Prevention of Renal Stone Complications in Space Exploration
Principal Investigator:
Michael R. Bailey, Ph.D.
Organization:
University of Washington
This project will refine and validate plug-and-play sensor and effector probes to integrate with the NASA Flexible Ultrasound (FUS) unit to address the medical condition Nephrolithiasis (kidney stones) listed in the ExMC Gap Report 4.02, specifically ExMC Gap Report 4.13 Limited capability to diagnose and treat a renal stone. In summary, astronauts are at an increased risk of stone development because of microgravity, dehydration, and altered bone metabolism associated with space flight. The risk is that a stone, while innocuous when still in the kidney, will cause debilitating pain as it passes or worse, become obstructing, which can lead to urinary tract infection, sepsis, renal failure, and death. Short of surgery there is currently no available technology to affect when the stone moves from the kidney or manipulate the stone once it has begun to move.
The University of Washington invented and developed ultrasound technology to reposition stones to facilitate stone passage from the kidney. Using a Verasonics FUS (VFUS), commercial handheld probe, and real-time imaging, the stone and kidney are visualized and, with a touch of the screen, a short burst of ultrasound waves are focused on the stone to reposition (push) the stone to a new location. Development of the technology has focused on the clearance of stone fragments after shock wave lithotripsy (SWL). This proposal will refine the probe and software, and validate use for space-based needs including to a) detect and move ureteral stones, b) prevent or relieve an obstruction, c) manipulate de novo stones attached to kidney papillae, and d) comminute stones and expel the residual fragments. The result will be delivery of a probe and software that can be implemented on the NASA FUS to provide an option, where currently in space there is none, to treat most any in-flight kidney stone situation.
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).
Device Description: We have invented a diagnostic ultrasound imager enhanced with hardware and software to add the novel capability to reposition kidney stones. This is a software based ultrasound unit that allows the user to control virtually all aspects of the transmit and receive processes.
The system is programmed and controlled through a COTS host personal computer using MATLAB. We have added/modified the software and graphical user interface (GUI) to image and reposition stones. The GUI is displayed on a touch screen monitor allowing easy control of the ultrasound system parameters. The system operates with three COTS transducers, Philips/ATL C5-2, C4-2, and P4-1. The system is programmed for Bmode, Harmonic, and Doppler imaging. This can be done both in scan line (conventional) imaging mode or flash imaging mode. In conventional imaging, the transmit phase on each transducer element is adjusted to create a focused ultrasound beam. In flash imaging all of the transducer elements are activated simultaneously and in-phase creating a planar excitation wave. The use of plane wave imaging allows for higher frame rates. Stone push is achieved through the use of a higher amplitude, longer duration burst similar to that used for elastography-type or transiently increased output imaging.
Treatment Protocol: The probe is placed in contact with the patient's skin, and the kidney and stone are imaged following standard ultrasound imaging procedures. The same probe is then used to focus the ultrasound and apply a burst of acoustic pulses to push the stone. The operator aligns the transducer with the desired direction of stone motion and then activates the push through either a mouse click or by touching the screen directly. Bmode imaging is interleaved with the "pushing" pulses to monitor stone movement. The push pulse can be applied to any location and any depth within the image.
Specific Aims:
AIM 1. Refine probes to detect, reposition, and fragment kidney stones. This aim follows a staged development process to systematically improve our ability to detect, reposition, and fragment stones. We successfully implemented stone repositioning with "older" probe technology and expelled 65% of stones implanted in a porcine model. Treatment was limited by the need to pause up to 30 s between push bursts to prevent the transducer from overheating. "Newer" probes use single crystal technology, and improved backing and matching layers to obtain greater efficiency and bandwidth. Greater bandwidth and efficiency provide the opportunity to incorporate improved techniques, such as harmonic imaging, which is now standard for kidney imaging.
AIM 2. Validate probes to detect, reposition, and fragment kidney stones. The probe will be validated to perform space-relevant stone treatment procedures in preclinical studies. The procedure to be selected largely depends on the stone size. A large stone (>9 mm) cannot pass: it may be desirable to keep it in the kidney (Task 2.1). A medium stone (6-9 mm) may pass but may need help (Task 2.2). A large or medium obstructing stone that cannot be moved likely needs to be fragmented (Task 2.3). Remaining fragments (<6mm) may require repositioning to pass (already demonstrated). And given the above options, it may be desirable to detach and expel a small stone (<6mm) before it becomes symptomatic (Task 2.4). AIM 3. Refine and validate imaging to guide therapy. Treatment planning is primarily based on stone size and location. Ultrasound, though, consistently overestimates stone size, making treatment planning difficult. It is also difficult to visualize a stone within the ureter using ultrasound because of the presence of bowel. Our goal for Aim 3 is to refine the FUS imaging capabilities to improve stone sizing, improve stone detection within the ureter, and incorporate 3D imaging to help guide in the repositioning and comminuting of stones.
Earth Applications
One in 11 Americans have had stones. Most form more than one stone over time. Our goal is an office based procedure to use ultrasound to image and treat these stones and thereby to avoid surgery and repeated x-ray monitoring. Some of the many applications of the novel technology may include relieving obstructing calculi, pre-positioning of stones for improved surgical outcomes, imaging confirmation of stone number and size, and repositioning small kidney stones or residual fragments to facilitate their passage. There is commercial and clinical interest in the technology as it has the potential to change the way stones are treated for many people.
