Histotripsy for Urinary Stone Comminution

描述：本提案的总体目标是通过将组织学声场与传统冲击波相结合，开发一种更完全粉碎尿路结石的新方法。初步证据表明，组织碎石术和碎石术可以通过多种方式协同作用，增强结石碎裂。组织切片超声治疗是一种软组织消融的方法，在这种方法中，极其强烈的声波爆发会导致微观气泡的形成和能量崩溃（空化），破坏细胞膜并破坏附近的组织。利用长达几十个声周期的短爆发和高度集中的声场，可以控制空化以实现精确的烧蚀。组织切片学研究已经对声产生的空化和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和保护邻近组织免受附带损伤。当直接应用于石头时，切片法产生快速的表面侵蚀，只产生微小的碎片。与冲击波相结合，空化放大的组织学序列有望增强结石粉碎，而抑制序列将“积极保护”周围肾实质免受损害。虽然冲击波碎石术（SWL）一直是治疗尿路结石的宝贵工具，但成功率一直低于侵入性干预。在3个月的随访中，20-40%的患者SWL不能达到无结石状态，即使是“成功”的手术也可能涉及到仅部分分解的碎片的痛苦通过。大的结石（直径约20毫米）、难组成的结石（如胱氨酸）和位于下极的结石都有较差的结果，进一步阻碍了SWL的治疗。使用历史图谱来控制岩石附近和邻近组织中的空化环境，可以将空化和非空化SWL机制解耦，否则就会紧密交织在一起。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，并为传统上困难的结石提供SWL的选择。

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.