###### Abstract  
Magnetic resonance (MR) imaging has demonstrated that CF subjects have a significantly higher lung density (e.g., fluid content) when compared with healthy control subjects, but, at present, there are no techniques to quantify the spatial presentation of these lung abnormalities. The excess fluid in MR lung images for CF subjects with mild (\(n=4\)), moderate (\(n=5\)), and severe (\(n=4\)) disease and age- and sex-matched healthy controls (\(n=13\)) in both the right and left lungs was identified and quantified using a thresholding-based image segmentation technique using healthy controls as a baseline. MR lung images were categorized into one of three spatial presentation groups based on their regional and global percent area of the lung covered by excess fluid (i.e., spatial distribution): (i) generalized for sparse, (ii) localized diffuse for a moderate focality, and (iii) localized for a strong focality. A total of 96% of the controls presented as generalized. CF subjects populated all three presentation groups and an individual's right and left lungs did not always categorize identically. The developed metrics for categorization provide a quantification method to describe the spatial presentation of CF disease and suggests the heterogeneous nature of the disease. c 202212120647 202212212212212122122122122122122122122122122212221222122212  
tissue (i.e., the ratio of gas to surrounding soft tissue) when compared to normal lung tissue. Peribronchial thickening, for instance, appears denser in imaging studies due to excess interstitial fluid and edema generated by the airway inflammatory response. Two of the most commonly used medical imaging techniques for CF are computed tomography (CT) and magnetic resonance (MR) imaging to visually assess defects and morphological changes. In healthy subjects, the attenuation measured in CT scans is determined by the presence of lung tissue, blood, and air [8], whereas MR imaging measures the water content of blood and lung tissue. Therefore, though CT provides a higher resolution of lung tissue, MR imaging is ideally suited for assessing lung water content. Quantitative methods to evaluate CF with CT imaging have been developed and are primarily focused on threshold and model-based techniques to automatically measure the size of airways [9] and localized air trapping [10]. Chest CT scoring systems, such as the Brasfield scoring system provide a fairly sensitive measure of airway secretions. The Brasfield scoring system of chest CT [11] has been shown to be reproducible and useful in assessing CF airways but has two drawbacks: (1) It utilizes a semi-quantitative scoring system based on subjective clinical review. (2) It utilizes CT, which should not be used in repeated measures due to ionizing radiation exposure [12; 13]. Due to the inherent risk of repetitive CT exams, there are new efforts to develop low-dose CT techniques to monitor lung disease in both pediatric and adult CF [9; 14; 15; 16]. However, low-dose CT techniques also use a semi-quantitative scoring system to evaluate lung health. The use of structural MR imaging has been suggested as a surrogate and has been shown to correlate well with chest CT assessments [17; 18; 19; 20; 21]. Although MR imaging can be used repeatedly, these assessments are still semi-quantitative. At present, none of the techniques discussed above have been able to determine if the spatial characteristics (e.g., size, location, and distribution of lung abnormalities) of CF are linked with disease status. Therefore, there is a need for new metrics that can quantify the spatial heterogeneity of CF disease. We hypothesize that lung abnormalities in CF can be identified on an individual-by-individual basis by spatially identifying locations in the lung that are outside of the range of lung density observed in the MR images of healthy control subjects. Once abnormalities have been identified, we also hypothesize that a quantitative metric can be developed that represents the heterogeneity of disease expression in CF.