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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要良性前列腺增生 (BPH) 是令人烦恼的下尿路症状的最常见原因 (LUTS) 影响半数 50 岁男性和约 90% 的 80 岁男性。 BPH 的特点是增生腺上皮细胞和纤维肌基质细胞的生长，导致中位和中位增大前列腺侧叶。由此产生的膀胱出口阻塞阻碍尿液流经前列腺尿道，导致 LUTS 的发展（紧迫性、频率、微弱尿流、紧张、犹豫、间歇性和夜间排尿）。尽管目前 BPH 的手术治疗是有效的，但越来越多的患者该患者群体的年龄和发病率导致临床需要相当大的同样有效但侵入性较小且并发症较少的手术。组织解剖学是一种新兴的非侵入性技术，可应用短时间、高振幅聚焦超声波脉冲以机械方式分解组织。组织解剖学正在研究中适用于多种疾病，包括良性前列腺增生、血栓、肿瘤治疗、先天性疾病等缺陷。该技术的研究主要集中在主要由细胞构成的软组织上。这生物效应、组织分解的成像和总体特征、组织学分析、暴露参数和治疗的其他方面是根据软腺体的反应来表征和进展的。组织。然而，包括良性前列腺增生在内的许多疾病都含有关键的纤维成分。初步数据表明不同的组织解剖暴露可以实现纤维组织的保留或消融。在这个建议，我们的目的是表征组织解剖学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此类组织，并专门应用这些方法来改进组织解剖学前列腺。我们建议开发气泡-纤维基质相互作用的物理和数值模型使用超声波和光学表征组织解剖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。先进策略将在体外进行测试人类前列腺标本以确认消融效果得到改善。急性和慢性生物效应将在 BPH 犬模型。我们还将测量治疗之间排尿模式和尿动力学的变化组以证明症状改善。该项目的成功实施将克服临床实施 BPH 组织解剖学存在障碍，并有助于其他疾病组织解剖学的发展应用程序。