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A3906 - Tissue Density-Based Micro-Computed Tomography Analyses of Whole Lung Remodeling In Vivo
Author Block: B. T. Ameredes1, J. Litvinov1, I. Patrikeev2, W. C. Spear1, K. K. Belanger1, B. Tian3, L. M. Hallberg4, M. Motamedi2, A. R. Brasier3; 1Pulmonary, Critical Care, and Sleep Medicine, Internal Medicine, Univ of Texas Med Branch, Galveston, TX, United States, 2Center for Biomedical Engineering, Univ of Texas Med Branch, Galveston, TX, United States, 3Endocrinology Division, Internal Medicine, Univ of Texas Med Branch, Galveston, TX, United States, 4Preventive Medicine and Community Health, Univ of Texas Med Branch, Galveston, TX, United States.
RATIONALE: The development of lung fibrosis and airway remodeling is considered to be associated with a number of immunomodulatory, environmental, and pathogenic triggers of airway inflammation in obstructive lung diseases, such as asthma and COPD. Typical animal models of those lung diseases, and others which can include fibrosis, utilize invasive methods of assessment, which are valuable, but terminal. Therefore, we have utilized a non-invasive micro-computed tomography (CT) imaging assessment of whole lung tissue density changes, associated with pro-inflammatory processes induced with administration of immunomodulatory, environmental, and pathogenic stimuli known to potentiate airway remodeling and lung pathology, in order to gain further insights into mechanisms of lung disease, and the utility of non-invasive imaging.
METHODS: Mice were administered either bleomycin, polyinosinic polycytidylic acid (Poly (I:C)), cigarette smoke, or PBS (vehicle control) over the course of 1 month, and were compared with Naïve (no treatments) controls. MicroCT images of the whole lung were obtained w/o contrast, using both black and white cross-sectional radiographs, or digital imaging coloration of 3-D images, designating specified ranges of lung tissue density, with density data plotted as a function of total lung tissue for each mouse, and comparisons by ANOVA. Assessments of lung stiffness, collagen-associated assays, and histology were performed to determine whether observed changes in tissue density were associated with characteristics of lung fibrotic processes.
RESULTS: Radiographic images showed increased opacities in both bleomycin and Poly (I:C) treated mice, suggestive of fibrotic lung tissue. Bleomycin administration significantly decreased the volume of low-density tissue, producing a right-shift of the tissue volume vs. tissue density relationship, suggestive of increased tissue density associated with fibrosis, and consistent with lung fibrosis assessments. Poly (I:C) administration likewise resulted in a significant diminution of low-density tissue, increased lung stiffness and collagen, but with no apparent shift in the lung tissue volume-density relationship. In contrast, cigarette smoke significantly increased the volume of low-density tissue, suggestive of destruction of lung tissue and increased airspace.
CONCLUSION: These results indicate that assessment of comparative lung tissue density using microCT imaging of the whole lung in vivo can provide a non-invasive quantitation of whole lung tissue remodeling with experimentally-induced airway inflammation and the induction of experimental lung fibrosis, in translationally-relevant animal models of lung disease.