Date of Award
Doctor of Philosophy (PhD)
Magnetic resonance imaging (MRI) is a modality that utilizes the phenomenon of nuclear magnetic resonance (NMR) to yield tomographic images of the body. Proton (1H) MRI has historically been successful in soft tissues but has suffered in the lung due to a variety of technical challenges, such as the low proton-density, rapid T2* relaxation time of the lung parenchymal tissue, and inherent physiological motion in the chest. Recent developments in radial ultrashort echo time (UTE) MRI have in part overcome these issues. In addition, there has been much progress in techniques for hyperpolarization of noble gases (3He and 129Xe) out of thermal equilibrium via spin exchange optical pumping, which can greatly enhance the gas NMR signal such that it is detectable within the airspaces of the lung on MRI.
The lung is a unique organ due to its complex structural and functional dynamics, and its early development through the neonatal (newborn) period is not yet well understood in normal or abnormal conditions. Pulmonary morbidities are relatively common in infants and are present in a majority of patients admitted to the neonatal intensive care unit, often stemming from preterm birth and/or congenital defects. Current clinical lung imaging in these patients is typically limited to chest x-ray radiography, which does not provide tomographic information and so has lowered sensitivity. More rarely, x-ray computed tomography (CT) is used but exposes infants to ionizing radiation and typically requires sedation, both of which pose increased risks to pediatric patients. Thus the opportunity is ripe for application of novel pulmonary MRI techniques to the infant population. However, MR imaging of very small pulmonary structure and microstructure requires fundamental changes in the imaging theory of both 1H UTE MRI and hyperpolarized gas diffusion MRI. Furthermore, such young patients are often non-compliant, yielding a need for new and innovative techniques for monitoring respiratory and bulk motion.
This dissertation describes methodology development and provides experimental results in both 1H UTE MRI and hyperpolarized 3He and 129Xe gas diffusion MRI, with investigation into the structure and function of infant lungs at both the macrostructural and microstructural level. In particular, anisotropically restricted gas diffusion within infant alveolar microstructure is investigated as a measurement of airspace size and geometry. Additionally, the phenomenon of respiratory and bulk motion-tracking via modulation of the k-space center's magnitude and phase is explored and applied via UTE MRI in various neonatal pulmonary conditions to extract imaging-based metrics of diagnostic value. Further, the proton-density regime of pulmonary UTE MRI is validated in translational applications. These techniques are applied in infants with various pulmonary conditions, including patients diagnosed with bronchopulmonary dysplasia, congenital diaphragmatic hernia, esophageal atresia/tracheoesophageal fistula, tracheomalacia, and no suspected lung disease. In addition, explanted lung specimens from both infants with and without lung disease are examined.
Development and implementation of these techniques involves a strong understanding of the physics-based theory of NMR, hyperpolarization, and MR imaging, in addition to foundations in hardware, software, and image analysis techniques. This thesis first outlines the theory and background of NMR, MRI, and pulmonary physiology and development (Part I), then proceeds into the theory, equipment, and imaging experiments for hyperpolarized gas diffusion MRI in infant lung airspaces (Part II), and finally details the theory, data processing methods, and applications of pulmonary UTE MRI in infant patients (Part III). The potential for clinical translation of the neonatal pulmonary MRI methods presented in this dissertation is very high, with the foundations of these techniques firmly rooted in the laws of physics.
Chair and Committee
Jason Mark C. Woods Conradi
Sophia E. Hayes, James G. Miller, Shankar Mukherji,
Higano, Nara Savoye, "Investigation of Neonatal Pulmonary Structure and Function via Proton and Hyperpolarized Gas Magnetic Resonance Imaging" (2017). Arts & Sciences Electronic Theses and Dissertations. 1203.