Motivation: It is unclear the extent to which abnormal lung ventilation is present in long COVID subjects without prior respiratory diseases. Goal(s): Evaluate 129Xe lung ventilation imaging in a cohort without prior respiratory disease, consisting of patients with long COVID (with and without dyspnea) and controls. Approach: 60 patients with long COVID (53 with dyspnea, 7 without dyspnea) and 20 controls underwent successful ventilation imaging and were included in analysis. Results: 129Xe ventilation imaging metrics did not find significant differences between controls and patients with long COVID, however a subset of long COVID patients with dyspnea had lung ventilation defects despite normal PFTs. Impact: Impact (40 words): The majority of patients with long COVID have normal 129Xe lung ventilation imaging. 129Xe ventilation imaging may be able to identify candidates with long COVID who may be candidates for treatments targeted at airways disease.

Introduction: The magnitude of bronchodilator (BD) response from Xe-MRI and FEV1 may be discordant due to differences in airways disease pathophysiology. Here we assessed BD responders and non responders using Xe-MRI and spirometry. Methods: 136 Patients from primary care with asthma and/or COPD taking part in the NOVELTY study [NCT02760329] were assessed pre and post-BD with Xe-MRI, spirometry and airwave oscillometry (AOS). From Xe-MRI, ventilation defect percent (VDP) assesses the proportion of non-ventilated lung. 4 groups were categorised; G1 = No clinically significant change (Δ) in FEV1 or VDP (n=58, 38% COPD), G2 = ΔFEV1 and ΔVDP (n=23, 39% COPD), G3 = ΔFEV1 only (n=20, 45% COPD), G4 = ΔVDP only (n=35, 69% COPD). Results: In G1, 86% and 41% had normal FEV1 or VDP respectively post-BD. In G2, ΔFEV1 was correlated to ΔVDP, but not to ΔAOS. Discordance of ΔFEV1 and ΔVDP was observed in 40% patients (G3 and G4). Of those with ΔFEV1 only (G3), 85% had normal post-BD FEV1 and 40% normal VDP. In G1 and G3 a visual change in ventilation was observed for some despite a static VDP. In G3, ΔFEV1 did not correlate to other Δmetrics. In G4, 57% had normal FEV1 and 2% had normal VDP post-BD. ΔVDP was correlated to ΔAX and ΔX5 but not to ΔFEV1 or ΔFVC. G4 had significantly (p<0.001) worse post-BD Xe-MRI acinar dimensions, FEV1, VDP, R5-R20, AX and X5 than G3. 7 patients with COPD had a significant worsening in VDP post-BD. Conclusions: FEV1 and VDP are complementary methods of assessing BD response. In G3 ΔFEV1 may reflect changes in larger conductive airways not assessed by VDP. G4 have more advanced disease where ΔVDP reflects Δlung compliance possibly due to dilation of the small airways.

Introduction 129Xe-MRI provides sensitive measures of pulmonary function and microstructure and may be useful in phenotyping patients and monitoring disease progression. Methods Patients with asthma and/or COPD from NOVELTY [NCT02760329] were recruited from primary care and assessed post-bronchodilator with 129Xe-MRI (ventilation, acinar dimensions and gas transfer), spirometry and transfer factor for carbon monoxide at 2 visits 1 year apart (mean±SD=60±6, range=47–79 weeks). For patients with normal FEV1 and patients with normal TLco (z-score>-1.64) at visit 1, differences between (i) physician-assigned diagnosis groups at visit 1 and (ii) metrics at visit 1 and visit 2 were assessed. Results 165 patients, aged 28–82 years were assessed at visit 1. 126 (76%) patients had normal FEV1 and 131 (79%) had normal TLco. 115 patients had normal FEV1 and TLco. Physiology by diagnosis (figure 1): In patients with normal FEV1, 129Xe-MRI metrics of ventilation abnormality and acinar dimensions were better in asthma than COPD or asthma+COPD groups (p<0.0001). In patients with normal TLco, 129Xe-MRI metrics of gas transfer and acinar dimensions were worse in COPD than asthma (p<0.001). Longitudinal change Gas transfer decreased from visit 1 to visit 2 in patients with normal TLco (average 129Xe-MRI red blood cell/membrane V1=0.334, V2=0.312, p=0.0001, n=102; average TLco z-score V1=0.187, V2=-0.044, p<0.0001, n=114). 31/114(27%) patients had a reduction in TLco>-0.5 z-score. 129Xe-MRI ventilation and acinar dimension metrics did not change significantly over 1 year when considering all patients with normal FEV1. However, in 43 patients with normal FEV1 and abnormal FEV1/FVC (z-score<-1.64), ventilation decreased from visit 1 to visit 2 (average 129Xe-MRI ventilation defect percent V1=8.3%, V2=9.9%, p=0.015). Conclusion Despite having normal lung function, patients with COPD diagnosis label had significantly higher 129Xe-MRI ventilation abnormalities, larger acinar dimensions and reduced gas transfer than those with asthma diagnosis, highlighting the high diagnostic sensitivity of 129Xe-MRI. 129Xe-MRI gas transfer and TLco decreased in patients with asthma and/or COPD over a period of 1 year in patients with normal TLco. Ventilation and acinar dimensions did not change significantly over 1 year when considering all patients with normal FEV1, however, ventilation worsened in patients with abnormally low FEV1/FVC and normal FEV1. Please refer to page A292 for declarations of interest related to this abstract.

