Introduction: Mechanical ventilation is a life-saving therapeutic tool for treating patients with impaired pulmonary function, yet it carries the risk of ventilator-induced lung injury (VILI). The primary barriers hindering more protective ventilation strategies are still insufficient knowledge and understanding of complex lung mechanics, mainly due to the limited ability for in vivo measurement or imaging techniques. To shed light into this issue, great efforts have been made in developing computational lung models. However, most of these works only focus on studying the effects of ventilation on tissue strains and stresses, while coupling with the pulmonary circulation is mostly neglected so far. This is despite the fact that the lungs’ main function, gas exchange, takes place through a dense network of blood vessels in the alveolar walls, and damage caused by improper ventilation is characterized by the impairment of this vital interface.
Materials and
Methods: We present a novel physics-based computational model for capturing the complex interplay of the respiratory and circulatory systems of the human lungs, including gas exchange. The coupled modeling follows a poroelastic media approach. On the one hand, it builds upon a powerful class of models we have developed for tumor growth modeling in recent years. On the other hand, it extends our rather unique and clinically tested computational lung model, which has been developed and continuously improved over the past two decades. Motivated by the structure of the lungs, larger airways and blood vessels are modeled as discrete zero-dimensional (0D) networks that are embedded into the three-dimensional (3D), multiphase porelastic medium, representing the smaller airways, smaller blood vessels, and lung tissue. Further, the respiratory gases, oxygen, and carbon dioxide are modeled as chemical subcomponents of air and blood with a suitable exchange model in the porous domain. To connect the homogenized and the discrete representations of airways and blood vessels, respectively, we developed a 0D-3D coupling method that allows a non-matching spatial discretization of both domains.
Results, Conclusions, and Discussions: After showing the details of the approach, we first demonstrate the feasibility and correctness of the model and the implementation with a well-defined academic test example that includes all essential aspects of the model, i.e. the multiphase model for the lung parenchyma, a small part of the pulmonary circulation as well as a small part of the reduced dimensional airway tree, as well as all coupling effects. After that, the potential and applicability will be demonstrated via the application to a fully coupled model of a real human lung. In conclusion, we will demonstrate that such a comprehensive coupled approach allows us to study the complex interplay of tissue deformation and perfusion, including pathological conditions such as transcapillary leakage - a hallmark of VILI - and its effects on oxygenation and carbon dioxide release. We consider our model to be a promising base for investigating clinically relevant questions, which will contribute to improved treatment in respiratory care.
Acknowledgements (Optional): We gratefully acknowledge financial support by European Research Council via the ERC Advanced Grant "BREATHE - Unlocking vital mysteries in respiratory biomechanics" (grant agreement No. 101021526-BREATHE).
