Novel, Noninvasive, Rapid Tumor Ablation Technology using Histotripsy

使用组织解剖学的新型、无创、快速肿瘤消融技术

• 批准号: 10322649
• 负责人: Zhen Xu
• 金额: $ 54.98万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-09 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10322649
• 关键词: Ablation; Address; Anatomy; Animal Model; Animals; Area; Benign; Brain; Breast; Breathing; Caliber; Cancer Patient; Cancerous; Cattle; Clinical; Clinical Data; Clinical Trials; Data; Development; Devices; Evaluation; Excision; Family suidae; Financial compensation; Focused Ultrasound Therapy; Future; Goals; Grant; Hour; Human; Intervention; Kidney; Lesion; Liver; Liver neoplasms; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of liver; Mechanics; Memory; Methods; Modeling; Monitor; Motion; Movement; Neoplasm Metastasis; Nodule; Normal tissue morphology; Operative Surgical Procedures; Organ; Pancreas; Pathologic; Patients; Phase; Positioning Attribute; Prostate; Radiation; Radiation therapy; Radiology Specialty; Recurrence; Residual Tumors; Rodent; Safety; Sampling; Scanning; Solid Neoplasm; Speed; System; Techniques; Technology; Time; Tissues; Toxic effect; Transducers; Treatment Efficacy; Ultrasonography; Uterus; Validation; Woodchuck; base; clinical application; clinical translation; design; design and construction; image guided; improved; in vivo; in vivo evaluation; invention; liver ablation; liver cancer model; liver cancer patient; liver tumor ablation; microwave electromagnetic radiation; millimeter; minimally invasive; novel; patient population; pre-clinical; preclinical development; preservation; prevent; radio frequency; rib bone structure; tumor; tumor ablation; ultrasound; ultrasound ablation

Title: Novel, Noninvasive, Rapid Tumor Ablation Technology using Histotripsy Abstract Our goal is to develop a noninvasive ablation technique that can achieve rapid, homogeneous tumor ablation with the ability to overcome the limitations of current tumor interventions. Many cancer patients are not eligible for surgery. Existing minimally invasive and non-invasive tumor interventions have significant limitations that prevent them from being effective at treating tumors near major vessels, large tumors (>3 cm diameter), or tumors with multiple (>3) nodules. Histotripsy is a non-invasive ultrasound ablation technique that produces cavitation to disrupt the target tissue with millimeter precision. Our previous in vivo studies in normal tissues and tumor models have shown 1) homogenous, complete cellular disruption in targeted areas without damaging the overlying tissue, 2) ability to treat tissue adjacent to large vessels, 3) ability to treat ~5 cm diameter tumors within one hour, 4) real-time treatment monitoring with ultrasound imaging, and 5) potential of complete tumor ablation without residual tumor, recurrence, or new metastasis. Further, our recent results show that histotripsy combined with electrical focal steering completely fractionated ~32 mL (~4cm diameter) ex vivo bovine liver within 10 min, more than twice the rate than any current non-surgical intervention method. These results suggest that histotripsy has the potential to significantly improve upon existing tumor intervention methods. For this proposal, the specific aims focus on technical advancements to allow histotripsy to overcome the limitations of current tumor intervention methods with liver cancer as the first target clinical application. The four aims are: 1) develop an electronic focal steering strategy and parameters to achieve rapid (>5mL/min), homogenous ablation of large (>3cm) and multiple (>3) volumes safely through overlying tissue; 2) develop a motion tracking method to achieve rapid and accurate treatment in the presence of breathing motion; 3) design and construct an integrated ultrasound image-guided histotripsy ablation system for human liver cancer patients; and 4) test the in vivo safety and efficacy of the techniques and device from Aims 1-3 for complete liver tumor ablation in a large animal (porcine) liver model and a woodchuck liver tumor model. The proposed technical improvements and the integrated liver ablation system, all validated in vivo, will be essential to advance histotripsy towards future clinical translation to treat liver tumors and could be extended to many other tumor types, including tumors in the kidney, prostate, pancreas, and uterus.

