From morphological heterogeneity at alveolar level to the overall mechanical lung behavior: an in vivo microscopic imaging study

Abstract

In six male anesthetized, tracheotomized, and mechanically ventilated rabbits, we imaged subpleural alveoli under microscopic view (60×) through a “pleural window” obtained by stripping the endothoracic fascia and leaving the parietal pleura intact. Three different imaging scale levels were identified for the analysis on increasing stepwise local distending pressure (Pld) up to 16.5 cmH2O: alveoli, alveolar cluster, and whole image field. Alveolar profiles were manually traced, clusters of alveoli of similar size were identified through a contiguity‐constrained hierarchical agglomerative clustering analysis and alveolar surface density (ASD) was estimated as the percentage of air on the whole image field. Alveolar area distributions were remarkably right‐skewed and showed an increase in median value with a large topology‐independent heterogeneity on increasing Pld. Modeling of alveolar area distributions on increasing Pld led to hypothesize that absolute alveolar compliance (change in surface area over change in Pld) increases fairly linearly with increasing initial alveolar size, the corollary of this assumption being a constant specific compliance. Clusters were reciprocally interweaved due to their highly variable complex shapes. ASD was found to increase with a small coefficient of variation (CV <25%) with increasing Pld. The CV of lung volume at each transpulmonary pressure was further decreased (about 6%). The results of the study suggest that the considerable heterogeneity of alveolar size and of the corresponding alveolar mechanical behavior are homogenously distributed, resulting in a substantially homogenous mechanical behavior of lung units and whole organ.

Self-organizing pattern of subpleural alveolar ducts

“…Alveoli in the region just below the pleural surface have been examined by light microscopy since the 1930s [1][2][3][4][5][6][7] . These studies have often examined how the alveoli expand with lung inflation and how they might change with lung pathology.…”

Effect of Airway Pressure Release Ventilation on Dynamic Alveolar Heterogeneity

“…6,7 This represents a length scale several orders of magnitude larger than that of the alveoli, which are directly affected by the stresses and strains of mechanical ventilation 16 and, therefore, might not accurately reflect the alveolar heterogeneity that occurs in the injured lung. 17 Applying a mechanical breath to a heterogeneous population of alveoli might result in localized regions of high stress without a significant increase in the overall stress of the whole lung. 6 Likewise, the changes in alveolar size distribution at inspiration vs expiration that occur when dynamic heterogeneity is present are indicative of abnormal alveolar microstrain 5 and intratidal derecruitment, which are known to accelerate the progression of lung injury.…”

Morphological Characterization of Acinar Cluster in Mouse Lung Using a Multiscale‐based Segmentation Algorithm on Synchrotron Micro‐CT Images

“…Observation and measurement of lung microstructure in vivo is expected, because it can avoid the deterioration of surfactant function. Recently, subpleural alveoli have been studied in vivo using optical coherence tomography (OCT) (Mertens et al, ), optical frequency domain imaging (OFDI) (Namati et al, ), and intravital microscopy (Mazzuca et al, ). With any of these techniques, it is virtually impossible to observe nonpleural alveoli in core regions of the lung because depth resolution is limited (<500 μm).…”