Lung disease is the third leading cause of mortality in the United States, has an economic impact of over $154 billion (USD) a year and in its chronic form impacts the lives of over 35 million Americans. Interstitial lung disease (ILD), which includes over 200 entities and involves volumetric as well as mechanical changes to lung parenchma is particularly problematic from both a clinical management as well as treatment perspective due to the dilema that, while clinical outcomes are well known, the underlying processes that govern them are not. Unfortunately, it is difficult to test hypotheses related to these processes because there is no practical method to directly measure and spatially resolve the local elastic (i.e. mechanical) properties of lung tissue in vivo. We propose to address this deficiency with a new technology known as magnetic resonance elastography (MRE) that uses phase-contrast magnetic resonance (MR) imaging of applied acoustic shear waves to map the mechanical properties of tissue in vivo. Attention will be initially focused on the development and mathematical modelling of new and novel methods for non-invasive shear wave generation and propagation within the lung on conventional (i.e. clinical) MR imaging systems. Mathematical inversion algorithms that generate elasticity maps will be applied to wave images to determine the optimal driver configuration for a variety of imaging conditions (pulse sequence type, lung volume, body habitus etc). Mathematical modelling will also be used to account for the widely-varying mass density of lung tissue by modelling the lung as a highly heterogeneous porous material. Finally, the sensitivity and specificity of this technique will be tested in a well established and characterized lung disease model. The overall hypothesis is that MRE can be implemented as a practical method for imaging the viscoelastic properties of lung tissue. Successful execution of this plan will yield a powerful new tool for studying the pathophysiology and natural history of ILD thereby facilitating the testing of important hypotheses relating to the timing, mechanism(s) of action, and effectiveness of therapies in not only ILD but all lung disease processes.
Significance While the outcome of interstitial lung disease is known - either full recovery or end stage fibrosis, the intermediate factors and/or trigger(s) that determine progression to either are not. As a result there is currently no reliable method for identification of responders or determining the appropriate timing of administration of targeted therapies. This proposal describes the development of a new magnetic resonance imaging based technique for characterizing these changes, thereby facilitating new treatment options and improved clinical care of interstitial lung disease patients.
