Experimental observations and numerical modeling of lipid-shell microbubbles with calcium-adhering moieties for minimally-invasive treatment of urinary stones

Abstract

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.