The candidate of the proposed Career Development Award is Dr. Adam Maxwell, a biomedical engineer with over 10 years of experience in medical ultrasound research, particularly shock wave lithotripsy and high- intensity focused ultrasound therapy. He has investigated physical interactions of acoustic waves with tissues, developed research and clinical prototype systems, and researched new applications for ultrasound therapies. The purpose of applying for this Career Development Award is for Dr. Maxwell to cultivate the qualities and abilities necessary to be a successful independent researcher and obtain expertise in urolithiasis under the guidance of three experienced mentors, Drs. Michael Bailey, Jonathan Harper, and Hunter Wessells. The University of Washington is a leading research institution at which Dr. Maxwell plans to pursue his research and career development. He will be supported by a collaborative team with expertise in stone management within the Department of Urology and medical ultrasound in the Center for Industrial and Medical Ultrasound at the Applied Physics Laboratory. His proposed research will investigate a potential new treatment for urolithiasis. Urolithiasis is a common disease that affects approximately 1 in 11 individuals during their lifetime and presents a large burden on U.S. healthcare resources. In the last 30 years, management of urinary tract stones has seen the introduction of several novel approaches, including shock wave lithotripsy (SWL), ureteroscopy, and percutaneous nephrolithotomy. SWL is the only noninvasive procedure for stones, but the likelihood of rendering patients stone-free in a single session is considerably lower than other methods, and has declined in newer lithotripters. Development of a more effective lithotripter remains an unmet clinical challenge. While the physical interactions between shocks and stones were not well understood during this technology's clinical introduction, recent research has established the mechanisms of stone fracture in SWL. Based on this work, a novel type of lithotripsy using widely focused bursts of ultrasound rather than shock waves is proposed. Preliminary data shows that burst wave lithotripsy (BWL) is capable of disintegrating stones in as little as 10 seconds. Furthermore, the size of fragments generated during the procedure can be controlled by the ultrasound frequency, potentiating a therapy that produces small fragments easily passed by patients. The goal of this proposal is to create a scientific rationale that will guide the development of burst wave lithotripsy. In particular, this project proposes to investigate the physical interactions of ultrasound bursts with stones and tissue, and use this information to determine therapy parameters.
The specific aims of the proposal are: 1) Develop and characterize a suitable ultrasound source for BWL research, 2) Determine the mechanistic interactions leading to stone fracture by BWL, and 3) Identify the mechanical effects of BWL leading to tissue damage. Dr. Maxwell's long-term research goal is to translate this technology into a clinically useful treatment that improves the standard of care for stone management.

Public Health Relevance

Urinary tract stones are commonly treated with shock wave lithotripsy, a noninvasive procedure that disintegrates stones into passable pieces but is unsuccessful in up to 50% of treatments. This proposal aims to investigate a new method to noninvasively fragment urinary calculi using focused ultrasound rather than shock waves. The unique characteristics of this method could improve success rates for noninvasive stone treatments, while reducing complications and increasing access to lithotripsy technology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DK104854-02
Application #
9069839
Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2015-06-01
Project End
2020-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Washington
Department
Urology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Khokhlova, Tatiana; Rosnitskiy, Pavel; Hunter, Christopher et al. (2018) Dependence of inertial cavitation induced by high intensity focused ultrasound on transducer F-number and nonlinear waveform distortion. J Acoust Soc Am 144:1160
Bader, Kenneth B; Haworth, Kevin J; Maxwell, Adam D et al. (2018) Post Hoc Analysis of Passive Cavitation Imaging for Classification of Histotripsy-Induced Liquefaction in Vitro. IEEE Trans Med Imaging 37:106-115
Zwaschka, Theresa A; Ahn, Justin S; Cunitz, Bryan W et al. (2018) Combined Burst Wave Lithotripsy and Ultrasonic Propulsion for Improved Urinary Stone Fragmentation. J Endourol 32:344-349
Maxwell, Adam D; Yuldashev, Petr V; Kreider, Wayne et al. (2017) A Prototype Therapy System for Transcutaneous Application of Boiling Histotripsy. IEEE Trans Ultrason Ferroelectr Freq Control 64:1542-1557
May, Philip C; Kreider, Wayne; Maxwell, Adam D et al. (2017) Detection and Evaluation of Renal Injury in Burst Wave Lithotripsy Using Ultrasound and Magnetic Resonance Imaging. J Endourol 31:786-792
Simon, Julianna C; Maxwell, Adam D; Bailey, Michael R (2017) Some Work on the Diagnosis and Management of Kidney Stones with Ultrasound. Acoust Today 13:52-59
Movahed, Pooya; Kreider, Wayne; Maxwell, Adam D et al. (2017) Ultrasound-Induced Bubble Clusters in Tissue-Mimicking Agar Phantoms. Ultrasound Med Biol 43:2318-2328
Khokhlova, Tatiana D; Haider, Yasser A; Maxwell, Adam D et al. (2017) Dependence of Boiling Histotripsy Treatment Efficiency on HIFU Frequency and Focal Pressure Levels. Ultrasound Med Biol 43:1975-1985
Vlaisavljevich, Eli; Xu, Zhen; Maxwell, Adam et al. (2016) Effects of Temperature on the Histotripsy Intrinsic Threshold for Cavitation. IEEE Trans Ultrason Ferroelectr Freq Control 63:1064-1077
Hunter, Christopher; Sapozhnikov, Oleg A; Maxwell, Adam D et al. (2016) An ultrasonic caliper device for measuring acoustic nonlinearity. Phys Procedia 87:93-98