Prevention of Renal Stone Complications in Space Exploration

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.

Kidney stones have long been near the top of NASA's list of concerns; mitigating Gap 4.02 medical condition Nephrolithiasis is a shall for all missions beyond the International Space Station (ISS). Likewise, stones have plagued humans since ancient Egypt. Currently, one in eleven Americans has suffered from stones -- more than have diabetes or cardiovascular disease. Dehydration, stasis, and bone demineralization are strong contributors to kidney stones, and occur in microgravity, increasing the risk of stones in space. Stones are often debilitating, and pilots cannot fly with stones. Stones occurred on a Russian space mission, and the mission was nearly aborted before the stone passed. Over 30 stones have occurred shortly following even short duration space flights. NASA has collected compelling evidence for concern on its website https://humanresearchroadmap.nasa.gov/Evidence/medicalConditions/Nephrolithiasis.pdf . Additionally, since the website publication, the total number of astronaut stone episodes has more than doubled, and a drug introduced to combat visual impairment/intracranial pressure has exacerbated the risk. Science, experience, and the negative medical consequences support concern for the risk of stones in space. NASA and NSBRI have focused considerable attention on stones and made progress. However, there are many types of stone disease, and it is unlikely that stone disease will ever be completely prevented on Earth or in space. We propose a way to prevent or minimize the consequences of any stones that form while in space. The treatment for most kidney stones is to encourage natural passage. To quote NASA's expectations in space Based on current Lifetime Surveillance of Astronaut Health (LSAH) data, 80 to 85% of in-flight cases of nephrolithiasis are expected to be best case scenarios (defined as a renal stone that responds to conservative treatment, e.g., analgesics and hydration), and 15 to 20% would be worst case scenarios (defined as a renal stone that does not respond to conservative treatment, e.g., requires lithotripsy or surgical treatment). Even surgery leaves residual fragments that must pass. Our technology provides the capability to reposition stones within the kidney and ureter, which will enhance conservative treatment or surgery by accelerating and facilitating passage of stones or fragments. However, this does not have to be the only use. The technology can also be used to reposition a stone to a non-obstructing location within the kidney to postpone surgery or to accelerate passage through the ureter, as proposed here. Finally, the technology proposed in this grant also provides the capability to comminute the stone as in shock wave lithotripsy (SWL) with what we call burst wave lithotripsy (BWL).

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