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

基本信息

批准号：
10709856
负责人：
George R Schade
金额：
$ 65.79万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
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/10709856
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 Electronics Elements Ensure FDA approved Feedback Focused Ultrasound Therapy Freezing Frequencies Funding Future Geometry Grant Heating Holography Image Image Enhancement Intestines 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 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 rectal research clinical testing side effect simulation sound standard care success tissue phantom tumor ultrasound urinary

项目摘要

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.

项目概要局限性前列腺癌的一线根治治疗与显着的发病率和副作用相关影响泌尿、肠道和性生活质量。因此，人们对局部治疗产生了浓厚的兴趣，其中癌症组织被根除，同时保留正常健康的前列腺和邻近结构（例如泌尿系统）括约肌、直肠和神经血管束），以维持肿瘤学结果，同时减少副作用影响。迄今为止，临床上可用的局部治疗依靠热消融（加热或冷冻）来诱导凝固性坏死和细胞死亡。目前，局部治疗中应用最广泛的热技术前列腺癌是经直肠高强度聚焦超声（HIFU）。虽然现有数据表明热 HIFU与根治性治疗相比发病率较低，其有效控制癌症的能力仍不确定据报告，治疗一年内高达 30-40% 的患者活检结果呈阳性。热 HIFU 的局限性系统，包括热扩散/下沉和最小的实时治疗反馈，可以解释疗效的担忧。我们的团队开发了一种基于 HIFU 的方法，称为沸腾组织解剖 (BH)，该方法使用序列毫秒长的 HIFU 脉冲与冲击前沿，以机械方式将目标组织消融为亚细胞碎片无热效应并具有实时超声成像反馈。我们开发了第一个原型临床前系统的研究，并证明了经直肠 BH 用于非热消融的可行性犬模型中的前列腺组织。该提案的具体目标是在先前工作的基础上进行完善的 BH 技术成为 PCa 局部治疗的临床可行形式。在目标 1 中，一种新颖的经直肠多元素将开发和建造阵列换能器，以利用电子技术促进有效的体积 BH 前列腺消融焦点的转向和机械平移。 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。综合声学将进行 BH 系统的表征，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估。目标 2 改进基于超声的成像将开发算法以使用剪切波弹性成像进行治疗前肿瘤定位使用平面波多普勒成像定量组织液化反馈。在目标 3 中，生成的 BH 数组系统、暴露协议和成像算法将在一系列急性和慢性体内进行评估在犬类模型中进行研究，以证明该设备的安全性和有效性。项目结束时在此期间，经直肠 BH 技术将准备好向 FDA 提交研究设备豁免为未来的临床试验做准备。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Pilot ex vivo study on non-thermal ablation of human prostate adenocarcinoma tissue using boiling histotripsy.

DOI：
10.1016/j.ultras.2023.107029
发表时间：
2023-08
期刊：
Ultrasonics
影响因子：
4.2
作者：
Rosnitskiy PB;Tsysar SA;Karzova MM;Buravkov SV;Malkov PG;Danilova NV;Ponomarchuk EM;Sapozhnikov OA;Khokhlova TD;Schade GR;Maxwell AD;Wang YN;Kadrev AV;Chernyaev AL;Okhobotov DA;Kamalov AA;Khokhlova VA
通讯作者：
Khokhlova VA