Exp Physiol 91.2 pp 285–293 285 Experimental Physiology – Modelling of Biological Systems Computational models of structure–function relationships in the pulmonary circulation and their validation Merryn H. Tawhai 1 , Kelly S. Burrowes 1 and Eric A. Hoffman 2 1 Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand 2 Departments of Radiology and Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA The pulmonary airway, arterial, venous and capillary networks are vast complex branching and converging systems that are mechanically coupled to the surrounding lung tissue. Early studies that examined vascular or airway geometry relied on measurements from casts, but medical imaging now enables measurement of the lung in vivo, at controlled lung volumes. The high- quality data that imaging provides have prompted development of increasingly sophisticated models of the geometry of the airway and pulmonary vascular trees. The accurate spatial relationships between airway, vessel and tissue in these imaging-derived models are necessary for computational analysis that aims to elucidate regional airway–vessel–tissue interactions. Predictions of blood flow through multiscale imaging-derived models of the pulmonary arteries and capillary bed reveal geometry-dependent patterns of perfusion in response to gravity and lung orientation that cannot be predicted with simplified, summary representations of the pulmonary transport trees. Validation of such predictions against measures from functional imaging holds significant potential for explaining and differentiating normal and disease-related heterogeneity in regional blood flow calculated using perfusion imaging. (Received 5 October 2005; accepted after revision 2 January 2006; first published online 11 January 2006) Corresponding author M. H. Tawhai: Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand. Email: m.tawhai@auckland.ac.nz To accomplish respiratory gas exchange, the mammalian lung comprises several major transport systems – the pulmonary airways, arteries and veins – that function to bring air and blood into close contact at a vast surface for gas exchange. The airway system includes conducting airways that do not take part in respiratory gas exchange but can exchange highly soluble gases with the bronchial circulation and act to humidify air that enters the lung at less than body temperature and saturation with water vapour, and respiratory airways that have their ‘walls’ comprised of openings to pulmonary alveoli. The alveolar septa are covered in an extremely dense network of capillaries; the fragile barrier between alveolar gas and blood comprises a single layer of epithelial cells lining the alveoli, the interstitium which accommodates the connective tissue fibres and basement membranes, and a single layer of endothelial cells that form the major component of the capillary wall (Weibel, 1984). The transport systems can be considered to be ‘embedded’ within the pulmonary parenchyma, or suspended in a vast fibre network as described by Weibel (1984). The fibre system initiates at the hilum and extends through the lung to the visceral pleura. The ‘axial’ fibre system begins at the main stem bronchus and progresses with the airways to the terminal bronchioles. The ‘peripheral’ fibre system is related to the visceral pleura and enwraps the lobar units. The pulmonary venous network follows the peripheral fibre system (between airways and arteries), while the arterial system follows the airways and therefore the axial fibre system. The axial fibre system continues into the respiratory tissue, encircling the entrances to the alveoli, and extending a fine fibre network over the alveolar septal surfaces and weaving through the capillary meshwork. An accurate and detailed representation of geometry in computational models of anatomical structures is essential to deliver meaningful results from numerical simulations. Because the lungs are comprised of several mechanically and functionally coupled subsystems, computational models of the lung must vary in structure over a range of scales of interest. The model structure is also dependent on the problem to which it is applied: fluid-flow simulation requires three-dimensional meshes that accurately represent the complex surface airway C  2006 The Authors. Journal compilation C  2006 The Physiological Society DOI: 10.1113/expphysiol.2005.030957