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Chest CT provides a way to quantify pulmonary airway and vascular tree measurements. In patients with COPD, CT airway measurement differences in females are concomitant with worse quality-of-life and other outcomes. CT total airway count (TAC), airway lumen area (LA), and wall thickness (WT) also differ in females with long-COVID. Our objective was to evaluate CT airway and pulmonary vascular and quality-of-life measurements in females with COPD as compared to ex-smokers and patients with long-COVID. Chest CT was acquired 3-months post-COVID-19 infection in females with long-COVID for comparison with the same inspiratory CT in female ex-smokers and COPD patients. TAC, LA, WT, and pulmonary vascular measurements were quantified. Linear regression models were adjusted for confounders including age, height, body-mass-index, lung volume, pack-years and asthma diagnosis. Twenty-one females (53 ± 14 years) with long-COVID, 17 female ex-smokers (69 ± 9 years) and 13 female COPD (67 ± 6 years) patients were evaluated. In the absence of differences in quality-of-life scores, females with long-COVID reported significantly different LA (p = 0.006) compared to ex-smokers but not COPD (p = 0.7); WT% was also different compared to COPD (p = 0.009) but not ex-smokers (p = 0.5). In addition, there was significantly greater pulmonary small vessel volume (BV5) in long-COVID as compared to female ex-smokers (p = 0.045) and COPD (p = 0.003) patients and different large (BV10) vessel volume as compared to COPD (p = 0.03). In females with long-COVID and highly abnormal quality-of-life scores, there was CT evidence of airway remodelling, similar to ex-smokers and patients with COPD, but there was no evidence of pulmonary vascular remodelling.Clinical Trial Registration: NCT05014516 and NCT02279329 [ABSTRACT FROM AUTHOR]

Background: Patients with eosinophilic asthma often report poor symptomatic control and quality of life. Anti-IL-5 therapy, including anti-IL-5Rα (benralizumab), rapidly depletes eosinophils in the blood and airways and also reduces asthma exacerbations and improves quality of life scores. In patients with severe asthma, eosinophilic inflammation-driven airway mucus occlusions have been measured using thoracic x-ray CT imaging. Pulmonary 129Xe MRI ventilation defect percentage (VDP) also sensitively measures asthma airway dysfunction caused by airway hyperresponsiveness, remodeling, and luminal mucus occlusions. Using 129Xe MRI and CT imaging together, it is feasible to measure both airway luminal occlusions and airway ventilation in relationship to anti-IL-5 therapy to ascertain the direct impact of therapy-induced eosinophil depletion on airway function.Research Question: Does 129Xe MRI detect airway functional responses to eosinophil depletion after a single benralizumab dose and do airway mucus occlusions mediate this response?Study Design and Methods: MRI, eosinophil count, spirometry, oscillometry, Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ), and St. George's Respiratory Questionnaire were completed on day 0 and 28 days after a single 30-mg subcutaneous benralizumab dose. CT scan mucus plugs were scored on day 0, and MRI VDP was quantified on days 0 and 28.Results: Twenty-nine participants (27 with baseline CT imaging) completed day 0 and day 28 visits. On day 28 after a single benralizumab dose, significantly improved blood eosinophil counts, VDP, ACQ 6 scores, AQLQ scores (all P < .001), and peripheral airway resistance (P = .04) were found in all participants. On day 28, significantly improved VDP and ACQ 6 scores also were found in the subgroup of nine participants with five or more mucus plugs, but not in the subgroup (n = 18) with fewer than five mucus plugs. Based on univariate relationships for change in ACQ 6 score, multivariate models were generated and showed that day 0 VDP (P < .001) and day 0 CT scan mucus score (P < .001) were significant variables for change in ACQ 6 score on day 28 after benralizumab injection.Interpretation: 129Xe ventilation significantly improved in participants with uncontrolled asthma and in those with significant mucus plugging after a single dose of benralizumab.Trial Registry: ClinicalTrials.gov; No.: NCT03733535; URL: www.Clinicaltrials: gov. [ABSTRACT FROM AUTHOR]

Bronchoscopy is not conventionally guided by prior knowledge of segmental airway obstruction. Hyperpolarized gas magnetic resonance imaging (MRI) ventilation abnormalities and computed tomography (CT) air trapping are related to lung function and asthma severity but have not been used to target segmental inflammation and remodeling. We evaluate the feasibility of using bronchoscopy guided by 3 He MRI and CT to reveal differences in inflammatory response, morphology, and cellular activity in poorly- (defect) versus well-ventilated (control) lung regions. Eleven participants (5 female; age, 22.8 ± 3.4 years; 9 asthma) who experienced a cold with increased lower airway symptoms underwent 3 He MRI and/or CT at least 6 weeks after recovery. Differences between defect and control regions were compared. In defect as compared to control sites, bronchoalveolar lavage neutrophils (p = 0.06) and granulocytes (p = 0.08) trended towards an increase; inflammatory mediators (i.e., 15-epi-LXA4, LXA4) were also significantly different (p < 0.05) between sites. Correlations