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Project Title:  Smart Therapeutic Ultrasound Device for Mission-Critical Medical Care Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP ExMC:Exploration Medical Capabilities
Start Date: 08/01/2008  
End Date: 09/30/2012  
Task Last Updated: 01/11/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Crum, Lawrence A. Ph.D. / University of Washington 
Address:  Applied Physics Laboratory 
1013 N.E. 40th Street 
Seattle , WA 98105-6606 
Email: lac@apl.washington.edu 
Phone: 206-685-8622  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Washington 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bailey, Michael  University of Washington 
Carter, Stephen  University of Washington 
Sapozhnikov, Oleg  University of Washington 
Project Information: Grant/Contract No. NCC 9-58-SMST01601 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-SMST01601 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) ExMC 4.13:We have limited capability to screen for, diagnose, and treat renal stones during exploration missions (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date should be 9/30/2012 (previously 7/31/2012) per NSBRI (Ed., 5/22/2012)

Task Description: 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.

Research Impact/Earth Benefits: We have been encouraged by our interactions with the urology, ultrasound, and business communities that our technology to detect and reposition stones could significantly alter the way kidney stones are treated in clinical medicine. We have won awards in the six poster or business plan competitions we have entered. Most stones are small enough to pass naturally and thus patients are encouraged, through hydration, to try to pass the stone without intervention. This natural process might take 6-8 weeks and result in considerable discomfort to the patient over this interval. With our innovative technology, a stone could potentially be cleared in the first office visit. Many stones do not clear with hydration, and thus more aggressive approaches are required. More invasive procedures are often necessary if the stone is in the lower pole because even if fragmented, the pieces are unlikely to pass from this location. Our technological approach would keep the least invasive option open for these patients. In most existing procedures, there is a significant chance stone pieces will remain behind as seeds for future stones and further surgery. Our technology could help these pieces pass. In addition, stones are often recurrent; recurring-stone patients are often monitored, so that new stones can be detected early—this monitoring could be done with our precise stone imaging approach. Our technology could also move these stones to the kidney exit before they are symptomatic. This technology reduces risk of surgery, complications of surgery for the patient, and the cost of surgery to the insurance companies; furthermore, the technology does not preclude any surgical options. Lastly, the algorithms to detect kidney stones alone stand to spare many patients the ionizing radiation of a CT scan, or to provide options to pregnant women or children with stones who are unlikely to receive CT. NSBRI quickly recognized the value of this technology and helped us initiate our commercialization effort that now has the full support of the UW, the Washington Research Foundation, and a commercial hardware provider, as well as the interest of several venture capitalists and ultrasound companies.

The applications of our technology to the control of bleeding and for tumor ablation are at least as profound. Specifically, this year we have worked with the latest clinical HIFU machine—one developed by Philips Medical. This machine is intended for many clinical applications. We have used some of our effort to characterize the output of the machine and assess its potential bio-effects. Our work provides the clinicians, who intend to use this machine, the ability to select a treatment dose. At UW alone, it helps train the clinicians and establish the specificity of what size targets are treated. With our contribution, the clinicians are then likely to pursue their own clinical studies, and regulatory approval for various tumor treatments. Before our involvement, the machine sat dormant for a year. We are also exploring the effects of HIFU on the immune system and have proposed clinical trials to combine HIFU with chemical therapeutic agents. We believe that our efforts to carefully describe outputs and bio-effects will help the U.S. catch up with the rest of the world where over 400,000 patients have been treated by HIFU. In addition, our intimate knowledge of these details enables us to consider ways in which a similar, much reduced-in-size system could be developed for NASA to reduce some critical risks to astronauts during long duration space travel.

Task Progress & Bibliography Information FY2012 
Task Progress: Task 1A. Perform studies of bleeding detection in a flow-phantom model: Successfully detected and treated sites in a phantom developed with Defense Advanced Research Projects Agency (DARPA) and FDA in a blind test with an automated system.

Task 1B. Perform studies to determine pressure and temperature in ex vivo tissue exposed to HIFU: Published several papers, which led to invitation to join IEC (International Electrotechnical Commission) working group on HIFU standards and the AIUM (American Institute of Ultrasound in Medicine) sub-committee on Transiently Increased Outputs, and to measure acoustic output of Philips clinical HIFU machine. Also, discovered and submitted patent application for a method to emulsify tissue with ultrasound.

Task 2A. Develop new stone detection techniques based on radiation force and reverberation responsible for twinkling artifact: As part of our graduate student's dissertation, discovered that bubbles are responsible for the twinkling artifact. We have developed, implemented, tested, and patented new software to better detect stones.

Task 2B. Test stone sizing technology in tissue: Published paper, filed U.S. and international utility patent applications, and are negotiating licensing. We have initiated human clinical studies to test ultrasound stone sizing versus CT.

Task 3A. We utilized the YUANDE HIFU tumor ablation device as a test platform: Performed a number of studies.

Task 3B. Engineer and optimize an image-guided, two-frequency HIFU system for renal stone comminution: We will work with Exploration Medical Capabilities (ExMC) Human Research Program Element to implement on the FUS system capability to detect, reposition, and comminute stones. All are implemented in a prototype for which we are pursuing an investigational device exemption (IDE) with the FDA. We have developed a concept of expelling small stones from a kidney before they require comminution or surgery. A system to detect and reposition stones based on an OEM diagnostic ultrasound platform has been built and demonstrated to be safe and effective in studies in a porcine model. Commercialization efforts are well underway. Our technology was called a "game changer" in the plenary session of the American Urological Association (AUA) Annual meeting in May 2012.

Task 4A. Perform in vivo tests of the imaging protocols developed in Task 2: our paper is in press comparing twinkling to standard B-mode for stone detection in patients. New algorithm for stone detection implemented on clinical machine and tests of the algorithm initiated on human subjects. Data from 15 subjects has been collected.

Task 4B. Performed studies to determine the potential for HIFU-induced stone comminution as well as any associated tissue injury. We used our stone repositioning system to fragment stones in an excised porcine kidney in which they were grown. In vivo tests scheduled for Oct 22, 2012. In vivo studies of our stone clearance system have been shown to be safe and effective. Several studies of safety in pigs have been complete and are in press. These data have been presented to the FDA as part of our application for investigational device exemption for a human feasibility study.

Bibliography Type: Description: (Last Updated: 03/22/2019) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Dunmire B, Sorensen MD, Hsi R, Kucewicz, J, Bailey M, Cunitz B, Harper J. "Overestimation of Kidney Stone Size Increases with Depth and Gain Ultrasound-Induced Renal Injury Threshold." 88th Annual Meeting, Western Section of the American Urological Association, Waikoloa, Hawaii, October 7-12, 2012.

88th Annual Meeting, Western Section of the American Urological Association, Waikoloa, Hawaii, October 7-12, 2012. , Oct-2012

Abstracts for Journals and Proceedings Kucewicz J, Dunmire B, Bailey MR. "Improved Detection of Kidney Stone Twinkling Using Autoregressive Signal Processing Method." American Urological Association (AUA) 2012, Atlanta, GA, May 19-23, 2012.

AUA 2012, Atlanta, GA, May 19-23, 2012. Abstract 1709. , May-2012

Abstracts for Journals and Proceedings Harper JD, Sorensen MD, Hsi R, Cunitz B, Simon J, Wang YN, Paun M, Starr F, Lu W, Evan A, Liggit D, McAteer J, Bailey M. "Preclinical Efficacy and Safety of Ultrasonic Propulsion of Kidney Stones." 88th Annual Meeting, Western Section of the American Urological Association, Waikoloa, Hawaii, October 7-12, 2012.

88th Annual Meeting, Western Section of the American Urological Association, Waikoloa, Hawaii, October 7-12, 2012. , Oct-2012

Abstracts for Journals and Proceedings Harper JD, Sorensen MD, Hsi R, Cunitz B, Simon J, Wang YN, Paun M, Starr F, Lu W, Evan A, Bailey M. "Preclinical testing of ultrasonic propulsion of kidney stones." 2012 IEEE International Ultrasonics Symposium (IUS), Dresden Germany, October 7-10, 2012.

2012 IEEE International Ultrasonics Symposium (IUS), Dresden Germany, October 7-10, 2012. , Oct-2012

Abstracts for Journals and Proceedings Harper JD, Sorensen MD, Hsi R, Simon J, Wang YN, Paun M, Starr F, Lu W, Cunitz B, Bailey M. "Endoscopic observation of ultrasonic propulsion of kidney stones." American Urological Association (AUA) 2012, Atlanta, GA, May 19-23, 2012.

AUA 2012, Atlanta, GA, May 19-23, 2012. Abstract V1720. , May-2012

Abstracts for Journals and Proceedings Harper JD, Hsi R, Wang YN, Simon J, Starr F, Paun M, Cunitz B, Liggit D, Evan A, McAteer J, Bailey M, Sorensen MD. "Ultrasound-Induced Renal Injury Threshold." 88th Annual Meeting, Western Section of the American Urological Association, Waikoloa, Hawaii, October 7-12, 2012.

88th Annual Meeting, Western Section of the American Urological Association, Waikoloa, Hawaii, October 7-12, 2012. , Oct-2012

Abstracts for Journals and Proceedings Khokhlova VA, Yuldashev PV, Kreider W, Bailey MR, Sapozhnikov OA, Crum LA. "Combined modeling and measurement methods to calibrate nonlinear acoustic fields of HIFU transducers," 12th International Symposium on Therapeutic Ultrasound, Heidelberg, Germany, June 10-13, 2012.

