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Fiscal Year: FY 2017  Task Last Updated:  05/11/2017 
PI Name: Bailey, Michael R. Ph.D. 
Project Title: Prevention of Renal Stone Complications in Space Exploration 
   
Division Name: Human Research 
Program/Discipline--
Element/Subdiscipline:
NSBRI--Smart Medical Systems and Technology Team 
 
Joint Agency Name:   TechPort:  Yes 
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) Medical:Risk of Adverse Health Outcomes & Decrements in Performance due to Inflight Medical Conditions (IRP Rev I)
 (2) Renal:Risk of Renal Stone Formation
Human Research Program Gaps: (1) Med12:We do not have the capability to mitigate select medical conditions (IRP Rev I)
Space Biology Element: None
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
PI Email: bailey@apl.washington.edu  Fax:  206-221-6578 
PI Organization Type: UNIVERSITY  Phone: 206-685-8618  
Organization Name: University of Washington 
PI Address 1: Applied Physics Laboratory/CIMU 
PI Address 2: 1013 NE 40th Street 
PI Web Page:  
City: Seattle  State: WA 
Zip Code: 98105-6698  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2012 Crew Health NNJ12ZSA002N 
Start Date: 06/01/2013  End Date:  12/31/2016 
No. of Post Docs: 12  No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment: NOTE: Extended to 12/31/2016 per NSBRI (Ed., 3/11/16)

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Wang, Yak-Nam   ( University of Washington )
Sorensen, Mathew   ( University of Washington )
Khohklova, Vera   ( M.V.Lomonosov Moscow State University )
Sapozhnikov, Oleg   ( University of Washington )
Crum, Lawrence   ( University of Washington )
Harper, Jonathan David   ( University of Washington )
Kreider, Wayne   ( University of Washington ) 
Grant/Contract No.: NCC 9-58-SMST03402 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: 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.

 

Rationale for HRP Directed Research:

 

Research Impact/Earth Benefits: 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).

 

Task Progress: All tasks were completed.

AIM 1. Refine the ultrasound probes to detect, reposition, and fragment kidney stones.

Task 1.1. Select imaging probe for stone repositioning. We enabled the capability to push stones on the as yet incomplete NASA FUS system with the NASA GE C1-6 abdominal imaging probe. These results were reported in an NSBRI Advanced Technology Demonstration: Prevention of Renal Stone Complications in Space Exploration in August 2016.

Deliverable of the grant

The capability to reposition kidney stones noninvasively has been added to the NASA flexible ultrasound system.

Task 1.2. Custom design probe to image, reposition, and fragment stones. We invented Burst Wave Lithotripsy which has fully comminuted stones of all compositions in under 20 minutes and has fragmented many stones in seconds. All work so far has been in water tanks or animals, not humans. The size fragments are controlled by the ultrasound frequency. The technique reduces peak pressure by 1/10th but increases pulse duration about five times and pulse repletion rate at least 20 times to deliver more energy more quickly and possibly without discomfort.

AIM 2. Validate probes to visualize, reposition, and fragment kidney stones.

Task 2.1. Validate capability to displace an obstructing stone.

Task 2.2. Validate capability to displace a ureter stone.

Task 2.3. Validate capability to comminute a stone.

These tasks were completed. A small probe embedded centrally within the Burst Wave Lithotripsy (BWL) therapy probe connected to the Verasonics FUS system provides image guidance for BWL. We have targeted and fragmented human stones surgically placed in over 10 pigs. Preclinical test results have been submitted for publication. A clinical trial of the system is underway.

AIM 3. Refine and validate imaging to guide therapy.

Task 3.1. Refine and validate capability to measure the size of kidney stones. In a series of 3 papers, we demonstrated how ultrasound imaging can be optimized to accuracy similar to CT with user controls as well as software modifications. The imaging we have implemented on the Verasonics FUS appears to size stones more accurately than clinical imagers.

Task 3.2. Refine capability to localize a stone.

Task 3.3. Refine and validate capability to detect a ureter stone. We have developed enhanced B-mode, enhanced Doppler-based twinkling, and combined them into a stone specific imaging mode called S-mode. S-mode has been published. S-mode has been used to image stones in the kidneys and ureters in human subjects. In our most recent study of hundreds of imaging frames from 40 stones and 28 subjects, the signal to noise ratio of S-mode was ten times the grayscale SNR. This paper won Best Abstract at the Engineering and Urology meeting of the AUA in 2016.

 

Bibliography Type: Description: (Last Updated: 04/30/2019) Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Janssen KM, Brand TC, Bailey MR, Cunitz BW, Sorensen MD, Harper JD, Dunmire B. "Effect of stone size and composition on ultrasonic propulsion in vitro." 2017 American Urological Association Annual Meeting, Boston, MA, May 12-16, 2017.

Journal of Urology. 2017 Apr;197(4 Suppl):e835. (2017 Annual Meeting Program Abstracts, AUA Annual Meeting, Boston, MA, May 12-16, 2017.) https://doi.org/10.1016/j.juro.2017.02.1951 , Apr-2017

