PROJECT SUMMARY/ABSTRACT The importance of achieving stone-free status during endoscopic kidney stone surgery is emphasized by the high rate of repeat stone procedures due to residual fragments after index surgery. Specifically, residual stone fragments can lead to obstruction, pain, kidney injury, and recurrent infections. Successful endoscopic stone surgery requires the surgeon to visualize the entire renal collecting system and locate all kidney stones during treatment. Several challenges can lead to incomplete stone treatment and include inadequate stone visibility and difficulty navigating through the kidney. Specifically, blood or debris can frequently obscure the already limited field of view during endoscopic stone surgery. Additionally, successfully navigating through the collecting system requires the surgeon to mentally create a 3D model of the patient’s anatomy from preoperative 2D axial computerized tomography (CT) images. During treatment, moreover, stones can fragment and disperse throughout the collecting system, further complicating intraoperative tracking. Though technical constraints of scopes may also impact surgical kidney stone outcomes, the above limitations of endoscopic stone treatment prevent many surgeons from achieving a complete stone-free status. Our overall goal is to create a navigational system that makes stone localization and tracking within the renal collecting system easier and more accurate for the surgeon. Toward this goal, our specific objective in this proposal is to test the hypothesis that a navigational system during endoscopic stone surgery can improve stone- free rates, mitigating recurrent surgeries or complications from residual fragments. To test this hypothesis, we propose two Specific Aims: Aim 1 involves the development of an automatic, real-time segmentation and tracking system of kidney stones during endoscopic stone surgery. Aim 2 integrates a 3D navigational map of collecting system anatomy and kidney stone location during endoscopic surgery. The endpoint of this R21 will be a fully validated navigational system for endoscopic stone surgery and the necessary experimental data to power a large-scale, multi-center clinical trial. As our navigational system would require only software integration to current endoscopic surgical cameras, all existing endoscopic surgical systems could in principle immediately benefit from the results of this project. In this way, we believe the success of our project will facilitate improved stone-free rates and mitigate repeat interventions or complications, benefiting patients, surgeons, and society.