were observed between macrophages, neutrophils, and eosinophils with inflammatory mediators (i.e., 15-epi-LXA4, LXA4, LTB4). Correlations were observed for macrophages and neutrophils with 15-epi-LXA4, and eosinophils with LXA4 and leukotriene B4. Basement membrane wall thickness was similar for defect versus control sites (p = 0.9). These results support the feasibility of image-guided methods to identify airway obstruction phenotypes., (© 2025 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Rationale and Objectives: Hyperpolarized 129 Xe MRI quantifies ventilation-defect-percent (VDP), the ratio of 129 Xe signal-void to the anatomic 1 H MRI thoracic-cavity-volume. VDP is associated with airway inflammation and disease control and serves as a treatable trait in therapy studies. Semi-automated VDP pipelines require time-intensive observer interactions. Current convolutional neural network (CNN) approaches for quantifying VDP lack external validation, which limits multicenter utilization. Our objective was to develop an automated and externally validated deep-learning pipeline to quantify pulmonary 129 Xe MRI VDP., Materials and Methods: 1 H and 129 Xe MRI data from the primary site (Site1) were used to train and test a CNN segmentation and registration pipeline, while two independent sites (Site2 and Site3) provided external validation. Semi-automated and CNN-based registration error was measured using mean-absolute-error (MAE) while segmentation error was measured using generalized-Dice-similarity coefficient (gDSC). CNN and semi-automated VDP were compared using linear regression and Bland-Altman analysis., Results: Training/testing used data from 205 participants (healthy volunteers, asthma, COPD, long-COVID; mean age=54 ± 16y; 119 females) from Site1. External validation used data from 71 participants. CNN and semi-automated 1 H and 129 Xe registrations agreed (MAE=0.3°, R 2 =0.95 rotation; 1.1%, R 2 =0.79 scaling; 0.2/0.5px, R 2 =0.96/0.95, x/y-translation; all p < .001). Thoracic-cavity and ventilation segmentations were also spatially corresponding (gDSC=0.92 and 0.88, respectively). CNN VDP correlated with semi-automated VDP (Site1 R 2 /ρ = .97/.95, bias=-0.5%; Site2 R 2 /ρ = .85/.93, bias=-0.9%; Site3 R 2 /ρ = .95/.89, bias=-0.8%, all p < .001)., Conclusion: An externally validated CNN registration/segmentation model demonstrated strong agreement with low error compared to the semi-automated method. CNN and semi-automated registrations, thoracic-cavity-volume and ventilation-volume segmentations were highly correlated with high gDSC for the datasets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background In individuals with postacute COVID-19 syndrome (PACS) and normal pulmonary function, xenon 129 ( 129 Xe) 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 129 Xe 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. 129 Xe 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 129 Xe 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 129 Xe 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.

129 Xe MRI red blood cell to alveolar tissue plasma ratio (RBC:TP) abnormalities have been observed in ever-hospitalised and never-hospitalised people with postacute COVID-19 syndrome (PACS). But, it is not known if such abnormalities resolve when symptoms and quality-of-life scores improve. We evaluated 21 participants with PACS, 7±4 months (baseline) and 14±4 months (follow-up) postinfection. Significantly improved diffusing capacity of the lung for carbon monoxide (DL CO , Δ=14% pred ;95%CI 7 to 21, p<0.001), postexertional dyspnoea (Δ=-0.7; 95%CI=-0.2 to -1.2, p=0.019), St George's Respiratory Questionnaire-score (SGRQ Δ=-6; 95% CI=-1 to -11, p=0.044) but not RBC:TP (Δ=0.03; 95% CI=0.01 to 0.05, p=0.051) were observed at 14 months. DL CO correlated with RBC:TP (r=0.60, 95% CI=0.22 to 0.82, p=0.004) at 7 months. While DL CO and SGRQ measurements improved, these values did not normalise 14 months post-infection. ClinicalTrials.gov NCT04584671., Competing Interests: Competing interests: SS has received honoraria for speaking engagements from AstraZeneca, Novartis and Polarean, personal fees from Arrowhead Pharma and received study funding from Cyclomedia, none of which was related to this work. JN has received honoraria from AstraZeneca, Horizon Therapeutics and Vertex outside the submitted work. GP has received research support and consulting fees from Novartis and AstraZeneca and personal fees for speaking engagements from AstraZeneca and Polarean Imaging. AMM, MJM, HKK, MA, MSA, ID and AO have no conflicts to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In patients with post-acute COVID-19 syndrome (PACS), abnormal gas-transfer and pulmonary vascular density have been reported, but such findings have not been related to each other or to symptoms and exercise limitation. The pathophysiologic drivers of PACS in patients previously infected with COVID-19 who were admitted to in-patient treatment in hospital (or ever-hospitalized patients) and never-hospitalized patients are not well understood., Purpose: To determine the relationship of persistent symptoms and exercise limitation with xenon 129 ( 129 Xe) MRI and CT pulmonary vascular measurements in individuals with PACS., Materials and Methods: In this prospective study, patients with PACS aged 18-80 years with a positive polymerase chain