12th International Symposium on Therapeutic Ultrasound, Heidelberg, Germany, June 10-13, 2012. Abstract A-211. , Jun-2012

Abstracts for Journals and Proceedings Kreider W, Yuldashev PV, Sapozhnikov OA, Farr N, Partanen A, Kaczkowski PJ, Bailey MR, Khokhlova VA. "Calibration of a Philips MR-Guided HIFU source by acoustic holography and nonlinear modeling." 12th International Symposium on Therapeutic Ultrasound, Heidelberg, Germany, June 10-13, 2012.

12th International Symposium on Therapeutic Ultrasound, Heidelberg, Germany, June 10-13, 2012. Abstract A-137. , Jun-2012

Abstracts for Journals and Proceedings Cunitz BW, Kucewicz JC, Wang YN, Simon JC, Lu W, Dunmire B, Kaczkowski PJ, Paun M, Starr F, Harper JD, Sorensen MD, Sapozhnikov OA, Crum LA, Bailey MR. "Ultrasonic propulsion of kidney stones." Ultrasonic Imaging and Tissue Characterization Symposium, Arlington, VA, June 11-13, 2012.

Ultrasonic Imaging and Tissue Characterization Symposium, Arlington, VA, June 11-13, 2012. , Jun-2012

Abstracts for Journals and Proceedings Crum LA, Harper JD, Sorensen MD, Cunitz BW, Wang YN, Simon JC, Bailey MR. "Smart Therapeutic Ultrasound for Mission-Critical Medical Care." 2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012.

2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012. , Feb-2012

Abstracts for Journals and Proceedings Crum LA, Simon JC, Khokhlova TD, Wang YN, Hwang JH, Khokhlova VA, Bailey MR. "Boiling histotripsy: a method of tissue emulsification using millisecond-long pulses of high intensity focused ultrasound." Focused Ultrasound 2012. 3rd International Symposium, Washington, DC, October 14-17, 2012. MRgFUS 2012.

Focused Ultrasound 2012. 3rd International Symposium, Washington, DC, October 14-17, 2012. MRgFUS 2012. Program and abstracts, p. 59. , Oct-2012

Abstracts for Journals and Proceedings Crum L, Bailey M, Khokhlova T, Khokhlova V, Kreider W, Simon J, Wang YN, Sapozhnikov O. "Therapeutic Ultrasound: A Potential Revolution in Health Care." International Workshop on Acoustic Waves for the Control of Microfluidics Flows, Leiden, the Netherlands, April 23-27, 2012.

International Workshop on Acoustic Waves for the Control of Microfluidics Flows, Leiden, the Netherlands, April 23-27, 2012. , Apr-2012

Abstracts for Journals and Proceedings Crum L, Bailey M, Khokhlova T, Khokhlova V, Kreider W, Simon J, Wang YN, Sapozhnikov O. "Therapeutic ultrasound: recent advances and future perspectives." 9th International Symposium on Modern Acoustics, Nanjing, China, May 20-22, 2012.

9th International Symposium on Modern Acoustics, Nanjing, China, May 20-22, 2012. , May-2012

Abstracts for Journals and Proceedings Sorensen MD, Harper JD, Hsi R, Paun M, Dighe M, Carter S. Moshiri M, Shah A, Lu W, Bailey M. "Independent Performance Characteristics of B-Mode versus Twinkling Artifact Ultrasound in Detecting Nephrolithiasis." 88th Annual Meeting, Western Section of the American Urological Association, Waikoloa, Hawaii, October 7-12, 2012., Oct-2012.

88th Annual Meeting, Western Section of the American Urological Association, Waikoloa, Hawaii, October 7-12, 2012. , Oct-2012

Abstracts for Journals and Proceedings Sorensen MD, Harper JD, Hsi R, Cunitz B, Simon J, Wang YN, Paun M, Starr F, Lu W, Evan A, Bailey M. "Preclinical Efficacy and Safety of Ultrasonic Propulsion of Kidney Stones." Society of Engineering and Urology, 27th Annual meeting, Atlanta, GA, May 19, 2012.

Society of Engineering and Urology, 27th Annual meeting, Atlanta, GA, May 19, 2012. , May-2012

Abstracts for Journals and Proceedings Sorensen MD, Harper JD, Hsi R, Cunitz B, Simon J, Wang YN, Paun M, Starr F, Lu W, Evan A, Bailey M. "Preclinical Efficacy and Safety of Ultrasonic Propulsion of Kidney Stones." 30th World Congress of Endourology & SW, Istanbul, Turkey, September 4-8, 2012.

Journal of Endourology. 2012 Sep;26 Suppl 1:VS05-09. Scientific Program for 30th World Congress of Endourology & SWL. , Sep-2012

Abstracts for Journals and Proceedings Kucewicz J, Dunmire B, Bailey M. "Improved detection of kidney-stone twinkling using autoregressive signal-processing method." Ultrasonic Imaging and Tissue Characterization Symposium, Arlington, VA, June 11-13, 2012.

Ultrasonic Imaging and Tissue Characterization Symposium, Arlington, VA, June 11-13, 2012., Jun-2012. , Jun-2012

Abstracts for Journals and Proceedings Sapozhnikov OA, Bailey MR. "A wide variety of nonlinear acoustic effects associated with a small kidney stone." 19th International Symposium on Nonlinear Acoustics, Tokyo, Japan, May 21-24, 2012. Opening lecture.

19th International Symposium on Nonlinear Acoustics, Tokyo, Japan, May 21-24, 2012. Opening lecture. , Jun-2012

Abstracts for Journals and Proceedings Sapozhnikov O, Simon J, Khokhlova V, Khokhlova T, Kreider W, Bailey M. "Comparison of Ultrasonic Atomization of Tissue and Liquids." 12th International Symposium on Therapeutic Ultrasound, Heidelberg, Germany, June 10-13, 2012.

12th International Symposium on Therapeutic Ultrasound, Heidelberg, Germany, June 10-13, 2012. Abstract A-298. , Jun-2012

Abstracts for Journals and Proceedings Khokhlova VA, Yuldashev PV, Kreider W, Sapozhnikov OA, Bailey MR, Crum LA. "Nonlinear modeling as a metrology tool to characterize high intensity focused ultrasound fields." 164th Meeting of the Acoustical Society of America, Kansas City, Missouri, October 22-26, 2012.

164th Meeting of the Acoustical Society of America, Kansas City, Missouri, October 22-26, 2012. , Oct-2012

Abstracts for Journals and Proceedings Kreider W, Khokhlova VA, Bailey MR, Sapozhnikov OA. "Acoustic holography as a metrological tool for medical ultrasound." 2012 IEEE International Ultrasonics Symposium (IUS), Dresden Germany, October 7-10, 2012.

2012 IEEE International Ultrasonics Symposium (IUS), Dresden Germany, October 7-10, 2012. , Oct-2012

Abstracts for Journals and Proceedings Sapozhnikov OA, Bailey MR. "Modeling of radiation force imparted to an elastic sphere from an ultrasound beam of arbitrary structure." 161st Meeting of the Acoustical Society of America, Seattle, Washington, May 23-27, 2011.

Journal of the Acoustic Society of America. 2011 Apr;129(4):2377. Program and abstracts of the 161st meeting of the Acoustical Society of America. http://dx.doi.org/10.1121/1.3587700 , Apr-2011

