Advancing Methods for MR-guided Focused Ultrasound Hyperthermia for Head and Neck Cancer

项目摘要/摘要 头颈癌在美国是一个公共卫生问题，也是肿瘤学的一个主要挑战。 化疗和放射治疗主要用于提高头颈部癌症患者的生存率。 然而，这种益处仍然仅限于并发症和毒性负担较高的患者。 对存活的头颈部癌症患者来说是严重的。热疗结合其他疗法， 如放射、化疗和免疫疗法，已经在临床试验中被证明可以提高反应 对于头颈部癌症，但成功与否高度依赖于所提供的热剂量分布。 因此，这项技术需要空间可控的热传递和足够的温度监测。 磁共振引导的聚焦超声(MRgFUS)可能被用于提供热疗。《聚焦》 超声技术由于其完全非侵入性的热传递而受到广泛的关注 高度的空间选择性和动态可控性。有了这些固有的优势，临床MRgFUS 已经开发和批准了用于各种部位的热消融治疗的系统，例如 脑、子宫肌瘤、前列腺、胰腺和骨转移。然而，主要的技术挑战是 头颈部肿瘤的MRgFUS热疗治疗：需要优化 增强温度分布和向HNC传递适形热疗的超声策略， 2)先进的磁共振成像方法，可在显著减少伪影的情况下进行精确的温度成像 以及快速磁共振成像以评估组织反应。拟议的项目将开发出更多的方法 在磁共振成像控制下进行有效的热疗，以提高应答率和 头颈部浅表和深部肿瘤患者的生存率，如鳞状细胞癌， 黑色素瘤和软组织肉瘤。在本项目中，具体目标是：1)开发实用性和最优化 头颈部肿瘤适形热疗的超声治疗策略，2)发展 复杂结构中伪影最小的温度成像的稳健实时磁共振测温方法 头部和颈部的解剖，以及3)开发温度和组织的实时同步磁共振成像 体温过高(R00期)的反应。这些技术发展将推动由MRgFUS调解的 热疗用于头颈部癌症，培训计划包括应用 新知识。我已经组建了一支由著名导师(Diederich博士、Larson博士和 Payne)和专业顾问(Ozhinsky博士、Bucknor博士和Chan博士)，他们在MR引导的重点领域拥有专业知识 超声波治疗、临床头颈部癌症治疗、定量核磁共振和磁共振测温。这个 拟议的奖项将为我提供必要的经验，使我成为一名独立的、跨学科的、 和致力于图像引导热疗和治疗性超声波的翻译科学家。

PROJECT SUMMARY/ABSTRACT Head and Neck Cancer is a public health concern in the United States and a major challenge in oncology. Chemoradiotherapy has been mainly adopted to improve survival for patients with head and neck cancers. However, the benefit remains limited to patients with a high risk of complications, and the burden of toxicity in surviving patients with head and neck cancers is severe. Hyperthermia combined with other treatments, such as radiation, chemotherapy, and immunotherapy, has been shown in clinical trials to increase response for head and neck cancers, but success is highly dependent upon the delivered thermal dose distributions. Hence, this technology requires spatially controllable heat delivery and adequate temperature monitoring. MR-guided focused ultrasound (MRgFUS) can potentially be used to deliver hyperthermia. The focused ultrasound technique has been received much interest due to its completely non-invasive heat delivery with a high degree of spatial selectivity and dynamic control. With these inherent advantages, clinical MRgFUS systems have been developed and approved for thermal ablation treatments of various sites, such as the brain, uterine fibroids, prostate, pancreas, and bone metastases. However, the major technical challenges remain for MRgFUS hyperthermia delivery to head and neck cancers: There is a need for 1) optimizing sonication strategies for enhancing temperature distributions and delivering conformal hyperthermia to HNC, and 2) advanced MR imaging methods for accurate temperature imaging with significantly reduced artifacts and rapid MR imaging to evaluate tissue response. The proposed project will develop methods for more effective hyperthermia delivery under magnetic resonance imaging control to increase response rate and survival for patients with superficial and deep tumors in the head and neck, such as squamous cell carcinoma, melanoma, and soft tissue sarcoma. In this project, the specific aims are 1) to develop practical and optimal sonication strategies for conformal delivery of hyperthermia to target head and neck cancer, 2) develop robust real-time MR thermometry methods for temperature imaging with a minimal artifact in the complex anatomy of the head and neck, and 3) develop real-time simultaneous MR imaging of temperature and tissue response during hyperthermia (R00 Phase). These technical developments will advance MRgFUS-mediated hyperthermia delivery to head and neck cancers and the training plan includes opportunities to apply the new knowledge. I have assembled an outstanding team of renowned mentors (Drs. Diederich, Larson, and Payne) and specialized advisors (Drs. Ozhinsky, Bucknor, and Chan) with expertise in MR-guided Focused Ultrasound therapy, clinical head and neck cancer treatment, quantitative MRI, and MR thermometry. The proposed award will provide me with the necessary experiences to become an independent, transdisciplinary, and translational scientist dedicated to image-guided thermal therapy and therapeutic ultrasound.