Abstract
This thesis describes two applications of magnetic resonance imaging (MRI) of spin-polarized (i.e. hyperpolarized) noble gases. One application is to explore the feasibility of using inertial confinement fusion (ICF) polymer shells to load and seal in spin-polarized <sup>3</sup>He suitable for cryogenic injection into the plasma core of a tokamak fusion reactor. This feasibility study is a step towards the first proof-of-principle <em>in-situ</em> test of polarization survival, inside the DIII-D tokamak. The other application is in lung imaging of human subjects with chronic obstructive pulmonary disease (COPD). In this research study, we use apparent diffusion coefficient (ADC) measurements obtained from diffusion-weighted MRI of inhaled hyperpolarized <sup>3</sup>He and <sup>129</sup>Xe to characterize emphysema, a smoking-induced chronic disease responsible for destruction of lung parenchymal tissue.
The main objectives of the feasibility study of ICF polymer shells in loading of spin-polarized <sup>3</sup>He were to determine (1) the polarization loss inherent to permeation through the shell wall, (2) the absolute polarization of the gas that has been loaded into the pellet, and (3) how fast the polarization decays after it has been loaded. For these measurements, we used nuclear magnetic resonance (NMR) and MRI techniques to measure the signal generated by the polarized helium gas during and after the permeation process, using a 1.5-Tesla clinical MRI scanner.
We developed a mathematical model that describes the polarization density of the helium gas inside and outside the pellet as a function of time. We then determined the measured signal evolution to our model. We report 81% ± 2 and 62% ± 2 polarization retention in the permeation process for shells with wall thickness of 15 μm and 26 μm, respectively. To determine the absolute polarization of the helium sealed inside the polymer shell, we calibrated the MRI signal obtained from hyperpolarized <sup>3</sup>He to the signal obtained from thermally polarized <sup>3</sup>He inside the precisely known field strength of a clinical 1.5-Tesla scanner. We measured the absolute polarization of iii the permeated <sup>3</sup>He sealed inside a 15-μm shell to be 22.1% ± 1.1 , with starting polarization of ~48%, prior to the permeation process. The T<sub>1</sub> of the polarized helium inside the shell at 77 K is 83 hours ±10.
In the diffusion-weighted lung MRI project, we introduced and tested a quantitative framework within which to characterize emphysema burden based on hyperpolarized <sup>3</sup>He and <sup>129</sup>Xe ADC maps and compared its diagnostic performance with CT-based emphysema metrics and pulmonary function tests. Twenty-seven patients with mild, moderate, or severe COPD and 13 age-matched healthy control subjects participated in this study. Participants underwent CT and multiple <em>b</em>-value diffusion-weighted <sup>3</sup>He and <sup>129</sup>Xe MRI examinations and standard pulmonary function tests. ADC-based emphysema index was computed separately for each gas and <em>b</em>-value as the fraction of lung voxels with ADC values greater than in the healthy group 99<sup>th</sup> percentile. The resulting values were compared with quantitative CT results (relative lung area , < -950 HU) as the reference standard.
We found that emphysema indices based on <sup>3</sup>He and <sup>129</sup>Xe ADC were strongly correlated (r = 0.95, P < .001) and both showed strong correlation with relative lung area with low attenuation (RA) on CT images (r ≥ 0.85, P < .001). The <sup>3</sup>He-based and <sup>129</sup>Xe-based ADC emphysema indices were also highly repeatable (intraclass correlation coefficient > 0.99) and showed highly significant differences between healthy, mild-moderate, and severe COPD groups, independent of the <em>b</em>-values used (P < .01). Both <sup>3</sup>He-based and <sup>129</sup>Xe-based ADC emphysema indices were also correlated with pulmonary function metrics used to characterize emphysema, including diffusing capacity of lung for carbon monoxide (r ≥ 0.80, P < .001) and residual lung volume divided by total lung capacity (r ≥ 0.61, P < .002), with a degree of correlation similar to that of quantitative CT (r ≥ 0.57, P < .001). We conclude that emphysema index based on hyperpolarized <sup>3</sup>He or <sup>129</sup>Xe diffusion MRI provides a robust and highly repeatable measure of emphysema burden that may offer higher sensitivity to early stage lung disease than quantitative CT or standard pulmonary function metrics.
