Introduction Hyperpolarised 129Xe MRI allows quantitative and regionally sensitive measurement of gas exchange. The objective of this work is to characterise longitudinal lung function abnormalities using hyperpolarised 129Xe MRI in patients hospitalised due to COVID-19. Methods A comprehensive 1H and 129Xe 1.5T MRI protocol has been implemented in two longitudinal studies of patients hospitalised due to COVID-19, up to 2 years after hospitalisation: i) with normal or near-normal CT[1] ii) with abnormal CT consistent with signs of interstitial lung damage at 12 weeks post-hospitalisation as part of the XMAS study[2]. Matching MRI protocols were performed in both studies including dissolved phase xenon imaging, from which the fraction of xenon dissolved in the pulmonary red blood cells compared to the xenon dissolved in the pulmonary membrane is calculated (RBC:M) as a measure of xenon gas transfer. PFTs were also performed. Longitudinal and group comparisons were assessed using non parametric tests. Results 8 patients with normal CT (6 months, n=7; 1 year, n=8; 2 years: n=5) and 25 patients with abnormal CT were recruited (6 months, n= 16; 1 year, n=14; 2 year, n=6). Patients with normal CT showed abnormal xenon gas transfer (RBC:M) with no longitudinal change between 6 months and 1 year. TLCO Z-score was normal in 7/7 patients at 6 months, 7/8 patients at 1 year and 3/3 patients with data available at 2 years. Patients with abnormal CT had significantly greater xenon gas transfer impairment at 1 year (6 months: p=0.056, 1 year: p=0.032) and lower TLCO Z-score predicted than patients, with normal TLCO Z-score in 4/16, 3/16, and 1/6 patients with data available at 6 months, 1 year and 2 years respectively. Conclusions Xenon gas transfer can detect ongoing abnormalities in patients hospitalised due to COVID-19 up to two years after hospitalisation, including in patients with normal CT and PFTs. Please refer to page A283 for declarations of interest related to this abstract.

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.

Pulmonary hypertension (PH) is a debilitating progressive disease characterised by abnormally high pulmonary blood pressures, leading to heart failure and, eventually, death. 12 Labours’ Exemplar Project 1 is focused on improving the diagnosis and phenotyping of PH disease through patient-specific models that are carefully calibrated to clinical imaging and physiological measurements. The personalised digital models can be used to uncover new potential treatment strategies for PH disease management. Our initial studies have established a modelling workflow to evaluate response to treatment in a chronic thromboembolic PH patient cohort for whom surgical treatment is an option. Here we present some of the results of this pilot study, outline how this pipeline can be applied to other cardiovascular conditions, and future studies that will build on this work.

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.

Chronic thromboembolic pulmonary hypertension (CTEPH) involves abnormally high blood pressure in the pulmonary vessels and is associated with small vessel vasculopathy and pre-capillary proximal occlusions. Management of CTEPH disease is challenging, therefore accurate diagnosis is crucial in ensuring effective treatment and improved patient outcomes. The treatment of choice for CTEPH is pulmonary endarterectomy, which is an invasive surgical intervention to remove thrombi. Following PEA, a number of patients experience poor outcomes or worse-than-expected improvements, which may indicate that they have significant small vessel disease. A method that can predict the extent of distal remodelling may provide useful clinical information to plan appropriate CTEPH patient treatment. Here, a novel biophysical modelling approach has been developed to estimate and quantify the extent of distal remodelling. This method includes a combination of mathematical modelling and computed tomography pulmonary angiography to first model the geometry of the pulmonary arteries and to identify the under-perfused regions in CTEPH. The geometric model is then used alongside haemodynamic measurements from right heart catheterisation to predict distal remodelling. In this study, the method is tested and validated using synthetically generated remodelling data. Then, a preliminary application of this technique to patient data is shown to demonstrate the potential of the approach for use in the clinical setting.Clinical relevance— Patient-specific modelling can help provide useful information regarding the extent of distal vasculopathy on a per-patient basis, which remains challenging. Physicians can be unsure of outcomes following pulmonary endarterectomy. Therefore, the predictive aspect of the patient’s response to surgery can help with clinical decision-making.

The patterns of idiopathic pulmonary fibrosis (IPF) lung disease that directly correspond to elevated hyperpolarised gas diffusion-weighted (DW) MRI metrics are currently unknown. This study aims to develop a spatial co-registration framework for a voxel-wise comparison of hyperpolarised gas DW-MRI and CALIPER quantitative CT patterns. Sixteen IPF patients underwent 3He DW-MRI and CT at baseline, and eleven patients had a 1-year follow-up DW-MRI. Six healthy volunteers underwent 129Xe DW-MRI at baseline only. Moreover, 3He DW-MRI was indirectly co-registered to CT via spatially aligned 3He ventilation and structural 1H MRI. A voxel-wise comparison of the overlapping 3He apparent diffusion coefficient (ADC) and mean acinar dimension (LmD) maps with CALIPER CT patterns was performed at baseline and after 1 year. The abnormal lung percentage classified with the LmD value, based on a healthy volunteer 129Xe LmD, and CALIPER was compared with a Bland–Altman analysis. The largest DW-MRI metrics were found in the regions classified as honeycombing, and longitudinal DW-MRI changes were observed in the baseline-classified reticular changes and ground-glass opacities regions. A mean bias of −15.3% (95% interval −56.8% to 26.2%) towards CALIPER was observed for the abnormal lung percentage. This suggests DW-MRI may detect microstructural changes in areas of the lung that are determined visibly and quantitatively normal by CT.