Articles in Other Journals or Periodicals Sorensen MD, Bailey MR. "Shock Wave Lithotripsy: Application and future direction." Scientific American. 2017 in press as of May 2017. , May-2017
Articles in Peer-reviewed Journals Karzova MM, Yuldashev PV, Sapozhnikov OA, Khokhlova VA, Cunitz BW, Kreider W, Bailey MR. "Shock formation and nonlinear saturation effects in ultrasound field of a diagnostic curvilinear probe." J Acoust Soc Am. 2017 Apr;141(4):2327. http://dx.doi.org/10.1121/1.4979261 ; PubMed PMID: 28464662 , Apr-2017
Articles in Peer-reviewed Journals Bailey MR. "Evaluation of renal calculi passage while riding a roller coaster. (Comment on Mitchell and Wartinger article, 'Validation of a functional pyelocalyceal renal model for the evaluation of renal calculi passage while riding a roller coaster.' PubMed PMID: 27669068 )" Journal of the American Osteopathic Association. 2017 Jun 1;117(6):349-50. https://doi.org/10.7556/jaoa.2017.069 ; PubMed PMID: 28556853 , Jun-2017
Articles in Peer-reviewed Journals Rosnitskiy PB, Yuldashev PV, Sapozhnikov OA, Maxwell AD, Kreider W, Bailey MR, Khokhlova VA. "Design of HIFU transducers for generating specified nonlinear ultrasound fields." IEEE Trans Ultrason Ferroelectr Freq Control. 2017 Feb;64(2):374-90. http://dx.doi.org/10.1109/TUFFC.2016.2619913 ; PubMed PMID: 27775904; PubMed Central PMCID: PMC5300962 , Feb-2017
Articles in Peer-reviewed Journals May PC, Bailey MR, Harper JD. "Ultrasonic propulsion of kidney stones. (Technological Innovations in Urologic Surgery section)" Curr Opin Urol. 2016 May;26(3):264-70. Review. http://dx.doi.org/10.1097/MOU.0000000000000276 ; PubMed PMID: 26845428; PubMed Central PMCID: PMC4821680 , May-2016
Articles in Peer-reviewed Journals May PC, Kreider W, Maxwell AD, Wang YN, Cunitz BW, Blomgren PM, Johnson C, Park JSH, Bailey MR, Lee D, Harper JD, Sorensen MD. "Detection and evaluation of renal injury in burst wave lithotripsy using ultrasound and magnetic resonance imaging." Journal of Endourology. 2017 Aug;31(8):786-92. Epub 2017 May 18. http://dx.doi.org/10.1089/end.2017.0202 ; PubMed PMID: 28521550 , Aug-2017
Articles in Peer-reviewed Journals May PC, Haider Y, Dunmire B, Cunitz BW, Thiel J, Liu Z, Bruce M, Bailey MR, Sorensen MD, Harper JD. "Stone-mode ultrasound for determining renal stone size." J Endourol. 2016 Sep;30(9):958-62. http://dx.doi.org/10.1089/end.2016.0341 ; PubMed PMID: 27393000; PubMed Central PMCID: PMC5031098 , Sep-2016
Articles in Peer-reviewed Journals Simon JC, Dunmire B, Bailey MR, Sorensen MD. "Developing complete ultrasonic management of kidney stones for spaceflight." J Space Safety Eng. 2016 Sep;3(2):50-7. Review. http://dx.doi.org/10.1016/S2468-8967(16)30018-0 , Sep-2016
Articles in Peer-reviewed Journals Khokhlova VA, Yuldashev PV, Rosnitskiy PB, Maxwell AD, Kreider W, Bailey MR, Sapozhnikov OA. "Design of HIFU transducers to generate specific nonlinear ultrasound fields." Physics Procedia. 2016;87:132-8. (45th Annual Symposium of the Ultrasonic Industry Association, UIA 45th Symposium, 4-6 April 2016, Seattle, WA, USA) https://doi.org/10.1016/j.phpro.2016.12.020 , Dec-2016
Articles in Peer-reviewed Journals Brisbane W, Bailey MR, Sorensen MD. "An overview of kidney stone imaging techniques." Nat Rev Urol. 2016 Nov;13(11):654-62. Epub 2016 Aug 31. Review. http://dx.doi.org/10.1038/nrurol.2016.154 ; PubMed PMID: 27578040 , Nov-2016
Articles in Peer-reviewed Journals Maxwell AD, Yuldashev PV, Kreider W, Khokhlova TD, Schade GR, Hall TL, Sapozhnikov OA, Bailey MR, Khokhlova VA. "A prototype therapy system for transcutaneous application of boiling histotripsy." IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control. 2017 Oct;64(10):1542-1557. https://doi.org/10.1109/TUFFC.2017.2739649 ; PubMed PMID: 28809681 [reported originally in May 2017 as in press] , Oct-2017
Articles in Peer-reviewed Journals Dunmire B, Harper JD, Cunitz BW, Lee FC, Hsi R, Liu Z, Bailey MR, Sorensen MD. "Use of the acoustic shadow width to determine kidney stone size with ultrasound." J Urol. 2016 Jan;195(1):171-7. Epub 2015 Aug 22. http://dx.doi.org/10.1016/j.juro.2015.05.111 ; PubMed PMID: 26301788; PubMed Central PMCID: PMC4821497 , Jan-2016
Articles in Peer-reviewed Journals Cunitz BW, Harper JD, Sorensen MD, Haider Y, Thiel J, May PC, Liu Z, Bailey MR, Dunmire B, Bruce M. "Quantification of renal stone contrast with ultrasound in human subjects." J Endourol. 2017 Nov;31(11):1123-30. https://doi.org/10.1089/end.2017.0404 ; PubMed PMID: 28847171; PubMed Central PMCID: PMC5695736 [reported originally in May 2017 as "in review"] , Nov-2017
Articles in Peer-reviewed Journals Lee FC, Hsi RS, Sorensen MD, Paun M, Dunmire B, Liu Z, Bailey M, Harper JD. "Renal vasoconstriction occurs early during shockwave lithotripsy in humans." J Endourol. 2015 Dec;29(12):1392-5. Epub Aug 2015. http://dx.doi.org/10.1089/end.2015.0315 ; PubMed PMID: 26239232; PubMed Central PMCID: PMC4677566 , Dec-2015
Articles in Peer-reviewed Journals Simon JC, Wang YN, Cunitz BW, Thiel J, Starr F, Liu Z, Bailey MR. "Effect of carbon dioxide on the twinkling artifact in ultrasound imaging of kidney stones: A pilot study." Ultrasound Med Biol. 2017 May;43(5):877-83. Epub 2017 Feb 9. http://dx.doi.org/10.1016/j.ultrasmedbio.2016.12.010 ; PubMed PMID: 28190622; PubMed Central PMCID: PMC5385287 , May-2017
Articles in Peer-reviewed Journals Harper JD, Cunitz BW, Dunmire B, Lee FC, Sorensen MD, Hsi RS, Thiel J, Wessells H, Lingeman JE, Bailey MR. "First-in-human clinical trial of ultrasonic propulsion of kidney stones." J Urol. 2016 Apr;195(4 Pt 1):956-64. Epub 2015 Oct 30. http://dx.doi.org/10.1016/j.juro.2015.10.131 ; PubMed PMID: 26521719; PubMed Central PMCID: PMC4851928 , Apr-2016
Articles in Peer-reviewed Journals Janssen KM, Brand TC, Cunitz BW, Wang YN, Simon JC, Starr F, Liggitt HD, Thiel J, Sorensen MD, Harper JD, Bailey MR, Dunmire B. "Safety and effectiveness of a longer focal beam and burst duration in ultrasonic propulsion for repositioning urinary stones and fragments." J Endourol. 2017 Aug;31(8):793-9. Epub 2017 Jun 26. https://doi.org/10.1089/end.2017.0167 ; PubMed PMID: 28537452 , Aug-2017
Articles in Peer-reviewed Journals Oweis GF, Dunmire BL, Cunitz BW, Bailey MR. "Non-invasive measurement of the temperature rise in tissue surrounding a kidney stone subjected to ultrasonic propulsion." Conf Proc IEEE Eng Med Biol Soc. 2015 Aug;2015:2576-9. http://dx.doi.org/10.1109/EMBC.2015.7318918 ; PubMed PMID: 26736818; PubMed Central PMCID: PMC4832570 , Aug-2015
Articles in Peer-reviewed Journals Khokhlova TD, Haider YA, Maxwell AD, Kreider W, Bailey MR, Khokhlova VA. "Dependence of boiling histotripsy treatment efficiency on HIFU frequency and focal pressure levels." Ultrasound Med Biol. 2017 Sep;43(9):1975-85. Epub 2017 Jun 20. https://doi.org/10.1016/j.ultrasmedbio.2017.04.030 ; PubMed PMID: 28641910 , Sep-2017
Articles in Peer-reviewed Journals Cunitz BW, Dunmire B, Bailey MR. "Characterizing the acoustic output of an ultrasonic propulsion device for urinary stones." IEEE Trans Ultrason Ferroelectr Freq Control. 2017 Dec;64(12):1818-27. Epub 2017 Oct 2. https://doi.org/10.1109/TUFFC.2017.2758647 ; PubMed PMID: 28981413; PubMed Central PMCID: PMC5733808 , Dec-2017
Articles in Peer-reviewed Journals Janssen KM, Brand TC, Bailey MR, Cunitz BW, Harper JD, Sorensen MD, Dunmire B. "Effect of stone size and composition on ultrasonic propulsion ex vivo." Urology. 2018 Jan;111:225-9. Epub 2017 Sep 28. https://doi.org/10.1016/j.urology.2017.09.013 ; PubMed PMID: 28964820 , Jan-2018
Articles in Peer-reviewed Journals Simon JC, Sapozhnikov OA, Kreider W, Breshock M, Williams JC, Bailey MR. "The role of trapped bubbles in kidney stone detection with the color Doppler ultrasound twinkling artifact." Phys Med Biol. 2018 Jan 9;63(2):025011. PubMed PMID: 29131810; PubMed Central PMCID: PMC5791757 , Jan-2018
Articles in Peer-reviewed Journals Dai JC, Dunmire B, Sternberg KM, Liu Z, Larson T, Thiel J, Chang HC, Harper JD, Bailey MR, Sorensen MD. "Retrospective comparison of measured stone size and posterior acoustic shadow width in clinical ultrasound images." World J Urol. 2018 May;36(5):727-32. Epub 2017 Dec 14. https://doi.org/10.1007/s00345-017-2156-8 ; PubMed PMID: 29243111 [reported originally in May 2017 as Epub ahead of print] , May-2018
Articles in Peer-reviewed Journals Ghanem MA, Maxwell AD, Kreider W, Cunitz BW, Khokhlova VA, Sapozhnikov OA, Bailey MR. "Field characterization and compensation of vibrational non-uniformity for a 256-element focused ultrasound phased array." IEEE Trans Ultrason Ferroelectr Freq Control. 2018 Sep;65(9):1618-30. Epub 2018 Jun 27. https://doi.org/10.1109/TUFFC.2018.2851188 ; PubMed PMID: 29994675 , Sep-2018
Awards Maxwell A. "Promotion to Research Assist. Prof., March 2017." Mar-2017
Awards Cunitz B. "Engineering and Urology Society Best Abstract award, May 2016." May-2016
Awards Purington B. "University of Washington Distinguished Staff Award, July 2016." Jul-2016
Awards Bailey M. "Promotion to Assoc. Prof., University of Washington, July 2016." Jul-2016
Awards Harper J. "Promotion to Assoc. Prof., University of Washington, July 2016." Jul-2016
Awards Lingeman J. "American Urological Association Distinguished Contribution Award, February 2017." Feb-2017
Awards Simon J. "Promotion to Assist. Prof., January 2017." Jan-2017
Awards Bruce M. "Best Poster. The 21st European Symposium on Ultrasound Contrast Imaging, June 2016. " Jun-2016
Books/Book Chapters Lingeman JE, Beiko D, Bailey MR, Gettman MT, Kohrmann KU, Liatskos E, Matlaga BR, Monga M, Tailly G, Timoney A. "Stone Technology: Shock Wave and Intracorporeal Lithotripsy." in "Stone Disease. A Joint SIU-ICUD International Consultation Glasgow, Scotland, October 12–15, 2014." Ed. J. Denstedt, J. de la Rosette. Montreal: Société Internationale d’Urologie (SIU), 2015. p. 179-278., Jan-2015
Papers from Meeting Proceedings Nikolaeva AV, Sapozhnikov OA, Bailey MR. "Acoustic radiation force of a quasi-Gaussian beam on an elastic sphere in a fluid." 2016 IEEE International Ultrasonics Symposium, Tours, France, September 18-21, 2016.

