Dynamic Oxygen-Enhanced MRI of Lung Structure and Function, PI: Sean B. Fain. Abstract This project will develop and optimize oxygen-enhanced (OE) imaging of dynamic ventilation of the lungs simultaneously with high resolution acquisition of lung parenchymal anatomy in a single, free-breathing 7-minute acquisition using 3D ultra-short time to echo (UTE) MRI. Advances in 3D UTE MRI now support regional imaging of lung anatomy with CT-like contrast, full chest coverage, and isotropic 1 mm spatial resolution. We will employ advanced motion compensation reconstruction with manifold-based deep learning and UTE center-out k-space trajectories to isolate respiratory motion from T1 changes due to oxygen wash-in and wash-out during free- breathing. The resulting motion compensated reconstruction provides both quantitative ventilation and high- resolution structure in a single 7-minute series. Multiple chronic lung diseases will be studied with this approach to establish utility and repeatability of the method in comparison to quantitative chest CT and hyperpolarized 129Xe MRI. Our preliminary data demonstrates the utility of MRI-only exam of lung structure and ventilation in a manner similar to that provided by nuclear SPECT with technegas and X-ray CT but without ionizing radiation. We hypothesize that 3D UTE MR imaging of ventilation dynamics will capture co-localized structure-function for monitoring ventilation heterogeneity relative to structural features of lung disease, including fibrosis, granulomas, mucus plugging, bronchiectasis, ground glass, and fibrosis. Radiology expert reader studies will be performed with direct comparison of UTE MRI with quantitative chest CT for depiction of structural and functional (derived from static multi-volumetric images) abnormalities, and OE MRI regional patterns of ventilation to hyperpolarized 129Xe MRI. We seek to create an MRI method and protocol for structure-function assessment of chronic lung disease with broad access, no exposure to ionizing radiation (allowing for longitudinal assessment at increased granularity), and using a safe, inexpensive and widely available paramagnetic gas. The specific aims of the project are to: 1) Improve data acquisition efficiency for 3D UTE MRI at clinical field strengths; 2) Develop dynamic OE MRI of oxygen ventilation wash-in and wash-out during free breathing, and 3) Develop OE MRI visualization and analysis tools for regional structure-function associations. The 3D OE MRI approach is inexpensive, uses proton-based contrast and can characterize both structural and functional aspects of chronic lung disease in a manner similar to SPECT/CT without concern for ionizing radiation exposure.