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Title: Multi-nuclear magnetic resonance imaging in the longitudinal assessment of idiopathic pulmonary fibrosis
Author: Weatherley, Nicholas David
ISNI:       0000 0004 7651 6126
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2018
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Idiopathic Pulmonary Fibrosis (IPF) is a lung scarring disease of old age, with a median life expectancy of 2-5 years. In spite of recent advances in our understanding of disease pathophysiology and the recent introduction of two efficacious antifibrotic agents, IPF remains a fatal disease, which is difficult to prognosticate. Low sensitivity of current markers of disease such as forced vital capacity (FVC) and carbon monoxide gas transfer (TLCO) contributes to this and so novel biomarkers have the potential to better understand disease progression. In this work, the potential role of hyperpolarised gas magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE) MRI is explored. Hyperpolarised 3- Helium (3He) ventilation MRI demonstrates interesting qualitative findings, including a sensitivity to small airway pathology and some features of IPF, including traction bronchiectasis and tracheomegaly. Ventilation heterogeneity does not appear to change and ventilation defects in IPF are more likely due to be attributable to co-existing airways disease, or possibly a physiological process of aging. 3He Diffusion-weighted MRI (DW-MRI) metrics show a correlation with TLCO and regions of increased Brownian motion are likely attributable to honeycombing and the bronchiolisation process, reflecting increased volume to surface area. Modelling of the diffusion-weighted signal generates mean linear intercept distances (LmD), a parallel to metrics used in histology. These demonstrate an increase over 12-months, suggesting progression of disease. 129-Xenon (129Xe) spectroscopy techniques were explored for the assessment of alveolar gas exchange. Chemical shift saturation recovery (CSSR) based metrics have previously demonstrated good reproducibility and correlation with clinical outcomes in chronic obstructive pulmonary disease, but in this IPF cohort were irreproducible. However, the red blood cell to tissue / plasma ratio (RBC:TP) derived from high-resolution spectroscopy was reproducible, correlated with TLCO, and demonstrated progression over 6 and 12 months, even where TLCO is static. Dynamic contrast-enhanced 1H MRI provides a means for measuring transit times through the pulmonary circulation which also shows progression over 12-months. This may provide a non-invasive means of pulmonary haemodynamic assessment, helping to identify patients at risk of developing pulmonary hypertension. It may also be used alongside existing and novel physiological data to assess perfusion and diffusion limitation of gases.
Supervisor: Wild, Jim M. ; Renshaw, Stephen A. ; Bianchi, Stephen M. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available