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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要这项多机构、多学科资助的总体目标是使组织解剖学更接近广泛应用通过开发基于 C 臂的平台来规划、定位和评估组织解剖消融，用于人类临床应用。组织切除术是一种独特的无创、非热、非电离和高精度消融方式，最近进行了成功的 I 期临床试验。啮齿动物研究证明了组织解剖学的前景增强抗癌免疫作用并与检查点抑制相结合。虽然组织解剖学具有非常有前景的治疗能力，采用的主要障碍是缺乏可靠的方法可视化和靶向肿瘤的方法。迄今为止的系统仅使用传统的超声成像用于瞄准肿瘤并监测和评估消融区域。不幸的是，超声波是操作者依赖，本质上限制于评估 3D 肿瘤和消融区域，无法穿透某些生物制剂骨和气体等组织，对于体型较大的患者使用有限。常规CT和由于空间和视野有限以及治疗过程中产生的伪影，MRI 不适用于组织解剖学传感器和机械臂。采用锥形束 CT (CBCT) 的 C 形臂 X 射线透视检查是以下情况的绝佳选择：组织解剖期间的靶向和基于 C 臂的平台将补充美国当前的引导技术。 C 形臂随处可见，分布于世界各地，拥有专业知识，采用开放式设计，可轻松访问患者，提供 CBCT 的体积数据用于治疗计划和消融区域评估，以及 2D 荧光透视可以提供实时自动和准确的定位。推进组织解剖学为了广泛应用于人类临床，我们将开发基于 C 臂荧光镜和 CBCT 的可用于计划、瞄准和评估组织解剖消融的方法。这笔赠款的目标 1 是开发和验证基于 C 形臂的算法，以准确、自动地瞄准特定体积的组织用于组织解剖消融。为了提高组织解剖治疗的精度，我们将开发呼吸系统目标 2 中的运动补偿技术。目标 3 将开发一种深度学习方法来补偿通过不同生物组织的声速可变（类似于像差校正）。在目标 4 中，我们将整合目标 1-3 的进展并在人类规模的猪中进行前瞻性验证研究和兔 VX2 肿瘤模型，以确定 C 臂引导组织解剖的准确性、有效性和安全性以及它对生存的影响。如果成功，这笔赠款将促进 C 形臂透视与 CBCT 的使用计划、瞄准和评估肝脏肿瘤的组织解剖学，并使该技术更接近广泛的人类临床使用。