Perspectives on lung visualization: Three-dimensional anatomical modeling of computed and micro-computed tomographic data in comparative evolutionary morphology and medicine with applications for COVID-19.

The vertebrate respiratory system is challenging to study. The complex relationship between the lungs and adjacent tissues, the vast structural diversity of the respiratory system both within individuals and between taxa, its mobility (or immobility) and distensibility, and the difficulty of quantifying and visualizing functionally important internal negative spaces have all impeded descriptive, functional, and comparative research. As a result, there is a relative paucity of three-dimensional anatomical information on this organ system in all vertebrate groups (including humans) relative to other regions of the body. We present some of the challenges associated with evaluating and visualizing the vertebrate respiratory system using computed and micro-computed tomography and its subsequent digital segmentation. We discuss common mistakes to avoid when imaging deceased and live specimens and various methods for merging manual and threshold-based segmentation approaches to visualize pulmonary tissues across a broad range of vertebrate taxa, with a particular focus on sauropsids (reptiles and birds). We also address some of the recent work in comparative evolutionary morphology and medicine that have used these techniques to visualize respiratory tissues. Finally, we provide a clinical study on COVID-19 in humans in which we apply modeling methods to visualize and quantify pulmonary infection in the lungs of human patients.

Architecture of the bronchial tree in Cuvier's dwarf caiman (Paleosuchus palpebrosus).

We imaged the lungs of five Cuvier's dwarf caiman (Paleosuchus palpebrosus) via computed tomography (CT) and micro-computed tomography (µCT) and compared these data to the lungs of the American alligator (Alligator mississippiensis). These data demonstrate anatomical commonalities between the lungs of P. palpebrosus and A. mississippiensis, and a few notable differences. The structural similarities are (a) a proximally narrow, distally widened, hook-shaped primary bronchus; (b) a cervical ventral bronchus that branches of the primary bronchus and immediately makes a hairpin turn toward the apex of the lung; (c) a sequential series of dorsobronchi arising from the primary bronchus caudal to the cervical ventral bronchus; (d) intraspecifically highly variable medial sequence of secondary airways; (e) sac-like laterobronchi; and (f) grossly dead-ended caudal group bronchi in the caudal and ventral aspects of the lung. The primary differences between the two taxa are in the overall number of large bronchi (fewer in P. palpebrosus), and the number of branches that contribute to the cardiac regions. Imaging data of both a live and deceased specimen under varying states (postprandial, fasting, total lung capacity, open to atmosphere) indicate that the caudal margin and position of the lungs shift craniocaudally relative to the vertebral column. These imaging data suggest that the smooth thoracic ceiling may be correlated to visceral movement during ventilation, but this hypothesis warrants validation. These results provide the scaffolding for future comparisons between crocodilians, for generating preliminary reconstructions of the ancestral crocodilian bronchial tree, and establishing new hypotheses of bronchial homology across Archosauria.

Anatomy, variation, and asymmetry of the bronchial tree in the African grey parrot (Psittacus erithacus).

The avian bronchial tree has a unique and elaborate architecture for the maintenance of unidirectional airflow. Gross descriptions of this bronchial arrangement have traditionally relied upon dissection and casts of the negative (air-filled) spaces. In this study, the bronchial trees of five deceased African grey parrots (Psittacus erithacus) were segmented from micro-computed tomography (µCT) scans into three-dimensional (3D) surface models, and then compared. Select metrics of the primary bronchi and major secondary branches in the µCT scans of 11 specimens were taken to assess left-right asymmetry and quantify gross lung structure. Analysis of the 3D surface models demonstrates variation in the number and distribution of secondary bronchi with consistent direct connections to specific respiratory air sacs. A single model of the parabronchi further reveals indirect connections to all but two of the nine total air sacs. Statistical analysis of the metrics show significant left-right asymmetry between the primary bronchi and the origins of the first four secondary bronchi (the ventrobronchi), consistently greater mean values for all right primary bronchus length metrics, and relatively high coefficients of variation for cross-sectional area metrics of the primary bronchi and secondary bronchi ostia. These findings suggest that the lengths of the primary bronchi distal to the ventrobronchi do not preserve lung symmetry, and that aerodynamic valving can functionally accommodate a wide range of bronchial proportions.