Noninvasive histotripsy ablation of fibrotic tissue in benign prostatic hyperplasia

良性前列腺增生纤维化组织的无创组织解剖消融

• 批准号: 9815826
• 负责人: Adam Douglas Maxwell
• 金额: $ 59.18万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9815826
• 关键词: Ablation; Accounting; Acoustics; Acute; Affect; Age; Aging; Benign Prostatic Hypertrophy; Biological; Bladder; Canis familiaris; Chronic; Clinical; Clinical Trials; Collagen; Comorbidity; Congenital Abnormality; Cost Effectiveness Analysis; Data; Development; Devices; Disease; Elements; Epithelial Cells; Evaluation; Failure; Feedback; Focused Ultrasound; Frequencies; Future; Goals; Growth; Health Expenditures; Histologic; Human; Hyperplasia; Image; Investigation; Lead; Life Expectancy; Measures; Mechanics; Methods; Modeling; Morbidity - disease rate; Obstruction; Pattern; Phase I Clinical Trials; Physiologic pulse; Population; Procedures; Prostate; Prostatic Urethra; Protocols documentation; Reaction; Research; Specimen; Speed; Stream; Stress; Stromal Cells; Structure; Surgical Management; Symptoms; System; Techniques; Technology; Testing; Thrombosis; Time; Tissues; Ultrasonography; Urine; Urodynamics; base; clinical implementation; effective therapy; functional outcomes; imaging modality; improved; in vivo; interest; lower urinary tract symptoms; men; novel; optical imaging; patient population; prostate lateral lobe; prototype; response; soft tissue; standard of care; success; symptomatic improvement; therapy development; tissue phantom; treatment group; treatment response; treatment strategy; tumor

PROJECT SUMMARY Benign prostatic hyperplasia (BPH) is the most common cause of bothersome lower urinary tract symptoms (LUTS) in men affecting half by age 50 and about 90% of men by age 80. BPH is characterized by hyperplastic growth of glandular epithelial cells and fibromuscular stromal cells, leading to enlargement of the median and lateral lobes of prostate. The resulting bladder outlet obstruction impedes the flow of urine through the prostatic urethra, accounting for the development of LUTS (urgency, frequency, weak stream, straining, hesitancy, intermittency and night time voiding). Although current surgical management of BPH is efficacious, the increasing age and morbidity of this patient population has resulted in considerable clinical need for equally effective but less invasive and less morbid procedures. Histotripsy is an emerging noninvasive technology that applies short, high-amplitude focused ultrasound pulses to mechanically disintegrate tissue. Histotripsy is being investigated for a variety of diseases, including benign prostate hyperplasia, thrombosis, tumor treatment, and congenital defects. Investigations of the technology have strongly focused on soft tissues that are primarily cellular; the bioeffects, imaging and gross signatures of tissue breakdown, histological analysis, exposure parameters, and other aspects of the treatment are characterized and progressed based on the response of soft, glandular tissues. However, many of these diseases including BPH contain a critical fibrous component. Preliminary data indicates that different histotripsy exposures can achieve either fibrous tissue sparing or ablation. In this proposal, we aim to characterize the physical and biological effects of histotripsy on fibrotic tissue, evaluate promising treatment strategies to treat such tissue, and apply these methods specifically to improve histotripsy of the prostate. We propose to develop physical and numerical models for bubble-fibrous matrix interaction and characterize the physical effects of histotripsy exposures on fibrous structures using ultrasound and optical imaging methods. New exposure strategies will be tested to promote disintegration of fibrous tissue and identification of tissue disruption via ultrasound imaging feedback. Advanced strategies will be tested in ex vivo human prostate specimens to confirm improved ablation. Acute and chronic bioeffects will be assessed in a canine model of BPH. We will also measure changes in voiding patterns and urodynamics between treatment groups to demonstrate symptomatic improvement. The successful implementation of this project will overcome existing obstacles to clinical implementation of histotripsy for BPH and aid development of histotripsy for other applications.

项目摘要 良性前列腺增生（BPH）是尿路症状的最常见原因 （LUTS）在50岁时影响一半的男性和约90％到80岁的男性。BPH的特征是增生 腺体上皮细胞和纤维肌间的基质细胞的生长，导致中位数增大 前列腺的侧叶。由此产生的膀胱出口阻塞阻碍了尿液通过前列腺的流动 尿道，考虑了LUTS的发展（紧迫性，频率，弱流，紧张，犹豫，犹豫， 间歇性和夜间无效）。尽管目前对BPH的手术管理有效，但增加 该患者人群的年龄和发病率已导致相当有效的临床需求，但 侵入性较小，病态程序较少。 Histotipsy是一种新兴的无创技术，适用于 高振幅集中的超声脉冲对机械分解组织。正在研究组织疗法 对于各种疾病，包括良性前列腺增生，血栓形成，肿瘤治疗和先天性 缺陷。对该技术的研究非常集中在主要是细胞的软组织上。这 组织分解，组织学分析，暴露参数和 根据软腺的响应，对治疗的其他方面进行了特征和进展 组织。但是，包括BPH在内的许多疾病都包含关键的纤维成分。初步数据 表明不同的组织疗法暴露可以实现纤维组织的损失或消融。在这个 提案，我们旨在表征组织疗法对纤维化组织的物理和生物学作用，评估 有希望治疗此类组织的有希望的治疗策略，并专门应用这些方法来改善组织疗法 前列腺。我们建议开发用于气泡纤维基质相互作用的物理和数值模型，以及 表征了使用超声和光学的组织疗法暴露对纤维结构的物理影响 成像方法。将测试新的暴露策略，以促进纤维组织的分解和 通过超声成像反馈识别组织破坏。高级策略将在离体中测试 人类前列腺标本以确认改善消融。将在A中评估急性和慢性生物效应 BPH的犬模型。我们还将衡量治疗之间的空隙模式和尿动力学的变化 分组表明有症状的改善。该项目的成功实施将克服 现有的临床实施组织障碍，用于BPH和帮助其他组织疗法的发展 申请。