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Structural and Functional Modeling of Chronic Lung Inflammation: Loss of Function Mechanisms
Author(s) -
Golden T,
Massa C,
Rusu M,
Wang H,
Madabhushi A,
Gow A
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1016.4
Subject(s) - inflammation , lung function , loss function , function (biology) , lung , medicine , biology , immunology , microbiology and biotechnology , phenotype , genetics , gene
Chronic obstructive pulmonary disease presents with heterogenous inflammation and altered lung structure. The contribution of airway and parenchymal structural change to impaired lung function is not known. Lung functional models constructed from ventilator measurements can estimate the relative contribution of structural elements. In surfactant protein D knockout (Sftpd ‐/‐ ) mice, there is chronic inflammation and tissue destruction that contribute to poor lung function. In this study we have combined imaging methodology with ventilator measurements to determine how chronic inflammation reduces lung function. C57Bl/6 and Sftpd ‐/‐ mice were assessed by MRI, histology and forced oscillation technique. Serial tissue sections were aligned using one‐to‐one registration followed by one‐to‐many groupwise affine registration. Constraints from an ex vivo MRI were utilized to create a 3D histology volume. 3D deformable registration (from ITK framework) was used to co‐register the 3D histology with the in‐vivo MRI lung volume, with the ex vivo MRI as intermediate. Large airways were identified on histological sections and an airway tree of up to 16 generations was constructed from the multi‐modal imaging at full inhalation. Lung function was measured at 5 levels of Positive End Expiratory Pressure and the data was fit to a forward model incorporating the measured airway tree to improve impedence estimates. Sftpd‐/‐ mice display decreased radial alveolar counts that are transmitted to changes in airway structural dynamics. These structural changes are quantified in terms of the forward model to determine the mechanisms underlying poor lung function in chronic inflammation. *GM108463, HL086621, ES005022, DOD (W81XH‐13‐1‐0487), DOD (W81XWH‐14‐1‐0323)