reaction COVID-19 test were recruited from a quaternary-care COVID-19 clinic between April and October 2021. Participants with PACS underwent spirometry, diffusing capacity of the lung for carbon monoxide (DLco), 129 Xe MRI, and chest CT. Healthy controls had no prior history of COVID-19 and underwent spirometry, DLco, and 129 Xe MRI. The 129 Xe MRI red blood cell (RBC) to alveolar-barrier signal ratio, RBC area under the receiver operating characteristic curve (AUC), CT volume of pulmonary vessels with cross-sectional area 5 mm 2 or smaller (BV5), and total blood volume were quantified. St George's Respiratory Questionnaire, International Physical Activity Questionnaire, and modified Borg Dyspnea Scale measured quality of life, exercise limitation, and dyspnea. Differences between groups were compared with use of Welch t-tests or Welch analysis of variance. Relationships were evaluated with use of Pearson ( r ) and Spearman (ρ) correlations., Results: Forty participants were evaluated, including six controls (mean age ± SD, 35 years ± 15, three women) and 34 participants with PACS (mean age, 53 years ± 13, 18 women), of whom 22 were never hospitalized. The 129 Xe MRI RBC:barrier ratio was lower in ever-hospitalized participants ( P = .04) compared to controls. BV5 correlated with RBC AUC (ρ = .44, P = .03). The 129 Xe MRI RBC:barrier ratio was related to DLco ( r = .57, P = .002) and forced expiratory volume in 1 second (ρ = .35, P = .03); RBC AUC was related to dyspnea (ρ = -.35, P = .04) and International Physical Activity Questionnaire score (ρ = .45, P = .02)., Conclusion: Xenon 129 ( 129 Xe) MRI measurements were lower in participants previously infected with COVID-19 who were admitted to in-patient treatment in hospital with post-acute COVID-19 syndrome, 34 weeks ± 25 after infection compared to controls. The 129 Xe MRI measures were associated with CT pulmonary vascular density, diffusing capacity of the lung for carbon monoxide, exercise capacity, and dyspnea. Clinical trial registration no.: NCT04584671 © RSNA, 2022 Online supplemental material is available for this article See also the editorial by Wild and Collier in this issue.

Background: Patients often report persistent symptoms beyond the acute infectious phase of COVID-19. Hyperpolarised 129 Xe MRI provides a way to directly measure airway functional abnormalities; the clinical relevance of 129 Xe MRI ventilation defects in ever-hospitalised and never-hospitalised patients who had COVID-19 has not been ascertained. It remains unclear if persistent symptoms beyond the infectious phase are related to small airways disease and ventilation heterogeneity. Hence, we measured 129 Xe MRI ventilation defects, pulmonary function and symptoms in ever-hospitalised and never-hospitalised patients who had COVID-19 with persistent symptoms consistent with post-acute COVID-19 syndrome (PACS)., Methods: Consenting participants with a confirmed diagnosis of PACS completed 129 Xe MRI, CT, spirometry, multi-breath inert-gas washout, 6-minute walk test, St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnoea scale, modified Borg scale and International Physical Activity Questionnaire. Consenting ever-COVID volunteers completed 129 Xe MRI and pulmonary function tests only., Results: Seventy-six post-COVID and nine never-COVID participants were evaluated. Ventilation defect per cent (VDP) was abnormal and significantly greater in ever-COVID as compared with never-COVID participants (p<0.001) and significantly greater in ever-hospitalised compared with never-hospitalised participants who had COVID-19 (p=0.048), in whom diffusing capacity of the lung for carbon-monoxide (p=0.009) and 6-minute walk distance (6MWD) (p=0.005) were also significantly different. 129 Xe MRI VDP was also related to the 6MWD (p=0.02) and post-exertional SpO 2 (p=0.002). Participants with abnormal VDP (≥4.3%) had significantly worse 6MWD (p=0.003) and post-exertional SpO 2 (p=0.03)., Conclusion: 129 Xe MRI VDP was significantly worse in ever-hospitalised as compared with never-hospitalised participants and was related to 6MWD and exertional SpO 2 but not SGRQ or mMRC scores., Trial Registration Number: NCT05014516., Competing Interests: Competing interests: The authors have reported to BMJ Open Respiratory Research the following: TH has received grants from Fisher & Paykel, honoraria for speaking engagements from AstraZeneca, and has participated on advisory boards for Sanofi, AstraZeneca and Valeo, outside the submitted work. JN has received honoraria for speaking engagements from AstraZeneca, Horizon Therapeutics and Vertix, outside the submitted work. PN has received grants from AstraZeneca, Teva, Sanofi, Foresee and Cyclomedica and personal fees from AstraZeneca, Teva, Equillium, Arrowhead Pharma and GlaxoSmithKline, outside the submitted work. SS has received grants from Cyclomedica, personal fees from Arrowhead Pharma and honoraria for speaking engagements from AstraZeneca, Novartis and Polarean, outside the submitted work. GP has received grants from AstraZeneca and Novartis and honoraria for speaking engagements from AstraZeneca, outside the submitted work. GES, MSA, AO, MK, SS and GP received grants from the Ministry of Health and Long-Term Care Ontario related to this work. HKK, MJM, AMM, CV, NR, EAH, NBK, MA and ID have no conflicts to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)