Histotripsy Tissue Interactions for BPH Therapy

描述(申请人提供)：组织摩擦学是将脉冲聚焦超声应用于目标组织，以诱导空化过程，从而导致非热的、机械的组织分割(最终将目标组织转化为无细胞液体)。每个超声脉冲都会产生一团局部的、高度动态的微泡(气泡云)，这些气泡会振荡并猛烈地崩塌。在连续脉冲的过程中，建筑结构被机械地分割，并且细胞在目标体积内被破坏。组织诊断学适用于各种器官内的多种疾病。为了这项建议的目的，我们专注于进一步研究前列腺内的这项技术，特别是评估组织镜检查治疗良性前列腺增生症(BPH)的适宜性。BPH是一种常见的疾病，前列腺组织过度生长导致排尿困难和衰弱的下尿路症状。不幸的是，目前设计用于去除或移除多余的BPH组织的治疗方法在经尿道前列腺电切术(TURP)中缺乏，尽管是一种有效的治疗方法，但它是一种具有手术风险的侵入性手术程序。虽然药物治疗和微创治疗被广泛应用于良性前列腺增生症，但与TURP相比，产生的结果一致较差。因此，组织电切术可能是治疗BPH的理想技术，它结合了微创消融技术的发病率和TURP的有效性(组织剥离)。我们之前已经在犬的模型中证明了使用组织摩擦学经皮消融前列腺组织的可行性。这项拟议的研究将量化前列腺周围关键结构，如尿括约肌、神经血管束、直肠和膀胱三角的附带损害的剂量依赖阈值。此外，超声引导的组织摩擦检查的准确性和精确度将在体内慢性犬模型中进行评估，该模型结合了炎症效应和伤口愈合过程。还计划在身体模型中进行前列腺组织学治疗，以探索犬和人之间前列腺组织成分和解剖位置的解剖差异如何影响组织学的有效性。对这些组织摩擦-组织相互作用的透彻了解将为进一步发展和优化组织摩擦治疗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.