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

Abstract

Products incorporating stone-targeting microbubbles have recently entered human clinical trials as a new minimally-invasive approach to treat urinary stones. Lipid-shell, gas-core microbubbles can be introduced into the urinary tract through a catheter. Calcium-binding moieties incorporated into the lipid shell can facilitate binding to stones. The microbubbles can be excited by an extracorporeal source of low-intensity ultrasound. Alternatively, the microbubbles can be excited by an intraluminal source, such as a fiber-optic laser. With either excitation technique, stone-targeting microbubbles can significantly increase rates of erosion, pitting, and fragmentation of stones, as has recently been reported for in-vitro experiments with synthetic stones [Wiener et al., J. Urology, v.199, no.4S, e322 (2018)]. We report here on new experiments using high-speed photography to characterize microbubbles expansion of cracks within a stone and resultant breaking-off of stone fragments. Numerical modeling shows that the direction of microjets produced by collapsing stone-bound microbubbles depends strongly on bubble shape and stand-off distance. For a wide range of stand-off distances and bubble shapes, microbubble collapse is associated with pressure increases of some two orders of magnitude compared to the excitation source pressures. This in-vitro study provides key insights into the use of stone-targeting microbubbles in treatment of urinary stones.