Articles in Peer-reviewed Journals Sapozhnikov OA, Bailey MR. "Radiation force of an arbitrary acoustic beam on an elastic sphere in a fluid." Journal of the Acoustic Society of America. 2013 Feb;133(2):661-76. http://dx.doi.org/10.1121/1.4773924 ; PubMed PMID: 23363086; PubMed Central PMCID: PMC3574112 (NOTE previously reported as "In press, as of December 2012.") , Feb-2013
Articles in Peer-reviewed Journals Crum LA, Bailey M, Hwang JH, Khokhlova V, Sapozhnikov O. "Therapeutic ultrasound: Recent trends and future perspectives." Physics Procedia. 2010 Jan;3(1):25-34. (International Congress on Ultrasonics, Santiago de Chile, January 2009) http://dx.doi.org/10.1016/j.phpro.2010.01.005 , Jan-2010
Articles in Peer-reviewed Journals Lu W, Sapozhnikov OA, Bailey MR, Kaczkowski PJ, Crum LA. "Evidence for trapped surface bubbles as the cause for the twinkling artifact in ultrasound imaging." Ultrasound Med Biol. 2013 Jun;39(6):1026-38. Epub 2013 Apr 3. http://dx.doi.org/10.1016/j.ultrasmedbio.2013.01.011 ; PubMed PMID: 23562014; PubMed Central PMCID: PMC3646957 , Jun-2013
Articles in Peer-reviewed Journals Wang YN, Khokhlova T, Bailey M, Hwang JH, Khokhlova V. "Histological and biochemical analysis of mechanical and thermal bioeffects in boiling histotripsy lesions induced by high intensity focused ultrasound." Ultrasound Med Biol. 2013 Mar;39(3):424-38. Epub 2013 Jan 11. http://dx.doi.org/10.1016/j.ultrasmedbio.2012.10.012 ; PubMed PMID: 23312958; PubMed Central PMCID: PMC3570648 , Mar-2013
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 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. PubMed PMID: 25977591; PubMed Central PMCID: PMC4428615 , Mar-2015
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 Poliachik SL, Khokhlova TD, Wang YN, Simon JC, Bailey MR. "Pulsed 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 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, Sorensen MD, Cunitz BW, Wang Y, 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. https://doi.org/10.1016/j.juro.2013.03.120 ; PubMed PMID: 23583535; PubMed Central PMCID: PMC4414252 [Note: reported originally in Jan 2013 as submitted to European Urology] , Sep-2013
Articles in Peer-reviewed Journals Harper JD, Shah A, Mitchell SB, Wang YN, Starr F, Bailey MR, Crum LA. "Novel high-intensity focused ultrasound clamp--potential adjunct for laparoscopic partial nephrectomy." J Endourol. 2012 Nov;26(11):1494-9. Epub 2012 Sep 10. http://dx.doi.org/10.1089/end.2012.0107 ; PubMed PMID: 22788221 , Nov-2012
Articles in Peer-reviewed Journals Simon JC, Sapozhnikov OA, Khokhlova VA, Wang YN, Crum LA, Bailey MR. "Ultrasonic atomization of tissue and its role in tissue fractionation by high intensity focused ultrasound." Physics in Medicine and Biology. 2012 Dec 7;57(23):8061-78. Epub 2012 Nov 16. http://dx.doi.org/10.1088/0031-9155/57/23/8061 ; PubMed PMID: 23159812 , Dec-2012
Articles in Peer-reviewed Journals Khokhlova TD, Canney MS, Khokhlova VA, Sapozhnikov OA, Crum LA, Bailey MR. "Controlled tissue emulsification produced by high intensity focused ultrasound shock waves and millisecond boiling." J Acoust Soc Am. 2011 Nov;130(5):3498-510. PubMed PMID: 22088025 , Nov-2011
Articles in Peer-reviewed Journals Kreider W, Crum LA, Bailey MR, Sapozhnikov OA. "A reduced-order, single-bubble cavitation model with applications to therapeutic ultrasound." J Acoust Soc Am. 2011 Nov;130(5):3511-30. http://dx.doi.org/10.1121/1.3626158 ; PubMed PMID: 22088026 , Nov-2011
Articles in Peer-reviewed Journals Kreider W, Crum LA, Bailey MR, Sapozhnikov OA. "Observations of the collapses and rebounds of millimeter-sized lithotripsy bubbles." J Acoust Soc Am. 2011 Nov;130(5):3531-40. http://dx.doi.org/10.1121/1.3626157 ; PubMed PMID: 22088027 , Nov-2011
Articles in Peer-reviewed Journals Sorensen MD, Bailey MR, Shah AR, Hsi RS, Paun M, Harper JD. "Quantitative assessment of shockwave lithotripsy accuracy and the effect of respiratory motion." J Endourol. 2012 Aug;26(8):1070-4. Epub 2012 Jun 13. http://dx.doi.org/10.1089/end.2012.0042 ; PubMed PMID: 22471349 , Aug-2012
Articles in Peer-reviewed Journals Sorensen MD, Harper JD, Hsi RS, Shah AR, Dighe MK, Carter SJ, Moshiri M, Paun M, Lu W, Bailey MR. "B-mode ultrasound versus color Doppler twinkling artifact in detecting kidney stones." J Endourol. 2013 Feb;27(2):149-53. Epub 2012 Oct 15. http://dx.doi.org/10.1089/end.2012.0430 ; PubMed PMID: 23067207; PubMed Central PMCID: PMC3573723 , Feb-2013
Articles in Peer-reviewed Journals Shah A, Harper JD, Cunitz BW, Wang YN, Paun M, Simon JC, Lu W, Kaczkowski PJ, Bailey MR. "Focused ultrasound to expel calculi from the kidney." J Urol. 2012 Feb;187(2):739-43. Epub 2011 Dec 16. http://dx.doi.org/10.1016/j.juro.2011.09.144 ; PubMed PMID: 22177202 , Feb-2012
Awards Simon J. "Runner-up, UW Student Entrepreneurial and Business Association business plan competition, September 2011." Sep-2011
Awards Simon J. "University of Washington College of Engineering Dean's Fellowship, August 2012." Aug-2012
Awards Simon J. "UW (University of Washington) Invents Graduate Student Award, February 2012." Feb-2012
Awards Crum L. "Awarded the Acoustical Society of America's Gold Medal, June 2013." Jun-2013
Awards Crum L, Bailey M, Simon J. "Best Poster, Society for Engineering and Urology, Annual meeting, May 2012." May-2012
Awards Bailey M. "Appointed to Membership Committee of the Acoustical Society of America, October 2012." Oct-2012
Awards Bailey M. "Awarded UW Applied Physics Laboratory Science and Technology Award, December 2011." Dec-2011
Awards Bailey M. "Member of Transiently Increased Output (TIO) subcommittee of the American Institute of Ultrasound in Medicine, April 2012." Apr-2012
Awards Khokhlova V. "Elected to Acoustical Society of America Executive Council, May 2012." May-2012
Awards Khokhlova V. "Elected to Board of the International Society for Therapeutic Ultrasound, April 2012." Apr-2012
Awards Lu W. "UW Invents Graduate Student Award. UW decided to give 2 awards instead of the usual 1 award; the other award was to student Julianna Simon. February 2012." Feb-2012
Awards Sorensen MD, Harper JD, Hsi R, Cunitz B, Simon J, Wang YN, Paun M, Starr F, Lu W, Evan A, Bailey M. "2012 Best Poster and Invited Talk for 'Preclinical Efficacy and Safety of Ultrasonic Propulsion of Kidney Stones,' Society of Engineering and Urology, 27th Annual meeting, Atlanta, GA, May 19, 2012." May-2012
Dissertations and Theses Lu W. "Ultrasonic Detection and Expulsion of Kidney Stones." Dissertation, University of Washington, August 2012. , Aug-2012
Papers from Meeting Proceedings Simon JC, Sapozhnikov OA, Khokhlova VA, Wang YN, Crum LA, Bailey MR. "Tissue Atomization by High Intensity Focused Ultrasound." 2012 IEEE International Ultrasonics Symposium (IUS), Dresden Germany, October 7-10, 2012.

2012 IEEE International Ultrasonics Symposium (IUS), Dresden Germany, October 7-10, 2012. , Oct-2012

Significant Media Coverage Ostrovsky G. "Finding, pushing kidney stones using ultrasound. Article about PI's research and finding kidney stones." MedGadget weblog. Feb 1, 2012. http://medgadget.com/2012/02/finding-pushing-kidney-stones-using-ultrasound.html ; accessed 2/5/2015., Feb-2012
Significant Media Coverage Williams M. "NSBRI, BCM Center for Space Medicine dedicated at BRC. Article on Rice University’s BioScience Research Collaborative (BRC) and dedication of the new home for the NSBRI on March 19, 2012, including awarding its fourth annual Pioneer Award to Sen. Kay Bailey Hutchison." Rice University News and Media.. March 20, 2012. http://news.rice.edu/2012/03/20/nsbri-bcm-center-for-space-medicine-dedicated-at-brc/ ; accessed 2/5/2015., Mar-2012
Significant Media Coverage Garner J. "Open for Business: Start-up takes aim at kidney stones. Article about PI's research and the start-up company the researchers are forming." Columns. UW Alumni Magazine. June 2012., Jun-2012
Significant Media Coverage Luiggi C. "Space Rocks. Orbiting ultrasound machines are being used to diagnose and treat astronauts' kidney stones. Article describing PI's research." The Scientist. June 1, 2012, p. 22. https://the-scientist.com/notebook/space-rocks-40934 , Jun-2012
Project Title:  Smart Therapeutic Ultrasound Device for Mission-Critical Medical Care Reduce
Fiscal Year: FY 2011 
Division: Human Research 
Research Discipline/Element:
HRP ExMC:Exploration Medical Capabilities
Start Date: 08/01/2008  
End Date: 09/30/2012  
Task Last Updated: 09/08/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   Crum, Lawrence A. Ph.D. / University of Washington 
Address:  Applied Physics Laboratory 
1013 N.E. 40th Street 
Seattle , WA 98105-6606 
Email: lac@apl.washington.edu 
Phone: 206-685-8622  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Washington 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bailey, Michael  University of Washington 
Carter, Stephen  University of Washington 
Sapozhnikov, Oleg  University of Washington 
Project Information: Grant/Contract No. NCC 9-58-SMST01601 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-SMST01601 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) ExMC 4.13:We have limited capability to screen for, diagnose, and treat renal stones during exploration missions (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date should be 9/30/2012 (previously 7/31/2012) per NSBRI (Ed., 5/22/2012)

Task Description: 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. Our methods and devices are countermeasures to specific risks described in the Human Research Program Integrated Research Plan, viz.,

(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 technologies 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.

The main findings and associated research productivity for year 3 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 my regrow to new stones, and provides a way to prophylactically remove small stones before they require surgery. This year, we have accomplished the following:

- Obtained approval from the University of Washington Institutional Review Board (IRB) for clinical testing of the stone detection technology.

- Obtained NIH Funding for regulatory consultants (Drug and Device Development Co. and Institute of Translational Health Sciences) to help us prepare an application to the U.S. Food and Drug Administration (FDA) for an Investigational Device Exemption (IDE) for an investigator-driven, pilot clinical trial of detecting and repositioning stones.

- Collected and documented about half the required safety data for the IDE application.

- Developed three iterations of a business plan culminating in one funded by NASA and NSBRI to be completed by Virtual Incubation Company, LLC. Our approach has been to not start a company yet, but instead to leverage university resources (research team, Center for Commercialization, Entrepreneur-in-Residence, and non-diluting state, federal and foundation funding to remove risk and attain the critical inflection point of "first in man." The business plans center on commercial partnerships or a start-up as well as NASA implementation at that inflection point.

