The major goals of this effort are to utilize existing ultrasound platforms and the concept of image-guided therapy to control traumatic bleeding, ablate cancerous tumors, and diagnose and clear kidney stones. Our methods and devices are countermeasures to specific risks described in the:

1. Lack of advanced therapeutic capability;

2. Lack of capability to treat renal stones; and

3. Lack of noninvasive diagnostic imaging capabilities.

1. Support ongoing leveraged efforts in acoustic hemostasis (AH) and high intensity focused ultrasound (HIFU) tumor ablation by addressing fundamental scientific issues as well as to ensure NSBRI relevance.

2. Develop methods and technology that would enable detection of renal stones with ultrasound.

3. Develop technology and perform in vitro studies of stone comminution.

4. Utilize the technology and protocols developed in Aims 2 and 3, to perform in vivo studies in a porcine model.

Key Findings and Associated Research Productivity

1. Developed an automated ultrasound-guided HIFU system to detect and stop bleeding. Published paper.

2. Began initial investigation of HIFU-induced tumor-specific immune response in collaboration with Fred Hutchinson Cancer Research Institute. Obtained NIH funding to support a Postdoctoral Fellow on the work.

3. Developed a body of evidence on methods to accelerate HIFU therapy with the use of shock waves. Papers published.

4. Tested new Doppler ultrasound-based kidney stone detection method in vitro, in animals and in humans. Filed three Records of Invention with the University of Washington Tech Transfer Office.

5. Developed method to use focused ultrasound to move kidney stones and stone fragments within the kidney to expedite stone clearance. Presented work to American Urology Association.

6. Miniaturized device to size stone fragments for safe extraction and tested operation in kidney. Submitted U.S. utility patent application and published paper.

7. Developed correlation between ultrasound-induced and monitored vasoconstriction; discovered that vasoconstriction reduces injury during stone fragmentation therapy. Published paper.

8. Participated in the generation of a white paper through gap analysis of medical risk 4.15 (Lack of lithotripsy or other capability to treat a renal stone) by the NASA Johnson Space Center Exploration Medical Capability element of the Human Research Program.

9. Copyrighted and licensed technology describing new HIFU sources and test equipment.

These findings are self-explanatory, but we wish to highlight the broader impact on kidney stone disease. Our new detection technique requires only a software change, at most, to existing ultrasound technology onboard the International Space Station (ISS). It is sensitive and easy to use. Our belief is that this approach will provide NASA with the capability to detect even small, asymptomatic stones. The next phase of our work will be to use focused ultrasound, which could also be generated with only modest software reprogramming of the existing ISS ultrasound device, to dislodge the stone and push it toward the opening of the ureter where it could be naturally passed. In this way, a potential critical clinical problem would be solved by early diagnosis and prevention, rather than by last-minute and difficult therapy. This methodology has obvious and significant Earth-based utility as well.

Future Plans
Future plans will focus on continued automation, cancer treatment and the prevention of complications from kidney stones. We have obtained access to a programmable ultrasound imager that we will program to test our new stone detection algorithms. The immune-response study, initiated by seed funds from our NSBRI cost match, will be continued under NIH sponsorship; hopefully, it will be determined that HIFU can induce a systemic tumor-specific immune response in mice. Investigation and improvement of the stone detection technique will continue by direct comparison of simulation and measurement. The technique to detect stones at pre-symptomatic levels will be tested against standard ultrasound, fluoroscopy and computed tomography (CT) in patients. Acceleration of stone passage by focused ultrasound will be investigated in a porcine animal model.

Earth-based Applications of Research Project
In general, this project advances a new technology, high-intensity focused ultrasound (HIFU), toward clinical application. HIFU machines have treated over 100,000 cancer patients in China and over 5,000 in Europe and Japan. The only indication approved by the FDA for the use of HIFU on patients is that of uterine fibroids. Dozens of start-up companies and the big three ultrasound companies GE, Philips, and Siemens are developing HIFU machines. We are beginning to license our intellectual property to the commercial sector. We were intimately involved in the founding of the International Society for Therapeutic Ultrasound and currently play major roles in its administration. Similarly, we have helped establish the International Kidney Stone Institute and have authored consensus reports on lithotripsy and ultrasound safety.

Specifically our work this year has provided the following Earth benefits:

1. We demonstrated a way to automate the detection and treatment of bleeding.

2. We designed and initiated a study to test the hypothesis that HIFU can generate a systemic immune response and have high hopes for progress in this area.

3. We offered the HIFU community significant insight into how to plan, execute and monitor HIFU treatments. For Earthbound HIFU, we have raised considerable concern over the accuracy of the gold standard (MR thermometry) used to ensure heating only where desired.

4. Our efforts to develop a Doppler ultrasound-based, kidney stone detection method have several applications. It appears at least as good a fluoroscopy in targeting and could therefore replace this approach and its ionizing radiation. It also can be used real-time, and therefore could compensate for respiratory motion during treatment. Lastly, an accurate ultrasound imaging system could be used in the urologist's office to localize stones and to replace the need for computed tomography (CT) scans.

5. Our new method to use focused ultrasound to move kidney stones could be used whenever residual stones are observed after treatment. These stones get trapped and do not pass naturally. They then serve as a nucleus for future stones.

6. Our miniaturized device to size stone fragments may soon be used during ureteroscopy to determine stone size before attempting to extract stones too large to pass through a finite-sized lumen.

7. We have licensed new HIFU sources and test equipment to a vendor who will provide these tools to researchers, clinicians, regulators and manufacturers to accelerate the implementation of clinical HIFU applications.

Project Description
NASA Task Book Entry