Background In individuals with postacute COVID-19 syndrome (PACS) and normal pulmonary function, xenon 129 (129Xe) MRI ventilation defects, abnormal quality-of-life scores, and exercise limitation were reported 3 months after infection; the longitudinal trajectory remains unclear. Purpose To measure and compare pulmonary function, exercise capacity, quality of life, and 129Xe MRI ventilation defect percent (VDP) in individuals with PACS evaluated 3 and 15 months after COVID-19 infection. Materials and Methods In this prospective study, participants with PACS aged 18-80 years were enrolled between July 2020 and August 2021 from two quaternary care centers. 129Xe MRI VDP, diffusing capacity of lung for carbon monoxide (Dlco), spirometry, oscillometry, 6-minute walk distance (6MWD), and St George Respiratory Questionnaire (SGRQ) scores were evaluated 3 months and 15 months after COVID-19 infection. Differences between time points were evaluated using the paired t test. Multivariable models were generated to explain exercise capacity and quality-of-life improvement. Odds ratios (ORs) were used to evaluate potential treatment influences. Results Overall, 53 participants (mean age, 55 years ± 18 [SD]; 27 women) attended both 3- and 15-month visits and were included in the analysis. The mean values for 129Xe MRI VDP (5.8% and 4.2%; P = .003), forced expiratory volume in the 1st second of expiration percent predicted (84% and 90%; P = .001), Dlco percent predicted (86% and 99%; P = .002), and SGRQ score (35 and 25; P < .001) improved between the 3- and 15-month visit. VDP measured 3 months after COVID-19 infection predicted the change in 6MWD (β = -0.643, P = .006), while treatment with respiratory medication at 3 months predicted an improved quality-of-life score at 15 months (OR, 4.0; 95% CI: 1.2, 13.8; P = .03). Conclusion Pulmonary function, gas exchange, exercise capacity, quality of life, and 129Xe MRI ventilation defect percent (VDP) improved in participants with postacute COVID-19 syndrome at 15 months compared with 3 months after infection. VDP measured at 3 months after infection correlated with improved exercise capacity, while treatment with respiratory medication was associated with an improved quality-of-life score 15 months after infection. ClinicalTrials.gov registration no. NCT05014516 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Vogel-Claussen in this issue.

Noble gas pulmonary magnetic resonance imaging (MRI) is transitioning away from (3)He to (129)Xe gas, but the physiological/clinical relevance of (129)Xe apparent diffusion coefficient (ADC) parenchyma measurements is not well understood. Therefore, our objective was to generate (129)Xe MRI ADC for comparison with (3)He ADC and with well-established measurements of alveolar structure and function in older never-smokers and ex-smokers with chronic obstructive pulmonary disease (COPD). In four never-smokers and 10 COPD ex-smokers, (3)He (b = 1.6 sec/cm(2)) and (129)Xe (b = 12, 20, and 30 sec/cm(2)) ADC, computed tomography (CT) density-threshold measurements, and the diffusing capacity for carbon monoxide (DLCO) were measured. To understand regional differences, the anterior-posterior (APG) and superior-inferior (∆SI) ADC differences were evaluated. Compared to never-smokers, COPD ex-smokers showed greater (3)He ADC (P = 0.006), (129)Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.006), but not for ADCb30 (P > 0.05). Never-smokers and COPD ex-smokers had significantly different APG for (3)He ADC (P = 0.02), (129)Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.01), but not for ADCb30 (P > 0.05). ∆SI for never- and ex-smokers was significantly different for (3)He ADC (P = 0.046), but not for (129)Xe ADC (P > 0.05). There were strong correlations for DLCO with (3)He ADC and (129)Xe ADCb12 (both r = -0.95, P < 0.05); in a multivariate model (129)Xe ADCb12 was the only significant predictor of DLCO (P = 0.049). For COPD ex-smokers, CT relative area <-950 HU (RA950) correlated with (3)He ADC (r = 0.90, P = 0.008) and (129)Xe ADCb12 (r = 0.85, P = 0.03). In conclusion, while (129)Xe ADCb30 may be appropriate for evaluating subclinical or mild emphysema, in this small group of never-smokers and ex-smokers with moderate-to-severe emphysema, (129)Xe ADCb12 provided a physiologically appropriate estimate of gas exchange abnormalities and alveolar microstructure.