Transrectal Histotripsy for Focal Ablation of Prostate Cancer

经直肠组织切除术治疗前列腺癌的局灶性消融

• 批准号: 10366109
• 负责人: George R Schade
• 金额: $ 62.32万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-23 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10366109
• 关键词: Ablation; Acoustics; Acute; Aftercare; Algorithms; American; Biopsy; Cancer Control; Canis familiaris; Cell Death; Chronic; Clinical; Clinical Trials; Coagulative necrosis; Data; Devices; Diffusion; Elements; Ensure; FDA approved; Feedback; Focused Ultrasound Therapy; Freezing; Frequencies; Funding; Future; Geometry; Grant; Heating; Holography; Image; Image Enhancement; Intestines; Investigation; Lesion; Localized Disease; Localized Malignant Neoplasm; Location; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Mechanics; Methods; Monitor; Morbidity - disease rate; Motion; Non-linear Models; Operative Surgical Procedures; Organ; Outcome; Patients; Physiologic pulse; Preparation; Prostate; Prostate Ablation; Prostate Cancer therapy; Protocols documentation; Public Health; Quality of life; Radiation therapy; Radical Prostatectomy; Rectum; Reporting; Reproducibility; Safety; Series; Shock; Solid; Specimen; Sphincter; Structure; System; Techniques; Technology; Testing; Thermal Ablation Therapy; Time; Tissues; Transducers; Translating; Translations; Transrectal High-Intensity Focused Ultrasound; Treatment Protocols; Tumor Volume; Ultrasonography; Work; active method; base; canine model; clinical implementation; design; elastography; flexibility; image guided; imaging capabilities; imaging probe; improved; in vivo; interest; men; millisecond; neurovascular; novel; patient population; pre-clinical; prostate cancer model; prototype; research clinical testing; side effect; simulation; sound; standard care; success; tissue phantom; tumor; ultrasound; urinary

PROJECT SUMMARY First line radical treatments for localized prostate cancer are associated with significant morbidity and side effects impacting urinary, bowel, and sexual quality of life. As a result, there is strong interest in focal therapy in which the cancer tissue is eradicated while sparing normal healthy prostate and adjacent structures (such as urinary sphincter, rectum, and neurovascular bundles) in order to maintain oncologic outcomes while reducing side effects. To date, clinically available focal therapies rely on thermal ablation (heating or freezing) to induce coagulative necrosis and cell death. Presently, the most widely used thermal technique for focal therapy of prostate cancer is transrectal high intensity focused ultrasound (HIFU). While existing data suggest that thermal HIFU has less morbidity than radical treatments, its ability to effectively control cancer is still uncertain with series reporting positive biopsies in up to 30-40% of patients within one year of treatment. Limitations of thermal HIFU systems, including heat diffusion/sinking and minimal real-time treatment feedback, may explain efficacy concerns. Our team has developed a HIFU-based method termed boiling histotripsy (BH) that uses sequences of milliseconds long HIFU pulses with shock fronts to mechanically ablate targeted tissue to subcellular debris without thermal effects and with real-time ultrasound imaging feedback. We have developed the first prototype of a pre-clinical system and have demonstrated the feasibility of transrectal BH for non-thermal ablation of prostate tissue in a canine model. The specific aims of this proposal are built upon the previous work to refine BH technology into a clinically viable format for focal therapy of PCa. In Aim 1, a novel transrectal multi-element array transducer will be developed and built facilitating efficient volumetric BH prostate ablation using electronic steering and mechanical translation of the focus. The BH transducer will be combined with an imaging probe and both will be controlled by a Verasonics Flexible Ultrasound platform. Comprehensive acoustic characterization of the BH system will be performed, and BH treatment protocols will be designed accordingly and evaluated in tissue phantoms and ex vivo prostate tissue. In Aim 2, improved ultrasound-based imaging algorithms will be developed to enable pre-treatment tumor localization using shear wave elastography and quantitative tissue liquefaction feedback using plane wave Doppler imaging. In Aim 3, the resulting BH array system, exposure protocols, and imaging algorithms will be evaluated in a series of acute and chronic in vivo studies in a canine model to demonstrate the safety and efficacy of the device. At the conclusion of the project period, transrectal BH technology will be ready for submission to FDA for an Investigational Device Exemption in preparation for future clinical trials.

项目摘要 局限性前列腺癌的一线根治性治疗与显著的发病率和副作用相关 影响泌尿、肠道和性生活质量。因此，人们对聚焦治疗产生了浓厚的兴趣，其中， 在保留正常健康前列腺和邻近结构（例如泌尿系统）的同时根除癌组织 括约肌、直肠和神经血管束），以维持肿瘤学结局，同时减少侧 方面的影响.迄今为止，临床上可用的局部治疗依赖于热消融（加热或冷冻）来诱导 凝固性坏死和细胞死亡。目前，最广泛使用的用于局部治疗的热技术， 前列腺癌是经直肠高强度聚焦超声（HIFU）。虽然现有数据表明， 高强度聚焦超声的发病率低于根治性治疗，但其有效控制肿瘤的能力仍不确定， 在治疗的一年内，高达30-40%的患者报告了阳性活检。热HIFU的局限性 系统，包括热扩散/散热和最小的实时治疗反馈，可以解释疗效 性问题我们的团队已经开发了一种基于HIFU的方法，称为沸腾组织摧毁术（BH）， 毫秒长的HIFU脉冲与冲击波阵面机械消融靶组织亚细胞碎片 没有热效应并且具有实时超声成像反馈。我们已经开发出了第一个原型 临床前系统，并证明了经直肠BH用于非热消融的可行性， 前列腺组织中。本建议的具体目标是建立在以前的工作，以完善 BH技术成为PCa局灶治疗的临床可行形式。在目标1中，一种新型的经直肠多元件 将开发和构建阵列换能器，以便于使用电子 焦点的操纵和机械平移。BH传感器将与成像探头结合使用 两者都将由Verasonics柔性超声平台控制。综合声学 将对BH系统进行表征，并相应地设计BH治疗方案 并在组织模型和离体前列腺组织中进行评价。在目标2中，改进的基于超声的成像 将开发算法，以使用剪切波弹性成像实现治疗前肿瘤定位， 使用平面波多普勒成像的定量组织液化反馈。在目标3中，所得到的BH阵列 将在一系列急性和慢性体内试验中评价系统、暴露方案和成像算法 在犬模型中进行的研究，以证明该器械的安全性和有效性。在项目结束时 在此期间，经直肠BH技术将准备提交给FDA，以获得试验用器械豁免 为将来的临床试验做准备。