Tumor hypoxia is one of the physiological factors for treatment resistance and likely contributes to poor overall survival among patients with head and neck cancer (HNC). Identifying hypoxic features of HNC may allow the personalizing treatment plan. The investigators propose multiparametric Hypoxia MR (HMR) imaging using diffusion, perfusion, and oxygenation as non-invasive, in-vivo imaging components of a hypoxia phenotype. Assessing the hypoxia phenotypes' expression will be critically important for characterizing and predicting CRT response among patients with advanced HNC.

A prospective cohort study will be conducted used multiparametric MR (MPMR) imaging correlated with treatment response assessed by 3 months fluorodeoxyglucose-positron emission tomography (FDG-PET). The image analysis approach will be developed to incorporate FDG-PET and quantitative MRI characteristics of tumor (ADC, oxygen-enhanced T1 and T2* maps, and volume transfer constant (Ktrans) to facilitate 3D visualization of multiparametric information. This proposed study's overarching goal is to develop and validate multiparametric HMR imaging using 18F - (fluoromisonidazole) FMISO-PET and immunohistochemistry (IHC) as the standard of references.

The objectives of this feasibility study are; 1) To obtain pilot data for a full-scale study and measure the distribution of parameters of the hypoxia MR (perfusion, diffusion, oxygenation, and acidosis) imaging, 2) To assess association of various hypoxia MR metrics with outcome, response to chemoradiotherapy (CRT) determined by 3 months post CRT FDG-PET/CT. 3) The metrics developed on hypoxia MRI wil be validated against F-18 FMISO-PET/CT and whole specimen IHC (immunohistochemistry). The data obtained from this pilot study will allow us to measure the effect size (difference in hypoxia MR metrics between responder and non-responder) for a larger, full-scale diagnostic study in the future, as well as to determine which hypoxia MR parameters have a strong association with desired outcome (response to CRT) in the future study.

The long-term objective of this research is to evaluate hypoxia MR phenotype that can be incorporated into treatment planning for IMRT (intensity-modulated radiotherapy), identify subregions of tumor hypoxia, and predict response to chemoradiotherapy (CRT) in newly diagnosed head and neck squamous cell carcinoma. The investigators will develop hypoxia MRI using a widely available MRI platform that allows broad patients access to novel hypoxia MRI. The investigators will evaluate the accuracy of the prediction of response to CRT using quantitative variables derived from hypoxia MR at the baseline as well as early interval changes between the baseline and 2 weeks of intra-treatment MR scans. Response to CRT will be determined by 3 months post-treatment FDG-PET/CT.

Inclusion Criteria:

• Newly diagnosed HNSCC (head and neck squamous cell carcinoma) by biopsy or fine needle aspiration originating from the oral cavity, larynx, hypopharynx, nasopharynx, and oropharynx
• Patients are scheduled to undergo chemoradiotherapy or surgery
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

• Pregnant patients
• Patients with claustrophobia
• Patients with pacemaker, spinal stimulator, or cochlear implant that are not MR compatible or any other metallic objects in the body
• Patients who had been treated for HNC, either surgery, radiation therapy, or chemotherapy
• Patients with thyroid, skin, sinonasal, and salivary gland cancer.
• Abnormal kidney function defined as estimated glomerular filtration rate (eGRF) < 30 mL/min/1.73 m2
• Patients with uncontrolled diabetes
• Patients who obtained outside FDG-PET/CT prior to initial treatment

1. Patients with newly diagnosed advanced-stage HNC with a primary tumor larger than 3 cm that are treated with CRT (chemoradiotherapy)
2. Patients with newly diagnosed localized HNC that are primarily treated with surgical resection for whole specimen IHC