Histotripsy Tissue Interactions for BPH Therapy

描述（由申请人提供）：组织摧毁术是将脉冲聚焦超声应用于靶组织，以诱导空化过程，从而导致非热机械组织分离（最终将靶组织转化为无细胞液体）。每个超声波脉冲都会产生一个局部的、高度动态的微泡簇（气泡云），这些微泡会振荡并剧烈塌陷。在连续脉冲的过程中，结构结构被机械地分离，并且细胞在目标体积内被破坏。组织破坏术适用于各种器官内的广泛疾病。出于本提案的目的，我们专注于在前列腺内进一步研究该技术，特别是评估组织碎石术治疗良性前列腺增生（BPH）的适用性。BPH是一种常见的疾病，其中前列腺组织过度生长导致排尿困难和下尿路症状。不幸的是，目前设计用于缩小或去除过量BPH组织的治疗缺乏，因为尽管是有效的治疗，但经尿道前列腺切除术（TURP）是具有相关手术风险的侵入性手术过程。药物管理和微创治疗，虽然广泛用于BPH，产生一致的结果不如TURP。因此，组织破坏术可能是治疗BPH的理想技术，将微创消融技术的发病率特征与TURP实现的有效性（组织减积）相结合。我们之前已经证明了在犬模型中使用组织摧毁术来transmitting消融前列腺组织的可行性。拟议的研究将量化关键前列腺周围结构，如尿道括约肌，神经血管束，直肠和膀胱三角区的附带损害的剂量依赖性阈值。此外，将在体内慢性犬模型中评估超声引导组织破坏术的准确度和精密度，该模型包含炎症效应和伤口愈合过程。还计划在尸体模型中进行前列腺组织碎石术治疗，以探索犬和人之间前列腺组织组成和解剖位置的解剖学差异如何影响组织碎石术的有效性。深入了解这些组织破坏-组织相互作用将为进一步开发和优化组织破坏BPH治疗提供合理的基础。 公共卫生相关性：组织破坏术是一种潜在的变革性技术，可以改变许多外科疾病的治疗方式。对于BPH的治疗，无创性前列腺移行区的减积是可能的，与分馏组织简单地排尿。提出研究以量化前列腺周围结构的组织损伤阈值，定义组织破坏消融的精度，并调查将该技术转化为人体模型的问题。在需要明确的前列腺减积治疗BPH的患者中，组织破坏术可以显著降低手术风险和共病并发症。

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. PUBLIC HEALTH RELEVANCE: Histotripsy is potentially a transformational technology that could evolutionize the way many surgical diseases are treated. For BPH treatment, noninvasive debulking of the transition zone of the prostate is possible with fractionated tissue simply voided with urination. Research is proposed to quantify tissue damage threshold for periprostatic structures, define the precision of histotripsy ablation, and investigate issues with translation of this technology to a human model. Histotripsy could significantly reduce surgical risk and comorbid complications among patients in need of definitive prostate debulking for BPH.