Functional Imaging of the Lungs using Magnetic Resonance Imaging of Inert Fluorinated Gases

Abstract

Fluorine-19 (19F) magnetic resonance imaging (MRI) of the lungs using inhaled inert fluorinated gases can potentially provide high quality anatomical and functional images of the lungs. This technique is able to visualize the distribution of the inhaled gas, similar to hyperpolarized (HP) helium-3 (3He) and xenon-129 (129Xe) MRI. Inert fluorinated gases have the advantages of being nontoxic, abundant, and inexpensive compared to HP gases. Due to the high gyromagnetic ratio of 19F, there is sufficient thermally polarized signal for imaging, and averaging within a single breath-hold is possible due to short longitudinal relaxation times. Since inert fluorinated gases do not need to be hyperpolarized prior to their use in MRI, this eliminates the need for an expensive polarizer and expensive isotopes. Inert fluorinated gas MRI of the lungs has been studied extensively in animals since the 1980s, and more recently in healthy volunteers and patients with lung diseases. This thesis focused on the development of static breath-hold inert fluorinated gas MR imaging techniques, as well as the development functional imaging biomarkers in humans and animal models of pulmonary disease. Optimized ultrashort echo time (UTE) 19F MR imaging was performed in healthy volunteers, and images from different gas breathing techniques were quantitatively compared. 19F UTE MR imaging was then quantitatively compared to 19F gradient echo imaging in both healthy volunteers and in a resolution phantom. A preliminary comparison to HP 3He MR imaging is also presented, along with preliminary 19F measurements of the apparent diffusion coefficient (ADC) and iv gravitational gradients of ventilation in healthy volunteers. The potential of inert fluorinated gas MRI in detecting pulmonary diseases was further explored by performing ventilation mapping in animal models of inflammation and fibrosis. Overall, interest in pulmonary 19F MRI of inert fluorinated gases is increasing, and numerous sites around the world are now interested in developing this technique. This work may help to demonstrate that inert fluorinated gas MRI has the potential to be a viable clinical imaging modality that can provide useful information for the diagnosis and management of chronic respiratory diseases.