Histotripsy Tissue Interactions for BPH Therapy

描述（由申请人提供）：组织切片术是将脉冲聚焦超声应用于目标组织，以诱导空化过程，导致非热的机械组织分离（最终将目标组织转化为脱细胞液体）。每个超声波脉冲都会产生一个局部的、高度动态的微气泡团（气泡云），这些微气泡团会振荡并剧烈崩溃。在连续脉冲的过程中，建筑结构被机械分解，细胞在目标体积内被破坏。组织切片法适用于多种器官内的广泛疾病。为了本提案的目的，我们专注于进一步研究前列腺内的这项技术，特别是评估组织切片术治疗良性前列腺增生（BPH）的适用性。前列腺增生是一种常见的疾病，前列腺组织的过度生长导致排尿困难和削弱下尿路症状。不幸的是，目前用于去除或切除过量前列腺增生组织的治疗方法缺乏，因为经尿道前列腺切除术（TURP）虽然是一种有效的治疗方法，但却是一种具有相关手术风险的侵入性手术。药物管理和微创治疗虽然广泛用于BPH，但与TURP相比，结果一致较差。因此，组织切片可能是治疗BPH的理想技术，结合了微创消融技术的发病率特征和TURP实现的有效性（组织缩小）。我们以前已经证明了可行性使用组织切片经皮消融前列腺组织在犬模型。拟议的研究将量化关键前列腺周围结构（如尿括约肌、神经血管束、直肠和膀胱三角区）附带损伤的剂量依赖阈值。此外，超声引导的组织切片的准确性和精度将在一个体内慢性犬模型中进行评估，该模型包括炎症效应和伤口愈合过程。我们还计划在尸体模型中进行前列腺组织切片治疗，以探索犬和人前列腺组织组成和解剖位置的解剖差异如何影响前列腺组织切片治疗的效果。深入了解这些组织学与组织的相互作用将为进一步发展和优化组织学治疗BPH提供合理的基础。

DESCRIPTION (provided by applicant): Histotripsy is the application of pulsed focused ultrasound to targeted tissue to induce cavitational processes that lead to non-thermal, mechanical tissue fractionation (ultimately converting the targeted tissue into an acellular liquid). Each ultrasound pulse creates a localized, highly dynamic cluster of microbubbles (a bubble cloud) that oscillates and violently collapses. Over the course of successive pulses architectural structure is mechanically fractionated and the cells destroyed within the targeted volume. Histotripsy is applicable to a broad spectrum of diseases within a variety of organs. For the purposes of this proposal, we focus on further studying this technology within the prostate, specifically assessing the suitability of histotripsy for treatment of benign prostatic hyperplasia (BPH). BPH is a common disease where overgrowth of prostate tissue results in difficulty urinating and debilitating lower urinary tract symptoms. Unfortunately, current therapy designed to debulk or remove excess BPH tissue is lacking in that surgical transurethral resection of the prostate (TURP), albeit an effective therapy, is an invasive operative procedure with associated surgical risks. Pharmacologic management and minimally invasive treatments, although widely employed for BPH, produce uniformly inferior results compared to TURP. Histotripsy may therefore be an ideal technology for treatment of BPH, combining the morbidity profile of minimally invasive ablative technologies with the effectiveness (tissue debulking) achieved with TURP. We have previously demonstrated the feasibility of using histotripsy to transcutaneously ablate prostate tissue in a canine model. The proposed research will quantify the dose dependent threshold for collateral damage of critical periprostatic structures such as the urinary sphincter, neurovascular bundles, rectum, and bladder trigone. Furthermore, the accuracy and precision of ultrasound guided histotripsy will be assessed in an in-vivo chronic canine model that incorporates inflammatory effects and wound healing processes. Histotripsy prostate treatment in cadaver models is also planned to explore how anatomic differences of prostate tissue composition and anatomic location between the canine and human will impact histotripsy effectiveness. A thorough understanding of these histotripsy-tissue interactions will provide a rational basis for further development and optimization of histotripsy BPH treatment.