Quantitative characterization of airspace enlargement in emphysema

Abstract

The mean linear intercept (L(m)) can be used to estimate the surface area for gas exchange in the lung. However, in recent years, it is most commonly used as an index for characterizing the enlargement of airspaces in emphysema and the associated severity of structural destruction in the lung. Specifically, an increase in L(m) is thought to result from an increase in airspace sizes. In this paper, we examined how accurately L(m) measures the linear dimensions of airspaces from histological sections and a variety of computer-generated test images. To this end, we developed an automated method for measuring linear intercepts from digitized images of tissue sections and calculate L(m) as their mean. We examined how the shape of airspaces and the variability of their sizes influence L(m) as well as the distribution of linear intercepts. We found that, for a relatively homogeneous enlargement of airspaces, L(m) was a reliable index for detecting emphysema. However, in the presence of spatial heterogeneities with a large variability of airspace sizes, L(m) did not significantly increase and sometimes even decreased compared with its value in normal tissue. We also developed an automated method for measuring the area and computed an equivalent diameter of each individual airspace that is independent of shape. Finally, we introduced new indexes based on the moments of diameter that we found to be more reliable than L(m) to characterize airspace enlargement in the presence of heterogeneities.

Autophagy protein microtubule-associated protein 1 light chain-3B (LC3B) activates extrinsic apoptosis during cigarette smoke-induced emphysema

“…Airspace enlargement caused by CS exposure in LC3B −/− and WT mice was also assessed separately by measuring the equivalent diameter of alveolar airspaces using a previously published automated image processing algorithm (16). Consistent with the MLI measurements, the equivalent diameter of CS-exposed LC3B +/+ mice (31.5 ± 1.6 μm) was significantly greater than airtreated LC3B +/+ mice (27.9 ± 1.4 μm; P = 0.001), whereas the equivalent diameter of CS-exposed LC3B −/− mice (30.7 ± 1.8 μm) was not different from the air-treated LC3B −/− mice (29.0 ± 3.1 μm).…”

“…Lung samples were processed for morphometric analysis, and airspace enlargement was quantified by using a previously published, automated image processing algorithm (16), and also using the MLI method (39-41) as described in detail in SI Methods.…”

Use of mean airspace chord length to assess emphysema

“…Such advanced statistical analyses may aid in the early detection of disease, but these alternatives have not yet been evaluated. Furthermore, the chord length distribution (and any metric based on it) or any alternative analytic strategies that amplify the effect of large airspaces by quantifying areas (12), must also take into consideration the potential effects of changes in the reference lung volume and other sampling biases.…”

Automated quantification of lung structures from optical coherence tomography images

“…In addition, this difference is less than the observed physiological changes in the size of airway structures observed under several disease conditions. For example, COPD has been found to double the mean chord length [7] and increase the weighted mean alveolar diameter by approximately 80% [5] in comparison to healthy lung. This suggests that the segmentation is a sufficiently accurate characterization of the OCT data to distinguish healthy lung from various disease processes, and highlights the potential for diagnostically relevant quantifications to be made from this segmentation.…”

“…Characterization of disease-related changes in lung parenchyma, reflected in the size of lung structures, may allow assessment of disease progression [5]. Such sizing could assist in the assessment and development of new treatments for these pathologies.…”