Evaluation of Quantitative Imaging Biomarkers in Interstitial Lung Disease

Despite evidence that hyperpolarised 129-Xenon (129Xe) MRI, combined with proton MRI, is able to provide useful structural and functional data, its clinical application has been relatively limited in the field of interstitial lung disease (ILD). However, the insensitivity of pulmonary function tests (PFTs) in early disease, and the ability of hyperpolarised 129Xe MRI to assess regional lung function makes it an appealing tool to explore the diagnosis and monitoring of ILD. CT involves ionising radiation and is unable to provide functional data. It has some advantages over MRI in terms of its speed, image contrast and spatial resolution. Various automated, computer based, quantitative CT (QCT) analysis methods have been reported in ILD. The findings reported in this thesis represent the first known longitudinal data combining hyperpolarised 129Xe MRI and dynamic contrast enhanced (DCE) MRI with QCT alongside PFTs in various ILD subtypes. It also expands upon previous work involving these novel MRI techniques in idiopathic pulmonary fibrosis (IPF). 129Xe spectroscopy derived red blood cell / tissue plasma ratio (RBC:TP) was used in the assessment of alveolar gas exchange, showing a statistically significant change over 6 and 12 months in IPF subjects, despite relatively stable PFTs. 129Xe diffusion-weighted (DW) MRI techniques demonstrate increased Brownian gas diffusion in fibrotic ILD. This is likely due to microstructural changes in the distal airways and alveoli as a result of honeycombing and/or traction bronchiectasis. There was also evidence that DW-MRI measurements may have utility in the monitoring and prediction of disease progression. Changes in pulmonary perfusion over short time periods were found using DCE-MRI in subjects with hypersensitivity pneumonitis, suggesting potential value in demonstrating an early inflammation response to steroid therapy. As new drug treatments are developed, the ability to quantify subtle changes using QCT and functional lung MRI could be particularly valuable.