Comprehensive Stereological assessment of the human lung using multi-resolution computed tomography

Abstract

RATIONALE: The application of stereology to lung casts and 2-dimensional microscopy images is the gold standard for quantification of the human lung anatomy. However, these techniques are labor intensive involving fixation, embedding and histological sectioning of samples and thus, have prevented comprehensive studies. OBJECTIVE: To demonstrate the application of stereology to volumetric multi-resolution computed tomography (CT) to efficiently and extensively quantify the human lung anatomy. METHODS: Non-transplantable donor lungs from individuals with no evidence of respiratory disease (n=13), were air inflated, frozen at 10cmH2O, and scanned using CT. Systematic uniform random (SUR) samples were taken, scanned using microCT, and assessed using stereology. RESULTS: The application of stereology to volumetric CT imaging enabled comprehensive quantification of total lung volume, volume fractions of alveolar, alveolar duct, and tissue, mean linear intercept, alveolar surface area, alveolar surface area density, septal wall thickness, alveolar number, number-weighted mean alveolar volume, and the number and morphometry of terminal and transitional bronchioles. Using this dataset, we found that women and men have the same number of terminal bronchioles (last generation of conducting airways), but men have longer terminal bronchioles, a smaller wall area %, and larger lungs due to a greater number of alveoli per acinus. CONCLUSIONS: The application of stereology to multi-resolution CT imaging enables comprehensive analysis of the human lung parenchyma that identifies differences between men and women. The reported dataset of normal donor lungs aged 25-77 years, provides reference data for future studies of chronic lung disease to determine exact changes in tissue pathology.