Patients with signs of interstitial lung disease at 12 weeks after hospitalisation due to COVID-19 underwent 1H and 129Xe MRI. 129Xe MRI showed impaired xenon gas transfer (RBC:M and RBC:gas) at 24 and 52 weeks after hospital admission, with no longitudinal change between 24 and 52 weeks observed in 129Xe MRI metrics or PFT transfer factor. Xenon MRI metrics correlated significantly with PFT transfer factor at 24 weeks (RBC:M, RBC:gas, LmD) and 52 weeks (RBC:M, RBC:gas, LmD).

Rationale: Preterm birth is associated with low lung function in childhood, but little is known about the lung microstructure in childhood. Objectives: We assessed the differential associations between the historical diagnosis of bronchopulmonary dysplasia (BPD) and current lung function phenotypes on lung ventilation and microstructure in preterm-born children using hyperpolarized 129Xe ventilation and diffusion-weighted magnetic resonance imaging (MRI) and multiple-breath washout (MBW). Methods: Data were available from 63 children (aged 9-13 yr), including 44 born preterm (<= 34 weeks' gestation) and 19 term-born control subjects (>= 37 weeks' gestation). Preterm-born children were classified, using spirometry, as prematurity-associated obstructive lung disease (POLD; FEV1, lower limit of normal [LLN] and FEV1/FVC, LLN), prematurity-associated preserved ratio of impaired spirometry (FEV1, LLN and FEV1/FVC >= LLN), preterm-(FEV1 >= LLN) and term-born control subjects, and those with and without BPD. Ventilation heterogeneity metrics were derived from 129Xe ventilation MRI and SF6 MBW. Alveolar microstructural dimensions were derived from Xe-129 diffusion-weighted MRI. Measurements and Main Results: Xe-129 ventilation defect percentage and ventilation heterogeneity index were significantly increased in preterm-born children with POLD. In contrast, mean Xe-129 apparent diffusion coefficient, Xe-129 apparent diffusion coefficient interquartile range, and Xe-129 mean alveolar dimension interquartile range were significantly increased in preterm-born children with BPD, suggesting changes of alveolar dimensions. MBW metrics were all significantly increased in the POLD group compared with preterm- and term-born control subjects. Linear regression confirmed the differential effects of obstructive disease on ventilation defects and BPD on lung microstructure. Conclusion: We show that ventilation abnormalities are associated with POLD, and BPD in infancy is associated with abnormal lung microstructure.

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.

BackgroundHyperpolarised 129-xenon (129Xe) magnetic resonance imaging (MRI) shows promise in monitoring the progression of idiopathic pulmonary fibrosis (IPF) due to the lack of ionising radiation and the ability to quantify functional impairment. Diffusion-weighted (DW)-MRI with hyperpolarised gases can provide information about lung microstructure. The aims were to compare129Xe DW-MRI measurements with pulmonary function tests (PFTs), and to assess whether they can detect early signs of disease progression in patients with newly diagnosed IPF.MethodsThis is a prospective, single-centre, observational imaging study of patients presenting with IPF to Northern General Hospital (Sheffield, UK). Hyperpolarised129Xe DW-MRI was performed at 1.5 T on a whole-body General Electric HDx scanner and PFTs were performed on the same day as the MRI scan.ResultsThere was an increase in global129Xe apparent diffusion coefficient (ADC) between the baseline and 12-month visits (mean 0.043 cm2·s−1, 95% CI 0.040–0.047 cm2·s−1versusmean 0.045 cm2·s−1, 95% CI 0.040–0.049 cm2·s−1; p=0.044; n=20), with no significant change in PFTs over the same time period. There was also an increase in129Xe ADC in the lower zone (p=0.027), and an increase in129Xe mean acinar dimension in the lower zone (p=0.033) between the baseline and 12-month visits.129Xe DW-MRI measurements correlated strongly with diffusing capacity of the lung for carbon monoxide (% predicted), transfer coefficient of the lung for carbon monoxide (KCO) andKCO(% predicted).Conclusions129Xe DW-MRI measurements appear to be sensitive to early changes of microstructural disease that are consistent with progression in IPF at 12 months. As new drug treatments are developed, the ability to quantify subtle changes using129Xe DW-MRI could be particularly valuable.

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.

This work uses a multinuclear 1 H and 129 Xe protocol to assess pathophysiological changes in patients with COVID-19 pneumonia, without signs of interstitial lung disease, at 6 and 12 weeks after hospital admission. 1 H and 129 Xe protocol: ultra-short echo time, dynamic contrast enhanced lung perfusion, 129 Xe lung ventilation, 129 Xe diffusion weighted MRI, 129 Xe 3D spectroscopic imaging. Though significant improvements in lung ventilation homogeneity (decreased low ventilation percentage and ventilation coefficient of variation), gas transfer (increased RBC:TP, decreased TP T 2 * ) and perfusion (increased pulmonary blood volume and flow) were seen between 6 and 12 weeks, low RBC:TP ratio persisted for some patients.

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.

The use of pulmonary MRI in a clinical setting has historically been limited. Whilst CT remains the gold-standard for structural lung imaging in many clinical indications, technical developments in ultrashort and zero echo time MRI techniques are beginning to help realise non-ionising structural imaging in certain lung disorders. In this invited review, we discuss a complementary technique – hyperpolarised (HP) gas MRI with inhaled 3 He and 129 Xe – a method for functional and microstructural imaging of the lung that has great potential as a clinical tool for early detection and improved understanding of pathophysiology in many lung diseases. HP gas MRI now has the potential to make an impact on clinical management by enabling safe, sensitive monitoring of disease progression and response to therapy. With reference to the significant evidence base gathered over the last two decades, we review HP gas MRI studies in patients with a range of pulmonary disorders, including COPD/emphysema, asthma, cystic fibrosis, and interstitial lung disease. We provide several examples of our experience in Sheffield of using these techniques in a diagnostic clinical setting in challenging adult and paediatric lung diseases.

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.