Introduction: Xe-MRI directly images the distribution of ventilation in the lung making it ideal for assessing bronchodilator response (BDR). Here we compared BDR using Xe-MRI, spirometry and airwave oscillometry (AOS) to determine if the magnitude of BDR is related to diagnosis or disease severity. Methods: 136 patients from primary care with asthma and/or COPD taking part in the NOVELTY study [NCT02760329] were assessed pre and post-BD with Xe ventilation MRI, spirometry and AOS. From Xe-MRI, the ventilation defect percent (VDP) assesses the proportion of non-ventilated lung and the treatment response map (TRM) quantifies voxel by voxel changes in ventilation. The magnitude of change (Δ) post-BD was compared by diagnosis and by FEV1 %predicted severity (mild >80%, moderate 50-80%, severe <50%). Results: Patients were aged 29-83years (53% female). 72 patients had a diagnosis of asthma, 41 had asthma+COPD and 23 had COPD. All PFT and Xe-MRI metrics had a statistically significant change post-BD for all patients and within diagnosis group (p<0.001). There were no significant differences between diagnosis groups for ΔPFT or ΔXe-MRI metrics post-BD. 93 patients had mild FEV1 severity, 34 moderate and 9 were severe. ΔFEV1 and ΔAOS were not different between severity groups, however there was an increase in ΔVDP (p=0.02), TRM (p<0.001) and ΔFVC (p=0.001) with increasing severity. Conclusions: There was no difference in the magnitude of ΔPFT and ΔXe-MRI metrics post-BD between asthma and/or COPD. The ΔFEV1 was also un-related to disease severity, however the magnitude of Xe-MRI BDR is effective at distinguishing disease severity and therefore especially useful in assessing more severe disease.

Airway clearance techniques (ACTs) are key in managing Primary Ciliary Dyskinesia (PCD) yet their effects are unknown. Clinically stable individuals with PCD were imaged with 129Xe-MRI immediately pre, post and 4-hours post ACT (or no-ACT). ACTs were based on the individual's usual regimen. Ventilation defect percent (VDP) and heterogeneity index (VHI) were calculated from 129Xe-MRI. 18 children with PCD (12 male, age 7-17 years, FEV1 -1.0±1.4) were assessed. ACT (n=15) and no-ACT (n=3) groups were similar at baseline (age, sex, FEV1, VDP, VHI). Heterogeneous ventilation distribution changes were visualised post-ACT and 4-hours including defect resolution, improvement, persistence and new defects (Fig 1). In the ACT group, no significant change in VDP from pre-ACT was seen immediately post or 4-hours post-ACT (Mean±SD VDP 7.4±6.5%, 9.3±9.2% and 7.4±6.7% respectively); VHI improved significantly at 4-hours (VHI 10.7±3.3%) when compared to pre-ACT (VHI 11.8±4.1 p<0.05) and immediately post-ACT (VHI 12.4±4.6% p=0.0005). Improved ventilation homogeneity is seen following a personalised ACT in children with PCD. Although lung ventilation percent is unchanged, the heterogeneous impact on ventilation abnormalities may be clinically informative.