- Filed a U.S. patent application that encompassed all the technologies.

- Developed a prototype from commercial-off-the-shelf (COTS) hardware, which will arguably accelerate production and regulatory approval of an eventual commercial product.

- The hardware for our prototype has advantages for space flight, namely radiation hardening, and with the ExMC Imaging Integration Team and the manufacturer, we are developing a system suitable for deployment and testing on ISS. We use the HDI-5000 probes currently available on ISS. The ultrasound system is a single box that was adapted to work with the IBM Lenovo laptops currently used on ISS. The system is open-architecture, software based, COTS technology, meaning that other NASA or NSBRI countermeasures could easily be implemented on it and upgrades do not require up-mass. Proposals for flight-testing, for integration of NSBRI countermeasures on the platform, for implementation of new technology, and for radiation testing were submitted with NSBRI, NSBRI researchers, ExMC, and NASA Glenn.

- Successfully completed a collaboration with Siemens of a DARPA-funded Phase II project to develop an automated system to detect and control bleeding on the battlefield and in remote environments. Phase III funding is pending. NSBRI funding was used to automate the detection and treatment for ease-of-use in a portable system. That work was published in year 2. The results were presented at international meetings.

- 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 60601-2-62 standards document. The technology was demonstrated on a Philips clinical HIFU system.

- 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.

- Negotiations are underway among UW, Philips, and a drug company for clinical trials for pancreatic cancer. Our measurements were used to define the "dose" to be applied to patients.

- Completed initial investigation of HIFU-induced, tumor-specific auto-immune response in collaboration with Fred Hutchinson Cancer Research Institute.

- Demonstrated with statistical significance in a small cohort that application of shocked ultrasound waves accelerated wound healing in a rat model over sham exposures.

- Obtained funding from US Army to investigate the application of shocked ultrasound to slow bone loss in a murine paralysis model. Our new approach was found to significantly slow, and in some cases halt, bone loss.

Research Impact/Earth Benefits: We have been encouraged by our interactions with the urology, ultrasound, and business communities that our technology to detect and reposition stones could significantly alter the way kidney stones are treated in clinical medicine. We have won awards in the six poster or business plan competitions we have entered. Most stones are small enough to pass naturally and thus patients are encouraged, through hydration, to try to pass the stone without intervention. This natural process might take 6-8 weeks and result in considerable discomfort to the patient over this interval. With our innovative technology, a stone could potentially be cleared in the first office visit. Many stones do not clear with hydration, and thus more aggressive approaches are required. More invasive procedures are often necessary if the stone is in the lower pole because even if fragmented, the pieces are unlikely to pass from this location. Our technological approach would keep the least invasive option open for these patients. In most existing procedures, there is a significant chance stone pieces will remain behind as seeds for future stones and further surgery. Our technology could help these pieces pass. In addition, stones are often recurrent; recurring-stone patients are often monitored, so that new stones can be detected early - this monitoring could be done with our precise stone imaging approach. Our technology could also move these stones to the kidney exit before they are symptomatic. This technology reduces risk of surgery, complications of surgery for the patient, and the cost of surgery to the insurance companies; furthermore, the technology does not preclude any surgical options. Lastly, the algorithms to detect kidney stones alone stand to spare many patients the ionizing radiation of a CT scan, or to provide options to pregnant women or children with stones who are unlikely to receive CT. NSBRI quickly recognized the value of this technology and helped us initiate our commercialization effort that now has the full support of the UW, the Washington Research Foundation, and a commercial hardware provider, as well as the interest of several venture capitalists and ultrasound companies.

The applications of our technology to the control of bleeding and for tumor ablation are at least as profound. Specifically, this year we have worked with the latest clinical HIFU machine - one developed by Philips Medical. This machine is intended for many clinical applications. We have used some of our effort to characterize the output of the machine and assess its potential bio-effects. Our work provides the clinicians, who intend to use this machine, the ability to select a treatment dose. At UW alone, it helps train the clinicians and establish the specificity of what size targets are treated. With our contribution, the clinicians are then likely to pursue their own clinical studies, and regulatory approval for various tumor treatments. Before our involvement, the machine sat dormant for a year. We are also exploring the effects of HIFU on the immune system and have proposed clinical trials to combine HIFU with chemical therapeutic agents. We believe that our efforts to carefully describe outputs and bio-effects will help the US catch up with the rest of the world where over 400,000 patients have been treated by HIFU. In addition, our intimate knowledge of these details enables us to consider ways in which a similar, much reduced-in-size system could be developed for NASA to reduce some critical risks to astronauts during long duration space travel.

Task Progress & Bibliography Information FY2011 
Task Progress: Task 1A. Perform studies of bleeding detection in a flow-phantom model: Successfully detected and treated sites in a phantom developed with DARPA and FDA in a blind test with an automated system.

Task 1B. Perform studies to determine pressure and temperature in ex vivo tissue exposed to HIFU: Published paper "Shock-induced heating and millisecond boiling in gels and tissue due to high intensity focused ultrasound", Michael Canney, et al., Ultrasound Med. & Biol., 36, 250-267 (2010), which led to invitation to join IEC working group on HIFU standards and to measure acoustic output of Philips clinical HIFU machine. Also, discovered and submitted patent application for method to emulsify tissue with ultrasound.

Task 2A. Develop new stone detection techniques based on radiation force and reverberation responsible for twinkling artifact: As part of our graduate student's dissertation, efforts continue toward understanding the origins of the twinkling artifact and to further refine the algorithms we have developed, implemented, tested, and patented.

Task 2B. Test stone sizing technology in tissue: Published paper, M.D. Sorensen, et al., "Proof of Principle of a Prototype Ultrasound Technology to Size Stone Fragments During Ureteroscopy," J. Endourology, 2009, 1161-1164; filed U.S. and international utility patent applications, and are negotiating licensing. We have initiated human clinical studies to test ultrasound stone sizing versus CT.

Task 3A. Utilize the YUANDE HIFU tumor ablation device as a test platform: Performed a number of studies.

Task 3B. Engineer and optimize an image-guided, two-frequency HIFU system for renal stone comminution: We are working with ExMC to fly one platform that detects, repositions, and comminutes stones. All are implemented in a prototype for which we are pursuing an investigational device exemption (IDE) with the FDA. We have developed a concept of expelling small stones from a kidney before they require comminution or surgery. A system to detect and reposition stones based on an OEM diagnostic ultrasound platform has been built and demonstrated to be safe and effective in studies in a porcine model. Commercialization efforts have begun. An update report on progress won best poster at the American Urology Association meeting.

Task 4A. Perform in vivo tests of the imaging protocols developed in Task 2: Paper in preparation comparing twinkling to standard B-mode for stone detection in patients. New algorithm for stone detection implemented on clinical machine and tests of the algorithm initiated on human subjects.

Task 4B. Perform studies to determine the potential for HIFU-induced stone comminution as well as any associated tissue injury: In vivo studies of our stone clearance system have been shown to be safe and effective. A safety study in pigs is complete and a study of safety under realistic clinical conditions in pigs has just begun. These data will be presented to the FDA to pursue a clinical trial.

Bibliography Type: Description: (Last Updated: 03/22/2019) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Khokhlova TD, Canney MS, Khokhlova VA, Sapozhnikov OA, Crum LA, Bailey MR. "Millisecond bursts of focused ultrasound shock waves to produce boiling and tissue emulsification." Journal of the Acoustical Society of America. In press, as of September 2011. , Sep-2011
Articles in Peer-reviewed Journals Kreider W, Sapozhnikov OA, Crum LA, Bailey MR. "A reduced-order, single-bubble cavitation model with applications to therapeutic ultrasound." Journal of the Acoustical Society of America. In press, as of September 2011. , Sep-2011
Articles in Peer-reviewed Journals Kreider W, Sapozhnikov OA, Crum LA, Bailey MR. "Observations of the collapses and rebounds of millimeter-sized lithotripsy bubbles." Journal of the Acoustical Society of America. In press, as of September 2011. , Sep-2011
Articles in Peer-reviewed Journals Rassweiler JJ, Knoll T, Köhrmann KU, McAteer JA, Lingeman JE, Cleveland RO, Bailey MR, Chaussy C. "Shock wave technology and application: an update." European Urology 2011 May;59(5):784-96. Epub 2011 Feb 23. Review. PMID: 21354696 ; http://dx.doi.org/10.1016/j.eururo.2011.02.033 , May-2011
Articles in Peer-reviewed Journals Shah A, Harper JD, Cunitz BW, Wang YN, Paun M, Simon JC, Lu W, Kaczkowski PJ, Bailey MR. "Focused ultrasound to expel calculi from the kidney." Journal of Urology. In press, as of September 2011. , Sep-2011
Articles in Peer-reviewed Journals Shah A, Owen NR, Lu W, Cunitz BW, Kaczkowski PJ, Harper JD, Bailey MR, Crum LA. "Novel ultrasound method to reposition kidney stones." Urol Res. 2010 Dec;38(6):491-5. Epub 2010 Oct 22. PMID:20967437 ; http://dx.doi.org/10.1007/s00240-010-0319-9 , Dec-2010
Awards Simon J. "Recipient, Baker Award Fellowship, UW College of Engineering, May 2011." May-2011
Awards Bailey M. "Appointment Adjunct Assist. Prof. of Urology, May 2011." May-2011
Awards Bailey M. "Appointment Assist. Prof. of Mechanical Engineering (WOT), September 2010." Sep-2010
Awards Hsi R. "Best Poster American Urological Assoc. Annual meeting, May 2011." May-2011
Awards Khokhlova V. "Elected to Board, International Society for Therapeutic Ultrasound, April 2011." Apr-2011
Awards Lu W. "Winner, Business Plan Poster Competition UW SEBA, February 2011." Feb-2011
Significant Media Coverage Assimos D. "Urolithiasis/Endourology. The PI's article, 'Novel ultrasound method to reposition kidney stones,' from Urol Res ( http://dx.doi.org/10.1007/s00240-010-0319-9 ) was chosen to be highlighted in the Journal of Urology, which is rare for a basic science article. The Editor provided favorable comment." Urolithiasis/Endourology Urological Survey Journal of Urology. 2011 Jun;185(6):2186-9. , Jun-2011
Project Title:  Smart Therapeutic Ultrasound Device for Mission-Critical Medical Care Reduce
Fiscal Year: FY 2010 
Division: Human Research 
Research Discipline/Element:
HRP ExMC:Exploration Medical Capabilities
Start Date: 08/01/2008  
End Date: 07/31/2012  
Task Last Updated: 08/06/2010 
Download report in PDF pdf
Principal Investigator/Affiliation:   Crum, Lawrence A. Ph.D. / University of Washington 
Address:  Applied Physics Laboratory 
1013 N.E. 40th Street 
Seattle , WA 98105-6606 
Email: lac@apl.washington.edu 
Phone: 206-685-8622  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Washington 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bailey, Michael  University of Washington 
Carter, Stephen  University of Washington 
Sapozhnikov, Oleg  University of Washington 
Project Information: Grant/Contract No. NCC 9-58-SMST01601 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-SMST01601 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) ExMC 4.13:We have limited capability to screen for, diagnose, and treat renal stones during exploration missions (IRP Rev E)
Task Description: 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. Our methods and devices are countermeasures to specific risks described in the Human Research Program Integrated Research Plan, viz.,

