Machine learning modeling of lung mechanics: Assessing the variability and propagation of uncertainty in respiratory-system compliance and airway resistance.

Background And Objective: Traditional assessment of patient response in mechanical ventilation relies on respiratory-system compliance and airway resistance. Clinical evidence has shown high variability in these parameters, highlighting the difficulty of predicting them before the start of ventilation therapy. This motivates the creation of computational models that can connect structural and tissue features with lung mechanics. In this work, we leverage machine learning (ML) techniques to construct predictive lung function models informed by non-linear finite element simulations, and use them to investigate the propagation of uncertainty in the lung mechanical response.

Methods: We revisit a continuum poromechanical formulation of the lungs suitable for determining patient response. Based on this framework, we create high-fidelity finite element models of human lungs from medical images. We also develop a low-fidelity model based on an idealized sphere geometry. We then use these models to train and validate three ML architectures: single-fidelity and multi-fidelity Gaussian process regression, and artificial neural networks. We use the best predictive ML model to further study the sensitivity of lung response to variations in tissue structural parameters and boundary conditions via sensitivity analysis and forward uncertainty quantification. Codes are available for download at https://github.com/comp-medicine-uc/ML-lung-mechanics-UQ RESULTS: The low-fidelity model delivers a lung response very close to that predicted by high-fidelity simulations and at a fraction of the computational time. Regarding the trained ML models, the multi-fidelity GP model consistently delivers better accuracy than the single-fidelity GP and neural network models in estimating respiratory-system compliance and resistance (R∼0.99). In terms of computational efficiency, our ML model delivers a massive speed-up of ∼970,000× with respect to high-fidelity simulations. Regarding lung function, we observed an almost matched and non-linear behavior between specific structural parameters and chest wall stiffness with compliance. Also, we observed a strong modulation of airways resistance with tissue permeability.

Conclusions: Our findings unveil the relevance of specific lung tissue parameters and boundary conditions in the respiratory-system response. Furthermore, we highlight the advantages of adopting a multi-fidelity ML approach that combines data from different levels to yield accurate and efficient estimates of clinical mechanical markers. We envision that the methods presented here can open the way to the development of predictive ML models of the lung response that can inform clinical decisions.