Advanced C-arm imaging platform for histotripsy treatment of liver tumors

用于肝脏肿瘤组织解剖治疗的先进 C 臂成像平台

• 批准号: 10364386
• 负责人: Paul F Laeseke
• 金额: $ 48.22万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10364386
• 关键词: 3-Dimensional; Ablation; Adoption; Alcoholism; Algorithms; Animals; Biological; Breathing; Cancer Etiology; Cessation of life; Clinical; Clinical Trials; Complement; Data; Dependence; Development; Disease; Effectiveness; Environment; Failure; Family suidae; Financial compensation; Fluoroscopy; Focused Ultrasound Therapy; Gases; Goals; Grant; Hepatic; Hepatitis B; Hepatitis C; Human; Image; Immune; Intestines; Kidney; Liver; Liver neoplasms; Location; Lung; Magnetic Resonance Imaging; Measures; Methods; Microbubbles; Modality; Modeling; Monitor; Morphologic artifacts; Motion; Oryctolagus cuniculus; Pancreas; Patients; Performance; Phase; Phase I Clinical Trials; Physiologic pulse; Positioning Attribute; Primary Malignant Neoplasm of Liver; Primary carcinoma of the liver cells; Radiation therapy; Respiration; Respiratory Diaphragm; Robotics; Rodent; Roentgen Rays; Safety; Shapes; Speed; System; Techniques; Testing; Therapeutic; Thermal Ablation Therapy; Time; Tissues; Training; Transducers; Ultrasonography; Work; X-Ray Computed Tomography; anti-cancer; arm; base; bone; checkpoint inhibition; clinical translation; cone-beam computed tomography; deep learning; design; expiration; image guided; imaging capabilities; imaging modality; imaging platform; imaging system; improved; in vivo; multidisciplinary; non-alcoholic fatty liver disease; novel; physical process; porcine model; prospective; respiratory; simulation; sound; standard of care; targeted imaging; treatment planning; tumor; tumor ablation; ultrasound; validation studies

PROJECT SUMMARY The overall goal of this multi-institutional, multi-disciplinary grant is to bring histotripsy closer to widespread human clinical use by developing a C-arm based platform to plan, target, and assess histotripsy ablations. Histotripsy is a unique noninvasive, nonthermal, nonionizing and highly precise ablation modality that has recently undergone a successful phase I clinical trial. Rodent studies demonstrate the promise of histotripsy to potentiate an anti-cancer immune effect and combine synergistically with check-point inhibition. Although histotripsy has highly promising therapeutic capability, a major barrier to adoption is the lack of a reliable method for visualizing and targeting tumors. Systems to date have only used conventional ultrasound imaging for targeting the tumor and monitoring and assessing the ablation zone. Unfortunately, ultrasound is operator dependent, inherently limited for evaluating 3D tumors and ablation zones, unable to penetrate certain biologic tissues such as bone and gas, and is of limited use in patients with large body habitus. Conventional CT and MRI are not ideal for histotripsy due to limited space and field of view as well as artifacts from the therapeutic transducer and robotic arm. C-arm x-ray fluoroscopy with cone-beam CT (CBCT) is an excellent option for targeting during histotripsy and a C-arm based platform would complement current US guidance techniques. C-arms are ubiquitous with world-wide distribution and expertise, have an open design with easy access to the patient, provide volumetric data from CBCT for treatment planning and ablation zone assessment, and 2D fluoroscopy can be adapted to deliver real-time automatic and accurate targeting. To advance histotripsy toward widespread human clinical use, we will develop a C-arm fluoroscopic and CBCT based approach that can be used to plan, target, and assess histotripsy ablations. Aim 1 of this grant will be to develop and validate C-arm based algorithms to accurately and automatically target a specific volume of tissue for histotripsy ablation. To improve the precision of histotripsy treatments, we will then develop respiratory motion compensation techniques in Aim 2. Aim 3 will develop a deep-learning approach to compensate for the variable speed of sound through different biologic tissues (analogous to aberration correction). In Aim 4, we will integrate the developments from Aims 1-3 and perform prospective validation studies in human-scale porcine and rabbit VX2 tumor models to determine the accuracy, efficacy and safety of C-arm guided histotripsy as well as its effect on survival. If successful, this grant will catalyze the use of C-arm fluoroscopy with CBCT to plan, target, and assess histotripsy of liver tumors, and bring the technique closer to widespread human clinical use.

项目摘要 这种多机构的多学科赠款的总体目标是使历史摄影更接近广泛 通过开发基于C臂的平台来计划，靶向和评估组织疗法消融，人类的临床用途。 组织疗法是一种独特的非侵入性，非热，非离子化和高度精确的消融方式 最近经过了一项成功的I期临床试验。啮齿动物研究证明了组织疗法的希望 增强抗癌免疫效应，并协同结合检查点抑制。虽然 组织疗法具有高度有希望的治疗能力，采用的主要障碍是缺乏可靠的 可视化和靶向肿瘤的方法。迄今为止的系统仅使用了常规超声成像 用于靶向肿瘤，监测和评估消融区。不幸的是，超声是操作员 依赖，固有地限制用于评估3D肿瘤和消融区，无法穿透某些生物学 骨和气体等组织，在大身体习惯的患者中使用有限。常规的CT和 由于空间和视野有限以及治疗性的伪像，MRI对于组织疗法并不理想 换能器和机器人臂。 C-ARM X射线透视透镜CT（CBCT）是一个绝佳的选择 在组织术和基于C臂的平台期间的靶向将补充当前的美国指导技术。 C臂无处不在，具有全球分销和专业知识，具有开放的设计，可轻松访问 患者，提供来自CBCT的体积数据进行治疗计划和消融区评估，以及2D 透视镜可以适应实时自动和准确的靶向。提高组织疗法 为了广泛的人类临床使用，我们将开发基于C臂的荧光镜和CBCT 可用于计划，靶向和评估组织疗法消融的方法。本赠款的目标1将是 开发和验证基于C臂的算法，以准确并自动针对特定的组织 用于组织疗法消融。为了提高组织疗法的精度，我们将发展呼吸道 AIM 2中的运动补偿技术。AIM3将开发一种深入学习的方法来补偿 通过不同的生物组织（类似于像差校正）的声音速度可变。在AIM 4中，我们将 整合目标1-3的发展并在人尺度猪中进行前瞻性验证研究 和兔VX2肿瘤模型，以确定C臂引导性组织疗法的准确性，功效和安全性 以及它对生存的影响。如果成功，该赠款将催化使用CBCT的C臂荧光检查的使用 计划和评估肝肿瘤的组织疗法，并使该技术更接近人类临床 使用。