(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 technologies 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.

The key findings and associated research productivity for year 1 are:

• Successfully completed a collaboration with Siemens of a DARPA-funded Phase II project to develop an automated system to detect and control bleeding on the battlefield. Phase III funding is pending. Leveraged this effort to build automated bleeding detection and ultrasound-based treatment monitoring with NSBRI funding. Paper published, presentation made, and Record of Invention submitted.

• Conducted in vitro and animal tests toward transcutaneous tumor ablation treatment with HIFU. Completing initial investigation of HIFU-induced, tumor-specific immune response in collaboration with Fred Hutchinson Cancer Research Institute and initiated a second animal study on Philips clinical HIFU system with Seattle Cancer Care Alliance. Characterized the acoustic output and optimized exposure parameters of the Philips machine. Efforts are underway for commercially sponsored clinical trials for pancreatic cancer. Utilized NSBRI funding to develop modeling and characterization tools, test ultrasound guidance, replicate acoustic output with smaller instrumentation, and initiate additional research. Papers published and others are pending approval by commercial collaborators.

• Developed new method to emulsify tissue with transcutaneous ultrasound. Our method has several potential advantages over the technique used in competitor's $11 million start-up. Our method also has promise as a potential surgical tool. Submitted provisional patent and published papers.

• Developed second prototype to detect and reposition kidney stones with ultrasound. This is a proposed new treatment for stones in microgravity for early detection as well as to reposition them near the exit of the kidney for natural clearance. It also has significant earthbound clinical and commercialization potential. Human studies of the detection algorithm have begun and approval in principle for treatment in human subjects has been granted pending final acoustic output measurements. Safety and efficacy has been demonstrated in pigs. An intellectual-property package has been prepared by UW for potential licensing. A business/commercialization plan has been developed. A commercial partner has been identified and initial investigation into the regulatory and reimbursement pathways has taken place. This information was shared during NASA's meetings to identify the next ultrasound system for ISS as our capabilities to address gaps could be integrated directly into certain existing ultrasound systems.

• A miniaturized device to size stone fragments for safe extraction has been tested in a porcine kidney: Submitted U.S. utility patent application and published paper. This topic has been the subject of licensing negotiations between the University of Washington and a potential commercial sponsor.

Ultrasound for treating bleeding, benign and malignant tumors, and stone disease are revolutionary therapies; as such, our approach is to leverage funding to demonstrate that they are clinically safe and efficacious. In particular, we utilized NSBRI funding to understand the acoustic exposures needed to develop light-weight instrumentation for potential use in microgravity. NSBRI has also embraced the commercialization of our system to detect and reposition stones, and great progress has been made this year. The earthbound, as well as the space application is to enable the passage of stones and residual fragments and thus prevent complications from impacted stones. We licensed revolutionary diagnostic ultrasound hardware from an Original Equipment Manufacturer and added a few changes of our own. With NSBRI's help, we made the case that if similar hardware were selected as the ultrasound system on ISS, our capability to detect and treat stones could be immediately deployed (TRL/CRL level 9) for emergency treatment of urolithiasis.

To summarize, in our acoustic hemostasis effort, we have results ready to publish, expect to continue our substantial DARPA-funded effort working toward human subjects testing, and will utilize our NSBRI-developed systems in animal studies. On our HIFU ablation studies, animal experiments should soon be completed and published this year, and all pieces should be in place for and IDE/IRB to initiate human studies. On stone disease, our device is expected to be tested on human subjects; a new transducer will be developed; acoustic output characterization for regulatory approval will begin, and it is planned to transfer some of this technology to a new start-up.

Research Impact/Earth Benefits: We have been encouraged by our interactions with the urology, ultrasound, and business communities that our technology to detect and reposition stones could significantly alter the way kidney stones are treated on Earth. We have won awards in the four poster or business plan competitions we have entered. Most stones are small enough to pass naturally and thus patients are encouraged, through hydration and a drug Flomax, to try to pass the stone without intervention. This natural process might take 6-8 weeks and result in considerable discomfort to the patient over this interval. With our technology, the stone could potentially be cleared in the first office visit. Many stones do not clear with hydration, and thus more aggressive approaches are required. More invasive procedures are often necessary if the stone is in the lower pole because even if fragmented the pieces are unlikely to pass from this location. Our technology might keep the least invasive option open for these patients. In most existing procedures, there is a significant chance stone pieces will remain behind as seeds for future stones and further surgery. Our technology could help these pieces pass. In addition, stones are often recurrent; recurring-stone patients are often monitored, so that new stones can be detected early - this monitoring could be done in astronauts with our precise stone imaging approach. Our technology could also move these stones to the kidney exit before they are symptomatic. This technology reduces risk of surgery, complications of surgery for the patient, and the cost of surgery to the insurance companies; furthermore, the technology does not preclude any surgical options. Lastly, the algorithms to detect kidney stones alone stand to spare many patients the ionizing radiation of a CT scan or provide options to pregnant women or children with stones who are unlikely to receive CT. NSBRI quickly recognized the value of this technology and help us initiate our commercialization effort that now has the full support of the UW, the Washington Research Foundation, and a commercial hardware provider as well as the interest of several venture capitalists and ultrasound companies.

The applications of our technology to the control of bleeding and for tumor ablation are at least as profound. Specifically, this year we have worked with the latest clinical HIFU machine - one developed by Philips Medical. This machine is intended for many clinical applications. We have used some of our effort to characterize the output of the machine and assess its potential bio-effects. Our work provides the clinicians, who intend to use this machine, the ability to select a thermal dose. At UW alone, it helps train the clinicians and establish the specificity of what size targets are treated. With our contribution, the clinicians are then likely to pursue their own clinical studies and with Philips backing regulatory approval for various tumor treatments. Before our involvement, the machine sat dormant for a year. We are also exploring the effect of HIFU on the immune system and have proposed clinical trials to combine HIFU with chemotherapy agents. We believe that our efforts to carefully describe outputs and bio-effects will help the US catch up with the rest of the world where over 400,000 patients have been treated by HIFU. In addition, our intimate knowledge of these details enable us to consider ways in which a similar, much reduced-in-size system could be developed for NASA to reduce some major risks to astronauts.

The control of bleeding with ultrasound has great potential to save lives from both civilian and battlefield trauma. Our most directed work leverages DARPA funding and is in partnership with a commercial entity. This ambitious project seeks to develop a fully autonomous system that would both detect bleeding and induce hemostasis without major user involvement.

Task Progress & Bibliography Information FY2010 
Task Progress: Task 1A. Perform studies of bleeding detection in a flow-phantom model. Successfully detected and treated sites in a phantom developed with DARPA and FDA in a blind test with an automated system.

Task 1B. Perform studies to determine pressure and temperature in ex vivo tissue exposed to HIFU. Paper M.S. Canney, et al., "Millisecond boiling produced by high intensity focused ultrasound," Ultrasound Med. Biol., 2009 and others led to invitation to join IEC working group on HIFU standards and to measure acoustic output of Philips clinical HIFU machine. Also, discovered method to emulsify tissue with ultrasound.

Task 2A. Develop new stone detection techniques based on radiation force and reverberation responsible for twinkling artifact and vibroacoustography. As part of our graduate student's dissertation, efforts continue to understand the origins of the twinkling artifact and to further refine the algorithms we have developed, implemented, tested, and submitted to UW for patent submission.

Task 2B. Test stone sizing technology in tissue. Published paper M.D. Sorensen, et al., "A Proof of Principle of a Prototype Ultrasound Technology to Size Stone Fragments During Ureteroscopy," J. Endourology 2010; 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. This project is ongoing.

