PROJECT SUMMARY/ABSTRACT End Stage Renal Disease (ESRD) impacts 4.3M patients worldwide and accounts for 7% of all Medicare and Medicaid costs. The most prevalent modality of renal replacement, hemodialysis, requires access to the circulation through which dialysis machinery is connected. The preferred method of access is an arteriovenous (AV) fistula as it confers lower rates of mortality, infection and interventions, however they are the most challenging for dialysis technicians to cannulate. Cannulation damage is one of the primary causes of AV fistula complications and failure. Cannulation failures and injury occur in 91% of patients within 6 months. These injuries can lead to serious complications, such as hematoma, infection, and aneurysm formation including death from hemorrhage, with a secondary impact on morbidity, hospitalization, access revision, and loss of access. The annual rate of major infiltration is 5.2%, with each incident leading to an extra 97 days of catheter dependency and a mean of 2.4 diagnostic tests, surgery appointments, or interventions. When factoring in the additional catheter time and secondary interventions, the financial impact is $21,441 per major infiltration. Ultrasound has been demonstrated to dramatically improve outcomes by reducing CVC time by >30% (50 days) and infections by 37%. However, this was in the hands of nephrology physicians in a study setting and current ultrasound options are too challenging for dialysis technicians and are therefore not used. We have developed an automated 3D ultrasound-based navigation solution, EchoGuide, that is purpose build for dialysis technicians to improve cannulation without specialized training. This study proposes to prove that EchoGuide, when used by dialysis technicians, can substantially reduce cannulation errors and infiltrations for AV fistulae. In this Phase II proposal, we will (1) develop the integrated EchoGuide with custom probe/display hardware, lumen detection algorithms, and real-time interactive navigation; (2) iterate user interface via human factors development to optimize navigation guidance; and (3) extend a validated AVF cannulation simulator to enable ultrasound compatibility in order to demonstrate EchoGuide effectiveness in improving cannulation success by technicians across challenging AVF scenarios. OVERALL IMPACT: EchoGuide will allow rapid and successful cannulation of AV fistulae. This will reduce both the morbidity and costs associated with major infiltration and the associated catheter time and additional interventions.