Longitudinal micro-CT as an outcome measure of interstitial lung disease in TNF-transgenic mice.
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ABSTRACT:
Methods: Cross sectional ?CT was performed on cohorts of male TNF-Tg mice and their WT littermates at 3, 4, 5.5 and 12 months of age (n = 4-6). Lung ?CT outcomes measures were determined by segmentation of the ?CT datasets to generate Aerated and Tissue volumes. After each scan, lungs were obtained for histopathology and 3 sections stained with hematoxylin and eosin. Automated histomorphometry was performed to quantify the tissue area (nuclei, cytoplasm, and extracellular matrix) and aerated area (white space) within the tissue sections. Spearman's correlation coefficients were used to evaluate the extent of association between ?CT imaging and histopathology endpoints.
Results: TNF-Tg mice had significantly greater tissue volume, total lung volume and mean intensity at all timepoints compared to age matched WT littermates. Histomorphometry also demonstrated a significant increase in tissue area at 3, 4, and 5.5 months of age in TNF-Tg mice. Lung tissue volume was correlated with lung tissue area (? = 0.81, p<0.0001), and normalize lung aerated volume was correlated with normalized lung air area (? = 0.73, p<0.0001).
Conclusions: We have validated in vivo ?CT as a quantitative biomarker of ILD in mice. Further, development of longitudinal measures is critical for dissecting pathologic progression of ILD, and ?CT is a useful non-invasive method to study lung inflammation in the TNF-Tg mouse model.
SUBMITTER: Bell RD
PROVIDER: S-EPMC5761871 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
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