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(2) Renal:Risk of Renal Stone Formation
Sapozhnikov, Oleg ( University of Washington )
Carter, Stephen ( University of Washington )
(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 are:
Specific Aim 1: Support ongoing leveraged efforts in Acoustic Hemostasis (AH) and HIFU Tumor Ablation (TA) by addressing fundamental scientific issues as well as to ensure NSBRI relevance.
Specific Aim 2: Develop methods and technology that would enable detection of renal stones with ultrasound.
Specific Aim 3: Develop technology and perform in vitro studies of stone comminution.
Specific Aim 4: Utilizing technology and protocols developed in SAs 2 and 3, perform in vivo studies in a porcine model.
(2) The key findings and associated research productivity for year 1 are:
- Developed an automated ultrasound guided high intensity focused ultrasound (HIFU) system to detect and stop bleeding: Published paper.
- 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.
- Developed a body of evidence on methods to accelerate HIFU therapy with the use of shock waves: Papers published.
- Tested new Doppler ultrasound-based kidney stone detection method in vitro, in animals, and in humans: Filed 3 Records of Invention with the University of Washington TechTransfer Office.
- 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.
- Miniaturized device to size stone fragments for safe extraction and tested operation in kidney: Submitted U.S. utility patent application and published paper.
- Developed correlation between ultrasound-induced and monitored vasoconstriction; discovered that vasoconstriction reduces injury during stone fragmentation therapy: Published paper.
- 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 JSC Exploration Medical Capability element of the Human Research Program.
- Copyrighted and licensed technology describing new HIFU sources and test equipment.
(3) 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 on board 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 earthbound utility as well.
(4) Our 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 CT in patients. Acceleration of stone passage by focused ultrasound will be investigated in a porcine animal model.
Specifically our work this year has provided the following Earthbound benefits, viz.,
1. We demonstrated a way to automate the detection and treatment of bleeding.
2. We have 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 have 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 has 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 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.
Task 1A1. Perform studies of bleeding detection in a flow-phantom model. A model and a method to excise but not detach the femoral arteries in live pigs have been developed.
Task 1B1. Perform studies to determine pressure and temperature in ex vivo tissue exposed to HIFU. A paper co-authored by M.S. Canney, V. A. Khokhlova, O.V. Bessonova, M. R. Bailey, and L. A. Crum, entitled "Millisecond boiling produced by high intensity focused ultrasound," was submitted in February 2009 to the journal Ultrasound in Medicine and Biology.
Task 2A. Develop new stone detection techniques based on radiation force and reverberation responsible for the twinkling artifact and vibroacoustography. We have completed considerable data collection and have begun an analysis of the data to improve understanding of the mechanisms and algorithms for use. Three records of invention describing the evidence for this new understanding have been filed. We also reported progress in the following paper: A. Shah, M. Paun, J. Kucewicz, O. A. Sapozhnikov, M. Dighe, H. A. McKay, M. D. Sorensen, and M. R. Bailey, "Investigation of an ultrasound imaging technique to target kidney stones in lithotripsy," J. Acoust. Soc. Am., 125(4, Pt. 2), 2620 (2009).
Task 2B. Investigate stone-sizing technology in tissue. We have submitted for publication our progress in this task in the following article: M.D. Sorensen, J.M.H. Teichman, and M.R. Bailey, "A Proof of Principle of a Prototype Ultrasound Technology to Size Stone Fragments During Ureteroscopy," J. Endourology in press 2009, We have also filed U.S. and international utility patent applications, and are negotiating licensing.
Task 3A. Utilize the YUANDE HIFU tumor ablation device as a platform for determining the acoustic protocols necessary for ultrasound-based stone comminution. No significant progress to report. For business reasons, effort has shifted to a second clinical device.
Task 3B. Engineer and optimize an image-guided, two-frequency HIFU system for renal stone comminution. In year one, we have focused on moving small stones within the kidney with ultrasound to facilitate natural stone clearance. Results were reported at the American Urology and Laparoendoscopic Surgeons meetings. Stone comminution work is scheduled to continue later in the Research Project.
Task 4A. Perform in vivo tests of the imaging protocols developed in Task 2. Investigations are underway for stone detection not only in animals but in humans. Human protocols have been approved and added to the grant.
Task 4B. Perform studies to determine the potential for HIFU-induced stone comminution as well as any associated tissue injury. In vivo studies of stone clearance are underway.
Proceedings of Acoustics '08 Paris, Joint meeting of the Acoustical Society of America, ASA, the European Acoustics Association, EAA, and the Société Française d’Acoustique, SFA, Paris, France, June 29-July 4, 2008. , Jul-2008
Proceedings of 2008 IEEE Ultrasonics Symposium, November 2008. , Nov-2008
Proceedings from 18th International Symposium on Nonlinear Acoustics, July 2008. , Jul-2008
Proceedings of 2nd International Urolithiasis Research Symposium. AIP Conference Proceedings, vol. 1049, p. 348-352, September 18, 2008. http://dx.doi.org/10.1063/1.2998057 , Sep-2008
J Acoust Soc Am. 2009 Apr;125(4, Pt 2):2620. , Apr-2009
(2) Renal:Risk of Renal Stone Formation
Carter, Stephen J ( University of Washington )
Bailey, Michael R ( University of Washington )
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