How high resolution 3-dimensional imaging changes our understanding of postnatal lung development

Abstract

During the last 10 + years biologically and clinically significant questions about postnatal lung development could be answered due to the application of modern cutting-edge microscopic and quantitative histological techniques. These are in particular synchrotron radiation based X-ray tomographic microscopy (SRXTM), but also 3Helium Magnetic Resonance Imaging, as well as the stereological estimation of the number of alveoli and the length of the free septal edge. First, the most important new finding may be the following: alveolarization of the lung does not cease after the maturation of the alveolar microvasculature but continues until young adulthood and, even more important, maybe reactivated lifelong if needed to rescue structural damages of the lungs. Second, the pulmonary acinus represents the functional unit of the lung. Because the borders of the acini could not be detected in classical histological sections, any investigation of the acini requires 3-dimensional (imaging) methods. Based on SRXTM it was shown that in rat lungs the number of acini stays constant, meaning that their volume increases by a factor of ~ 11 after birth. The latter is very important for acinar ventilation and particle deposition.Electronic supplementary materialThe online version of this article (10.1007/s00418-018-1749-7) contains supplementary material, which is available to authorized users.

Assessment of the Alveolar Capillary Network in the Postnatal Mouse Lung in 3D Using Serial Block-Face Scanning Electron Microscopy

“…This double-layered capillary network is believed to be formed by intussusceptive angiogenesis (Schittny et al, 2008; Ackermann et al, 2013). More recent work has led to the concept that even after micro-vascular maturation, alveolarization continues to take place and that a new layer of the ACN is rather formed by sprouting than intussusception (Schittny et al, 2008; Schittny, 2018). Tissue pillars that match the description of intussusceptive pillars can be found in the presented dataset (Figure 9), but their exact role in angiogenesis and lung development is still unclear (Spiegelaere et al, 2012).…”

Stereology as the 3D tool to quantitate lung architecture

“…Three-dimensional imaging of the lung not only gave important insights into the pathophysiology of human lung diseases but also into postnatal lung development (Schittny 2018 ). High resolution, synchrotron radiation-based X-ray tomography has been shown to be useful to identify the bronchiole-alveolar duct junction in rat lungs allowing segmentation of complete acini and investigation of the internal acinar structure including the branching pattern of intra-acinar pathways (Haberthür et al 2013 ).…”

The Development of Integrin Alpha-8 Deficient Lungs Shows Reduced and Altered Branching and a Correction of the Phenotype During Alveolarization

“…Mostly postnatally in rodents and human the gas exchange surface of the lungs is enlarged during alveolarization; new septa are lifted off of pre-existing ones subdividing the most distal airspaces ( Mund et al, 2008 ; Schittny et al, 2008 ). Alveolarization is a process, which does not finish during early childhood but continues until young adulthood (for a review see Schittny, 2017 , 2018 ). Throughout lung postnatal development of rodents the size of the alveoli first decreases and later increases ( Mund et al, 2008 ; Tschanz et al, 2014 ).…”