标题：新颖，无创，快速肿瘤消融技术使用Histototy 抽象的 我们的目标是开发一种无创的消融技术，该技术可以实现快速，均匀的肿瘤消融 有能力克服当前肿瘤干预的局限性。许多癌症患者不符合资格 进行手术。现有的最小侵入性和非侵入性肿瘤干预措施具有重大局限性 防止它们有效治疗主要血管附近的肿瘤，大肿瘤（> 3 cm直径）或 具有多个（> 3）结节的肿瘤。组织疗法是一种非侵入性超声消融技术，可产生 空化以用毫米精度破坏目标组织。我们以前在正常组织中的体内研究 肿瘤模型已显示1）在没有目标区域的同质，完全的细胞中断 损害上覆的组织，2）治疗与大容器相邻的组织的能力，3）能够治疗〜5 cm的能力 一小时内的直径肿瘤，4）超声成像的实时治疗监测，5） 完全消融，没有残留肿瘤，复发或新转移。此外，我们最近的结果 证明组织肌肉与电焦点转向完全分级〜32 mL（直径约4厘米） 离体牛肝内10分钟内，比当前任何非手术干预方法的速率是两倍以上。 这些结果表明，组织疗法有可能显着改善现有的肿瘤干预 方法。对于此提案，具体的目的是专注于技术进步，以允许历史疗法克服 肝癌当前肿瘤干预方法的局限性是第一个靶向临床应用。这 四个目标是：1）制定电子焦点转向策略和参数以实现快速（> 5ml/min）， 大型（> 3厘米）和多个（> 3）的同质消融通过上覆的组织安全地安全； 2）发展 运动跟踪方法在呼吸运动的存在下实现快速而准确的治疗方法； 3）设计 并为人肝癌构建一个集成的超声图像引导的组织疗法消融系统 患者; 4）测试AIMS 1-3的技术和设备的体内安全性和功效 大动物（猪）肝模型和木结肝肿瘤模型中的肝肿瘤消融。提议 技术改进和综合的肝脏消融系统，均经体内验证，对于 提前对未来临床翻译的组织疗法以治疗肝肿瘤，可以扩展到许多其他 肿瘤类型，包括肾脏，前列腺，胰腺和子宫中的肿瘤。

项目成果

Histotripsy: the first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound.

• DOI: 10.1080/02656736.2021.1905189
• 发表时间: 2021
• 期刊: International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

Integrated Histotripsy and Bubble Coalescence Transducer for Thrombolysis.

• DOI: 10.1016/j.ultrasmedbio.2018.08.013
• 发表时间: 2018-12
• 期刊: Ultrasound in medicine & biology
• 影响因子: 2.9
• 作者: Shi A;Lundt J;Deng Z;Macoskey J;Gurm H;Owens G;Zhang X;Hall TL;Xu Z
• 通讯作者: Xu Z

Using the cavitation collapse time to indicate the extent of histotripsy-induced tissue fractionation.

• DOI: 10.1088/1361-6560/aaae3b
• 发表时间: 2018-03-08
• 期刊: Physics in medicine and biology
• 影响因子: 3.5
• 作者: Macoskey JJ;Choi SW;Hall TL;Vlaisavljevich E;Lundt JE;Lee FT;Johnsen E;Cain CA;Xu Z
• 通讯作者: Xu Z

Real-Time Transcranial Histotripsy Treatment Localization and Mapping Using Acoustic Cavitation Emission Feedback.

使用声空化发射反馈进行实时经颅组织解剖治疗定位和绘图。

• DOI: 10.1109/tuffc.2020.2967586
• 发表时间: 2020
• 期刊: IEEE transactions on ultrasonics, ferroelectrics, and frequency control
• 作者: Sukovich,JonathanR;Macoskey,JonathanJ;Lundt,JonathanE;Gerhardson,TylerI;Hall,TimothyL;Xu,Zhen
• 通讯作者: Xu,Zhen

Impact of Histotripsy on Development of Intrahepatic Metastases in a Rodent Liver Tumor Model.

• DOI: 10.3390/cancers14071612
• 发表时间: 2022-03-22
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Worlikar T;Zhang M;Ganguly A;Hall TL;Shi J;Zhao L;Lee FT;Mendiratta-Lala M;Cho CS;Xu Z
• 通讯作者: Xu Z