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: 10652668
• 负责人: Adam Douglas Maxwell
• 金额: $ 60.17万
• 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/10652668
• 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; 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; 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 岁男性和大约 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 有前景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 分组以证明症状改善。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。

项目成果

Development of Tough Hydrogel Phantoms to Mimic Fibrous Tissue for Focused Ultrasound Therapies.

• DOI: 10.1016/j.ultrasmedbio.2022.05.002
• 发表时间: 2022-09
• 期刊: Ultrasound in medicine & biology
• 影响因子: 2.9
• 作者: Nanda Kumar Y;Singh Z;Wang YN;Schade GR;Kreider W;Bruce M;Vlaisavljevich E;Khokhlova TD;Maxwell AD
• 通讯作者: Maxwell AD