doi:10.1155/2012/734734 Research Article Quantification of Lung Damage in an Elastase-Induced Mouse Model of Emphysema

Copyright © 2012 Arrate Muñoz-Barrutia et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. To define the sensitivity of microcomputed tomography- (micro-CT-) derived descriptors for the quantification of lung damage caused by elastase instillation. Materials and Methods. The lungs of 30 elastase treated and 30 control A/J mice were analyzed 1, 6, 12, and 24 hours and 7 and 17 days after elastase instillation using (i) breath-hold-gated micro-CT, (ii) pulmonary function tests (PFTs), (iii) RT-PCR for RNA cytokine expression, and (iv) histomorphometry. For the latter, an automatic, parallel software toolset was implemented that computes the airspace enlargement descriptors: mean linear intercept (Lm) and weighted means of airspace diameters (D0, D1, and D2). A Support Vector Classifier was trained and tested based on three nonhistological descriptors using D2 as ground truth. Results. D2 detected statistically significant differences (P < 0.01) between the groups at all time points. Furthermore, D2 at 1 hour (24 hours) was significantly lower (P < 0.01) than D2 at 24 hours (7 days). The classifier trained on the micro-CT-derived descriptors achieves an area under the curve (AUC) of 0.95 well above the others (PFTS AUC = 0.71; cytokine AUC = 0.88). Conclusion. Micro-CT-derived descriptors are more sensitive than the other methods compared, to detect in vivo early signs of the disease. 1