Histotripsy Tissue Interactions for BPH Therapy

用于 BPH 治疗的组织解剖学组织相互作用

• 批准号: 8699758
• 负责人: William W Roberts
• 金额: $ 31.69万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8699758
• 关键词: Ablation; Acoustics; Anatomy; Anogenital region; Benign Prostatic Hypertrophy; Cadaver; Canis familiaris; Catheters; Cells; Chronic; Coagulative necrosis; Complication; Development; Disease; Dose; Effectiveness; Excision; Focused Ultrasound Therapy; Fractionation; Goals; Gold; Histologic; Human; Image; Inferior; Inflammatory; Injury; Intention; Lasers; Lead; Liquid substance; Location; Measurement; Mechanics; Medication Management; Microbubbles; Modality; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Organ; Patients; Periprostatic; Physiologic pulse; Positioning Attribute; Process; Prostate; Radiofrequency Interstitial Ablation; Rectum; Research; Risk; Sphincter; Stress; Structure; Technology; Therapeutic; Thermal Ablation Therapy; Tissues; Transducers; Translations; Tumor Debulking; Ultrasonography; Urination; Wound Healing; base; bladder trigone; effective therapy; falls; improved; in vivo; interstitial; lower urinary tract symptoms; microwave electromagnetic radiation; minimally invasive; mortality; pressure; prostate transurethral resection; response; therapy design; urinary

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.

描述（由申请人提供）：组织练习是将脉冲焦点超声伸向靶向组织的应用，以诱导导致非热，机械组织分馏的空洞过程（最终将靶向组织转化为细胞液体）。每个超声脉冲都会产生一个局部的，高度动态的微泡（气泡云），可振荡并猛烈崩溃。在连续的脉冲过程中，建筑结构是机械分离的，并且在目标体积内破坏了细胞。组织疗法适用于各种器官中的各种疾病。出于该提案的目的，我们专注于在前列腺中进一步研究这项技术，专门评估了组织疗法对治疗良性前列腺增生（BPH）治疗的适用性。 BPH是一种常见的疾病，其中前列腺组织过度生长会导致难以排尿和使较低的尿路症状衰弱。不幸的是，缺乏旨在删除或去除多余的BPH组织的当前治疗方法，即前列腺（TURP）的外科手术切除术，尽管是一种有效的疗法，这是一种具有相关手术风险的侵入性手术手术。与TURP相比，尽管广泛用于BPH，但药物管理和微创治疗虽然被广泛使用，但其结果均匀较低。因此，组织疗法可能是治疗BPH的理想技术，将最小侵入性的消融技术的发病率与用TURP实现的有效性（组织删除）相结合。我们先前已经证明了在犬模型中使用组织疗法以透射灌溉前列腺组织的可行性。拟议的研究将量化关键紧急抑制结构（例如尿括约肌，神经血管束，直肠和膀胱三角形）等剂量依赖性阈值。此外，将在体内慢性犬模型中评估超声引导性组织疗法的准确性和精度，该模型结合了炎症作用和伤口愈合过程。还计划在尸体模型中进行组织疗法的前列腺治疗，以探讨前列腺组织组成的解剖学差异和犬类和人之间的解剖位置如何影响组织治治的有效性。对这些组织疗法组织相互作用的透彻理解将为进一步开发和优化Histotipy BPH治疗提供合理的基础。

项目成果

Prostate histotripsy: evaluation of prostatic urethral treatment parameters in a canine model.

• DOI: 10.1111/bju.12333
• 发表时间: 2014-03
• 期刊: BJU international
• 影响因子: 4.5
• 作者: Schade GR;Styn NR;Ives KA;Hall TL;Roberts WW
• 通讯作者: Roberts WW

Development and translation of histotripsy: current status and future directions.

• DOI: 10.1097/mou.0000000000000001
• 发表时间: 2014-01
• 期刊: Current opinion in urology
• 影响因子: 2.5
• 作者: Roberts WW