Quantitative morphometric analysis of asthmatic mouse lungs using micro-CT: A preclinical imaging study.

Abstract

Asthma is a heterogeneous disease comprising eosinophilic (EOS) and neutrophilic (NEU) phenotypes with distinct airway and parenchymal alterations. Using murine models, this study explored phenotype-specific structural and densitometric changes that are difficult to capture in human cohorts. Sixteen female C57BL/6NCrlOri mice were assigned to negative control (n = 5), EOS (n = 6), or NEU (n = 5) asthma groups. High-resolution micro-computed tomography (micro-CT) was used to quantify airway and parenchymal alterations. Morphometric parameters included bifurcation angle (θ), circularity (Cr), hydraulic diameter (D), wall thickness (WT), and luminal volume (LV). Voxel-wise parenchymal analysis, based on CT Hounsfield unit (HU) thresholds, classified regions as emphysema-like lung, ground-glass opacity (GGO), semi-consolidation, consolidation, and fibrosis. Compared with controls, asthmatic groups showed distinct but partially overlapping structural patterns. EOS demonstrated predominant alterations in distal airways and main bronchi, with increased Cr and D, accompanied by higher GGO and semi-consolidation. NEU caused widespread proximal airway dilation, reflected by greater LV, but showed minimal parenchymal changes. Tracheal Cr, D, and LV, correlated positively with GGO and semi-consolidation, suggesting a potential association between airway enlargement and parenchymal alterations. Besides, bronchoalveolar lavage (BAL) flow cytometry confirmed distinct inflammatory endotypes, with eosinophil enrichment in EOS mice and increased neutrophils and monocytes in NEU mice. Consistently, lung histopathology showed greater peribronchial inflammation and collagen-associated airway remodeling in NEU mice, whereas EOS mice exhibited moderate inflammatory infiltration with localized matrix deposition. Overall, quantitative micro-CT differentiates EOS and NEU asthma phenotypes by capturing airway and parenchymal features, supporting non-invasive preclinical phenotyping and phenotype-targeted therapy development.