Engineered microbubbles to augment laser lithotripsy of urinary stones

摘要 意义：输尿管镜下激光碎石术是目前最常见的泌尿系疾病外科治疗方法。 结石--一种痛苦的疾病，每11个人中就有一个受到影响，给美国带来了巨大的负担。 医疗保健系统，每年的医疗费用超过100亿美元。虽然激光碎石术打破了 所有类型的结石，一个紧急的问题是，很大一部分患者(大约二分之一)被遗留下来 当用计算机断层扫描评估残留的结石碎片时，这些碎石太小而不能激光 有效，但太大，不能随尿流自发通过。而残留物碎片很小 尽管如此，与处理前的结石相比，残留的碎石仍然导致了较高的后处理率。 手术急诊科就诊、额外干预和结石复发。 初步研究表明，特殊设计的微泡可以增强激光碎石术，产生 较小的残留碎片，这应该会导致临床结果的改善。我们假设 工程微泡通过将能量聚焦到结石和结石碎片来增强激光碎石术 通过两种主要机制：光学机制和机械机制。这与机制是一致的 传统的激光碎石术通过直接激光与结石相互作用来消融尿路结石。 由于快速汽化和随后的剧烈坍塌而产生的表面和机械效应 水环境伴随着每个激光脉冲。 此第一阶段SBIR的目标是确定使用专门设计的 微泡能显著减少残留结石碎片，提高激光碎石效果。在目标1中， 我们将确定激光碎石术中工程微泡的作用机制和作用部位。在目标2中， 我们将制定策略，以提高工程微泡激光碎石术的有效性。 提出的方法的创新之处在于使用了工程微泡，这些微泡积累在 激光碎石术中增加结石碎石和减少残余结石碎石的作用。 这种方法有可能显著改善尿路结石的治疗，因为它减少了 受伤的风险、程序并发症和其他程序，以及导致显著 减少程序时间和成本。此外，从这项可行性研究中获得的知识将 有助于我们理解传统激光碎石术的操作机制，并产生 对生物矿化相关疾病治疗的进一步见解。

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.