Engineered microbubbles to augment laser lithotripsy of urinary stones

工程微泡增强尿路结石激光碎石术

• 批准号: 10255749
• 负责人: Yuri A. Pishchalnikov
• 金额: $ 25.65万
• 依托单位: APPLAUD MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2023-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10255749
• 关键词: Affect; American; Chemicals; Clinical; Data; Devices; Disease; Distal; Dust; Effectiveness; Emergency department visit; Engineering; Environment; Feasibility Studies; Fiber; Frequencies; Goals; Healthcare Systems; Injury; Intervention; Irrigation; Knowledge; Laser Lithotripsy; Lasers; Lead; Left; Life; Light; Lipids; Longevity; Mechanics; Microbubbles; Operative Surgical Procedures; Optics; Outcome; Pain; Patients; Pattern; Penetration; Phase; Physiologic pulse; Postoperative Period; Procedures; Pulse Rates; Recurrence; Research; Residual state; Risk; Shock; Site; Small Business Innovation Research Grant; Specific qualifier value; Speed; Surface; Techniques; Time; Treatment Cost; Treatment Protocols; Ureteroscopes; Urinary Calculi; Urinary system; Urine; Video Microscopy; Violence; Water; Work; X-Ray Computed Tomography; aqueous; base; biomineralization; care costs; common treatment; cost; detector; energy density; improved; innovation; insight; minimally invasive; patient safety; pressure; product development; public health relevance; sensor; therapy development; vapor; vaporization

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.

摘要 意义：输尿管镜下激光碎石术是目前泌尿系结石最常见的手术治疗方法。 结石是一种痛苦的疾病，每11人中就有1人患病，给美国带来了沉重的负担。 医疗保健系统，每年的护理费用超过100亿美元。虽然激光碎石术 所有类型的结石，一个紧急的问题是，很大一部分患者（约二分之一） 当用计算机断层扫描评估时，残留结石碎片太小，无法进行激光治疗 但太大而不能随尿流自发通过。虽然残留的碎片很小， 与治疗前的结石相比，残留的碎片仍然会导致高比例的后结石， 手术急诊、额外干预和结石复发。 初步研究表明，特别设计的微泡增强了激光碎石术， 更小的残余碎片，这将导致改善的临床结果。我们假设 工程微泡通过将能量聚焦到结石和结石碎片中来增强激光碎石术 通过两种主要机制：光学和机械。这是符合的机制， 传统的激光碎石术通过激光与结石的直接相互作用来消融泌尿系统结石 表面以及机械效应，由于快速蒸发和随后的暴力崩溃， 水环境伴随着每个激光脉冲。 第一阶段SBIR的目的是确定使用专门设计的 微泡，以显着减少残余结石碎片，并改善激光碎石术。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， 我们将开发策略，以提高工程微泡激光碎石术的有效性。 所提出的方法的创新之处在于使用了工程微泡， 在激光碎石术中增加结石破碎并减少残余结石碎片。 这种方法有可能通过减少尿结石的发生而显著改善尿结石的治疗。 损伤、手术并发症和额外手术的风险，以及导致显著 减少手术时间和成本。此外，从该可行性研究中获得的知识将 帮助我们理解传统激光碎石术的机制， 进一步了解生物矿化相关疾病的治疗。

项目成果

Plasma formation in holmium:YAG laser lithotripsy.

钬：YAG 激光碎石术中的等离子体形成。

• DOI: 10.1002/lsm.23659
• 发表时间: 2023
• 期刊: Lasers in surgery and medicine
• 影响因子: 2.4
• 作者: Pishchalnikov,YuriA;Behnke-Parks,WilliamM;Stoller,MarshallL
• 通讯作者: Stoller,MarshallL