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: 10436315
• 负责人: Adam Douglas Maxwell
• 金额: $ 61.18万
• 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/10436315
• 关键词: Ablation; Accounting; Acoustics; Acute; Affect; Age; Aging; Benign Prostatic Hypertrophy; Biological; Bladder; Canis familiaris; Chronic; Clinical; Clinical Trials; Collagen; 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; canine model; clinical implementation; comorbidity; 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.

项目总结 良性前列腺增生症(BPH)是引起麻烦的下尿路症状的最常见原因。 (LUTS)在50岁之前影响一半的男性，在80岁之前影响大约90%的男性。良性前列腺增生症的特点是增生性疾病 腺上皮细胞和纤维肌肉基质细胞生长，导致中位和中位增大 前列腺的侧面小叶。由此导致的膀胱出口阻塞阻碍了尿液通过前列腺的流动。 导致LUTS(紧迫感、频发率、弱血流、劳损、迟疑、 间歇性和夜间排尿)。虽然目前手术治疗BPH是有效的，但越来越多的人 这种患者的年龄和发病率导致了相当大的临床需求，需要同样有效的但 侵入性更小，病态更少的手术。组织旅行是一种新兴的非侵入性技术，它适用于短时间、 高幅度聚焦超声脉冲，以机械方式分解组织。组织临床试验正在调查中 治疗多种疾病，包括良性前列腺增生症、血栓形成、肿瘤治疗和先天性 缺陷。对这项技术的研究主要集中在主要是细胞的软组织上； 生物效应、组织破坏的成像和大体特征、组织学分析、暴露参数和 治疗的其他方面的特征和进展是基于软的，腺体的反应 纸巾。然而，包括前列腺增生症在内的许多疾病都含有一种关键的纤维成分。初步数据 表明不同的组织学暴露可以实现纤维组织的保留或消融。在这 建议，我们的目标是表征组织摩擦对纤维化组织的物理和生物学影响，评估 有希望的治疗策略来治疗这种组织，并特别应用这些方法来改善组织摩擦学 前列腺的组织。我们建议开发气泡-纤维基质相互作用的物理和数值模型，并 用超声波和光学技术表征组织摩擦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裂。先进的策略将在体外进行测试 人类前列腺标本以确认改进的消融术。急性和慢性生物效应将在一项 犬良性前列腺增生症模型。我们还将测量两次治疗之间排尿模式和尿动力学的变化。 以显示症状改善的小组。该项目的成功实施将克服 前列腺增生症组织学临床实施中存在的障碍及其他组织学的发展 申请。