Towards a virtual lung: multi-scale, multi-physics modelling of the pulmonary system

Abstract

The essential function of the lung, gas exchange, is dependent on adequate matching of ventilation and perfusion, where air and blood are delivered through complex branching systems exposed to regionally varying transpulmonary and transmural pressures. Structure and function in the lung are intimately related, yet computational models in pulmonary physiology usually simplify or neglect structure. The geometries of the airway and vascular systems and their interaction with parenchymal tissue have an important bearing on regional distributions of air and blood, and therefore on whole lung gas exchange, but this has not yet been addressed by modelling studies. Models for gas exchange have typically incorporated considerable detail at the level of chemical reactions, with little thought for the influence of structure. To date, relatively little attention has been paid to modelling at the cellular or subcellular level in the lung, or to linking information from the protein structure/interaction and cellular levels to the operation of the whole lung. We review previous work in developing anatomically based models of the lung, airways, parenchyma and pulmonary vasculature, and some functional studies in which these models have been used. Models for gas exchange at several spatial scales are briefly reviewed, and the challenges and benefits from modelling cellular function in the lung are discussed.

Figure 1

Volumetric FE mesh of the left lung derived from geometry fitting to imaging data. The surfaces of the geometry-fitted CT-defined airways are in dark grey. Note that models of the lung and airway are fitted to imaging data from a single individual. The models can be used in independent studies, or in studies that consider interaction between tissue and airway.

Figure 2

Subject-specific models generated to represent the human conducting airway tree for an imaged subject. (a) Left upper (yellow) and left lower (orange) lobe-generated airways, viewed from the r.h.s. (b) Airways generated in all five lobes using a VFB method, with CT-defined airway surfaces (grey). (c) Right upper (green), right middle (red) and right lower (blue) lobe-generated airways.

Figure 3

Illustration of previous perfusion predictions across multi-scale circulatory models from the arteries (Burrowes & Tawhai 2006) to the capillary network (Burrowes et al. 2004). The colour spectrum ranges from red (highest flow) to dark blue (lowest flow). (a) Flow predictions at terminal vessel locations in the arterial model plotted with respect to vertical height. Results are averaged within 1 mm (blue circles) and 50 mm (black line) slices. (b) Flow solutions (relative to mean) in the isolated capillary model plotted with respect to gravitationally dependent height. Experimental flow data are included from supine dogs (green down triangles and grey up triangles; Hogg et al. 1985), upright baboons (blue line; Glenny et al. 1999) and supine pigs (black circles; Glenny et al. 2000). Pink diamonds, model results.