The major goal of this effort is to utilize existing ultrasound platforms and the concept of image-guided therapy to control traumatic bleeding, ablate benign and malignant tumors, and to diagnose and reposition kidney stones. We address (1) Lack of advanced therapeutic capability, (2) lack of capability to treat renal stones, and (3) lack of non-invasive diagnostic imaging capabilities. The original specific aims (SAs) are 1) Support ongoing leveraged efforts in Acoustic Hemostasis and High-intensity Focused Ultrasound (HIFU) Tumor Ablation by addressing fundamental scientific issues as well as to ensure National Space Biomedical Research Institute (NSBRI) relevance. 2) Develop methods and technologies that would enable detection of renal stones with ultrasound. 3) Develop technology and perform in vitro studies of stone comminution. 4) Utilizing technology and protocols developed in SAs 2 and 3, perform in vivo studies in a porcine model. The main findings and associated research productivity for year 4 are:
• We have continued to advance ultrasound technology to detect and reposition kidney stones. The imaging technology provides an alternative to imaging techniques that expose the patient to ionizing radiation on Earth and provides a user-friendly technique to detect even small stones in space. The repositioning technology provides an adjunctive treatment to surgery by which to facilitate the passage of residual fragments that may regrow to new stones, and provides a way to prophylactically remove small stones before they require surgery. The technology is also used to move a large obstructing stone to a non-obstructing location to delay the need for surgery. This year our major accomplishments were entering into the Food and Drug Administration (FDA) approval process for a human feasibility study and starting a company. In pigs we also moved a stone growing de novo, moved an obstructing stone, and moved a stone in the ureter.
• We contributed to the solicitation for a Flexible Ultrasound System (FUS), both as leaders in the platform and inventors of a required clinical capability (detecting and repositioning kidney stones), and an award for delivery of an FUS has now been granted.
• Developed a method and device to characterize the acoustic output of high intensity focused ultrasound (HIFU) devices. The University of Washington (UW) Center for Commercialization (C4C) has filed a provisional patent. The technique was added to the IEC TC87 62256 60601-2-62 standards document. The technology has now been demonstrated on several clinical HIFU systems. NIH (National Institute of Health) funding was obtained.
• Developed a method to accelerate and control tissue ablation with transcutaneous ultrasound. In particular, tissue was mechanically emulsified by millisecond bursts of HIFU at output levels that produce shock waves. C4C has filed a U.S. patent application. The Philips machine was modified to produce these outputs. Our method has several potential advantages over technique used in competitor's $11 million start-up. This year we discovered and published the mechanism by which tissue is fractionated and joined University of Washington (UW) Urology in a proposal to develop urology cancer treatments.
• We published an explanation of the mechanism of the twinkling artifact (TA) that frequently occurs during Doppler ultrasound imaging of kidney stones. These findings lead to the conclusion that bubbles cause the twinkling artifact and as such we have developed and patented several algorithms to exploit this mechanism to better detect kidney stones. Because twinkling is seen on other calcifications in the body, the result also implies bubbles may be present throughout the body, which has significant implications for decompression sickness.
• Due to cost and concerns for repeated ionizing radiation exposure from CT (computed tomography) scans on Earth, ultrasound is often used for the initial evaluation and monitoring of kidney stone patients. In space ultrasound is the only option and size of the stone is critical in treatment planning. We published work, submitted a patent application, and began preliminary work to measure the inaccuracy of ultrasound in sizing stones and develop improvements.
• Obtained funding from U.S. Army to investigate the application of shocked ultrasound to slow bone loss in a murine paralysis model. Bone loss with our best but still not optimized exposure was less than 15% which was statistically significantly lower than the over 30% loss in the control.
• We published results in a porcine model to stop bleeding in a partial nephrectomy. We secured commercialization funding and contracted a vendor to build a refined system. We obtained NIH funding to develop the technology to clinical implementation. This is the same technology we developed with the military to stop bleeding on the battlefield and provides an avenue to develop an commercial off-the-shelf (COTS) device for NASA.
Proposed plan for the next year. We have developed extensive plans to continue forward and have submitted many proposals to continue funding. The efforts are on three fronts. One is to conduct a human feasibility study. The second is to start the company. The third is to secure NSBRI funding to develop the same capabilities for the FUS and to refine and test the system for NASA's unique applications. We were subcontract on one proposal to develop the FUS but did not receive that award. The NSBRI proposal aims are to refine and validate probes to detect, reposition, and fragment kidney stones.
Tasks are 1. Implement capability to image and reposition stones on the selected FUS manufacturer's state-of-the-art kidney imaging probe. 2. Integrate a clinical mechanically scanned 4D imaging probe with the FUS and refine and validate stone imaging and repositioning. 3. Develop and integrate a prototype 2D array probe to reposition and fragment stones. 4. Refine and validate capability to displace a large blocking stone, to detect a ureter stone, to displace a ureter stone, to expel a stone attached to tissue, and to measure the size of kidney stones.