(113) Development and Characterization of Pulmonary Disease in G551D Ferret Model on Chest CT Imaging

Background: Cystic Fibrosis (CF) animal models are needed to further develop novel therapies in efforts to cure the condition. The G551D ferret model has shown promise in fulfilling this role, but needs sensitive endpoints for physiological assessments. Micro-resolution chest computed tomography (CT) can be used both in vivo and in the lungs of euthenaized ferrets in situ. Here, we developed a scoring system based on clinical CT scoring to help characterize pulmonary disease in ferrets with CF.

Methods: A semi-quantitative clinical scoring system based upon the extent of airway and parenchymal disease in each lobe was developed. This was generally based on Alan Brody CT scoring in humans to help characterize extent and distribution of disease in airways and parenchyma.1 Multiple in situ CT scans of ferrets were initially reviewed to develop understanding of anatomy and lung disease patterns. Following this learning phase, a blinded, pediatric pulmonologist (TSP) scored available CT scans in a consistent fashion with standard lung window (-1350 to 150 HU) in the axial plane. In situ scans were scored from CF G551D ferrets off Ivacaftor for 2-3 months, wild type controls of a similar age, and WT ferrets exposed to intratracheal bleomycin to induce lung injury.

Results: CF CT scans had substantially more lung disease than WT controls (p=0.01). The extent of parenchymal/small airway disease in CF ferrets were the greatest contributor to total score, and was variable among animals. In comparison, bleomycin exposed WT ferrets exhibited had prominent large airway and parenchymal/small airway disease that were more equal in severity (Figure). This trend persisted when adding aged bleomycin scores to the bleomycin group as well, showing a greater difference between parenchymal to airway percent contribution to total scores in CF ferrets compared to bleomycin exposed ferrets (n=5 vs 14 respectively, p=0.03).

Conclusions: Ferret chest CT scoring can be helpful in characterizing lung disease. CF CT scans show more extensive parenchyma/small airway disease, a similar pattern observed in early lung disease in humans. This contrasted with bleomycin-induced injury which exhibited a distinct large airway-centric pattern. Analysis of serial in vivo CT scans are in progress. CT imaging of ferrets may be useful in monitoring lung pathology and as an indicator of therapeutic response.

Acknowledgements: This work is supported by the Cystic Fibrosis Foundation (POORE20D0), UAB CF Research and Translation Core Center – (P30DK072482) and UAB Research and Development Program (CFF, ROWE19RO)

References: 1. Brody, Alan S.^*; Kosorok, Michael R.^†; Li, Zhanhai^†; Broderick, Lynn S.^‡; Foster, Jeffrey L.^§; Laxova, Anita^∥; Bandla, Hari^¶; Farrell, Philip M.^∥ Reproducibility of a Scoring System for Computed Tomography Scanning in Cystic Fibrosis, Journal of Thoracic Imaging: March 2006 - Volume 21 - Issue 1 - p 14-21 doi: 10.1097/01.rti.0000203937.82276.ce