Introduction Xe MRI and PFTs provide complex information about lung physiology which may allow improved patient phenotyping. Objective To investigate possible data driven phenotypes of obstruction based on Xe MRI and lung physiology using cluster analysis. Methods Patients with asthma and/or COPD taking part in the NOVELTY study [NCT02760329] were recruited from primary care and assessed post-bronchodilator. K-means clustering was performed on 10 metrics derived from Xe MRI (ventilation, acinar dimensions and gas transfer) and PFTs (spirometry, body plethysmography and gas transfer). Inter-cluster analysis on clinical outcomes was then performed. Results 148 patients, aged 28–82 years, with asthma (73), asthma+COPD (50) or COPD (25) were grouped into 3 clusters (C). There were significant differences between all clusters for 9/10 of the MRI and PFT metrics. C1 (n=24) had the most disease measured by Xe MRI and PFTs. 54% had COPD and 42% had asthma+COPD. 96% were ever smokers. C2 (n=67) had mild lung physiology on MRI and PFTs (69% had normal PFTs) and were the youngest. 84% had asthma and 15% had asthma+COPD. C3 (n=57) MRI and PFT metrics were poorer than cluster 2 and better than cluster 1. 53% had asthma+COPD and 28% had asthma. Inter-cluster analysis; C1 had more exacerbations over the previous 3 years, more symptoms (RSQ, CAAT), lower quality of life (SGRQ) and more neutrophils than C2 and C3. Conclusions Three data driven clusters of obstructive lung disease severity were identified based on MRI and PFT measurements and independent of clinical diagnosis which link to clinical outcomes. These clusters may therefore help to predict worsening quality of life and future exacerbations.

Introduction 129Xe-MRI directly images the distribution of ventilation in the lung making it ideal for assessing bronchodilator response (BDR). Here we compared the concordance of BDR using 129Xe-MRI and FEV1 and also assessed if the magnitude of BDR is related to diagnosis or disease severity. Methods 136 Patients from primary care with asthma and/or COPD taking part in the NOVELTY study [NCT02760329] were assessed pre and post-BD with 129Xe-MRI and spirometry. From 129Xe-MRI, ventilation defect percent (VDP) assesses the proportion of non-ventilated lung. Four BDR responder groups were categorised; G1= No clinically significant change (Δ) in FEV1 or VDP (n=58), G2= ΔFEV1 and ΔVDP (n=23), G3= ΔFEV1 only (n=20), G4= ΔVDP only (n=35). The magnitude of change post-BD was compared between diagnoses and by FEV1%predicted severity (mild >80%, moderate 50–80%, severe <50%). Results Patients were aged 29–83 years (Female=53%). 72 patients had a diagnosis of asthma, 41-asthma+COPD and 23-COPD. In G1, 86% and 41% of patients had normal FEV1 or VDP respectively, post-BD. In G2, ΔFEV1 correlated to ΔVDP. Discordance of ΔFEV1 and ΔVDP was observed in 40% of patients (G3 and G4). Of those with ΔFEV1 only (G3), 85% had normal FEV1 and 40% normal VDP, post-BD. In G4, 57% had normal FEV1 and 2% had normal VDP post-BD. G4 had significantly worse post-BD 129Xe-MRI acinar dimensions, FEV1, VDP than G3 (p<0.001). Notably, seven patients with COPD had a significant worsening in VDP post-BD. There were no significant differences between diagnosis groups for Δspirometry or Δ129Xe-MRI metrics post-BD. 93 patients had mild FEV1 severity, 34 moderate and 9 severe. ΔFEV1 was not different between severity groups, however there was an increase in ΔVDP (p=0.02) and ΔFVC(p=0.001) with increasing severity. Conclusions FEV1 and VDP are complementary methods of assessing BD response. For patients in G3 ΔFEV1 may reflect changes in larger conductive airways not assessed by VDP. G4 have more advanced disease where ΔVDP and ΔFVC may reflect dilation of the smaller airways. There was no difference in the magnitude of ΔFEV1 and ΔVDP metrics post-BD between asthma and/or COPD, however ΔVDP was significantly larger in more severe lung disease. Please refer to page A292 for declarations of interest related to this abstract.

Longitudinal changes of 129Xe MRI metrics in patients with asthma and/or COPD have not yet been reported. 140 patients with asthma and/or COPD were scanned at 2 visits, 1 year apart, using 129Xe gas transfer and diffusion MRI. From visit 1 to visit 2 red blood cell (RBC) / membrane (M) and RBC/gas decreased and the amplitude of red blood cell oscillations (ARBCO) increased when all patients were considered. RBC/M and RBC/gas decreased in asthma+COPD, and RBC/M decreased and ARBCO increased in asthma from visit 1 to visit 2. M/gas and acinar microstructure metrics did not change significantly between visits.

