PROJECT SUMMARY/ABSTRACT Knee osteoarthritis (KOA) is a pervasive and debilitating disease, affecting over 15 million people in the US alone. Symptoms include pain, stiffness, and ultimately loss of joint function. Medical therapies are the mainstay of treatment as surgical joint replacement is typically reserved for advanced disease. Only half of patients treated by medical management with disease not severe enough to warrant surgery experience adequate pain relief, resulting in an estimated population of 3.6 million Americans who are left suffering. Genicular artery embolization (GAE) is a novel, minimally invasive treatment that uses radiologic techniques to catheterize pathologically hyperemic genicular arteries using live X-ray guidance with subsequent occlusion of these vessels using injected microspheres. GAE is performed to inhibit or blunt synovial inflammation thought to be a primary phenotype of KOA. While initial GAE studies have shown to significantly reduce pain associated with KOA, these studies do not account for the greater than 40% placebo effect known to occur with KOA treatments. A sham-controlled study is therefore central to validating the efficacy of this procedure. Prior to performing this pivotal trial, we propose to conduct a pilot sham-controlled GAE study of 40 patients to document feasibility of enrollment and understand the magnitude of effect between these two interventions for future statistical power analysis. We also hope to establish MRI as an objective imaging biomarker for positive remodeling of the knee that occurs after GAE due to decreased synovitis. If the results of this study are positive, we plan to conduct a definitive sham-controlled study to justify the use of GAE in medically refractory KOA and help provide a treatment option to the millions of people with this disease.