Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Dr. Grace Parraga

Abstract

Obstructive lung diseases such as chronic-obstructive-lung-disease (COPD), bronchiectasis, and asthma are characterized by airflow obstruction. They affect over six million Canadians costing the economy $12 billion/year. Despite decades of research, therapies that modify obstructive-lung-disease progression and control are lacking because patient diagnosis, monitoring, and response to therapy are currently made using airflow measurements that may conceal the independent contributions of underlying pathologies. One goal of obstructive-lung-disease research is to develop ways to identify patients with specific underlying pathological phenotypes to improve patient care and outcomes. Thoracic computed-tomography (CT) and magnetic-resonance-imaging (MRI) provide ways to regionally identify the underlying pathologies associated with obstructive-lung-disease, and offer quantitative biomarkers of obstructive-lung-disease (e.g. lung-density, airway dimensions, ventilation abnormalities, and lung microstructure). As the first step to identify patients with specific underlying pathological phenotypes, it is important to understand the physiological and clinical consequences of these imaging derived measurements. Accordingly, our objective was to evaluate lung structure and function using multi-nuclear pulmonary MRI in aging and obstructive-lung-disease to provide a better understanding of MR-derived biomarkers. In older never-smokers, the majority of subjects had 3He MR ventilation abnormalities that were not responsive to bronchodilation. 3He ventilation abnormalities were related to airflow obstruction and airways resistance, but not occupational exposure or exercise limitation. We then developed and evaluated ultra-short-echo-time MRI in COPD subjects with and without bronchiectasis. This work demonstrated that ultra-short-echo-time MR-derived measurements were reproducible and significantly related to CT tissue-density measurements. In the COPD subjects with bronchiectasis, ultra-short-echo-time signal-intensity was related to airway measurements. In COPD subjects without bronchiectasis, ultra-short-echo-time signal-intensity was related to the severity of emphysema. Finally, based on the ultra-short-echo-time MR biomarkers developed in patients with COPD and bronchiectasis, patients that share some of the airway and inflammatory features common in asthmatics, we produced ultra-short-echo-time MR measurements in asthma. These measurements not only provided similar information as CT, but also information about regional ventilation deficits. These results demonstrated that ultra-short-echo-time MR biomarkers may reflect ventilation heterogeneity and/or gas-trapping in asthma. These important findings indicate that multi-nuclear pulmonary MRI has the potential to quantitatively evaluate the different pathologies of obstructive-lung-disease.

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