In: 2016 IEEE International Ultrasonics Symposium. http://dx.doi.org/10.1109/ULTSYM.2016.7728608 , Sep-2016

Significant Media Coverage Lyndon B. Johnson Space Center. "Article 'Soft-Tissue Emulsification Using a Mechanism of Ultrasonic Atomization Inside Gas or Vapor Cavities.' about PI Michael Bailey's work." NASA Tech Briefs, July 2016. MSC-25191-1. http://www.techbriefs.com/component/content/article/ntb/tech-briefs/bio-medical/24976 , Jul-2016
Significant Media Coverage McGrane C. "Article about PI's research, 'NASA-funded UW researchers develop kidney-stone zapping technology.' " GeekWire July 4 2016. https://www.geekwire.com/2016/nasa-funded-uw-researchers-develop-kidney-stone-zapping-technology/ , Jul-2016
Significant Media Coverage Bailey MR. "Dissolving Kidney Stones With Ultrasound." AIUM (American Institute of Ultrasound in Medicine) Soundwaves July 13, 2016, http://www.aium.org , Jul-2016
Significant Media Coverage NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) research update. " 'Moving stones with sound—new ultrasound technology repositions kidney stones in people.' Article about PI's research and journal article in J Urol--Harper JD, Cunitz BW, Dunmire B, Lee FC, Sorensen MD, Hsi RS, Thiel J, Wessells H, Lingeman JE, and Bailey MR. First in human clinical trial of ultrasonic propulsion of kidney stones. J Urol 195: 956-964, 2016. " NIH NIDDK newsletter Jun 10 2016. https://www.niddk.nih.gov/news/research-updates/Pages/moving-stones-sound-new-ultrasound-technology-repositions-kidney-stones-people.aspx , Jun-2016
Significant Media Coverage Focused Ultrasound Foundation. "News highlighting PI's research and new funding: 'Focused Ultrasound in Outer Space?' " Focused Ultrasound Foundation newsletter. July 21, 2016. http://us8.campaign-archive2.com/?u=09c0cdb2fbbdcb0745213c8c5&id=70219944eb&e=44188d89b9 , Jul-2016
Significant Media Coverage American Urological Association. "Newsletter references NIDDK article on 'Moving kidney stones with ultrasound.' referencing journal article in J Urol--Harper JD, Cunitz BW, Dunmire B, Lee FC, Sorensen MD, Hsi RS, Thiel J, Wessells H, Lingeman JE, and Bailey MR. First in human clinical trial of ultrasonic propulsion of kidney stones. J Urol 195: 956-964, 2016. " AUA newsletter Eureka June 2016., Jun-2016
Download in PDF pdf     
Fiscal Year: FY 2015  Task Last Updated:  07/07/2015 
PI Name: Bailey, Michael R. Ph.D. 
Project Title: Prevention of Renal Stone Complications in Space Exploration 
   
Division Name: Human Research 
Program/Discipline--
Element/Subdiscipline:
NSBRI--Smart Medical Systems and Technology Team 
 
Joint Agency Name:   TechPort:  Yes 
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) Medical:Risk of Adverse Health Outcomes & Decrements in Performance due to Inflight Medical Conditions (IRP Rev I)
 (2) Renal:Risk of Renal Stone Formation
Human Research Program Gaps: (1) Med12:We do not have the capability to mitigate select medical conditions (IRP Rev I)
Space Biology Element: None
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
PI Email: bailey@apl.washington.edu  Fax:  206-221-6578 
PI Organization Type: UNIVERSITY  Phone: 206-685-8618  
Organization Name: University of Washington 
PI Address 1: Applied Physics Laboratory/CIMU 
PI Address 2: 1013 NE 40th Street 
PI Web Page:  
City: Seattle  State: WA 
Zip Code: 98105-6698  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2012 Crew Health NNJ12ZSA002N 
Start Date: 06/01/2013  End Date:  12/31/2016 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment: NOTE: Extended to 12/31/2016 per NSBRI (Ed., 3/11/16)

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Wang, Yak-Nam   ( University of Washington )
Sorensen, Mathew   ( University of Washington )
Khohklova, Vera   ( M.V. Lomonosov Moscow State University )
Sapozhnikov, Oleg   ( University of Washington )
Crum, Lawrence   ( University of Washington )
Harper, Jonathan David   ( University of Washington )
Kreider, Wayne   ( University of Washington ) 
Grant/Contract No.: NCC 9-58-SMST03402 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: 1. Specific aims

We will refine and validate probes to integrate with the NASA Flexible Ultrasound System to address Exploration Medical Capability (ExMC) Gap 4.02 Nephrolithiasis. [Ed. note 9/22/2016: This Gap was merged into the following Gap: Med13: We do not have the capability to implement medical resources that enhance operational innovation for medical needs]

