Grant: Discovery Grants Program - Individual

Recent advances in lung imaging using conventional and inhaled gas magnetic resonance imaging (MRI) have accelerated the acquisition of high-resolution, three-dimensional non-invasive in vivo lung measurements that until now have never been possible. ******Our current understanding of lung tissue architecture and morphology derive from stereiological investigations of excised tissue, typically from cadavers or explanted lungs from patients undergoing transplant. Such measurements are typically focused on diseased lung and may be biased because of the methods used to generate these samples. Another approach involves micro-CT of ex vivo tissue samples and this provides the advantage of 3-dimensional sampling. Unfortunately, neither histology, nor micro-CT of excised samples can be used for large studies of normal physiology and the developing lung because they rely on the excised samples which is highly invasive and carries some risk. Another approach is to model the lung components as a regionally uniform system of airways (resistors) and airspaces (capacitors). Such lung micromechanical models have been derived mainly using pressure and flow measurements at the mouth or using retrograde catheters implanted at the end of the trachea of excised lungs. Despite the importance of these approaches and the huge body of work that provide their strong foundation, it has not been possible to incorporate regional functional lung information to interrogate these models or to assist in their development. This is a critical limitation because it is well understood that the lung is in fact, a regionally heterogeneous organ. ******Therefore there has been, for decades, a significant unmet need for lung regional morphological information derived from physiologically-relevant in vivo measurements for inclusion in mathematical models of lung micromechanics. To directly address this decades-old problem, we propose to develop new ways to generate and incorporate in vivo lung imaging measurements of airway and airspace structure into existing models of lung growth, development and micromechanics and to develop new models and test these using regional imaging information. ******Therefore, in this proposal we will develop new ways to use lung imaging measurements to generate models of lung development and biomechanics. Over 5 years, we will: 1) improve spatial and temporal resolution of pulmonary MRI using novel pulse sequences, 2) derive alveolar and 3) airway dimensions in different lung states and conditions, and, 4) incorporate and validate regional imaging measurements into computational models. This research provides a way to test and validate imaging measurements for the generation of novel micromechanical models of the lung and highly qualified personnel for academia and the private sector in medical imaging, MR pulse sequence development, lung tissue generation, molecular modelling and computer science. **