Focal Therapy of Prostate Cancer using Non-Thermal Tumor Ablation with Focused Ultrasound

使用聚焦超声非热肿瘤消融对前列腺癌进行局部治疗

• 批准号: 9568746
• 负责人: George R Schade
• 金额: $ 12.29万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9568746
• 关键词: Ablation; Acoustics; Acute; Adoption; Adverse effects; Asia; Autopsy; Cancer Patient; Canis familiaris; Clinic; Clinical; Clinical Trials; Collaborations; Dependence; Devices; Diagnosis; Diffusion; Disease; Electron Microscopy; Erectile dysfunction; Europe; FDA approved; Feedback; Focused Ultrasound; Focused Ultrasound Therapy; Frequencies; Future; Gel; Geometry; Goals; Heating; Histologic; Histology; Holography; Human; Incontinence; Intervention; Investigation; Joints; Lead; Lesion; Literature; Local Therapy; Localized Disease; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Mechanics; Methods; Modality; Modeling; Modification; Monitor; Morbidity - disease rate; Morphology; Moscow; Nature; Outcome; Patients; Physiologic pulse; Process; Prostate; Prostate Ablation; Prostate Cancer therapy; Prostatic Tissue; Public Health; Quality of life; Recommendation; Reproducibility; Safety; Sampling; Series; Shapes; Shock; Site; Structure; Structure of base of prostate; System; Technology; Testing; Thermal Ablation Therapy; Time; Tissues; Transducers; Translating; Treatment Efficacy; Treatment Protocols; Treatment outcome; Ultrasonic Transducer; Ultrasonic wave; Ultrasonography; Ultrasound, High-Intensity Focused, Transrectal; United States; Universities; Visit; Washington; base; clinical translation; comparative; design; experimental study; first-in-human; image guided; imaging probe; improved; improved outcome; in vivo; innovation; men; millisecond; novel; oncology; optimal treatments; pre-clinical; preclinical study; prostate cancer model; prototype; simulation; treatment optimization; treatment strategy; tumor

Thermal ablation of focal prostate cancer (PCa) with high intensity focused ultrasound (HIFU) has recently received FDA approval as a non-invasive alternative to first-line treatment options that are still associated with significant morbidity and adverse side effects. However, current clinical transrectal HIFU systems have several limitations including the potential for collateral damage due to heat diffusion and minimal real-time ability to monitor treatment efficacy. These limitations associated with the thermal nature of the method delayed FDA approval and subsequent proliferation of this technology. Our joint team at the University of Washington (UW) and Moscow State University (MSU) has recently developed a non-thermal HIFU-based method termed boiling histotripsy (BH). The method uses sequences of milliseconds long HIFU pulses with shock fronts to mechanically fractionate targeted tissue to subcellular levels, with real-time ultrasound imaging feedback. Preliminary analysis by our joint group suggests that delivery of BH treatments with shocks may be feasible using the miniature transrectal probes similar to the existing clinical HIFU systems. The main goal of this project thus is to combine complementary strengths of the UW/MSU teams for developing the BH modality to realize effective and safe focal treatment of PCa. Specifically, we propose to determine relationships among the miniature transducer form-factor, shock wave amplitude at the focus, and BH treatment outcome through numerical modelling (performed at MSU); modeling results will guide the design (at UW) and fabrication of two HIFU probes for BH studies, one at each site. A series of experiments in ex vivo canine tissue (at UW) and human prostatic tissue from autopsy (at MSU) will be performed to develop BH exposures and provide recommendations for the design of BH treatments for future clinical trials (SA2). In SA3, the optimized treatment protocol will be applied more in the orthotopic canine PCa tumor model using a preclinical transrectal BH system developed at UW based on the results from SA1 and SA2. The initial feasibility, safety, and tolerab ility of this intervention will be evaluated in a series of acute and short-term (14 days) survival studies. Comparative morphological analysis of the treatment outcomes will be performed at UW and MSU and ultrastructural analysis will be done at MSU. Mutual visits are planned for major joint experiments on transducer characterization as well as for ex vivo and in vivo studies. We expect that the proposed method of nonthermal ablation of PCa through BH can be translated rapidly to the clinic to improve both the efficacy and safety of focal PCa therapies, thereby improving outcomes with regard to patient oncology and quality of life.

高强度聚焦超声 (HIFU) 热消融局灶性前列腺癌 (PCa) 最近获得 FDA 批准作为一线治疗方案的非侵入性替代方案 仍然与显着的发病率和不良副作用相关。然而，目前 临床经直肠 HIFU 系统有一些局限性，包括潜在的侧支循环 由于热扩散造成的损害以及监测治疗效果的实时能力极低。这些 与该方法的热性质相关的限制延迟了 FDA 的批准和 随后这项技术的扩散。我们在华盛顿大学 (UW) 的联合团队 莫斯科国立大学 (MSU) 最近开发了一种基于非热 HIFU 的方法 称为沸腾组织解剖（BH）。该方法使用毫秒长的 HIFU 脉冲序列 通过冲击前沿将目标组织机械分级至亚细胞水平，并实时 超声成像反馈。我们联合小组的初步分析表明，交付 使用微型经直肠探头进行电击 BH 治疗可能是可行的，类似于 现有的临床 HIFU 系统。因此，该项目的主要目标是将互补性结合起来 UW/MSU 团队开发 BH 模式的优势，以实现有效和 PCa 的安全局部治疗。具体来说，我们建议确定之间的关系 微型换能器形状系数、焦点处的冲击波振幅和 BH 处理 通过数值建模得出结果（在密歇根州立大学进行）；建模结果将指导 设计（在华盛顿大学）和制造两个用于 BH 研究的 HIFU 探头，每个站点一个。一系列 犬离体组织（华盛顿大学）和尸检人类前列腺组织（密歇根州立大学）的实验 将进行开发BH暴露并为BH的设计提供建议 未来临床试验（SA2）的治疗方法。在SA3中，将应用优化的治疗方案 更多的 在 使用临床前经直肠 BH 系统开发原位犬 PCa 肿瘤模型 华盛顿大学基于 SA1 和 SA2 的结果。初步的可行性、安全性和耐受性 的能力 该干预措施将通过一系列急性和短期（14 天）生存研究进行评估。 治疗结果的比较形态学分析将在华盛顿大学和 MSU 和超微结构分析将在 MSU 进行。计划进行重大联合互访 传感器表征实验以及离体和体内研究。我们期望 所提出的通过 BH 非热消融 PCa 的方法可以快速转化为 诊所旨在提高局灶性前列腺癌治疗的有效性和安全性，从而改善 关于患者肿瘤学和生活质量的结果。