Deployable Ultrasound Applicators for MRI Guided Thermal Therapy of Pancreatic Cancer

用于 MRI 引导胰腺癌热治疗的可展开超声探头

• 批准号: 9917574
• 负责人: Chris John Diederich
• 金额: $ 58.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9917574
• 关键词: 3-Dimensional; Abdomen; Ablation; Acoustics; Aftercare; Anatomy; Animals; Biological Models; Cessation of life; Chemotherapy and/or radiation; Clinical Research; Clinical Treatment; Complex; Computer Simulation; Custom; Data; Development; Devices; Diagnosis; Disease; Dose; Drug Delivery Systems; Drug Targeting; Duodenum; Endoscopic Ultrasonography; Ensure; Evaluation; Experimental Designs; Family suidae; Feedback; Fire - disasters; Focused Ultrasound Therapy; Future; Gastrointestinal tract structure; Goals; Heating; Histology; Histopathology; Hybrids; Hyperthermia; Image; Immunotherapy; Intestines; Investigation; Laboratory Study; Lead; Local Therapy; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of abdomen; Malignant neoplasm of pancreas; Malignant neoplasm of thorax; Measurement; Mechanics; Methods; Modality; Modeling; Monitor; Morbidity - disease rate; Motion; Movement; Operative Surgical Procedures; Organ; Pancreas; Patients; Pattern; Pelvic Cancer; Penetration; Performance; Phase; Physiological; Positioning Attribute; Radiation; Radiation therapy; Research; Resected; Role; Side; Slice; Sonication; Stomach; Structure; Subtraction Technique; Survival Rate; System; Techniques; Temperature; Therapeutic; Thermal Ablation Therapy; Thermometry; Time; Tissues; Toxic effect; Tumor Burden; Ultrasonic Therapy; Ultrasonics; Ultrasonography; base; chemotherapy; clinical implementation; contrast enhanced; design; dosimetry; effective therapy; experience; hyperthermia treatment; image guided; in vivo; innovation; lens; minimally invasive; novel; palliation; pancreas imaging; pancreatic neoplasm; preservation; simulation; standard of care; three-dimensional visualization; tissue phantom; treatment planning; tumor; tumor ablation

PROJECT ABSTRACT: The overall objectives of this research plan are to produce low profile endoluminal ultrasound applicators with deployable lens/reflector systems, in conjunction with real-time MRI guidance and MR temperature imaging (MRTI), to allow for localization and precise delivery of thermal ablation or hyperthermia in the treatment of pancreatic cancer. Pancreatic cancer is the fourth most deadly cancer in the USA, with only ~20% of patients eligible for surgery. Radiation therapy and chemotherapy remain the standard of care, but have modest improvements to survival and significant morbidity. Recent clinical studies indicate thermal therapies may provide palliation, reduce tumor burden, and increase survival. Extracorporeal High-Intensity Focused Ultrasound (HIFU) systems can deliver precision pancreatic tumor ablation, although there are limitations with respect to tumor size, accessible locations, damage to adjacent tissues, and an inability to deliver deep volumetric hyperthermia into the abdomen. Recent laboratory and clinical studies support a possible role for hyperthermia therapy as an adjunct to radiation, chemotherapy, targeted drug release, and immunotherapies. Our expertise and experience developing ultrasonic devices and techniques for MR guided thermal therapy, along with preliminary data, indicate that ultrasound applicators with deployable assemblies, positioned within the stomach or duodenum under MR guidance, are feasible and have potential to provide the means to deliver precision ablation and hyperthermia for the treatment of pancreatic cancer. These innovative reflector/lens balloon systems allow the ultrasound applicators to be positioned with MR guidance in a body lumen under low profile, and then deployed and expanded when in position to produce a larger acoustic aperture for deeper focusing or volumetric hyperthermia, expanding the range and utility of this approach. The goals of this project are: (1) to apply theoretical and advanced experimental design to develop forward-fire and side-fire ultrasound deployable reflector/lens assemblies suitable for endoluminal insertion into the stomach or duodenum, and optimized for penetration and spatial control required for localization of therapy; (2) to further develop acoustic and thermal computer simulations, apply 3D patient specific simulations to assess heating performance, design delivery strategies, and develop a treatment planning framework; (3) to develop MRI guidance and MRTI for accurate delivery and monitoring, using rapid acquisition with hybrid referenceless and multibaseline MR thermometry to accommodate physiologic organ motion; and (4) to perform in vivo studies of the deployable ultrasound applicators and MR guidance platform, and to use MRTI, contrast enhanced MRI, and histology to assess the ability and accuracy to target ablation and hyperthermia of pancreatic tissue while sparing adjacent tissues. Completion of this proposed study has potential to lead to a novel and accurate minimally-invasive method for treating pancreatic cancer with thermal therapy, with discretion to avoid damage to non-target tissues, and can be used alone or as a powerful adjunct to other therapies.

项目摘要： 该研究计划的总体目标是生产薄型腔内超声探头 具有可展开的透镜/反射器系统，结合实时 MRI 引导和 MR 温度 成像 (MRTI)，以实现热消融或热疗的定位和精确传递 胰腺癌的治疗。胰腺癌是美国第四大致命癌症，仅 约 20% 的患者适合手术。放射治疗和化学治疗仍然是标准治疗方法， 但生存率略有改善，发病率显着提高。最近的临床研究表明 热疗法可以提供姑息治疗、减轻肿瘤负荷并提高生存率。体外 高强度聚焦超声 (HIFU) 系统可以提供精确的胰腺肿瘤消融、 尽管肿瘤大小、可到达位置、邻近组织损伤等方面存在限制， 以及无法将深度容积热疗输送到腹部。最近的实验室和临床 研究支持热疗作为放疗、化疗、靶向治疗的辅助疗法的可能作用。 药物释放和免疫疗法。我们开发超声波设备的专业知识和经验 MR 引导热疗技术以及初步数据表明，超声治疗仪 具有可展开组件，在 MR 引导下定位在胃或十二指肠内，是可行的 并有潜力提供精确消融和热疗的方法来治疗 胰腺癌。这些创新的反射器/透镜球囊系统使超声探头能够 在 MR 引导下以低轮廓定位在体腔中，然后在进入时展开和扩展 位置产生更大的声孔径，以进行更深的聚焦或体积热疗，扩大 这种方法的范围和实用性。本项目的目标是：（1）应用理论和先进的 开发前射和侧射超声可部署反射器/透镜组件的实验设计 适用于腔内插入胃或十二指肠，并针对穿透和空间进行了优化 治疗定位所需的控制； (2)进一步发展声热计算机 模拟，应用 3D 患者特定模拟来评估加热性能、设计交付 策略，并制定治疗计划框架； (3) 开发MRI引导和MRTI 通过混合无参考和多基线 MR 进行快速采集，实现准确的传输和监控 测温以适应生理器官运动； (4) 进行体内研究 可部署的超声探头和 MR 引导平台，并使用 MRTI、对比增强 MRI、 和组织学评估胰腺组织靶向消融和热疗的能力和准确性 同时保护邻近组织。完成这项拟议的研究有可能产生一种新颖且 精确的微创热疗治疗胰腺癌方法，可酌情 避免对非靶组织造成损害，可以单独使用或作为其他疗法的有力辅助。