Histotripsy for Urinary Stone Comminution

产品说明： 该提案的总体目标是开发一种新的方法，通过将组织破碎声场与常规冲击波相结合，更完全地粉碎泌尿系结石。初步证据表明，组织碎石术和碎石术可以以多种方式协同工作，以增强结石破碎。 组织破坏超声治疗是一种软组织消融方法，其中极其强烈的声脉冲导致微观气泡形成并能量性地塌陷（空化），破坏细胞膜并使附近组织破碎。使用高达几十个声学周期的短脉冲和高度聚焦的声场允许控制空化以进行精确消融。组织破坏研究已经对声学产生的空化以及用于增强和抑制空化活动的技术有了更深入的了解，这些技术已被用于提高消融率并保护邻近组织免受附带损伤。 当直接应用于结石时，组织碎石术产生快速的表面侵蚀，仅产生微观碎片。结合冲击波，空化放大组织碎石序列预计将增强结石粉碎，而抑制序列将“积极保护”周围肾实质免受损伤。 虽然冲击波碎石术（SWL）是治疗泌尿系结石的宝贵工具，但成功率始终低于更具侵入性的干预措施。在3个月随访时，20-40%的患者的SWL未能实现结石清除状态，即使是“成功”的手术也可能涉及仅部分崩解的碎片的疼痛通过。大结石（直径> 20 mm）、成分复杂的结石（即胱氨酸）和位于下极的结石的结局都更差，进一步阻碍了SWL治疗。 使用组织碎石术来控制结石附近和邻近组织中的空化环境，允许空化和非空化SWL机制的解耦，否则会紧密交织在一起。这将有助于他们的研究和优化，最终导致更有效的结石粉碎策略，产生更好的治疗效果，并将传统上困难的结石开放给SWL选择。 公共卫生相关性：估计有5-10%的美国人在一生中的某个时候患有尿结石。首选的非侵入性治疗（冲击波碎石术）仅对60-80%的患者成功。我们寻求开发一种新的非侵入性超声治疗，这将实现更高的成功率。

DESCRIPTION: The overall goal of this proposal is to develop a new process for more complete comminution of urinary calculi (stones) by combining histotripsy acoustic fields with conventional shockwaves. Preliminary evidence shows that histotripsy and lithotripsy can operate synergistically in multiple ways to enhance stone fragmentation. Histotripsy ultrasound therapy is a method of soft tissue ablation where extremely intense acoustic bursts cause microscopic bubbles to form and collapse energetically (cavitation) disrupting cell membranes and fragmenting nearby tissues. Using short bursts up to a few tens of acoustic cycles and highly focused sound fields allows cavitation to be controlled for precise ablation. Histotripsy research has yielded a greater understanding of acoustically generated cavitation and techniques for the enhancement and suppression of cavitation activity, which have been employed to increase the ablation rate and to protect adjacent tissue from collateral injury. When applied directly to stones, histotripsy produces rapid surface erosion with the generation of only microscopic debris. In combination with shockwaves, cavitation amplifying histotripsy sequences are expected to enhance stone comminution while suppressing sequences will "actively protect" surrounding kidney parenchyma from damage. While shockwave lithotripsy (SWL) has been an invaluable tool in the treatment of urinary stones, success rates have been consistently worse than more invasive interventions. SWL fails to achieve stone free status in 20-40% of patients at 3 month follow up and even "successful" procedures may involve the painful passage of fragments which have been only partially disintegrated. Large stones (> 20 mm diameter), stones of difficult composition (i.e. cystine), and stones located in the lower pole all have worse outcomes further discouraging treatment with SWL. Using histotripsy to control the cavitation environment immediately near a stone and in neighboring tissues allows a decoupling of cavitational and non-cavitational SWL mechanisms otherwise closely intertwined. This will aid in their study and optimization ultimately leading to more efficient stone comminution strategies producing better treatment outcomes and opening up traditionally difficult stones to the option of SWL. PUBLIC HEALTH RELEVANCE: Urinary stones afflict an estimated 5-10% of Americans at some point in their lifetime. The preferred non- invasive treatment (shockwave lithotripsy) is only successful for 60-80% of patients. We seek to develop a new non-invasive ultrasound treatment, which will achieve much higher success rates.