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

Area of Science:

• Pulmonary Medicine
• Medical Imaging
• Preclinical Research

Background:

• Asthma is a complex disease with distinct eosinophilic (EOS) and neutrophilic (NEU) inflammatory phenotypes.
• These phenotypes present unique airway and parenchymal structural changes that are challenging to characterize in human studies.
• Murine models offer a controlled environment to investigate phenotype-specific pathological alterations.

Purpose of the Study:

• To explore and differentiate phenotype-specific structural and densitometric changes in EOS and NEU asthma using high-resolution micro-computed tomography (micro-CT) in a murine model.
• To correlate imaging findings with inflammatory endotypes and histopathology.
• To support non-invasive preclinical phenotyping and the development of targeted therapies.

Main Methods:

• Sixteen female C57BL/6NCrlOri mice were assigned to control, EOS asthma, or NEU asthma groups.
• High-resolution micro-CT was employed to quantify airway morphometrics (bifurcation angle, circularity, hydraulic diameter, wall thickness, luminal volume) and parenchymal alterations (emphysema-like changes, ground-glass opacity, consolidation, fibrosis) using Hounsfield unit thresholds.
• Bronchoalveolar lavage (BAL) flow cytometry and lung histopathology were performed to confirm inflammatory endotypes and tissue remodeling.

Main Results:

• EOS asthma showed predominant distal airway and main bronchi alterations with increased circularity and hydraulic diameter, alongside higher ground-glass opacity and semi-consolidation.
• NEU asthma exhibited widespread proximal airway dilation with increased luminal volume but minimal parenchymal changes.
• Tracheal parameters positively correlated with GGO and semi-consolidation. BAL confirmed eosinophil enrichment in EOS and increased neutrophils/monocytes in NEU. Histopathology revealed greater peribronchial inflammation and remodeling in NEU mice.

Conclusions:

• Quantitative micro-CT effectively differentiates EOS and NEU asthma phenotypes by capturing distinct airway and parenchymal structural and densitometric features in a preclinical model.
• The findings support the use of micro-CT for non-invasive preclinical phenotyping of asthma.
• This approach can facilitate the development and testing of phenotype-targeted therapeutic strategies for asthma.