Task 3B. Engineer and optimize an image-guided, two-frequency HIFU system for renal stone comminution. We have focused on moving small stones within the kidney with ultrasound to facilitate natural stone clearance. A system to detect and reposition stones based on an OEM diagnostic ultrasound platform has been built and demonstrated to be safe and effective in a porcine model. Commercialization effort has begun. Results were reported at the American Urology and Laparoendoscopy Society meetings. Efforts to generate shorter higher amplitude pulses such as those used in shock wave lithotripsy (SWL) to break stones have begun, both to add a useful capability as well as to pursue a SWL regulatory pathway.

Task 4A. Perform in vivo tests of the imaging protocols developed in Task 2. Paper in preparation comparing twinkling to standard B-mode for stone detection in patients. New algorithm for stone detection implemented on clinical machine and tests of the algorithm initiated on human subjects.

Task 4B. Perform studies to determine the potential for HIFU-induced stone comminution as well as any associated tissue injury. In vivo studies of our stone clearance system have been shown to be safe and effective. A new assay and ultrasound imaging technology are being tested by a graduate student to quantify tissue injury. Stone clearance and injury measurements will begin on human subjects.

Bibliography Type: Description: (Last Updated: 03/22/2019) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Khokhlova VA, Canney MS, Khokhlova TD, Wang YN, Hwang JH, Crum LA, Bailey MR. "Mechanical erosion of tissue using millisecond bursts of high amplitude shock waves." Presented at the 20th International Conference on Acoustics, ICA-2010, Sydney, Australia, August 23-27, 2010.

20th International Conference on Acoustics, ICA-2010, Sydney, Australia, August 2010. , Aug-2010

Abstracts for Journals and Proceedings Khokhlova VA, Yuldashev PV, Canney MS, Bailey MR, Sapozhnikov OA, Crum LA. "A combined measurement and modeling method to characterize nonlinear HIFU fields." Presented at Advanced Metrology for Ultrasound in Medicine, National Physical Laboratory, Teddington, UK, May 12-14, 2010.

Advanced Metrology for Ultrasound in Medicine, National Physical Laboratory, Abstract Book, May 2010. , May-2010

Abstracts for Journals and Proceedings Kreider W, Chen H, Bailey M, Brayman A, Matula T. "Bubble-boundary interactions relevant to medical ultrasound." Presented at the Joint 159th Meeting of the Acoustical Society of America and NOISE-CON 2010, Baltimore, MD, April 19-23, 2010.

Journal of the Acoustical Society of America. 2010 Mar;127(3):1978. http://dx.doi.org/10.1121/1.3385074 , Mar-2010

Abstracts for Journals and Proceedings Lee D, Marro K, Cunitz B, Bailey MR. "Does proton resonance frequency linearly change with temperature?" Presented at the International Society for Magnetic Resonance in Medicine, 19th Annual Meeting, Stockholm, Sweden, May 1-7, 2010.

International Society for Magnetic Resonance in Medicine, 19th Annual Meeting, Stockholm, Sweden, May 2010. , May-2010

Abstracts for Journals and Proceedings Lu W, Cunitz BW, Kaczkowski PJ, Shah A, Sapozhnikov OA, Bailey MR. "Radiation pressure from ultrasound to help kidney stones pass." Presented at the 158th Meeting of the Acoustical Society of America, San Antonio, Texas, October 26-30, 2009.

Journal of the Acoustical Society of America. 2009 Oct;126(4, Pt 2):2213. http://dx.doi.org/10.1121/1.3248749 , Oct-2009

Abstracts for Journals and Proceedings Sapozhnikov OA, Bailey MR. "Theoretical modeling of radiation force imparted on a kidney stone by a focused ultrasound beam." Presented at the 20th International Congress on Acoustics, ICA 2010, Sydney, Australia, August 23-27, 2010.

20th International Congress on Acoustics, ICA-2010, Sydney, Australia, August, 2010. , Aug-2010

Abstracts for Journals and Proceedings Shah A, Bailey MR. "Focused ultrasound to facilitate stone clearance." Presented at the 2009 Western Section American Urological Association (WSAUA) 85th Annual Meeting, Las Vegas, NV, October 25-29, 2009.

2009 Western Section American Urological Association (WSAUA) 85th Annual Meeting, October 2009. , Oct-2009

Abstracts for Journals and Proceedings Shah A, Cunitz B, Lu W, Sorensen M, Crum L, Bailey M. "Clearance of lower pole kidney stones using focused ultrasound techniques." Presented at the 27th World Congress of Endourology & SWL, Munich, Germany, October 6-10, 2009.

Journal of Endourology. 2009 Oct;23(Suppl 1):A286. http://www.wce2009.de/pdf/Final_Files.pdf , Oct-2009

Abstracts for Journals and Proceedings Shah A, Mitchell S, Wang YN, Bailey M, Sorensen M, Crum L, Harper J. "Novel high intensity focused ultrasound instrument for partial nephrectomy." Presented at the 28th World Congress of Endourology & SWL, Chicago, IL, September 1-4, 2010.

Journal of Endourology 2010 Sep;24(Suppl 1):A1-394. , Sep-2010

Abstracts for Journals and Proceedings Shah A, Paun M, Owen NR, Sapozhnikov OA, Lu W, Illian R, Mourad PD, Bailey MR, Crum LA. "Measurement of stone targeting during shock wave lithotripsy." 10th International Symposium on Therapeutic Ultrasound, Tokyo, Japan, June 9-12, 2010.

10th International Symposium on Therapeutic Ultrasound, Tokyo, Japan, June 2010. , Jun-2010

Abstracts for Journals and Proceedings Shah A, Sorensen M, Canney M, Sapozhnikov O, Teichman J, Bailey M. "Miniaturization of an ureteroscopic ultrasound technology to size kidney stone fragments in a porcine model." Presented at the Society of Laparoendoscopic Surgeons, Boston, MA, September 9-12, 2009.

Society of Laparoendoscopic Surgeons, September 2009. , Sep-2009

Abstracts for Journals and Proceedings Shah A, Sorensen M, Dighe M, Paun M, Wright J, Bailey M, Harper J. "Novel use of diagnostic ultrasound imaging to assess efficacy of shockwave lithotripsy treatment." Presented at the 28th World Congress of Endourology & SWL, Chicago, IL, September 1-4, 2010.

Journal of Endoeurology 2010 Sep;24(Suppl 1):A1-A394. , Sep-2010

Abstracts for Journals and Proceedings Shah A, Sorensen M, Paun M, Dunmire B, Kucewicz J, Cunitz B, Starr F, Kaczkowski P, Sapozhnikov O, Bailey M. "Ultrasound to facilitate clearance of residual stones." Presented at the 18th Society of Laparoendoscopic Surgeons Annual Meeting, Boston, MA, September 9-12, 2009.

18th Society of Laparoendoscopic Surgeons Annual Meeting, September 2009. , Sep-2009

Abstracts for Journals and Proceedings Shah A, Sorensen M, Harper J, Cunitz B, Lu W, Bailey M. "Focused ultrasound application to reposition kidney stones and facilitate passage of residual fragments." American Urological Association 2010 Annual Meeting, San Francisco, California, May 29-June 3, 2010.

Journal of Urology 2010 Apr;183(4 Suppl):e819. http://dx.doi.org/10.1016/j.juro.2010.02.2194 , Apr-2010

Abstracts for Journals and Proceedings Bailey M, Cunitz B, Shah A, Paun M, Kaczkowski P, Sapozhnikov O. "Focused ultrasound to move kidney stones." Presented at the 9th International Symposium on Therapeutic Ultrasound, Aix-en-Provence, France, September 23-26, 2009.

9th International Symposium on Therapeutic Ultrasound, Aix-en-Provence, France, September 2009. , Sep-2009

Abstracts for Journals and Proceedings Canney MS, Khokhlova TD, Wang YK, Khokhlova VA, Bailey MR, Crum LA. "Tissue erosion using millisecond boiling in high-intensity focused ultrasound fields." Presented at the Joint 159th Meeting of the Acoustical Society of America and NOISE-CON 2010, Baltimore, MD, April 19-23, 2010.

Journal of the Acoustical Society of America. 2010 Mar;127(3):1760. http://dx.doi.org/10.1121/1.3383729 , Mar-2010

Abstracts for Journals and Proceedings Crum LA, Canney MS, Bailey MR, Bessonova OV, Khokhlova VA. "Toward a better understanding of high intensity focused ultrasound therapy using the Khokhlov–Zabolotskaya–Kuznetsov equation." Presented at the 158th Meeting of the Acoustical Society of America, San Antonio, Texas, October 26-30, 2009.

Journal of the Acoustical Society of America. 2009 Oct;126(4, Pt 2):2201. http://dx.doi.org/10.1121/1.3248617 , Oct-2009

Abstracts for Journals and Proceedings Cunitz B, Marro K, Lee D, Bailey M. "A test bed to calibrate MR thermometry." Presented at the 9th International Symposium on Therapeutic Ultrasound, Aix-en-Provence, France, September 23-26, 2009.

9th International Symposium on Therapeutic Ultrasound, Aix-en-Provence, France, September 2009. , Sep-2009

Abstracts for Journals and Proceedings Harper JD, Mitchell SB, Wang YN, Shah AR, Bailey MR, Crum LA. "Novel high-intensity focused ultrasound clamp–potential adjunct for laparoscopic partial nephrectomy." American Urological Association 2010 Annual Meeting, San Francisco, California, May 29-June 3, 2010.

