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

基本信息

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
项目类别：
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

项目摘要

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：利用组织解剖学的新型、无创、快速肿瘤消融技术抽象的我们的目标是开发一种无创消融技术，能够实现快速、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用于手术。现有的微创和非侵入性肿瘤干预措施具有显着的局限性阻止它们有效治疗主要血管附近的肿瘤、大肿瘤（直径 > 3 厘米）或具有多个（>3）结节的肿瘤。组织解剖学是一种非侵入性超声消融技术，可产生空化以毫米精度破坏目标组织。我们之前对正常组织的体内研究肿瘤模型显示 1) 在目标区域均匀、完全的细胞破坏，而无需损伤上层组织，2) 治疗邻近大血管的组织的能力，3) 治疗 ~5 cm 的能力一小时内检测直径肿瘤，4) 通过超声成像进行实时治疗监测，以及 5) 肿瘤彻底消融，无肿瘤残留、复发、新转移。此外，我们最近的结果显示组织解剖结合电焦点转向完全分割约 32 mL（约 4cm 直径） 10分钟内离体牛肝，速度是目前任何非手术干预方法的两倍以上。这些结果表明组织解剖学有可能显着改善现有的肿瘤干预措施方法。对于该提案，具体目标侧重于技术进步，以克服组织解剖学的困难当前以肝癌为第一靶点临床应用的肿瘤干预方法的局限性。这四个目标是：1）开发电子焦点控制策略和参数以实现快速（> 5mL/min），通过覆盖组织安全地均匀消融大体积（>3cm）和多个体积（>3）； 2）开发一个运动追踪方法，在存在呼吸运动的情况下实现快速、准确的治疗； 3）设计构建超声图像引导的人体肝癌一体化组织解剖消融系统患者; 4) 测试目标 1-3 中的技术和设备的体内安全性和有效性，以全面了解大型动物（猪）肝脏模型和土拨鼠肝脏肿瘤模型中的肝脏肿瘤消融。拟议的技术改进和综合肝脏消融系统均经过体内验证，对于推进组织解剖学未来临床转化以治疗肝脏肿瘤，并可扩展到许多其他领域肿瘤类型，包括肾脏、前列腺、胰腺和子宫肿瘤。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（1）

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
影响因子：
0
作者：
通讯作者：

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
影响因子：
0
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