Grant: Research Tools and Instruments

Our current understanding of lung microstructure and biomechanics derives mainly from stereological and micro-CT investigations of excised tissue from cadavers or explanted lungs. However, neither histology, nor micro-CT may be considered for large-scale studies of normal lung physiology because they rely on excised samples which is highly invasive and carries some risk. In silico mathematical lung models have also been constructed as a system with airways (resistors) and alveoli (capacitors) using pressure and flow measurements made at the mouth or catheters implanted at the trachea. These global lung measurements ignore very recent work that showed that the normal healthy lung is regionally heterogenous and this heterogeneity is enhanced in lung disease. In other words, there are non-stochastic differences and abnormalities that must be considered. Unfortunately, a lack of regional lung structural and functional information has made it difficult to incorporate regional dependencies into lung micromechanical models, and made it impossible to validate them. To directly address this decades-old problem, Dr Parraga's lab and her collaborators are developing new ways to incorporate in vivo lung imaging measurements into existing models of lung micromechanics, to develop new micromechanical models and to test and validate them. To accomplish this important goal, we require a state-of-the art radiofrequency (RF) MRI coil for high spatial resolution 129Xe inhaled-gas ventilation and diffusion-weighted measurements. This critically-needed infrastructure will drive the development and validation of novel lung imaging biomarkers the team will use to generate models of lung development and biomechanics. Daily access to a similar (and now catastrophically failed) radiofrequency coil has already played a critical role in our local and transnational research program. The new radiofrequency coil, once commissioned, will accelerate: 1) improved spatial and temporal resolution of pulmonary MRI using novel pulse sequences, 2) the acquisition of alveolar and airway dimensions in different lung states and conditions, and, 3) the incorporation and validation of regional imaging measurements into computational models. Due to the high throughput nature of our collaborative research, a custom-designed multichannel 129Xe MRI coil is required. Conversely, the lack of such equipment would significantly compromise our innovative basic research that aims to generate novel lung micromechanical models of normal and regenerated lung tissue in vivo. Moreover, this infrastructure will accelerate the training of highly qualified personnel for academia and the private sector in medical imaging, MR physics, lung tissue regeneration, molecular modelling and computer science including graduate students and postdoctoral fellows at Western, McMaster and Dalhousie Universities.