications outweigh the relatively low natural aneurysm rupture risk, about 1% per patient per year on average, the assessment of a patient's individual aneurysm rupture risk is essential. The mechanisms leading to aneurysm rupture are, however, not fully understood, complicating the risk assessment. Different risk factors have been associated with aneurysm rupture in previous studies, including hemodynamic, morphological, anatomical, and patient-related parameters. Combining such factors into a statistical model for predicting aneurysm rupture could assist physicians in their treatment decision of unruptured aneurysms. Currently available models either do not include hemodynamic or morphological information, or are based on small sample sizes. This dissertation addresses this current problem with the development of statistical models for aneurysm rupture combining the different types of risk factors and using data of large patient cohorts with about 2,000 aneurysms for model development and evaluation. The models encompass a general aneurysm risk assessment model, a specialized model for aneurysms at one particular location in the cerebral vasculature, models extended to different patient populations, and models taking the influence of variations of a patient's blood flow on the aneurysm hemodynamics into account. Hemodynamic parameters are particularly included in the analyses and models because of their role in aneurysm development, growth, and rupture through biomechanical signaling mechanisms in the vessel wall. We will show that the combination of hemodynamic, morphological, anatomical, and patient-related factors in a statistical model enables accurate prediction of aneurysm rupture status. Once evaluated with longitudinal data, translation of such a model into the clinic could support physicians in their treatment decisions of unruptured aneurysms and potentially improve patient outcome.