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

Technology developed in this research has been licensed to a spin-off company SonoMotion Inc. Three articles are cited that independently review our technology. The first human trial of repositioning kidney stones was completed. A report was presented to National Space Biomedical Institute (NSBRI), FDA (Food and Drug Administration), NASA, and OMB (Office of Management and Budget). A manuscript has been submitted to the Journal of Clinical Investigation. The trial was successful. Two patients reported skin discomfort and sensation at depth with a few pushes. Otherwise, there was no pain or adverse effects associated with the treatment. Stones were localized with the system and repositioned in 14 of 15 subjects. In total, the system targeted and repositioned stones from all parts of the kidney and ureteropelvic juncture (UPJ, kidney outflow tract) including the lower pole (20 targets), midpole (10 targets), upper pole (6 targets), and renal pelvis/UPJ (7 targets). Stones were imaged and repositioned at depths as great as 11 cm. Stones were repositioned to a new location in all 6 post-lithotripsy patients, while 4 of the 6 passed over 30 stone fragments within a few days of treatment. One passed two 2 mm fragments immediately after the completion of treatment. De novo stones and stones as large as 8 mm were repositioned in awake patients and during URS, although movement was not as great as seen with residual fragments. In four of the 15 subjects, what was noted in clinical imaging as a single, potentially unpassable stone was shown to be several passable stones upon repositioning with ultrasound. One subject with a potentially obstructing UPJ stone felt relief. FDA has granted 15 more subjects for the next clinical trial. We have developed and tested new probes and systems to continue to improve and validate performance of ultrasonic propulsion. We have participated in several meetings with GE (General Electric) and ExMC about NASA's flexible ultrasound system (FUS), and have recently received the GE probe used on the FUS. We have started integrating our ultrasonic propulsion onto the GE probe. A new stone specific imaging mode was developed and reported, and a patent application was submitted. In the first step the system automatically identifies the location of stones in the image and highlights them with color during real-time scanning. In the second step, the system automatically determines the size of the kidney stone. In a series of publications, we showed that stone size could be determined more accurately by measuring the shadow width not directly the stone width in the ultrasound image. The first paper on Burst Wave Lithotripsy (BWL) was published in the Journal of Urology and reviewed in Nature Reviews Urology. Progress has been made in measuring effectiveness and safety and on image guidance. We have used preclinical data generated with NSBRI funds to obtain funding from NIH (National Institute of Health) to pursue additional clinical trials to investigate the benefit of expelling small asymptomatic kidney stones, stone clearance with repositioning, obstructing stone displacement, and stone detachment. We continue to present demonstrations of ultrasonic propulsion and BWL. We presented at the American Urological Association in 2012, 2013, 2014, and 2015 and at NSBRI's Congressional demonstration in 2014.

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. This opens the path to refine the system and repeat, to commercialize the system, to add refined imaging as a software upgrade, and to repeat the process with BWL to demonstrate an improved way to comminute stones in humans. 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 could provide. Our software continues to be refined and validated. The preclinical work funded by NSBRI enables us to pursue demonstration in humans to assess where best this technology fits into care in the clinic and in space exploration. 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 Emergency Room visits. Stone size similarly determines risk and course of action in space.

4. Proposed Research

We have undertaken a prospective study to see how commonly the shadow is seen and to compare accuracy of stone size from the stone or the shadow. We are beginning a clinical trial of S-mode for automatic stone detection and stone sizing. We have built a new ultrasound propulsion probe and optimized outputs with the old probe. We are now completing preclinical testing and an FDA modification for human testing. We continue to refine the BWL probe and now have built a BWL probe for transcutaneous testing. We are testing safety and effectiveness in clinical simulation in animal studies. We are testing new image guidance technologies.

 

Rationale for HRP Directed Research:

 

Research Impact/Earth Benefits: 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. 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).

 

Task Progress: Task 1.1. Select imaging probe for stone repositioning. Major activities include refining our instrumentation and validation studies in humans. We have made ultrasonic propulsion work in vitro on two flexible ultrasound systems and with half a dozen probes. We are awaiting delivery of the abdominal probe used with the GE Flexible Ultrasound System for testing. We have built three prototype probes that are being tested. We have reported our work at conferences and in publications and participated in many outreach events and demonstrations.

Task 1.2. Custom design probe to image, reposition, and fragment stones. Three transducers have been built and demonstrated to break stones under both in vitro and in vivo conditions. Patents have been submitted on the amplifier and probe design. The results were published in the Journal of Urology.

Task 2.1. Validate capability to displace an obstructing stone.

Task 2.2. Validate capability to displace a ureter stone. Stones were moved in humans causing a relief from releasing obstruction at the ureter. This result was reported in our report on the clinical trial. Experiments continue in pigs to improve the stone pushing capability.

Task 2.3. Validate capability to comminute a stone.

Task 2.4. Validate capability to expel an attached stone. Small stones have been implanted ureteroscopically in a kidney and fragmented transcutaneously at 5 MPa. The threshold of cavitation (as detected on B-mode) and injury was measured in 7 animals and determined to be 7 MPa at 330 kHz. Cavitation detection correlated with injury and provides safety feedback. Results have been reported at the International Symposium on Therapeutic Ultrasound.

Task 3.1. Refine and validate stone size measurement. We showed measurement of the shadow width was significantly more accurate then measurement directly of the stone width in the Image in 3 studies -- preclinical, retrospective, and prospective. Preliminary results were presented at the World Congress of Endourology in 2014 and will be presented at the American Urological Association (AUA) annual meeting in 2015. The preclinical paper is in press in the Journal of Urology.

Task 3.2. Refine capability to localize a stone. To date 12 subjects have been enrolled in a study of the ability to detect stones with S-mode and we are actively enrolling about 2 per week. The system and technique as well as preclinical studies were published in the Proceedings of the IEEE International Ultrasonics Symposium in 2014.

Task 3.3. Refine and validate capability to detect a ureter stone. Our system was further improved to improve resolution of kidney stone size on the image by several changes to the image process. Part of the paper in press also shows data supporting how to set the knobs on the ultrasound for the best sizing accuracy.

 

Bibliography Type: Description: (Last Updated: 04/30/2019) Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Bailey M, Dunmire B, Cunitz B, Harper J, Lee F, Lingeman J, Sorensen M. "Preliminary results of the initial human clinical trial of focused ultrasound to reposition kidney stones. stones" Oral presentation. 4th International Symposium Current and Future Applications of Focused Ultrasound 2014, Washington, DC, October 2014.

Journal of Therapeutic Ultrasound. 2015 Jun;3(Suppl 1):O71. http://dx.doi.org/10.1186/2050-5736-3-S1-O71 ; PMCID: PMC4489637 , Jun-2015

