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

项目总结/摘要 头颈癌是美国的一个公共卫生问题，也是肿瘤学的一个重大挑战。 放化疗主要用于提高头颈部肿瘤患者的生存率。 然而，受益仍然限于并发症风险高的患者，以及毒性负担 头颈部癌症存活患者的死亡率很高。热疗结合其他治疗， 如放疗、化疗和免疫疗法，已在临床试验中显示可增加反应 但成功与否高度依赖于所输送的热剂量分布。 因此，该技术需要空间可控的热传递和足够的温度监测。 MR引导聚焦超声（MRgFUS）可用于提供热疗。聚焦 超声技术由于其完全非侵入性的热传递而受到广泛关注， 高度的空间选择性和动态控制。凭借这些固有优势，临床MRgFUS 已经开发并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 MRgFUS热疗输送到头颈部癌症：需要1）优化 用于增强温度分布和向HNC递送适形热疗的超声处理策略， 和2）先进的MR成像方法，用于精确的温度成像，显著减少伪影 和快速磁共振成像来评估组织反应。拟议的项目将制定更多的方法， 在磁共振成像控制下有效的热疗递送，以增加响应率， 头颈部浅表和深部肿瘤，如鳞状细胞癌， 黑素瘤和软组织肉瘤。在本项目中，具体目标是：1）开发实用和最佳的 用于适形递送热疗以靶向头颈癌的超声处理策略，2）开发 用于温度成像的鲁棒实时MR测温方法，在复杂环境中具有最小伪影 头部和颈部的解剖结构，以及3）开发温度和组织的实时同步MR成像 热疗期间的反应（R 00阶段）。这些技术发展将推动MRgFUS介导的 热疗输送到头部和颈部癌症和培训计划，包括机会，应用 新知识我组建了一个由著名导师组成的杰出团队（Diederich博士，Larson博士， Payne）和专业顾问（Ozhinsky博士、Bucknor博士和Chan博士），他们在MR引导的聚焦 超声治疗，临床头颈癌治疗，定量MRI和MR测温。的 建议的奖项将为我提供必要的经验，成为一个独立的，跨学科的， 他是一位致力于图像引导热疗和治疗性超声的翻译科学家。

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.