Abstract Atrial fibrillation is the most common form of cardiac arrhythmia, with prevalence estimated to be 5.2 million in 2010 and predicted to increase to 12.1 million in 2030. Atrial fibrillation is a major risk factor for blood clots and stroke, independently increasing stroke risk 4- to 5-fold throughout all ages. Therefore, the vast majority of patients with atrial fibrillation require some form of stroke prevention therapy. Current first line stroke prevention therapy for atrial fibrillation patients is life-long use of oral anti-coagulation medications, which are associated with increase in bleeding risk by approximately 2- to 2.5-fold, including intracranial hemorrhage, that may lead to hospitalization, transfusion, surgery, and death. The purpose of the present study is to improve stroke prevention treatment for non-valvular atrial fibrillation by transforming the Left Atrial Appendage Occlusion (LAAO) procedure into a first line therapy for a larger segment of patient populations, especially for younger patients with 20+ year of life expectancy who are likely to experience bleeding problems in their lifetimes. LAAO is a minimally invasive procedure where an implant delivered using an intravascular catheter is used to permanently seal off the left atrial appendage mechanically to reduce the risk of blood clots. The barriers preventing LAAO from becoming a first line therapy are primarily safety and cost. The investigators aim to overcome these barriers and transform LAAO into a first line therapy by developing a real-time Magnetic Resonance Imaging (MRI)-guided robotic intravascular catheter system for performing LAAO procedures by synergistically combining novel medical imaging, robotic catheter control, and advanced visualization technologies to improve the safety, cost, and workflow of LAAO procedures. The proposed technology expands on novel approaches initiated by the investigators in earlier work in the areas of real-time MRI image acquisition and reconstruction, robotic catheters actuated using the magnetic field of the MRI scanner, advanced visualization, and volumetric planning of LAAO. The project is organized into three Specific Aims, each focusing on one key aspect of the procedure workflow, namely, procedure planning, transseptal puncture, and LAAO implant delivery. These Specific Aims build on crosscutting technical research on MRI, robotics, and human-machine interface technologies, where the investigators will develop novel technologies for rapid and flexible 2D/3D cardiac MRI imaging, robotically controlled MRI-compatible dexterous cardiac catheters, and human-machine interfaces with advanced visualization. The end result of this proposal will be the complete prototype of an MRI-guided robotic catheter system for performing LAAO procedures combining real-time intraoperative MRI, robotic catheter control, and advanced visualization technologies to facilitate safer, more efficient, and cost-effective LAAO procedures. The ...