Extracorporeal shockwave lithotripsy (SWL) revolutionized the treatment of urinary stones when first introduced three decades ago. Instead of open stone surgery, acoustic energy could be applied from outside the body to fragment stones in situ. Although widely utilized for treatment of stones, SWL has not fully lived up to its potential. Incomplete fragmentation of stones can result in significant pain (when fragments migrate down the ureter and obstruct urine outflow) and a high rate of residual fragments that need subsequent additional therapy. SWL research has shown the complex role of acoustic cavitation in the stone comminution process. While cavitation has been demonstrated to be an essential component of the fragmentation process, the bubbles produced also interfere with subsequent shockwaves reducing their effectiveness and sometimes causing tissue injury. SWL treatments at extremely low rates (i.e. <30 shocks/min) have been shown in the laboratory to be substantially more efficient and cause less tissue injury because there is sufficient time for most of the cavitation bubbles to dissolve. However, ultra-low rates have not been adopted clinically because of the impractically long procedure times that would be required. We have previously demonstrated that unfocused low amplitude acoustic bursts can stimulate rapid coalescence and dispersion of cavitation bubbles during SWL clearing the pathway for subsequent shockwaves within tens of milliseconds. By this method we can recover the stone fragmentation efficiency and safety of very low shockwave rates at standard clinical rates. Initial studies outlined in this proposal are designed to optimize the bubble coalescence and dispersion process for use with a standard clinical electromagnetic shockwave lithotripsy system. The following studies will then demonstrate safety and improved efficacy on a porcine model such that a pilot clinical trial could be initiated following this work.

Public Health Relevance

Urinary stones afflict an estimated 10% of Americans at some point in their lifetime. The preferred non- invasive treatment (shockwave lithotripsy) is only successful for 60-80% of patients. We seek to greatly improve the efficacy of shockwave lithotripsy with the addition of a specially designed low amplitude ultrasound field produced by a supplemental transducer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK091267-06
Application #
9380126
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kirkali, Ziya
Project Start
2011-09-15
Project End
2021-04-30
Budget Start
2017-07-01
Budget End
2018-04-30
Support Year
6
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Duryea, Alexander P; Tamaddoni, Hedieh A; Cain, Charles A et al. (2015) Removal of residual nuclei following a cavitation event: a parametric study. IEEE Trans Ultrason Ferroelectr Freq Control 62:1605-14
Khokhlova, Vera A; Fowlkes, J Brian; Roberts, William W et al. (2015) Histotripsy methods in mechanical disintegration of tissue: towards clinical applications. Int J Hyperthermia 31:145-62
Duryea, Alexander P; Roberts, William W; Cain, Charles A et al. (2015) Removal of residual cavitation nuclei to enhance histotripsy erosion of model urinary stones. IEEE Trans Ultrason Ferroelectr Freq Control 62:896-904
Duryea, Alexander P; Cain, Charles A; Roberts, William W et al. (2015) Removal of residual cavitation nuclei to enhance histotripsy fractionation of soft tissue. IEEE Trans Ultrason Ferroelectr Freq Control 62:2068-78
Lin, Kuang-Wei; Hall, Timothy L; Xu, Zhen et al. (2015) Histotripsy Lesion Formation Using an Ultrasound Imaging Probe Enabled by a Low-Frequency Pump Transducer. Ultrasound Med Biol 41:2148-60
Vlaisavljevich, Eli; Maxwell, Adam; Warnez, Matthew et al. (2014) Histotripsy-induced cavitation cloud initiation thresholds in tissues of different mechanical properties. IEEE Trans Ultrason Ferroelectr Freq Control 61:341-52
Lin, Kuang-Wei; Duryea, Alexander P; Kim, Yohan et al. (2014) Dual-beam histotripsy: a low-frequency pump enabling a high-frequency probe for precise lesion formation. IEEE Trans Ultrason Ferroelectr Freq Control 61:325-40
Kim, Yohan; Maxwell, Adam D; Hall, Timothy L et al. (2014) Rapid prototyping fabrication of focused ultrasound transducers. IEEE Trans Ultrason Ferroelectr Freq Control 61:1559-74
Duryea, Alexander P; Roberts, William W; Cain, Charles A et al. (2014) Acoustic bubble removal to enhance SWL efficacy at high shock rate: an in vitro study. J Endourol 28:90-5
Duryea, Alexander P; Cain, Charles A; Tamaddoni, Hedieh A et al. (2014) Removal of residual nuclei following a cavitation event using low-amplitude ultrasound. IEEE Trans Ultrason Ferroelectr Freq Control 61:1619-26

Showing the most recent 10 out of 14 publications