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: 10538595
• 负责人: Paul F Laeseke
• 金额: $ 47.36万
• 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/10538595
• 关键词: 3-Dimensional; Ablation; Adoption; Alcoholism; Algorithms; Animals; Biological; Breathing; Cancer Etiology; Cessation of life; Clinical; Clinical Trials; Compensation; Complement; Data; Dependence; Development; Disease; Effectiveness; Environment; Failure; Family suidae; Fluoroscopy; Focused Ultrasound Therapy; Gases; Goals; Grant; Hepatic; Hepatitis B; Hepatitis C; Human; Image; Immune; Institution; Intestines; Kidney; Liver; Liver neoplasms; Location; Lung; Magnetic Resonance Imaging; Measures; Methods; Microbubbles; Modality; Modeling; Monitor; Morphologic artifacts; Motion; Oryctolagus cuniculus; Pancreas; Patients; Penetration; 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; Ultrasonic Therapy; Ultrasonography; Visualization; Work; X-Ray Computed Tomography; anti-cancer; arm; 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; 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，多学科赠款的总体目标是使组织解剖学更接近于广泛的 通过开发基于C形臂的平台来计划、定位和评估组织摧毁消融，用于人体临床。 组织摧毁术是一种独特的无创、非热、非电离和高度精确的消融方式， 最近成功进行了一期临床试验。啮齿动物研究表明，组织破坏法有望 增强抗癌免疫效果并与检查点抑制协同联合收割机。虽然 组织摧毁术具有非常有前途的治疗能力，采用的主要障碍是缺乏可靠的 用于可视化和靶向肿瘤的方法。迄今为止的系统仅使用常规超声成像 用于靶向肿瘤并监测和评估消融区。不幸的是，超声波 依赖性，固有局限性，无法穿透某些生物 组织如骨和气体，并且在体型大的患者中使用有限。常规CT和 由于有限的空间和视野以及来自治疗的伪影，MRI对于组织破坏不是理想的。 C形臂X线透视与锥形束CT（CBCT）是一个很好的选择， 在组织摧毁术期间的瞄准和基于C形臂的平台将补充当前的US引导技术。 C形臂无处不在，具有全球分销和专业知识，具有开放式设计，易于访问 患者，提供CBCT的体积数据，用于治疗计划和消融区评估，以及2D 荧光透视法可适于提供实时自动和精确的靶向。为了推进组织分解术 为了广泛的人类临床应用，我们将开发一种基于C形臂荧光镜和CBCT的 可用于计划、定位和评估组织摧毁消融的方法。该补助金的目标1将是 开发并验证基于C形臂的算法，以准确自动定位特定组织体积 用于组织摧毁术消融。为了提高组织破坏治疗的精确度，我们将开发呼吸道 Aim 2中的运动补偿技术Aim 3将开发一种深度学习方法来弥补 通过不同生物组织的可变声速（类似于像差校正）。在目标4中，我们 整合目标1-3的发展，并在人规模猪中进行前瞻性验证研究 和兔VX 2肿瘤模型，以确定C臂引导组织碎石术的准确性、有效性和安全性， 以及它对生存的影响。如果成功，该基金将促进C形臂荧光透视与CBCT的使用， 计划、靶向和评估肝肿瘤的组织摧毁术，并使该技术更接近广泛的人类临床 使用.