This project focused on the pulmonary application of magnetic resonance (MR) quantitative equilibrium signal (qS0) mapping, dynamic oxygen-enhanced (OE-) magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE-) MRI in asthma and chronic obstructive pulmonary disease (COPD). Initially, a retrospective analysis of MRI and X-ray computed tomography (CT) data from 24 COPD patients and 12 healthy controls demonstrated that MR qS0 mapping had good one-week reproducibility and was comparable to CT in the localization and quantification of emphysema in patients with COPD. In the same data, a reduced oxygen (O2) delivery signal was detected by dynamic OE-MRI in COPD patients regardless of the presence or absence of emphysema on CT, while a significantly reduced baseline spin-lattice relaxation time (T1air) was only observed in emphysematous COPD. Emphysematous COPD also showed significant correlations between dynamic OE-MRI readouts, i.e. enhancing fraction (EF) and the change in the partial pressure of O2 in lung parenchyma (DeltaPO2max), and pulmonary diffusion capacity and CT estimates of emphysema. A prospective pilot study was conducted in 10 asthmatic patients which demonstrated that dynamic OE-MRI readouts, including EF, DeltaPO2max and O2 wash-in time constant (τup), were reproducible within one month, sensitive to asthma severity and strongly correlated with spirometric readouts of airway function and lung volume. This was followed by a second prospective intervention study in 30 asthmatic patients and 10 healthy controls which revealed a pattern of decreased O2 delivery signal as a response to salbutamol inhalation in severe asthmatics but not in mild asthmatics or healthy controls using short-term repeated dynamic OE-MRI. In addition, DCE-MRI was also performed on 30 asthmatic patients and 10 healthy subjects. A semi-quantitative analysis demonstrated that contrast agent kinetics in asthmatic lungs were characterised by a reduced first-pass peak (SI%max) and a shallower downslope during the late redistribution phase (kwashout) than was observed in healthy controls, and that these were related to pulmonary function test measurements. An extended Tofts model-based quantitative analysis further revealed a significantly increased fractional extravascular extracellular space (ve) in patients with asthma than in healthy controls while the contrast agent transfer coefficient (Ktrans), an index related to vascular permeability, and the fractional blood plasma volume (vp), did not distinguish asthmatics from controls. In conclusion, this project demonstrated the promise of 1) MR qS0 mapping for the assessment of emphysema in COPD lungs, 2) dynamic OE-MRI for the assessment of impaired pulmonary oxygenation in COPD and asthma and for the monitoring of short-term treatment effects in asthma and 3) DCE-MRI for the evaluation of pulmonary microvascular inflammation in asthma. The non-invasive non-ionizing properties and simple setup requirements make these three proton MRI techniques attractive options in the assessment of structural and functional alterations of the lungs in asthma and COPD in clinical settings.
|Date of Award
|1 Aug 2015
- The University of Manchester
|Josephine Naish (Supervisor), Robert Niven (Supervisor) & Geoff Parker (Supervisor)
- Asthma, COPD, MRI, Proton, DCE-MRI, OE-MRI, Human