Micro-Computed Tomography Measurements of Peripheral Lung Pathology in Chronic Obstructive Pulmonary Disease

Abstract

Background: The smaller airways, , 2 mm in diameter, offer little resistance in normal lungs, but become the major site of obstruction in chronic obstructive pulmonary disease (COPD). Objective: To examine bronchiolar remodeling and alveolar destruction in COPD using micro-computed tomography (micro-CT). Methods: Micro-CT was used to measure the number and crosssectional lumen area of terminal bronchioles (TB) and alveolar mean linear intercept (Lm) in 4 lungs removed from patients with very severe (GOLD-4) COPD and 4 unused donor lungs that served as controls. These lungs were inflated with air to a transpulmonary pressure (P L ) of 30 cm H 2 O and held at P L 10 cm H 2 O while they were frozen solid in liquid nitrogen vapor. A high resolution CT scan was performed on the frozen specimen prior to cutting it into 2-cm thick transverse slices. Representative core samples of lung tissue 2 cm long and 1 cm in diameter cut from each slice were fixed at 2808C in a 1% solution of gluteraldehyde in pure acetone, post-fixed in osmium, critically point dried, and examined by micro-CT. Results: A 10-fold reduction in terminal bronchiolar number and a 100-fold reduction in their minimal cross-sectional lumen area were measured in both emphysematous and non-emphysematous regions of the COPD lungs. Conclusions: The centrilobular emphysematous phenotype of COPD is associated with narrowing and obliteration of the terminal bronchioles that begins prior to the onset of emphysematous destruction.

The role of small airways in obstructive airway diseases

“…It has the advantage over HRCT to achieve a better resolution, allowing for direct images of both bronchiolar and alveolar structures [91]. However, with current technology, use of micro-CT is limited to ex vivo tissue samples because the level of radiation associated with micro-CT damages tissue [92]. HOGG et al [92] used micro-CT to evaluate morphological changes in human lungs obtained during transplantation in subjects with severe COPD and in unused donor lungs that served as controls.…”

“…However, with current technology, use of micro-CT is limited to ex vivo tissue samples because the level of radiation associated with micro-CT damages tissue [92]. HOGG et al [92] used micro-CT to evaluate morphological changes in human lungs obtained during transplantation in subjects with severe COPD and in unused donor lungs that served as controls. The entire lungs were inflated near TLC and frozen with liquid nitrogen.…”

Quantitative 3D Micro-CT Imaging of Human Lung Tissue

“…Quantitative micro-CT studies of human lung pathologies focus most often on airway alterations in emphysema. 2 D measurements like mean linear intercept, and the quantification of terminal bronchioles in number and diameter provide insight into the rarefaction of small airways and the different temporal onset of narrowing and collapse of terminal bronchioles versus the emphysematous destruction of alveolar tissue [18,19]. Nevertheless, it does not quantify the loss of tissue.…”

Update on the roles of distal airways in COPD

“…Importantly, BLACK et al [53] have recently reported a similar loss of elastic fibres in small conducting airways of COPD subjects, suggesting that small conducting airways may also disappear. A major question resulting from these findings relates to the number of small conducting airways in COPD subjects [54,55]. HOGG et al [55] have reported preliminary data using micro-computed tomography (CT) in isolated lungs and suggested a reduction in the number of small conducting airways in subjects with centrilobular emphysema.…”

“…A major question resulting from these findings relates to the number of small conducting airways in COPD subjects [54,55]. HOGG et al [55] have reported preliminary data using micro-computed tomography (CT) in isolated lungs and suggested a reduction in the number of small conducting airways in subjects with centrilobular emphysema. Decreased numbers of small conducting airways may contribute to increased resistance in small airways because mathematical computation indicates that a 50% reduction in the number of small conducting airways will result in a two-fold increase in resistance.…”