Articles in Peer-reviewed Journals Poliachik SL, Khokhlova TD, Wang YN, Simon JC, Bailey MR. "Pulse focused ultrasound treatment of muscle mitigates paralysis-induced bone loss in the adjacent bone: a study in a mouse model." Ultrasound Med Biol. 2014 Sep;40(9):2113-24. Epub 2014 May 21. http://dx.doi.org/10.1016/j.ultrasmedbio.2014.02.027 ; PubMed PMID: 24857416; PubMed Central PMCID: PMC4410740 , Sep-2014
Articles in Peer-reviewed Journals Simon JC, Sapozhnikov OA, Khokhlova VA, Crum LA, Bailey MR. "Ultrasonic atomization of liquids in drop chain acoustic fountains." J Fluid Mech. 2015 Mar;766:129-46. http://dx.doi.org/10.1017/jfm.2015.11 ; PubMed PMID: 25977591; PubMed Central PMCID: PMC4428615 , Mar-2015
Articles in Peer-reviewed Journals Simon JC, Sapozhnikov OA, Wang YN, Khokhlova VA, Crum LA, Bailey MR. "Investigation into the mechanisms of tissue atomization by high-intensity focused ultrasound." Ultrasound Med Biol. 2015 May;41(5):1372-85. http://dx.doi.org/10.1016/j.ultrasmedbio.2014.12.022 ; PubMed PMID: 25662182; PubMed Central PMCID: PMC4398613 , May-2015
Articles in Peer-reviewed Journals Maxwell AD, Cunitz BW, Kreider W, Sapozhnikov OA, Hsi RS, Harper JD, Bailey MR, Sorensen MD. "Fragmentation of urinary calculi in vitro by burst wave lithotripsy." J Urol. 2015 Jan;193(1):338-44. Epub 2014 Aug 9. http://dx.doi.org/10.1016/j.juro.2014.08.009 ; PubMed PMID: 25111910; PubMed Central PMCID: PMC4384893 , Jan-2015
Articles in Peer-reviewed Journals Maxwell AD, Hsi RS, Bailey MR, Casale P, Lendvay TS. "Noninvasive ureterocele puncture using pulsed focused ultrasound: An in vitro study." J Endourol. 2014 Mar;28(3):342-6. Epub 2013 Dec 27. http://dx.doi.org/10.1089/end.2013.0528 ; PubMed PMID: 24171441; PubMed Central PMCID: PMC3929044 , Mar-2014
Articles in Peer-reviewed Journals Dunmire B, Lee FC, Hsi RS, Cunitz BW, Paun M, Bailey MR, Sorensen MD, Harper JD. "Tools to improve the accuracy of kidney stone sizing with ultrasound." J Endourol. 2015 Feb;29(2):147-52. Epub 2014 Sep 17. http://dx.doi.org/10.1089/end.2014.0332 ; PubMed PMID: 25105243; PubMed Central PMCID: PMC4313404 , Feb-2015
Articles in Peer-reviewed Journals Cunitz B, Dunmire B, Paun M, Sapozhnikov O, Kucewicz J, Hsi R, Lee F, Sorensen M, Harper J, Bailey M. "Improved detection of kidney stones using an optimized doppler imaging sequence." IEEE Int Ultrason Symp. 2014 Sep 3;2014:452-5. http://dx.doi.org/10.1109/ULTSYM.2014.0112 ; PubMed PMID: 26203346; PubMed Central PMCID: PMC4507569 , Sep-2014
Articles in Peer-reviewed Journals Bailey M, Cunitz B, Dunmire B, Paun M, Lee F, Ross S, Lingeman J, Coburn M, Wessells H, Sorensen M, Harper J. "Ultrasonic propulsion of kidney stones: preliminary results of human feasibility study." IEEE Int Ultrason Symp. 2014 Sep 3;2014:511-4. http://dx.doi.org/10.1109/ULTSYM.2014.0126 ; PubMed PMID: 26203347; PubMed Central PMCID: PMC4507572 , Sep-2014
Articles in Peer-reviewed Journals Bailey M, Lee F, Hsi R, Paun M, Dunmire B, Liu Z, Sorensen M, Harper J. "Shockwave lithotripsy with renoprotective pause is associated with renovascular vasoconstriction in humans." IEEE Int Ultrason Symp. 2014 Sep 3;2014:1013-6. http://dx.doi.org/10.1109/ULTSYM.2014.0248 ; PubMed PMID: 26203348; PubMed Central PMCID: PMC4507567 , Sep-2014
Articles in Peer-reviewed Journals Lee FC, Hsi RS, Sorensen MD, Dunmire B, Liu Z, Bailey MR, Harper JD. "Renal vasoconstriction occurs early during clinical SWL using a renal protection protocol." J Endourol. 2015 Aug 3. [Epub ahead of print] PubMed PMID: 26239232 , Aug-2015
Awards McClenny A. "Mary Gates Undergraduate Research Scholarship, May 2015." May-2015
Awards Simon J. "Second Prize, NSBRI Dr. David Watson Poster Contest at the NASA Human Research Program Investigators' Workshop, January 2015." Jan-2015
Awards Crum L. "Senior Visiting Fellow. Magdalen College, University of Oxford, January 2015." Jan-2015
Awards Hubbard M. "Mary Gates Undergraduate Research Scholarship, May 2015." May-2015
Awards Schade, Khokhlova, Kreider, Bailey. "Best Paper. Engineering and Urology Society meeting at the American Urological Association annual meeting, May 2015." May-2015
Books/Book Chapters Lingeman JE, Beiko D, Bailey MR, Gettman MT, Kohrmann KU, Liatsikos E, Matlaga BR, Monga M, Gailly G, Timoney A. "Stone technology: shock wave and intracorporeal lithotripsy." in "3rd International Consultation on Stone Disease." Societe Internationale Urologique (Paris), In press as of June 2015., Jun-2015
Books/Book Chapters Sapozhnikov OA. "High-intensity ultrasonic waves in fluids: Nonlinear propagation and effects." in "Power Ultrasonics. Applications of High-intensity Ultrasound." Ed. J.A. Gallego-Juarez, K.F. Graff. Cambridge : Elsevier, 2015. p. 9-35. Woodhead Publishing Series in Electronic and Optical Materials: Number 66. http://dx.doi.org/10.1016/B978-1-78242-028-6.00002-8 , Jan-2015
Papers from Meeting Proceedings Oweis GF, Dunmire BL, Cunitz BW, Bailey MR. "Non-Invasive Measurement of the Temperature Rise in Tissue Surrounding a Kidney Stone Subjected to Ultrasonic Propulsion." 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS), Milan, Italy, August 25-29, 2015.

Proceedings of the 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS), MiCo - Milano Conference Center - Milan, Italy, August 25-29, 2015. In press as of June 2015. , Jun-2015

Significant Media Coverage Krader CG. (Cheryl Guttman Krader) "Rolling stones with ultrasound: Novel non-invasive technique shows diagnostic and therapeutic potential." Urology Times 2014., Sep-2014
Significant Media Coverage Yard DH. (Delicia Honen Yard) "Ultrasonic Propulsion of Stones: Interview with Jonathan Harper, MD." Renal and Urology News Expert Q+A 2014. http://www.renalandurologynews.com/expert-qa/ultrasonic-propulsion-of-kidney-stones-interview-with-jonathan-harper-md/article/346605/ , Jul-2014
Significant Media Coverage Collins M. (Martha Collins) "Results of first clinical test of feasibility of ultrasound to reposition kidney stones." American Urological Association. AUA Daily News, p. 21. May 2015., May-2015
Download in PDF pdf     
Fiscal Year: FY 2014  Task Last Updated:  06/06/2014 
PI Name: Bailey, Michael R. Ph.D. 
Project Title: Prevention of Renal Stone Complications in Space Exploration 
   
Division Name: Human Research 
Program/Discipline--
Element/Subdiscipline:
NSBRI--Smart Medical Systems and Technology Team 
 
Joint Agency Name:   TechPort:  Yes 
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) Medical:Risk of Adverse Health Outcomes & Decrements in Performance due to Inflight Medical Conditions (IRP Rev I)
 (2) Renal:Risk of Renal Stone Formation
Human Research Program Gaps: (1) Med12:We do not have the capability to mitigate select medical conditions (IRP Rev I)
Space Biology Element: None
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
PI Email: bailey@apl.washington.edu  Fax:  206-221-6578 
PI Organization Type: UNIVERSITY  Phone: 206-685-8618  
Organization Name: University of Washington 
PI Address 1: Applied Physics Laboratory/CIMU 
PI Address 2: 1013 NE 40th Street 
PI Web Page:  
City: Seattle  State: WA 
Zip Code: 98105-6698  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2012 Crew Health NNJ12ZSA002N 
Start Date: 06/01/2013  End Date:  05/31/2016 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment:

