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 ima...