Journal of Urology 2010 Apr;183(4 Suppl):e283. http://dx.doi.org/10.1016/j.juro.2010.02.1213 , Apr-2010

Abstracts for Journals and Proceedings Khokhlova T, Bailey M, Canney M, Hwang JH, Yee C, Crum L. "Tumor-specific immune response induced by HIFU therapy: a study in a mouse model." Presented at the 9th International Symposium on Therapeutic Ultrasound, Aix-en-Provence, France, September 23-26, 2009.

9th International Symposium on Therapeutic Ultrasound, Aix-en-Provence, France, September 2009. , Sep-2009

Abstracts for Journals and Proceedings Khokhlova T, Canney M, Khokhlova V, Wang YN, Hwang JH, Crum L, Bailey M. "Physical mechanisms and bioeffects of explosive boiling induced by millisecond pulses of high intensity focused ultrasound." Presented at the 2010 IEEE International Ultrasonics Symposium, San Diego, CA, October 11-14, 2010.

2010 IEEE International Ultrasonics Symposium, October 2010. , Oct-2010

Abstracts for Journals and Proceedings Khokhlova TD, Canney MS, Khokhlova VA, Wang YN, Hwang JH, Crum LA, Bailey MR. "Mechanical tissue erosion by boiling produced by millisecond pulses of high intensity focused ultrasound." Presented at the 10th International Symposium on Therapeutic Ultrasound, Tokyo, Japan, June 9-12, 2010.

10th International Symposium on Therapeutic Ultrasound, Tokyo, Japan, June 2010. , Jun-2010

Abstracts for Journals and Proceedings Poliachik SL, Khokhlova TD, Bailey MR. "High-intensity focused ultrasound as a potential treatment modality for heterotopic ossification." Presented at the Joint 159th Meeting of the Acoustical Society of America/NOISE-CON 2010, Baltimore, MD, April 19-23, 2010.

Journal of the Acoustical Society of America. 2010 Mar;127(3):1759. http://dx.doi.org/10.1121/1.3383721 , Mar-2010

Articles in Peer-reviewed Journals Bessonova OV, Khokhlova VA, Bailey MR, Canney MS, Crum LA. "Focusing of high power ultrasound beams and limiting values of shock wave parameters." Acoust Phys. 2009 Jul 21;55(4-5):463-76. PMID: 20161349 , Jul-2009
Articles in Peer-reviewed Journals Bessonova OV, Khokhlova VA, Canney MS, Bailey MR, Crum LA. "A derating method for therapeutic applications of high intensity focused ultrasound." Acoust Phys. 2010 Jan 1;56(3):354-63. PMID: 20582159 , Jan-2010
Articles in Peer-reviewed Journals Canney MS, Khokhlova VA, Bessonova OV, Bailey MR, Crum LA. "Shock-induced heating and millisecond boiling in gels and tissue due to high intensity focused ultrasound." Ultrasound Med Biol. 2010 Feb;36(2):250-67. PMID: 20018433 , Feb-2010
Articles in Peer-reviewed Journals Sapozhnikov OA, Kreider W, Bailey MR. "Effect of elastic waves in the metal reflector on bubble dynamics at the focus of an electrohydraulic lithotripter." Nelineinyi mir (Nonlinear world), 2009 Jul;7(7):575-80. (in Russian). , Jul-2009
Articles in Peer-reviewed Journals Sorensen MD, Shah AR, Canney MS, Sapozhnikov OA, Teichman JM, Bailey MR. "Ureteroscopic ultrasound technology to size kidney stone fragments: proof of principle using a miniaturized probe in a porcine model." J Endourol. 2010 Jun;24(6):939-42. PMID: 20136398 , Jun-2010
Awards Shah A, Bailey M, Crum L. "1st Place 4th Annual Science & Technology Showcase, January 2010." Jan-2010
Awards Shah A, Bailey M, Crum LA. "Invitation to present at 10th Annual Life Science Innovation Northwest, March 2010." Mar-2010
Awards Wallace J, Bailey M. "1st Place UW Executive MBA Business Plan Competition, June 2010." Jun-2010
Awards Crum L. "Elected member of Danish Academy of Natural Sciences, February 2010." Feb-2010
Awards Crum L. "President of International Society for Therapeutic Ultrasound, September 2010." Sep-2010
Awards Bailey M. "UW Assist. Prof. Mechanical Engineering and Adjunct Assist. Prof. of Urology WOT, March 2010." Mar-2010
Awards Sapozhnikov O. "Fellow, Acoustical Society of America, October 2010." Oct-2010
Awards Lu W, Bailey M, Crum L. "2nd prize best poster, National Academy Grand Challenges Meeting Seattle, May 2010." May-2010
Papers from Meeting Proceedings Bessonova OV, Khokhlova VA, Canney MS, Bailey MR, Crum LA. "Nonlinear derating methods for high intensity focused ultrasound (HIFU) fields." 2009 IEEE International Ultrasonics Symposium, Rome, Italy, September 20-23, 2009.

In: 2009 IEEE International Ultrasonics Symposium. New York : Institute of Electrical and Electronics Engineers, 2009. p. 216-219. http://dx.doi.org/10.1109/ULTSYM.2009.5441494 , Sep-2009

Papers from Meeting Proceedings Canney MS, Khokhlova TD, Khokhlova VA, Bailey MR, Hwang JH, Crum LA. "Tissue erosion using shock wave heating and millisecond boiling in HIFU fields." 9th International Symposium on Therapeutic Ultrasound, Aix-en-Provence, France, September 23-26, 2009.

In: 9th International Symposium on Therapeutic Ultrasound: ISTU-2009. AIP Conference Proceedings, Volume 1215, p. 36-39, March 2010. http://dx.doi.org/10.1063/1.3367183 , Mar-2010

Papers from Meeting Proceedings Crum LA, Owen NR, Lu W, Shah A, Bailey MR, Sapozhnikov OA. "The use of the twinkling artifact for improved stone detection and characterization." 3rd International Urolithiasis Research Symposium, Indianapolis, IN, December 3-4, 2009.

3rd International Urolithiasis Research Symposium, Indianapolis, IN, 2009. , Dec-2009

Papers from Meeting Proceedings Kreider W, Bailey MR, Sapozhnikov OA, Crum LA. "Potential temperature limitations of bubble-enhanced heating during HIFU." 9th International Symposium on Therapeutic Ultrasound, Aix-en-Provence, France, September 23-26, 2009.

In: 9th International Symposium on Therapeutic Ultrasound: ISTU-2009. AIP Conference Proceedings, Volume 1215, p. 367-370, March 2010. http://dx.doi.org/10.1063/1.3367182 , Mar-2010

Papers from Meeting Proceedings Kreider W, Bailey MR, Sapozhnikov OA, Khokhlova VA, Crum LA. "The dynamics of histotripsy bubbles." 10th International Symposium on Therapeutic Ultrasound, Tokyo, Japan, June 9-12, 2010.

10th International Symposium on Therapeutic Ultrasound, Tokyo, Japan, June 2010. , Jun-2010

Papers from Meeting Proceedings Kreider W, Chen H, Bailey MR, Brayman AA, Matula TJ. "Potential mechanisms for vessel invagination caused by bubble oscillations." 2009 IEEE International Ultrasonics Symposium, Rome, Italy, September 20-23, 2009.

In: 2009 IEEE International Ultrasonics Symposium. New York : Institute of Electrical and Electronics Engineers, 2009. p. 353-356. http://dx.doi.org/10.1109/ULTSYM.2009.5441744 , Sep-2009

Papers from Meeting Proceedings Sapozhnikov O, Bailey M, Cunitz B, Kaczkowski P, Oweis G. "Moving stones inside a kidney using acoustic radiation force." 2009 IEEE International Ultrasonics Symposium, Rome, Italy, September 20-23, 2009.

2009 IEEE International Ultrasonics Symposium, Rome, Italy, September, 2009. , Sep-2009

Papers from Meeting Proceedings Shah A, Lu W, Cunitz BW, Kaczkowski P, Bailey MR. "Ultrasound to move kidney stones." 3rd International Urolithiasis Research Symposium, Indianapolis, IN, December 3-4, 2009.

3rd International Urolithiasis Research Symposium, Indianapolis, IN, 2009. , Dec-2009

Papers from Meeting Proceedings Khokhlova VA, Bessonova OV, Soneson JE, Canney MS, Bailey MR, Crum LA. "Bandwidth limitations in characterization of high intensity focused ultrasound fields in the presence of shocks." Presented at the 9th International Symposium on Therapeutic Ultrasound, Aix-en-Provence, France, September 24-26, 2009.

In: 9th International Symposium on Therapeutic Ultrasound: ISTU-2009. AIP Conference Proceedings, Volume 1215, p. 363-366, March 2010. http://dx.doi.org/10.1063/1.3367181 , Mar-2010

Patents US 7,621,873 B2. Patented, November 24, 2009. Nov-2009 Owen NO, Bailey MR, Hossack J. "Method and system to synchronize acoustic therapy with ultrasound imaging."
Project Title:  Smart Therapeutic Ultrasound Device for Mission-Critical Medical Care Reduce
Fiscal Year: FY 2009 
Division: Human Research 
Research Discipline/Element:
HRP ExMC:Exploration Medical Capabilities
Start Date: 08/01/2008  
End Date: 07/31/2012  
Task Last Updated: 08/12/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   Crum, Lawrence A. Ph.D. / University of Washington 
Address:  Applied Physics Laboratory 
1013 N.E. 40th Street 
Seattle , WA 98105-6606 
Email: lac@apl.washington.edu 
Phone: 206-685-8622  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Washington 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bailey, Michael  University of Washington 
Sapozhnikov, Oleg  University of Washington 
Carter, Stephen  University of Washington 
Project Information: Grant/Contract No. NCC 9-58-SMST01601 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-SMST01601 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) ExMC 4.13:We have limited capability to screen for, diagnose, and treat renal stones during exploration missions (IRP Rev E)
Task Description: The major goals of this effort is 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 Human Research Program Integrated Research Plan, viz.,

(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.