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Wang, Yak-Nam   ( University of Washington )
Sorensen, Mathew   ( University of Washington )
Khohklova, Vera   ( M.V. Lomonosov Moscow State University )
Sapozhnikov, Oleg   ( University of Washington )
Crum, Lawrence   ( University of Washington )
Harper, Jonathan David   ( University of Washington )
Kreider, Wayne   ( University of Washington ) 
Grant/Contract No.: NCC 9-58-SMST03402 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: 1. Specific aims. We will refine and validate probes to integrate with the NASA Flexible Ultrasound System to address 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 new stone specific imaging mode was developed, reported, and a patent submitted. In the first step the system automatically identifies the location of stones in the image and highlights them with color during real-time scanning. In the second step, the system automatically determines the size of the kidney stone. Published a clinical study showing reduced false positives with S-mode. Submitted a paper showing improved accuracy in stone size determination with our system. Presented and submitted a patent and paper showing stone size measurement across the shadow behind the stone is more accurate than measurement not across the image of the stone itself. Hence anyone can improve his or her stone size measurement. Published several preclinical safety and effectiveness studies of repositioning stones. Published a study of training techniques and outcomes for reposition stones. Initiated first clinical study of repositioning stones and reported preliminary results. In summary, stones were moved in all six subjects. No subjects observed any discomfort associated with the procedure. Invented, reported, patented, and submitted paper on a new method to comminute kidney stones, termed Burst Wave Lithotripsy BWL. Published paper 'Pulse focused ultrasound treatment of muscle mitigates paralysis-induced bone loss in the adjacent bone: a study in a mouse model.' Since the start of the clinical trial we have doubled the effectiveness of ultrasonic propulsion as measured by vertical stone displacement. Simultaneously we have reduced the channels needed. We have published and used a numerical model of radiation force and the acoustic field in tissue to design an improved probe. We have begun implementing BWL on the flexible ultrasound system. We have participated in several meetings with GE and ExMC about NASA's flexible ultrasound system (FUS). We stand by to integrate GE probe into our FUS and refine and validate ultrasonic propulsion on these probes. We await a probe and a probe description (pin-out) from GE. We continue to present demonstrations of ultrasonic propulsion and BWL. We presented at the American Urological Association in 2012, 2013, and 2014 and at NSBRI's Congressional demonstration in 2014.

3. Impact. We have invented a technology to reposition kidney stones and demonstrated it works in people. In 3 of the 6 cases, what appeared as one large stone on x-ray was 2 or 3 small passable stones. This had direct diagnostic benefit to these subjects and changed their course of treatment. In two other subjects we moved stones out of the kidney, which they passed and which was a direct therapeutic benefit to these subjects. 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. This opens the path to refine the system and repeat, to commercialize the system, to add refined imaging as a software upgrade, and to repeat the process with BWL to demonstrate an improved way to comminute stones in humans. 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 could provide. Our software continues to be refined and validated. The preclinical work funded by NSBRI enables us to pursue demonstration in humans to assess where best this technology fits into care in the clinic and in space exploration.

4. Proposed Research. We have undertaken a retrospective study to see how commonly the shadow is seen and to compare accuracy of stone size from the stone or the shadow. We are beginning a clinical trial of S-mode for automatic stone detection and stone sizing. Our numerical codes and bench top testing will be used to optimize radiation force used to move stones. We will characterize the acoustic and thermal outputs of the new probes. We plan preclinical safety and effectiveness studies of imaging, repositioning, and comminution studies with improved probe outputs. Preclinical data will be resubmitted to FDA for a second clinical trial with the improved probe and outputs. We will work toward clinical trials with BWL. We have used preclinical data generated with NSBRI funds to apply to NIH to pursue additional clinical trials to investigate the benefit of expelling small asymptomatic kidney stones, stone clearance with repositioning, obstructing stone displacement, and stone detachment.

 

Rationale for HRP Directed Research:

 

Research Impact/Earth Benefits: Kidney stones have long been near the top of NASA's list of concerns; mitigating Gap 4.02 medical condition Nephrolithiasis is a must for all missions beyond the 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://humanresearchwiki.jsc.nasa.gov/index.php?title=Nephrolithiasis . 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).

 

Task Progress: AIM 1. Refine ultrasound probes to detect, reposition, and fragment kidney stones. Task 1.1. Select imaging probe for stone repositioning. Clinical trials are underway with the C5-2 probe of ISS Ultrasound 1. Awaiting delivery of probe to be used with NASA FUS-GDU. Task 1.2. Custom design probe to image, reposition, and fragment stones. Developed and tested probe. Integrating probe with FUS and modifying imaging portion to be smaller.

AIM 2. Validate probes to visualize, reposition, and fragment stones. Task 2.1. Validate capability to displace an obstructing stone. Pursuing initial test in current clinical trial and applying for follow-on trial. Pre-clinical investigations of safety and effectiveness conducted with upgraded outputs. Task 2.2. Validate capability to displace a ureter stone. Followed schedule and did not pursue in year 1. Task 2.3. Validate capability to comminute a stone. Invented, patented, and reported burst wave lithotripsy BWL. Appears to have faster comminution than SWL, comminute stones that are difficult to break with SWL, have effectiveness and safety feedback, and be operable in a safe range. Task 2.4. Validate capability to expel a stone attached to tissue. Enhanced outputs and developed BWL to address this task. Testing underway.

AIM 3. Refine and validate imaging to guide therapy. Task 3.1. Refine and validate capability to measure stone size. Reported and patented significant enhancement with our technology and technique. Task 3.2. Refine capability to localize a stone. Initiated clinical validation now at the end of year 1. Task 3.3. Refine and validate capability to detect a ureter stone. Followed schedule and did not pursue in year 1.

 

Bibliography Type: Description: (Last Updated: 04/30/2019) Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Lee F, Hsi R, Sorensen M, Paun M, Dunmire B, Liu Z, Bailey M, Harper J. "Shockwave Lithotripsy with Renoprotective Pause Is Associated with Renovascular Vasoconstriction in Humans." 2014 Annual Meeting of the American Urological Association, Orlando, FL, May 16-21, 2014.

Journal of Urology 2014 Apr;19(4 Suppl):e203. http://dx.doi.org/10.1016/j.juro.2014.02.741 , Apr-2014

Abstracts for Journals and Proceedings Bailey MR, Wang YN, Simon J, Hsi RS, Harper JD, Sorensen MD, Starr F, Paun M, Cunitz B, Liggitt HD, Evan AP, McAteer JA. "Ultrasonic propulsion of kidney stones." American Urological Association (AUA) Annual Meeting, San Diego, CA, May 4-8, 2013. Invited plenary presentation.

AUA Annual Meeting, San Diego, CA, May 4-8, 2013. , May-2013

Abstracts for Journals and Proceedings Crum LA. "Recent advances in medical ultrasound." APS (American Physical Society) March Meeting 2014, Denver, CO, March 3-7, 2014.

Bulletin of the American Physical Society. 2014 Mar;59(1):Abstract ID: BAPS.2014.MAR.M23.4. http://meetings.aps.org/link/BAPS.2014.MAR.M23.4 ; accessed 6/4/2014. , Mar-2014

Abstracts for Journals and Proceedings Crum L, Cunitz BW, Dunmire B, Harper J, Kaczkowski P, Kucewicz J, Lu W, Paun M, Sapozhnikov O, Simon J, Sorensen MD, Starr F, Wang YN, Bailey MR. "Recent developments in therapeutic ultrasound: Kidney stone imaging and repositioning by ultrasound." Opening Plenary Paper at the 2013 International Congress on Ultrasonics, Singapore, May 2-5, 2013.

2013 International Congress on Ultrasonics, Singapore, May 2-5, 2013. , May-2013

Abstracts for Journals and Proceedings Bailey M, Cunitz B, Dunmire B, Wang YN, Maxwell A, Sapozhnikov O, Harper J, Sorensen M, Hsi R, Lee F, Crum L. "Stone Specific Ultrasound Mode for the Diagnoses and Treatment of Kidney Stones in Space." 85th Annual Scientific Meeting, Aerospace Medical Association, San Diego, CA, May 10-15, 2014.

