<b>Purpose</b> Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. The standard method for assessing lung function in COPD is spirometry, which provides global lung function information but is a poor predictor of disability and quality of life. The overall aim of this thesis is to develop utility of hyperpolarised xenon gas magnetic resonance imaging (HP ¹²⁹Xe-MRI) as a technique to evaluate regional lung function. <b>Methods</b> Studies were approved by the National Research Ethics Service (NRES). Eleven volunteers and 25 patients with COPD underwent HP ¹²⁹Xe-MRI, pulmonary function tests (PFTs) and quantitative computerised tomography (QCT). Gravitational-dependent gradients of HP ¹²⁹Xe-MRI were compared between prone and supine postures in healthy volunteers. Lobar quantification of HP ¹²⁹Xe-MRI was completed in COPD patients, who also underwent time-resolved HP ¹²⁹Xe-MRI and HP ¹²⁹Xe-MRI pre- and post-salbutamol to determine feasibility of detecting regional delayed ventilation and post-intervention change. The relationship between study measures was assessed using Pearson's correlation coefficient. <b>Results</b> HP ¹²⁹Xe-MR ventilation gradients were more marked in the supine than prone posture in healthy volunteers, whereas diffusion-weighted gradients were more uniform. HP ¹²⁹Xe-MRI was successfully quantified according to pulmonary lobes and correlated with lobar lung anatomy (QCT) and global functional transfer capability (TLCO) (r=-0.61, p&LT;0.005). Delayed ventilation was observed with time-resolved breath-hold HP ¹²⁹Xe-MRI. Differential regional ventilation change was detected with HP ¹²⁹Xe-MRI post-salbutamol. <b>Conclusion</b> These data demonstrate technical optimisation of HP ¹²⁹Xe-MRI in healthy volunteers and COPD patients. Successful generation of lobar HP ¹²⁹Xe-MRI parameters offers an automated analysis method that can be adopted into the clinical workflow. Finally proof-of-principle data have identified roles for HP ¹²⁹Xe-MRI in evaluating regional treatments and assessing therapeutic response. Future work will evaluate the role of HP ¹²⁹Xe-MRI in patient selection for lung volume reduction therapy and as a surrogate end-point in drug development studies.

Chronic obstructive pulmonary disease (COPD) describes a range of lung conditions including emphysema, chronic bronchitis and small airways disease. While COPD is a major cause of death and debilitating illness, current clinical assessment methods are inadequate: they are a poor predictor of patient outcome and insensitive to mild disease. A new imaging technology, hyperpolarised xenon MRI, offers the hope of improved diagnostic techniques, based on regional measurements using functional imaging. There is a need for quantitative analysis techniques to assist in the interpretation of these images. The aim of this work is to develop these techniques as part of a clinical trial into hyperpolarised xenon MRI. In this thesis we develop a fully automated pipeline for deriving regional measurements of lung function, making use of the multiple imaging modalities available from the trial. The core of our pipeline is a novel method for automatically segmenting the pulmonary lobes from CT data. This method combines a Hessian-based filter for detecting pulmonary fissures with anatomical cues from segmented lungs, airways and pulmonary vessels. The pipeline also includes methods for segmenting the lungs from CT and MRI data, and the airways from CT data. We apply this lobar map to the xenon MRI data using a multi-modal image registration technique based on automatically segmented lung boundaries, using proton MRI as an intermediate stage. We demonstrate our pipeline by deriving lobar measurements of ventilated volumes and diffusion from hyperpolarised xenon MRI data. In future work, we will use the trial data to further validate the pipeline and investigate the potential of xenon MRI in the clinical assessment of COPD. We also demonstrate how our work can be extended to build personalised computational models of the lung, which can be used to gain insights into the mechanisms of lung disease.