| Emphysema is a major public health concern resulting in significant morbidity and mortality. Current technologies for assessing emphysema are insensitive to early disease, and the development of new medical treatments will necessitate novel sensitive methods for evaluating emphysematous changes in the lung.; Hyperpolarized 3He gas is a new magnetic resonance imaging (MRI) contrast agent which enables visualization of gas-filled structures, such as the lung, following laser polarization of the gas. By taking advantage of the high self-diffusion coefficient of 3He, the MR technique can be modified to be sensitive to the restriction of the gas motion by the microstructure. Thereby, the apparent diffusion coefficient (ADC) of the gas can be measured, serving as a new contrast mechanism for assessing lung microstructure.; The goal of this dissertation project was to develop and understand methods for measuring the ADC in the human lung, and to apply these methods for the regional assessment of microstructural changes. A theoretical framework was developed through stochastic, numerical and image-based simulations to provide insight into the properties of ADC measurement in the presence of noise. To characterize fundamental properties of hyperpolarized-gas-based ADC imaging, measurements were made in a phantom designed to approximate free diffusion, and a packed-glass bead phantom to simulate diffusion in a restricting medium. The results of these studies provided insight into the measurement of ADC values in the human lung.; Measurements in healthy and emphysema subjects characterized the anisotropy and time-dependence of ADC values, and helped determine appropriate MR pulse sequence parameters for human imaging. The ADC parameters were statistically significantly different between our healthy and emphysema groups. Furthermore, the ADC showed regional variations of disease within the lung and correlated with spirometry and CT. As current implementations of 3He-diffusion imaging cannot assess the whole lung volume for subjects with ventilatory compromise, we developed an interleaved-spiral pulse sequence capable of assessing ADC values over the whole lung volume in a clinically acceptable breath hold of 10 seconds. This research has demonstrated that measurement of the ADC in the human lung is a promising new tool for differentiating healthy from emphysematous parenchyma. |
