Reproducibility of Hyperpolarized Xenon-129 Magnetic Resonance Imaging

Spirometry and plethysmography provide gold standard measurements of obstructive lung disease, although these are global measurements of lung function made at the mouth, of a highly regionally heterogeneous disease. Hyperpolarized 129Xe magnetic resonance imaging (MRI) is a non-invasive, non-radiation-based imaging tool for visualizing regional lung structure and function. However, the reproducibility of 129Xe MRI measurements has not yet been studied or determined. Hence, in this thesis, we evaluated the reproducibility of 129Xe MRI using quantitative measurements such as ventilation defect percent (VDP). We showed that 129Xe VDP had high intra-observer and inter-observer reproducibility for repeated scans acquired on the same-day and after 1-week and its reproducibility was comparable to that of 3He VDP. 129Xe VDP showed strong and significant correlations with pulmonary function tests. These results suggested that 129Xe VDP is reproducible over short periods of time and can be a reliable measurement to study pulmonary function in imaging studies

Assessing the feasibility of hyperpolarized 129

Purpose: To assess the feasibility of hyperpolarized 129Xe multiple‐breath washout MRI in pediatric cystic fibrosis (CF) participants with preserved lung function. Fractional ventilation (r), defined as the fractional gas replacement per breath, was mapped using 2 signal models: (1) constant T1 and (2) variable T1 as a function of the hyperpolarized gas washout. Methods: A total of 17 pediatric participants were recruited (mean age 11.7 ± 2.8 years), including 7 children with clinically stable CF and 10 aged‐matched healthy controls. Pulmonary function tests were performed, including spirometry, to measure the forced expiratory volume in 1 second and nitrogen multiple‐breath washout to measure the lung clearance index. Hyperpolarized 129Xe MRI was performed during consecutive breaths of air following a single 129Xe inhalation, and fractional ventilation maps were calculated. Results: The forced expiratory volume in 1 second was similar in both groups (P = .32), but there was a statistically significant difference in lung clearance index between healthy and CF participants (P = .001). With variable T1 modeling, CF participants had a mean r of 0.44 ± 0.08 and healthy participants had a mean r of 0.37 ± 0.12 (P = .20). With constant T1 modeling, CF participants had a mean r′ of 0.48 ± 0.08, and healthy participants had a mean r′ of 0.43 ± 0.12 (P = .32). Therefore, assuming a constant T1 leads to a relative bias in r of 15.1% ± 6.4% and 20.8% ± 7.4% for CF and healthy participants, respectively (P = .12). Conclusion: This study demonstrates that hyperpolarized 129Xe multiple‐breath washout imaging is feasible in pediatric participants with CF, and inclusion of variable T1 modeling reduces bias in the fractional ventilation measurements.Canadian Institutes of Health Research. Grant Numbers: MOP 123431, PJT 153099 Hospital for Sick Children. Grant Number: Cystic Fibrosis Research Catalyst Natural Sciences and Engineering Research Council of Canada. Grant Number: RGPIN 217015‐2013 Mitacs Cystic Fibrosis Canad

Pulmonary ventilation visualized using hyperpolarized helium-3 and xenon-129 magnetic resonance imaging: Differences in COPD and relationship to emphysema

In subjects with chronic obstructive pulmonary disease (COPD), hyperpolarized xenon-129 ((129)Xe) magnetic resonance imaging (MRI) reveals significantly greater ventilation defects than hyperpolarized helium-3 ((3)He) MRI. The physiological and/or morphological determinants of ventilation defects and the differences observed between hyperpolarized (3)He and (129)Xe MRI are not yet understood. Here we aimed to determine the structural basis for the differences in ventilation observed between (3)He and (129)Xe MRI in subjects with COPD using apparent diffusion coefficients (ADC) and computed tomography (CT). Ten COPD ex-smokers provided written, informed consent and underwent MRI, CT, spirometry, and plethysmography. (3)He and (129)Xe MRI ventilation volume was generated using semiautomated segmentation, and ADC maps were registered to generate ADC values for lung regions of interest ventilated by both gases (ADCHX) and by (3)He gas only (ADCHO). CT wall area percentage and the lowest 15th percentile point of the CT lung density histogram (HU15%) were also evaluated. For lung regions accessed by (3)He gas only, mean (3)He ADCHO was significantly greater than for regions accessed by both gases (ADCHO = 0.503 ± 0.119 cm(2)/s, ADCHX = 0.470 ± 0.125 cm(2)/s, P \u3c 0.0001). The difference between (3)He and (129)Xe ventilation volume was significantly correlated with CT HU15% (r = -65, P = 0.04) and (3)He ADCHO (r = 0.70, P = 0.02), but not CT wall area percentage (r = -0.34, P = 0.33). In conclusion, in this small study in COPD subjects, we observed significantly decreased (129)Xe MRI ventilation compared with (3)He MRI, and these regions of decreased (129)Xe ventilation were spatially and significantly correlated with regions of increased pulmonary emphysema, but not airway wall thickness