Research Impact/Earth Benefits: 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 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 Progress & Bibliography Information FY2009 
Task Progress: The second tier research tasks described in the proposal are listed below and the progress on them for this year is as follows.

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.

Bibliography Type: Description: (Last Updated: 03/22/2019) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Bessonova OV, Khokhlova VA, Bailey MR, Canney MS, Crum LA. "Focusing of high intensity ultrasound beams and ultimate values of shock wave parameters." Acoustical Physics. In press, June 2009. , Jun-2009
Articles in Peer-reviewed Journals Canney MS, Bailey MR, Crum LA, Khokhlova VA, Sapozhnikov OA. "Acoustic characterization of high intensity focused ultrasound fields: a combined measurement and modeling approach." J Acoust Soc Am. 2008 Oct;124(4):2406-20. PMID: 19062878 , Oct-2008
Articles in Peer-reviewed Journals Khokhlova TD, Canney MS, Lee D, Marro KI, Crum LA, Khokhlova VA, Bailey MR. "Magnetic resonance imaging of boiling induced by high intensity focused ultrasound." J Acoust Soc Am. 2009 Apr;125(4):2420-31. PMID: 19354416 , Apr-2009
Articles in Peer-reviewed Journals Kreider W, Bailey MR, Ketterling JA. "Beamwidth measurement of individual lithotripter shock waves." J Acoust Soc Am. 2009 Feb;125(2):1240-5. PMID: 19206897 , Feb-2009
Articles in Peer-reviewed Journals Kucewicz JC, Bailey MR, Kaczkowski PJ, Carter SJ. "Focused ultrasound: concept for automated transcutaneous control of hemorrhage in austere settings." Aviat Space Environ Med. 2009 Apr;80(4):391-4. PMID: 19378911 , Apr-2009
Articles in Peer-reviewed Journals Sorensen MD, Shah AR, Canney MS, Sapozhnikov OA, Teichman TM H, Bailey MR. "Ureteroscopic ultrasound technology to size kidney stone fragments: Proof of principle using a miniaturized probe in a porcine model." J Endourol. Submitted, June 2009. , Jun-2009
Articles in Peer-reviewed Journals Sorensen MD, Teichman JM, Bailey MR. "Proof of principle in vitro study of a prototype ultrasound technology to size stone fragments during ureteroscopy." J Endourol. 2009 Jul;23(7):1161-4. PubMed PMID: 19538061 , Jul-2009
Articles in Peer-reviewed Journals Canney MS, Khokhlova VA, Bessonova OV, Bailey MR, Crum LA. "Millisecond boiling produced by high intensity focused ultrasound." Ultrasound in Medicine & Biology, Submitted February 2009. , Feb-2009
Awards Bailey MR. "Re-elected AIUM Bio-effects committee, February 2009." Feb-2009
Awards Crum LA. "Invited tutorial lecture at 2009 IEEE Ultrasonics Symposium, September 2009." Sep-2009
Awards Khokhlova TD. "NIH T32 Training grant postdoctoral fellowship, July 2009." Jul-2009
Awards Bailey M. "Elected to the Governing Board of the Interntional Society for Therapeutic Ultrasound, June 2009." Jun-2009
Awards Sapozhnikov OA. "Fellow of the Acoustical Society of America, June 2009." Jun-2009
Dissertations and Theses Canney MS. "Nonlinear enhancement of heating due to shock formation in high intensity focused ultrasound fields." Dissertation, University of Washington, June 2009. , Jun-2009
Papers from Meeting Proceedings Crum L, Bailey M, Canney M, Chen H, Matula T, Mc Innes C. "Direct observation of surface particle removal by an ultrasonic toothbrush." 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.

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

Papers from Meeting Proceedings Maxwell AD, Sapozhnikov OA, Pishchalnikov YA, Bailey MR. "Simulation and measurement of PVDF membrane hydrophone low-frequency response for accurate measurements of lithotripsy shockwaves." 2008 IEEE Ultrasonics Symposium, Beijing, China, November 2-5, 2008.

Proceedings of 2008 IEEE Ultrasonics Symposium, November 2008. , Nov-2008

Papers from Meeting Proceedings Pishchalnikov YA, McAteer JA, Pishchalnikova IV, Williams JC Jr, Bailey MR, Sapozhnikov OA. "Bubble proliferation in shock wave lithotripsy occurs during inertial collapse." 18th International Symposium on Nonlinear Acoustics, Stockholm, Sweden, July 7-10, 2008.

Proceedings from 18th International Symposium on Nonlinear Acoustics, July 2008. , Jul-2008

Papers from Meeting Proceedings Sorensen MD, Teichman JM H, Bailey MR. "A prototype ultrasound instrument to size stone fragments during ureteroscopy." 2nd International Urolithiasis Research Symposium, Indianapolis, IN, April 17-18, 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

Papers from Meeting Proceedings Shah A, Paun M, Kucewicz J, Sapozhnikov OA, Dighe M, McKay HA, Sorensen MD, Bailey MR, Crum LA. "Invited paper: Investigation of an ultrasound imaging technique to target kidney stones." 157th Meeting of the Acoustical Society of America, Portland, Oregon, May 18-22 2009.

J Acoust Soc Am. 2009 Apr;125(4, Pt 2):2620. , Apr-2009

Patents 111. Patent, June 2008. Jun-2008 Bailey MB, Carter S, Kaczkowski P, Kucewicz J. "Method and system for automation of focused ultrasound treatment."
Patents None yet. Patent in process, May 2008. May-2008 Bailey MB, Sorensen MD, Teichman J. "Method and device to measure stone size in surgical removal of kidney stones."
Significant Media Coverage Evangelista B. "Newspaper article: Some 'Star Trek' gadgets no longer futuristic." San Francisco Chronicle newspaper, Sunday, May 10, 2009., May-2009
Significant Media Coverage Shah A, Paun M, Kucewicz J, Sapozhnikov OA, Dighe M, McKay HA, Sorensen MD, Bailey MR, Crum LA. "Lay version of paper for Meeting Press: Investigation of an ultrasound imaging technique to target kidney stones." Acoustical Society of America lay paper, May 2009. http://acoustics.org/pressroom/httpdocs/157th/bailey.html , May-2009
Project Title:  Smart Therapeutic Ultrasound Device for Mission-Critical Medical Care Reduce
Fiscal Year: FY 2008 
Division: Human Research 
Research Discipline/Element:
HRP ExMC:Exploration Medical Capabilities
Start Date: 08/01/2008  
End Date: 07/31/2012  
Task Last Updated: 07/08/2008 
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Principal Investigator/Affiliation:   Crum, Lawrence A. Ph.D. / University of Washington 
Address:  Applied Physics Laboratory 
1013 N.E. 40th Street 
Seattle , WA 98105-6606 
Email: lac@apl.washington.edu 
Phone: 206-685-8622  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Washington 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Sapozhnikov, Oleg A  University of Washington 
Carter, Stephen J  University of Washington 
Bailey, Michael R  University of Washington 
Project Information: Grant/Contract No. NCC 9-58-SMST01601 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-SMST01601 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:  
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No. of Bachelor's Candidates:  
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No. of Bachelor's Degrees:  
Human Research Program Elements: (1) ExMC:Exploration Medical Capabilities
Human Research Program Risks: (1) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) ExMC 4.13:We have limited capability to screen for, diagnose, and treat renal stones during exploration missions (IRP Rev E)
Task Description: The principal, long-term objective of this proposed effort is to develop a smart medical device that would be lightweight, portable, FDA-approved, commercially produced, and capable of addressing a variety of risks described in the Bioastronautics Roadmap [NASA/SP-2005-6113]. This device would be based upon the platform technology of ultrasound, would potentially incorporate other imaging and therapy modalities, and would not require high skill levels from the user. Such a device supports the goals of the Strategic Plan of the Smart Medical Systems Team, which seeks to develop portable, autonomous systems, based upon a limited number of platform technologies, to address critical medical care in space medicine. In particular, we seek to address under Risk 18, the risk of blunt internal trauma and internal bleeding. The device we propose would be capable of detecting internal bleeding and inducing transcutaneous hemostasis. Under Risks 18 and 28, as recent experiences in Antarctica demonstrate (Nielsen, 2001), malignant tumors that require some form of surgery may well appear without warning, especially under the high-radiation load of outside LEO, even when extensive pre-screening is undertaken. The device we propose would be capable of performing transcutaneous, bloodless ablation of detectable tumors without fear of metastasis. Under Risk 4, the formation of renal calculi has been suggested by Schneider, et al. (1994) and Ball and Evans (2001) as a likely result in extended space flight; indeed, precedent exists of early mission termination due to a ureteral stone (Pietrzyk, et al, 2003; Moran, 2007). The proposed device would be capable of detecting and sufficiently comminuting a calculus for it to pass without obstructing the urinary system. In addition, such a multi-capability device, based on the platform technology of ultrasound (which is probably to be included in lunar and Martian missions) is likely to have applications beyond the risks outlined here.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2008 
Task Progress: New project for FY2008.

Bibliography Type: Description: (Last Updated: 03/22/2019) 

Show Cumulative Bibliography Listing
 
 None in FY 2008