Standard and hyperpolarised MRI for detecting normal tissue toxicity and antitumor activity of ionizing radiation Head and Neck Squamous Cell Carcinoma (HNSCC) affects approximately 500,000 patients around the world each year. Mortality for advanced HNSCC continues to exceed 50% even in the United States and Europe. Survivors of HNSCC treatment often exhibit significant sequela of treatment (surgery, ionizing radiation (IR), chemotherapy) including difficulties speaking, swallowing, cosmetic deformity and chronic pain. The increasing utilization of IR in the treatment of HNSCC over the last 2 decades has resulted in a complex, and highly unpredictable pattern of sub-acute and chronic toxicity which remains a difficult clinical dilemma. Over the last 10 years our group has begun to define a role for MRI in refining IR algorithms for HNSCC in order to maximize antitumor efficacy and minimize normal tissue toxicity. Pre-clinical animal models have demonstrated that dynamic contrast-enhanced (DCE) MRI can detect treatment effects acutely within the tumor volume. In patients, diffusion weighted (DW) MRI can identify rapid changes in tumor size and viability during IR. Finally, using pre-clinical cancer models we showed that hyperpolarized (HP) MRI can be used to measure acute changes in oxidative stress within the tumor volume following IR administration. Taken together, these data suggest that multi-parametric (mp) MRI can be developed into a predictive tool for IR-based treatment regimens in HNSCC. In parallel, we have begun to show that mp MRI, particularly DCE-MRI can detect acute, subacute and chronic changes in normal tissue vascularity, inflammation and viability during and following IR-based treatment. Based on our preliminary data, we believe that integration of mp MRI into clinical application can potentially revolutionize the effectiveness of IR-based treatment for HNSCC and allow us to develop truly personalized IR-regimens.