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： 本研究计划的总体目标是生产低剖面腔内超声施源器 具有可展开的透镜/反射器系统，结合实时MRI引导和MR温度 磁共振成像（MRTI），以允许定位和精确输送热消融或热疗在 胰腺癌的治疗胰腺癌是美国第四大致命癌症， 约20%的患者适合手术。放疗和化疗仍然是标准的治疗方法， 但对存活率和显著的发病率有适度的改善。最近的临床研究表明 热疗法可以提供缓解、减少肿瘤负荷和增加存活率。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， 尽管在肿瘤大小、可接近的位置、对邻近组织的损伤 以及不能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、靶向治疗的辅助治疗的可能作用。 药物释放和免疫疗法。我们的专业知识和经验开发超声波设备和 MR引导热治疗技术以及初步数据沿着表明超声施加器 在MR引导下定位在胃或十二指肠内的可展开组件是可行的 并有可能提供提供精确消融和热疗的手段， 胰腺癌这些创新的反射器/透镜球囊系统允许超声施加器 在MR引导下在低切迹下定位在体腔中，然后在 位置，以产生更大的声学孔径，用于更深的聚焦或体积热疗，扩展 这种方法的范围和效用。本课题的目标是：（1）将理论和先进的 研制前射和侧射超声可展开反射器/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 控制所需的治疗定位;（2）进一步发展声学和热计算机 模拟，应用3D患者特定模拟来评估加热性能，设计输送 策略，并制定治疗计划框架;（3）制定MRI指导和MRTI， 通过混合无参考和多基线MR的快速采集，实现准确的传输和监测 温度测量以适应生理器官运动;以及（4）进行对所述组织的体内研究。 可部署的超声施加器和MR引导平台，并使用MRTI，对比增强MRI， 和组织学，以评估胰腺组织靶向消融和热疗的能力和准确性 同时不伤害邻近组织。这项拟议研究的完成有可能导致一种新的， 采用热疗治疗胰腺癌的准确微创方法，可酌情 避免对非靶组织的损伤，可单独使用或作为其他疗法的有力辅助。