BACKGROUND: Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pulmonary changes in these patients remains unclear.RESEARCH QUESTION: Do patients hospitalized with COVID-19 without evidence of architectural distortion on structural imaging exhibit longitudinal improvements in lung function measured by using 1H and 129Xe MRI between 6 and 52 weeks following hospitalization?STUDY DESIGN AND METHODS: Patients who were hospitalized with COVID-19 pneumonia underwent a pulmonary 1H and 129Xe MRI protocol at 6, 12, 25, and 51 weeks following hospital admission in a prospective cohort study between November 2020 and February 2022. The imaging protocol was as follows: 1H ultra-short echo time, contrast-enhanced lung perfusion, 129Xe ventilation, 129Xe diffusion-weighted, and 129Xe spectroscopic imaging of gas exchange.RESULTS: Nine patients were recruited (age 57 +/- 14 [median +/- interquartile range] years; six of nine patients were male). Patients underwent MRI at 6 (n = 9), 12 (n = 9), 25 (n = 6), and 51 (n = 8) weeks following hospital admission. Patients with signs of interstitial lung damage were excluded. At 6 weeks, patients exhibited impaired 129Xe gas transfer (RBC to membrane fraction), but lung microstructure was not increased (apparent diffusion coefficient and mean acinar airway dimensions). Minor ventilation abnormalities present in four patients were largely resolved in the 6-to 25-week period. At 12 weeks, all patients with lung perfusion data (n = 6) showed an increase in both pulmonary blood volume and flow compared with 6 weeks, although this was not statistically significant. At 12 weeks, significant improvements in 129Xe gas transfer were observed compared with 6-week examinations; however, 129Xe gas transfer remained abnormally low at weeks 12, 25, and 51.INTERPRETATION: 129Xe gas transfer was impaired up to 1 year following hospitalization in patients who were hospitalized with COVID-19 pneumonia, without evidence of architectural distortion on structural imaging, whereas lung ventilation was normal at 52 weeks.

Introduction: There is limited evidence as to whether the spirometric pattern of airways dysanapsis (low FEV1/FVC and normal FEV1) represents a normal physiological variant of lung function or is an indicator of airways disease. 129Xe ventilation, diffusion and gas exchange MRI are highly sensitive to assess airways disease pathophysiology and may help identify the clinical significance of airways dysanapsis. Methods: Patients from primary care in the UK, with a diagnosis of asthma and/or COPD were assessed (NOVELTY study NCT02760329) with 129Xe ventilation, diffusion and gas exchange MRI in addition to lung clearance index (LCI), airwave oscillometry (AOS) and spirometry, on the same day and post-bronchodilator. Patients with airways dysanapsis were defined as an FEV1/FVC LLN and were age-matched to patients with normal spirometry. Results: From 164 patients, 43 had airways dysanapsis (median [IQR] age = 62 [55–72] years) and 83 had normal spirometry. Compared to an age matched group of 43 patients with normal spirometry (aged 64 [55–73] years), patients with dysanapsis had significantly increased ventilation defects (p<0.001) and heterogeneity (p<0.001) and also increased acinar dimensions (p=0.009) from 129Xe MRI, in addition to increased R5 (p=0.006) and R5–20 (p=0.02) from AOS. In contrast there was no significant difference between groups for 129Xe gas exchange or LCI. Conclusion: Patients with airways dysanapsis have abnormal ventilation and acinar spaces on 129Xe MRI and increased respiratory resistance, consistent with airways disease pathophysiology. In these patients, airways dysanapsis is likely an indicator of significant airways disease.

AbstractIntroductionMicrovascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pathophysiological pulmonary changes during the post-acute period in these patients remains unclear.MethodsPatients who were hospitalised due to COVID-19 pneumonia underwent a pulmonary1H and129Xe MRI protocol at 6, 12, 25 and 51 weeks after hospital admission. The imaging protocol included: ultra-short echo time, dynamic contrast enhanced lung perfusion,129Xe lung ventilation,129Xe diffusion weighted and129Xe 3D spectroscopic imaging of gas exchange.Results9 patients were recruited and underwent MRI at 6 (n=9), 12 (n=9), 25 (n=6) and 51 (n=8) weeks after hospital admission. Patients with signs of interstitial lung damage at 3 months were excluded from this study. At 6 weeks after hospital admission, patients demonstrated impaired129Xe gas transfer (RBC:M) but normal lung microstructure (ADC, LmD). Minor ventilation abnormalities present in four patients were largely resolved in the 6–25 week period. At 12 week follow up, all patients with lung perfusion data available (n=6) showed an increase in both pulmonary blood volume and flow when compared to 6 weeks, though this was not statistically significant. At 12 week follow up, significant improvements in129Xe gas transfer were observed compared to 6-week examinations, however129Xe gas transfer remained abnormally low at weeks 12, 25 and 51. Changes in129Xe gas transfer correlated significantly with changes in pulmonary blood volume and TLCOZ-score.ConclusionsThis study demonstrates that multinuclear MRI is sensitive to functional pulmonary changes in the follow up of patients who were hospitalised with COVID-19. Impairment of xenon transfer may indicate damage to the pulmonary microcirculation.

Patients with asthma and/or COPD are characterised by airflow obstruction. Significant spirometric overlap exists and sensitive metrics of ventilation heterogeneity may better phenotype each condition. Methods: Patients from primary care with asthma (Group 1), asthma+COPD (G2) or COPD only (G3) were assessed (NOVELTY study NCT02760329) with 129Xe ventilation MRI, spirometry, lung clearance index (LCI) and oscillometry (AOS) on the same day and post-bronchodilator. Ventilation defect percentage (VDP) and heterogeneity index (VHI) were calculated from 129Xe-MRI. Results: 164 patients (median [IQR] age=60.4 years [49.6,70.9] 52% female) were assessed, including 82 in G1, 55 in G2 and 27 in G3. Significant (p<0.001) correlations between both VDP and VHI existed respectively with LCI (r=0.58,r=0.62), R5 (r=0.33,r=0.3), R5-20 (r=0.42,r=0.41), AX ((area of reactance curve) r=0.51,r=0.49), FEV1 (r=-0.58,r=-0.59) and FEV1/FVC (r=-0.72,r=-0.71). There were no significant differences between G2 and G3. However, G1 had significantly better lung function and 129Xe-MRI, compared to G2 and G3. 127 patients (78-G1, 37-G2 and 12-G3) had an FEV1 >-1.64 z-score. Between groups, FEV1, FEV1/FVC and AOS metrics were not significantly different, however LCI, VDP and VHI were significantly (p<0.001) worse in G2 and G3 when compared to G1 (but not between G2 and G3). In G1, 25% had abnormal AX, LCI=41% and VDP=49%. In G2, 44% had abnormal AX, LCI=65% and VDP=84%. In G3, 36% had abnormal AX, LCI=100% and VDP=100%. Conclusion:129Xe VDP, VHI and LCI were raised in COPD when compared to asthma, even when FEV1 was normal. In patients with asthma+COPD, 129Xe-MRI and LCI may better identify asthma-like or COPD-like phenotypes.

Introduction: A substantial proportion of patients with obstructive lung disease have clinical features of both asthma and COPD. 129Xe MRI is highly sensitive to lung function and may be able to assist in phenotyping patients. Objective: To investigate relationships between 129Xe MRI and pulmonary function test metrics in patients with asthma and/or COPD. Methods: 50 patients with asthma and/or COPD taking part in the NOVELTY study (NCT02760329, Reddel HK et al ERJ Open Res 2019 5(1):00036-2018) were recruited from 2 primary care centres. Patients were assessed with 129Xe MRI (ventilation, acinar microstructure and gas exchange) and pulmonary function tests. Results:129Xe MRI ventilation, acinar dimension and gas exchange metrics showed moderate-to-strong correlations with spirometry and TLCO, and with each other. Example images are shown in fig 1. VDP correlated strongly with FEV1/FVC and lung clearance index, and weakly with R20 and AX. RBC/gas and acinar airway dimensions correlated strongly with TLCO. Conclusion: Preliminary MRI analyses show reduced ventilation, increased acinar airway dimensions and reduced gas transfer ratios with increasing disease severity (decreased spirometry and TLCO) in a broadly defined group of patients with asthma and/or COPD, consistent with airway obstruction, enlarged alveolar airspaces, reduced alveolar-capillary barrier thickness and reduced gas transfer.