The overall goal of this proposal is to develop a new process for more complete comminution of urinary calculi (stones) by combining histotripsy acoustic fields with conventional shockwaves. Preliminary evidence shows that histotripsy and lithotripsy can operate synergistically in multiple ways to enhance stone fragmentation. Histotripsy ultrasound therapy is a method of soft tissue ablation where extremely intense acoustic bursts cause microscopic bubbles to form and collapse energetically (cavitation) disrupting cell membranes and fragmenting nearby tissues. Using short bursts up to a few tens of acoustic cycles and highly focused sound fields allows cavitation to be controlled for precise ablation. Histotripsy research has yielded a greater understanding of acoustically generated cavitation and techniques for the enhancement and suppression of cavitation activity, which have been employed to increase the ablation rate and to protect adjacent tissue from collateral injury. When applied directly to stones, histotripsy produces rapid surface erosion with the generation of only microscopic debris. In combination with shockwaves, cavitation amplifying histotripsy sequences are expected to enhance stone comminution while suppressing sequences will "actively protect" surrounding kidney parenchyma from damage. While shockwave lithotripsy (SWL) has been an invaluable tool in the treatment of urinary stones, success rates have been consistently worse than more invasive interventions. SWL fails to achieve stone free status in 20-40% of patients at 3 month follow up and even "successful" procedures may involve the painful passage of fragments which have been only partially disintegrated. Large stones (>20 mm diameter), stones of difficult composition (i.e. cystine), and stones located in the lower pole all have worse outcomes further discouraging treatment with SWL. Using histotripsy to control the cavitation environment immediately near a stone and in neighboring tissues allows a decoupling of cavitational and non-cavitational SWL mechanisms otherwise closely intertwined. This will aid in their study and optimization ultimately leading to more efficient stone comminution strategies producing better treatment outcomes and opening up traditionally difficult stones to the option of SWL.

Public Health Relevance

Urinary stones afflict an estimated 5-10% 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 develop a new non-invasive ultrasound treatment, which will achieve much higher success rates.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01DK091267-04
Application #
8726972
Study Section
Urologic and Kidney Development and Genitourinary Diseases Study Section (UKGD)
Program Officer
Kirkali, Ziya
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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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
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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
Lin, Kuang-Wei; Kim, Yohan; Maxwell, Adam D et al. (2014) Histotripsy beyond the intrinsic cavitation threshold using very short ultrasound pulses: microtripsy. IEEE Trans Ultrason Ferroelectr Freq Control 61:251-65
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Lin, Kuang-Wei; Hall, Timothy L; McGough, Robert J et al. (2014) Synthesis of monopolar ultrasound pulses for therapy: the frequency-compounding transducer. IEEE Trans Ultrason Ferroelectr Freq Control 61:1123-36
Vlaisavljevich, Eli; Kim, Yohan; Owens, Gabe et al. (2014) Effects of tissue mechanical properties on susceptibility to histotripsy-induced tissue damage. Phys Med Biol 59:253-70
Duryea, Alexander P; Roberts, William W; Cain, Charles A et al. (2013) Controlled cavitation to augment SWL stone comminution: mechanistic insights in vitro. IEEE Trans Ultrason Ferroelectr Freq Control 60:301-9