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

项目总结 这项多机构、多学科拨款的总体目标是使组织摩擦学更接近广泛传播 通过开发基于C臂的平台来计划、定位和评估组织电切消融，从而实现人类的临床应用。 组织电切是一种独特的无创、非热、非电离和高精度的消融方式，具有 最近进行了一次成功的I期临床试验。啮齿动物研究展示了组织旅行的前景 增强抗癌免疫作用，与检查点抑制协同作用。虽然 组织摩擦疗法具有非常有希望的治疗能力，采用的一个主要障碍是缺乏可靠的 可视化和靶向肿瘤的方法。到目前为止，系统只使用传统的超声成像 用于靶向肿瘤以及监测和评估消融区。不幸的是，超声波是操作员 对3D肿瘤和消融区的评估具有依赖性，固有的局限性，无法穿透某些生物 该药适用于骨骼和气体等组织，对体型较大的患者使用有限。常规CT和 由于有限的空间和视野以及治疗过程中的伪影，MRI不是组织摩擦检查的理想方法 传感器和机械臂。C臂X-射线透视和锥束CT(CBCT)是诊断 组织摩擦期间的靶向和基于C臂的平台将补充美国目前的制导技术。 C形臂随处可见，具有世界范围的分布和专业知识，具有开放式设计，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评估，以及2D 荧光透视可用于提供实时、自动和准确的靶向。推进组织诊断学 为了广泛应用于人类临床，我们将开发一种基于C臂透视和CBCT的 可用于计划、定位和评估组织电切消融的方法。这笔赠款的目标1将是 开发和验证基于C-ARM的算法，以准确和自动地定位特定体积的组织 用于组织化学消融。为了提高组织学治疗的精确度，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不同声速(类似于像差校正)。在目标4中，我们将 整合AIMS 1-3的发展，并在人体规模的猪身上进行前瞻性验证研究 和兔VX2肿瘤模型，以确定C臂引导下组织块活检的准确性、有效性和安全性 以及它对生存的影响。如果成功，这笔赠款将催化C形臂透视与CBCT的使用，以 计划、定位和评估肝肿瘤的组织学检查，并使这项技术更接近广泛的人类临床 使用。

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.