1. Specific aims We will refine and validate probes to integrate with the NASA Flexible Ultrasound System (FUS) to address Exploration Medical Capabilities (ExMC) Gap 4.02 Nephrolithiasis. AIM 1. Refine ultrasound probes to detect, reposition, and fragment kidney stones. AIM 2. Validate probes to visualize, reposition, and fragment stones. AIM 3. Refine and validate imaging to guide therapy. 2. Key Findings A probe and software to image and reposition kidney stones were developed and integrated on a radiation hardened flexible ultrasound system (FUS) and demonstrated effectively on human subjects. A probe to image, reposition, and fragment stones was designed, fabricated, and integrated into an FUS and is currently in clinical trials to expel stone fragments. Software was developed and integrated on an FUS and validated in human subjects to improve kidney stone detection and size determination. The ability to reposition stones was also integrated into the partially completed NASA FUS with the NASA FUS probes and demonstrated. The work has garnered attention. Reports have been sent to NSBRI (National Space Biomedical Research Institute), FDA (Food & Drug Administration), NIH (National Institutes of Health), NASA, and OMB (Office of Management and Budget). Demonstrations have been conducted at American Urological Association (AUA) annual meetings each year, Congress twice, and several other professional societies. Over 40 papers have been published. Over 40 patent applications have been submitted. Students, residents, and fellows have trained on the project. Technology developed in this research has been licensed to a spin-off company SonoMotion Inc. 3. Impact We have invented a technology to reposition kidney stones and demonstrated it works in people. In four of the cases, what appeared as one large stone on x-ray was two or three small passable stones. This had direct diagnostic benefit to these subjects and changed their course of treatment. In four other subjects, we moved stones out of the kidney, which they passed. This result was a direct therapeutic benefit to these subjects. One subject felt relief from a painful obstructing stone. We have shown we can produce a working prototype, develop sufficiently high-quality imaging to guide treatment, train new users, and conduct a successful clinical trial. We refined the system design, submitted for publication in vitro results quantifying the improvement, and entered a second clinical trial. The refined design also has the capability to fragment stones. This design is being commercialized. Specifically, we have now implemented our technologies with different probes making it efficient to add the probes NASA selects or to continue to refine the probes we can provide. Our imaging software can be added to an FUS or commercial imager. Our pushing capability has been added as a software upgrade to the FUS. Our advanced repositioning and fragmenting probe is readily integrated with any standard or FUS imager with minimal additional mass and software change to the system. Our final system and the system being commercialized, when validated in human in a flight analog, largely close the gap of nephrolithiasis or exploration mission and extends application to the emergency department on Earth. Our new stone sizing technique can be used on any imager by any user to improve the accuracy of stone size determination with ultrasound. Overestimated stone size leads to unnecessary surgeries, and underestimated stone size leads to obstructions and ER (emergency room) visits. Stone size similarly determines risk and course of action in space. 4. Proposed Research We are conducting a clinical trial of S-mode software for automatic stone detection and stone sizing. We are conducting a clinical trial of expelling stone fragments. We have received approval and set up the infrastructure for an test of ultrasonic propulsion in an Emergency Department (ED) analog to a space emergency, and seek funding for that trial. We are testing safety and effectiveness in clinical simulation in animal studies of stone breaking to add this capability to our ED trial. The technology is also being tested for gallstones.