Aviation, Space, and Environmental Medicine. 2014 Mar;85(3):318-9. Abstract #357. See http://www.ingentaconnect.com/content/asma/asem/2014/00000085/00000003 for searching. , Mar-2014

Abstracts for Journals and Proceedings Maxwell AD, Cunitz BW, Kreider W, Sapozhnikov OA, Hsi RS, Harper JD, Bailey MR, Sorensen MD. "Fragmentation of kidney stones in vitro by focused ultrasound bursts without shock waves." 166th Meeting of the Acoustical Society of America, San Francisco, CA, December 2-6, 2013.

J Acoust Soc Am. 2013 Nov;134(5):4183. http://dx.doi.org/10.1121/1.4831340 , Nov-2013

Articles in Peer-reviewed Journals Bailey MR, Wang Y-N, Simon JC, Cunitz BW, Harper JD, Hsi RS, Starr F, Paun M, Dunmire B, Sapozhnikov OA, Crum LA, Sorensen MD. "Acoustic radiation force to reposition kidney stones." Proceedings of Meetings on Acoustics. 2013 Jun;19(1):045016. http://dx.doi.org/10.1121/1.4799599 , Jun-2013
Articles in Peer-reviewed Journals Connors BA, Evan AP, Blomgren PM, Hsi RS, Harper JD, Sorensen MD, Wang YN, Simon JC, Paun M, Starr F, Cunitz BW, Bailey MR, Lingeman JE. "Comparison of tissue injury from focused ultrasonic propulsion of kidney stones versus extracorporeal shock wave lithotripsy." J Urol. 2014 Jan;191(1):235-41. Epub 2013 Aug 2. http://dx.doi.org/10.1016/j.juro.2013.07.087 ; PubMed PMID: 23917165; PubMed Central PMCID: PMC3865142 , Jan-2014
Articles in Peer-reviewed Journals Wang YN, Simon JC, Cunitz BW, Starr FL, Paun M, Liggitt DH, Evan AP, McAteer JA, Liu Z, Dunmire B, Bailey MR. "Focused ultrasound to displace renal calculi: threshold for tissue injury." J Ther Ultrasound. 2014 Mar 31;2:5. eCollection 2014. http://dx.doi.org/10.1186/2050-5736-2-5 ; PubMed PMID: 24921046; PubMed Central PMCID: PMC4036593 , Mar-2014
Articles in Peer-reviewed Journals Harper JD, Dunmire B, Wang YN, Simon JC, Liggitt D, Paun M, Cunitz BW, Starr F, Bailey MR, Penniston KL, Lee FC, Hsi RS, Sorensen MD. "Preclinical safety and effectiveness studies of ultrasonic propulsion of kidney stones." Urology. 2014 Aug;84(2):484-9. http://dx.doi.org/10.1016/j.urology.2014.04.041 ; PubMed PMID: 24975708; PubMed Central PMCID: PMC4304777 , Aug-2014
Articles in Peer-reviewed Journals Harper JD, Sorensen MD, Cunitz BW, Wang YN, Simon JC, Starr F, Paun M, Dunmire B, Liggitt HD, Evan AP, McAteer JA, Hsi RS, Bailey MR. "Focused ultrasound to expel calculi from the kidney: safety and efficacy of a clinical prototype device." J Urol. 2013 Sep;190(3):1090-5. Epub 2013 Apr 9. http://dx.doi.org/10.1016/j.juro.2013.03.120 ; PubMed PMID: 23583535 ; PubMed Central PMCID: PMC4414252 , Sep-2013
Articles in Peer-reviewed Journals Kreider W, Maxwell AD, Khokhlova TD, Simon JC, Khokhlova VA, Sapozhnikov OA, Bailey MR. "Rectified growth of histotripsy bubbles." Proceedings of Meetings on Acoustics. 2013 Jun;19(1):075035. http://dx.doi.org/10.1121/1.4800326 , Jun-2013
Articles in Peer-reviewed Journals Sorensen MD, Bailey MR, Hsi RS, Cunitz BW, Simon JC, Wang YN, Dunmire BL, Paun M, Starr F, Lu W, Evan AP, Harper JD. "Focused ultrasonic propulsion of kidney stones: review and update of preclinical technology." J Endourol. 2013 Oct;27(10):1183-6. Review. http://dx.doi.org/10.1089/end.2013.0315 ; PubMed PMID: 23883117; PubMed Central PMCID: PMC3787400 , Oct-2013
Articles in Peer-reviewed Journals Hsi RS, Dunmire B, Cunitz BW, He X, Sorensen MD, Harper JD, Bailey MR, Lendvay TS. "Content and face validation of a curriculum for ultrasonic propulsion of calculi in a human renal model." J Endourol. 2014 Apr;28(4):459-63. http://dx.doi.org/10.1089/end.2013.0589 ; PubMed PMID: 24228719; PubMed Central PMCID: PMC3961775 , Apr-2014
Articles in Peer-reviewed Journals Poliachik SL, Khokhlova TD, Wang YN, Simon JC, Bailey MR. "Pulse focused ultrasound treatment of muscle mitigates paralysis-induced bone loss in the adjacent bone: a study in a mouse model." Ultrasound Med Biol. Published online May 23, 2014. In press. http://dx.doi.org/10.1016/j.ultrasmedbio.2014.02.027 ; PubMed PMID: 24857416 , May-2014
Articles in Peer-reviewed Journals Sapozhnikov O, Lu W, Bailey M, Kaczkowski P, Crum L. "Bubbles trapped on the surface of kidney stones as a cause of the twinkling artifact in ultrasound imaging." Proceedings of Meetings on Acoustics. 2013 Jun;19(1):075033. http://dx.doi.org/10.1121/1.4800292 , Jun-2013
Articles in Peer-reviewed Journals Simon JC, Sapozhnikov OA, Khokhlova VA, Wang Y-N, Crum LA, Bailey MR. "Ultrasonic atomization: A mechanism of tissue fractionation." Proceedings of Meetings on Acoustics. 2013 Jun;19(1):075036. http://dx.doi.org/10.1121/1.4800304 , Jun-2013
Articles in Peer-reviewed Journals Khokhlova TD, Wang YN, Simon JC, Cunitz BW, Starr F, Paun M, Crum LA, Bailey MR, Khokhlova VA. "Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model." Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8161-6. http://dx.doi.org/10.1073/pnas.1318355111 ; PubMed PMID: 24843132 ; PubMed Central PMCID: PMC4050569 , Jun-2014
Articles in Peer-reviewed Journals Wang Y-N, Simon JC, Cunitz B, Starr F, Paun M, Liggitt D, Evan A, McAteer J, Williams J, Liu Z, Kaczkowski P, Hsi R, Sorensen M, Harper J, Bailey MR. "Ultrasound intensity to propel stones from the kidney is below the threshold for renal injury." Proceedings of Meetings on Acoustics. 2013 Jun;19(1):075066. http://dx.doi.org/10.1121/1.4800361 , Jun-2013
Articles in Peer-reviewed Journals Kreider W, Yuldashev PV, Sapozhnikov OA, Farr N, Partanen A, Bailey MR, Khokhlova VA. "Characterization of a multi-element clinical HIFU system using acoustic holography and nonlinear modeling." IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control. 2013 Aug;60(8):1683-98. http://dx.doi.org/10.1109/TUFFC.2013.2750 , Aug-2013
Awards Cunitz B, Dunmire B, Paun M, Starr F, Wang Y. "University of Washington Distinguished Staff Award, April 2014." Apr-2014
Awards Simon J. "NSBRI Fellowship, February 2014." Feb-2014
Awards Crum L. "Acoustical Society of America Gold Medal, June 2013." Jun-2013
Awards Crum L. "The William and Francis Fry Honorary Fellowship for Contributions to Therapeutic Ultrasound, April 2014." Apr-2014
Awards Bailey M. "Elected to Acoustical Society of America Executive Council, April 2014." Apr-2014
Dissertations and Theses Simon J. "The thresholds and mechanisms of injury by focused ultrasound." Dissertation, Bioengineering, University of Washington, December 2013. , Dec-2013
NASA Technical Documents Bailey MR. "Draft plan to integrate kidney stone imaging and repositioning into the Flexible Ultrasound Ground Demonstration Unit." Submitted to William Thompson, FUS Integration Lead and NSBRI headquarters, September 2013. , Sep-2013
Significant Media Coverage Sullivan C. "Online news article, 'UW testing kidney stone treatment that doesn't need a hospital visit.' Online article about Dr. Bailey's research. " MYNorthwest.com January 14, 2014 @ 6:26 am (Updated: 11:03 am - 1/14/14) http://mynorthwest.com/11/2432495/UW-testing-kidney-stone-treatment-that-doesnt-need-a-hospital-visit ; accessed 6/4/14., Jan-2014
Significant Media Coverage Yard DH. (Delicia Honen Yard) "Expert Q&A." Renal & Urology News Q and A series. May 2014. http://www.renalandurologynews.com/expert-qa/section/2304/ ; accessed 6/4/14., May-2014
Significant Media Coverage Fulwiler D. "Online article about Dr. Bailey's research, 'Former ITHS Grant Awardee's Ultrasound Device Begins Clinical Trials.' " Institute of Translational Health Sciences online article, January 2014., Jan-2014
Significant Media Coverage AUA Daily News Editor. "Article about Dr. Bailey's research, 'New Device uses ultrasonic propulsion to move stones in the kidney.' " TriStar AUA Daily News, May 7, 2013, p. 13., May-2013
Significant Media Coverage Hickey H. "Article about Dr. Bailey's research: 'Trial to test using ultrasound to move kidney stones.' " University of Washington online article, January 10, 2014. http://www.washington.edu/news/2014/01/10/trial-to-test-using-ultrasound-to-move-kidney-stones/?utm_source=rss&utm_medium=rss&utm_campaign=trial-to-test-using-ultrasound-to-move-k ; accessed 6/4/14., Jan-2014
Significant Media Coverage Wessells H. " 'Rolling Stones' article on Dr. Bailey's research." UW Urology Newsletter 2013., Jul-2013
Significant Media Coverage Enerson J. "TV report, King 5 evening news, about PI's research." Healthlink section, TV report, King 5 evening news, January 10 2014. , Jan-2014
Significant Media Coverage Hsi R, Sorensen M. "Focused ultrasonic propulsion of kidney stones, 'Beyond the Abstract.' Online article expanding on previously published article, 'Focused Ultrasonic Propulsion of Kidney Stones: Review and update of preclinical technology.' Published J Endourol. 2013 Oct;27(10):1183-6. http://dx.doi.org/10.1089/end.2013.0315 ; PubMed PMID: 23883117 " UroToday – Beyond the Abstract, January 8, 2014., Jan-2014
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Fiscal Year: FY 2013  Task Last Updated:  02/06/2014 
PI Name: Bailey, Michael R. Ph.D. 
Project Title: Prevention of Renal Stone Complications in Space Exploration 
   
