ABSTRACT Quantitation and Spatial Registration of Airways Dysfunction with Dynamic 19F MRI in Cystic Fibrosis Rationale: Currently available endpoints for testing of new therapies in CF typically are either insensitive to focal changes in lung disease and early lung disease (e.g. spirometry), or require ionizing radiation (e.g. chest CT). These problems limit their utility, and typically prevent repetitive use, particularly in young children. The addition of an inhaled gas as a contrast agent to quantify ventilation while preserving spatial inforrmation using MRI techniques is an important advance in pulmonary imaging, but is not yet widely available. We propose to develop the use of a perfluorinated gas for MRI imaging, which may have several important advantages over other techniques, including being readily transferrable to other research centers. Methods: Subjects with cystic fibrosis will undergo perfluoropropane (PFP)-enhanced magnetic resonance imaging (19F MRI), in addition to 1H ultrashort echo time (UTE) MRI. In a longitudinal study, we will evaluate the short-term variability and responsiveness of 19F MRI to disease state changes while exploring the relationship between functional changes in ventilation and lung structure. Parallel measurement of traditional outcome measures (spirometry, lung clearance index, and patient symptoms) will help evaluate whether additional sensitivity and value is added by this technique. Subjects will be tested in relation to pulmonary exacerbations as well to determine measure performance over different physiologic states. 19F MRI will be extended down to the pediatric age range to determine the feasibility of performing these studies in young children, and the ability to detect disease in children with normal spirometry. Training: Dr. Goralski will embark upon specialized training in clinical research topics (advanced study design and biostatistics), as well as training in medical imaging analysis to further her goal in becoming an independent investigator. She will also seek both formal and informal education in advance study design and biostatistical methods. Expected Results: We expect that 19F MRI will readily detect abnormalities in small airway function in subjects with CF lung disease, that measurements will be valid over short time frames, and that they will reflect acute changes in disease activity (i.e. exacerbations). We further expect that 19F MRI will be feasible in young children and will be able to detect ventilation inhomogeneity, even in young CF subjects with normal lung function tested by conventional means (i.e. spirometry).