Experimental observations and numerical modeling of lipid-shell microbubbles with calcium-adhering moieties for minimally-invasive treatment of urinary stones
A novel treatment modality incorporating calcium-adhering microbubbles has recently entered human clinical trials as a new minimally-invasive approach to treat urinary stones. In this treatment method, lipid-shell gas-core microbubbles can be introduced into the urinary tract through a catheter. Lipid moities with calcium-adherance properties incorporated into the lipid shell facilitate binding to stones. The microbubbles can be excited by an extracorporeal source of quasi-collimated ultrasound. Alternatively, the microbubbles can be excited by an intraluminal source, such as a fiber-optic laser. With either excitation technique, calcium-adhering microbubbles can significantly increase rates of erosion, pitting, and fragmentation of stones. We report here on new experiments using high-speed photography to characterize microbubble expansion and collapse. The bubble geometry observed in the experiments was used as one of the initial shapes for the numerical modeling. The modeling showed that the bubble dynamics strongly depends on bubble shape and stand-off distance. For the experimentally observed shape of microbubbles, the numerical modeling showed that the collapse of the microbubbles was associated with pressure increases of some two-to-three orders of magnitude compared to the excitation source pressures. This in-vitro study provides key insights into the use of microbubbles with calcium-adhering moieties in treatment of urinary stones.
© 2019 Acoustical Society of America. Published Online: 17 January 2019. We thank Dr. R. Shiraki for chemical analysis of stones' composition. MS and TK are founding members of Applaud Medical. YP, WBP, MM, MH and DL are employees/investigators for Applaud Medical, where the experimental part of this work was done. Numerical modeling was performed in Caltech by TC and KM, who acknowledge support from the National Institutes of Health (P01-DK043881) and the Office of Naval Research (N00014-17-1-2676 and N0014-18-1-2625).
Published - 2.0000958.pdf
Accepted Version - nihms-1583247.pdf