Division Name: Human Research 
Program/Discipline--
Element/Subdiscipline:
NSBRI--Smart Medical Systems and Technology Team 
 
Joint Agency Name:   TechPort:  Yes 
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) Medical:Risk of Adverse Health Outcomes & Decrements in Performance due to Inflight Medical Conditions (IRP Rev I)
 (2) Renal:Risk of Renal Stone Formation
Human Research Program Gaps: (1) Med12:We do not have the capability to mitigate select medical conditions (IRP Rev I)
Space Biology Element: None
Space Biology Cross-Element Discipline: None
Space Biology Special Category: None
PI Email: bailey@apl.washington.edu  Fax:  206-221-6578 
PI Organization Type: UNIVERSITY  Phone: 206-685-8618  
Organization Name: University of Washington 
PI Address 1: Applied Physics Laboratory/CIMU 
PI Address 2: 1013 NE 40th Street 
PI Web Page:  
City: Seattle  State: WA 
Zip Code: 98105-6698  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2012 Crew Health NNJ12ZSA002N 
Start Date: 06/01/2013  End Date:  05/31/2016 
No. of Post Docs:   No. of PhD Degrees:   
No. of PhD Candidates:   No. of Master' Degrees:   
No. of Master's Candidates:   No. of Bachelor's Degrees:   
No. of Bachelor's Candidates:   Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment:

 

Key Personnel Changes/Previous PI:  
COI Name (Institution): Crum, Lawrence   ( University of Washington )
Cunitz, Bryan   ( University of Washington )
Dunmire, Barbrina   ( University of Washington )
Harper, Jonathan   ( University of Washington )
Khokhlova, Vera   ( University of Washington )
Kreider, Wayne   ( University of Washington )
Maxwell, Adam   ( University of Washington )
Paun, Marla   ( University of Washington )
Sapozhnikov, Oleg   ( University of Washington )
Sorensen, Matthew   ( University of Washington )
Starr, Frank   ( University of Washington ) 
Grant/Contract No.: NCC 9-58-SMST03402 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: The objective of this proposal is to refine and validate ultrasound to reposition kidney stones to prevent medical complications on space exploration missions. The objective will be met by adding a probe and software to the Flexible Ultrasound System. The probe will send ultrasound through the skin to create real time images of the stone and kidney and also to move or fragment the stone within the kidney. In Aim 1, the probe(s) will be refined. The capability to image and reposition stones will be added to 1) the kidney imaging probe of the FUS manufacturer and 2) a clinical 3D probe. A third plug-and-play probe will also be developed to fragment kidney stones as a last resort. In Aim 2, the first probe will be validated as a countermeasure for the contingency of stone formation. The five tasks in Aim 2 are to refine and validate the capability 1) to displace a large blocking stone from occluding the exit of the kidney to delay treatment and complications, 2&3) to detect and displace a medium-sized stone in the ureter to alleviate complications, 4) to expel a small stone from the kidney to avoid complications, and 5) to measure the size of kidney stones to inform decision making. Repositioning experiments will be conducted in animals where stones will be surgically implanted by retrograde percutaneous nephrostolithotomy in a porcine model. Stone detachment will be tested in a second porcine model in which a diet high in hydroxyproline produces small, attached kidney stones. Imaging and stone sizing will be conducted first in animals and then in human subjects. This proposal is in response to the emphasis point of the solicitation: “Refine and validate plug-and-play sensor and effector probes that integrate seamlessly with the proposed NASA Flexible Ultrasound System and address or mitigate medical conditions likely to be encountered during exploration missions.” It specifically addresses “ExMC Gap Report 4.13 Limited capability to diagnose and treat a renal stone.” The work is significant because if a stone forms in space, there are limited options to minimize or reduce complications – primarily analgesics, anti-inflammatories, and muscle relaxants – and potentially life threatening consequences. With the substitution of a probe and new software, the proposed work provides the crew and flight surgeons options to pass the stone, to prevent the stone from passing, to accelerate a stone that is passing, and if needed to break the stone. And it works without restricting any other possible options.

 

Rationale for HRP Directed Research:

 

Research Impact/Earth Benefits: 0

 

Task Progress: New project for FY2013.

 

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