Locally advanced non-small-cell lung cancer (NSCLC) is a common disease with a low overall survival even with aggressive treatments. Standard imaging (CT and PET/CT) provide no information about normal lung function. We therefore, sought to pilot HeMRI in patients with non-small-cell lung cancer before and after definitive radiotherapy (RT). Five patients with NSCLC receiving RT were enrolled on a prospective IRB approved study. Patients underwent CT, FDG-PET and HeMRI before and (within 10 days) following RT. All images (CT, FDG-PET and HeMRI) were co-registered. The CT and PET GTVs were contoured, as well as the ventilation defects on HeMRI caused by the tumor. Patients also underwent pulmonary function tests (PFTs). Correlations between the images and PFTs were evaluated by linear regression. CT and FDG-PET tumor volumes were highly correlated (r² = 0.91 before treatment and 0.99 following RT). There was less correlation between HeMRI and CT or PET (r² = 0.67 (CT) and 0.38 (PET)) prior to treatment and 0.27 following RT). However, HeMRI volumes correlated very well with FEV1, both prior to and following RT. (r² = 0.89 and 0.83, respectively). ³Helium MRI scanning is feasible in NSCLC before and after treatment. HeMRI provides important functional information in addition to CT and CT/PET scanning.