Unlocking vital mysteries in respiratory biomechanics

While the human lung is undoubtedly an essential organ, and respiratory diseases are leading causes of death and disability in the world, there still exist a lot of mysteries wrt vital processes. The main reason for this is the complete lack of measurement methods or medical imaging techniques that would allow to study dynamic processes in essential parts of a living human lung. While this would be a perfect setup for computational modeling, existing models suffer from severe constraints disabling them to unveil those essential secrets. This project aims to build on a number of most promising recent advances in modeling and high-performance simulation to present the first comprehensive computational model of the respiratory system. For this purpose, it builds upon a recent exascale-ready incompressible flow solver, toughen it up for lung specific challenges and enrich it with multiphysics capabilities to capture tissue interaction and gas transport. Parts of the respiratory zone will be represented by multiphase poroelastic media and novel pleural boundary conditions will be developed. The coupled pulmonary circulation will be included and represented by an embedded reduced dimensional network and additional phases. In order to appropriately individualize the model and also being able to adapt it during disease progression, a novel physics-based probabilistic learning approach will be developed. This will allow to use most of the very diverse and scarce data in clinical settings. Finally, special models will be developed to bridge to the micro scale. The models developed and studied here will provide unprecedented insights for biomedical scientists, and practitioners at the same time, and will help to substantially reduce elaborate animal and multicenter studies. This will be a crucial step in order to establish a shift of paradigm in health care. Novel models/tools developed here will also be very useful in other areas of biomedical engineering and beyond.

Main focus in the beginning was to recruit excellent people and then, as all the topics of the proposal are not covered in any standard curriculum, to bring them up to a level needed for the high quality science that is intended. The main tasks that have been the focus so far are listed in the following, together with some keywords on innovative achievements that have already been realized so far):
WP1:
- realization of both H-DIV conforming elements as well as simplex elements for our HPC CFD code, that will be beneficial for air flow simulations in the lung
- design of novel concept of highly efficient matrix-free approaches for (fluid-structure) couple approaches
- high performance approach for Darcy flow (based on matrix free DG)
WP2:
- development and implementation of two novel poroelastic approaches for lungs (one for a two-phase model based on velocity and pressure and a general multiphase and multispecies model purely pressure based)
- formulation for highly anisotropic and inhomogeneous (to capture effects of airway trees) poroelasticity
- embedding of airway networks into 3D poroelastic continuum models for lung tissue
- embedding and coupling withe/to pulmonary circulation
- development of a novel novel alveolar recruitment/derecruitment model
WP3:
- development of improved approaches for inverse analysis
- first steps for adapting such approaches to special multiphysics models
- combination of such approaches to automatically identify model parameters for patients for reduced dimensional models of the respiratory system
WP4:
- first steps to model collagen fibers taking into account intermolecular effects
- approach to embed nonlinear fiber models into 3D continua tissue models

For progress see above and the expected results are still as ambitious as in the original proposal.

Periodic Reporting for period 1 - BREATHE (Unlocking vital mysteries in respiratory biomechanics)

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