Engineered microbubbles to augment laser lithotripsy of urinary stones

Abstract Significance: Ureteroscopic laser lithotripsy is currently the most common surgical treatment for urinary stones—a painful disease affecting 1 in 11 people and imposing a significant burden on the U.S. healthcare system, with the cost of care exceeding $10 billion annually. Although laser lithotripsy breaks all types of stones, an emergent concern is that a large fraction of patients (around one in two) is left with residual stone fragments when evaluated with computed tomography that are too small to laser efficiently but too large to pass spontaneously with urine flow. While the residual fragments are small in comparison with the pre-treatment stone, the residual fragments nonetheless lead to high rates of post- operative emergency department visits, additional interventions, and recurrence of stones. Preliminary studies suggest that specially engineered microbubbles augment laser lithotripsy, producing smaller residual fragments, which should lead to improved clinical outcomes. We hypothesize that engineered microbubbles augment laser lithotripsy by focusing energy into stones and stone fragments via two main mechanisms: optical and mechanical. This is consistent with the mechanisms by which conventional laser lithotripsy ablates urinary stones, via direct laser light interactions with the stone surface as well as mechanical effects due to the rapid vaporization and subsequent violent collapse of the aqueous environment concomitant with each laser pulse. The objective of this Phase I SBIR is to determine the feasibility of using specially engineered microbubbles to significantly reduce residual stone fragments and improve laser lithotripsy. In Aim 1, we will identify mechanisms and sites of action of engineered microbubbles in laser lithotripsy. In Aim 2, we will develop strategies to improve the effectiveness of laser lithotripsy with engineered microbubbles. The innovation of the proposed approach is the use of engineered microbubbles that accumulate on urinary stones to augment stone fragmentation and reduce residual stone fragments in laser lithotripsy. This approach has the potential to significantly improve the treatment for urinary stones by reducing the risk of injury, procedural complications, and additional procedures, as well as result in a significant reduction in procedural time and cost. In addition, the knowledge gained from this feasibility study will aid our understanding of the mechanisms by which conventional laser lithotripsy operates, and produce further insights into the treatment of biomineralization-related diseases.Public Health Relevance Urinary stones afflict millions of Americans every year and are associated not only with severe pain, but also with high treatment costs and potentially life-threatening complications. Currently, the most common treatment for urinary stones involves a minimally invasive ureteroscopic laser procedure that intends to break urinary stones into sufficiently small fragments to allow them to pass naturally out of the urinary system. This project aims at improving the laser procedure by using engineered microbubbles that will further reduce the residual stone fragment size—an innovative way to pulverize stones into easily passed fragments.