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Background Post-COVID-19 condition encompasses symptoms following COVID-19 infection that linger at least 4 weeks after the end of active infection. Symptoms are wide ranging, but breathlessness is common. Purpose To determine if the previously described lung abnormalities seen on hyperpolarized (HP) pulmonary xenon 129 (129Xe) MRI scans in participants with post-COVID-19 condition who were hospitalized are also present in participants with post-COVID-19 condition who were not hospitalized. Materials and Methods In this prospective study, nonhospitalized participants with post-COVID-19 condition (NHLC) and posthospitalized participants with post-COVID-19 condition (PHC) were enrolled from June 2020 to August 2021. Participants underwent chest CT, HP 129Xe MRI, pulmonary function testing, and the 1-minute sit-to-stand test and completed breathlessness questionnaires. Control subjects underwent HP 129Xe MRI only. CT scans were analyzed for post-COVID-19 interstitial lung disease severity using a previously published scoring system and full-scale airway network (FAN) modeling. Analysis used group and pairwise comparisons between participants and control subjects and correlations between participant clinical and imaging data. Results A total of 11 NHLC participants (four men, seven women; mean age, 44 years ± 11 [SD]; 95% CI: 37, 50) and 12 PHC participants (10 men, two women; mean age, 58 years ±10; 95% CI: 52, 64) were included, with a significant difference in age between groups (P = .05). Mean time from infection was 287 days ± 79 (95% CI: 240, 334) and 143 days ± 72 (95% CI: 105, 190) in NHLC and PHC participants, respectively. NHLC and PHC participants had normal or near normal CT scans (mean, 0.3/25 ± 0.6 [95% CI: 0, 0.63] and 7/25 ± 5 [95% CI: 4, 10], respectively). Gas transfer (DLCO) was different between NHLC and PHC participants (mean DLCO, 76% ± 8 [95% CI: 73, 83] vs 86% ± 8 [95% CI: 80, 91], respectively; P = .04), but there was no evidence of other differences in lung function. Mean red blood cell–to-tissue plasma ratio was different between volunteers (mean, 0.45 ± 0.07; 95% CI: 0.43, 0.47]) and PHC participants (mean, 0.31 ± 0.10; 95% CI: 0.24, 0.37; P = .02) and between volunteers and NHLC participants (mean, 0.37 ± 0.10; 95% CI: 0.31, 0.44; P = .03) but not between NHLC and PHC participants (P = .26). FAN results did not correlate with DLCO) or HP 129Xe MRI results. Conclusion Nonhospitalized participants with post-COVID-19 condition (NHLC) and posthospitalized participants with post-COVID-19 condition (PHC) showed hyperpolarized pulmonary xenon 129 MRI and red blood cell–to-tissue plasma abnormalities, with NHLC participants demonstrating lower gas transfer than PHC participants despite having normal CT findings.

Hyperpolarized gas MRI can quantify regional lung ventilation via biomarkers, including the ventilation defect percentage (VDP). VDP is computed from segmentations derived from spatially co-registered functional hyperpolarized gas and structural proton (We hypothesized that a DL-based dual-channel approach, leveraging bothRetrospective.A total of 480 corresponding1.5-T, three-dimensional (3D) spoiled gradient-recalledWe developed a multimodal DL approach, integratingFriedman tests with post hoc Bonferroni correction for multiple comparisons compared single-channel and dual-channel DL approaches using Dice similarity coefficient (DSC), average boundary Hausdorff distance (average HD), and relative error (XOR) metrics. Bland-Altman analysis and paired t-tests compared manual and DL-generated VDPs. A P value 0.05 was considered statistically significant.The dual-channel approach significantly outperformed single-channel approaches, achieving a median (range) DSC, average HD, and XOR of 0.967 (0.867-0.978), 1.68 mm (37.0-0.778), and 0.066 (0.246-0.045), respectively. DL-generated VDPs were statistically indistinguishable from manually generated VDPs (P = 0.710).Our dual-channel approach generated LCEs, which could be integrated with ventilated lung segmentations to produce biomarkers such as the VDP without manual intervention.4.Stage 1.

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.

IntroductionMicrovascular 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.

BackgroundLong-COVID is an umbrella term used to describe ongoing symptoms following COVID-19 infection after four weeks. Symptoms are wide-ranging but breathlessness is one of the most common and can persist for months after the initial infection. Investigations including Computed Tomography (CT), and physiological measurements (lung function tests) are usually unremarkable. The mechanisms driving breathlessness remain unclear, and this may be hindering the development of effective treatments.MethodsEleven non-hospitalised Long-COVID (NHLC, 4 male), 12 post-hospitalised COVID-19 (PHC, 10 male) patients were recruited from a Post-COVID Assessment clinic, and thirteen healthy controls (6 female) were recruited to undergo Hyperpolarized Xenon Magnetic Resonance Imaging (Hp-XeMRI). NHLC and PHC participants underwent contemporaneous CT, Hp-XeMRI, lung function tests, 1-minute sit-to-stand test and breathlessness questionnaires. Statistical analysis included group and pair-wise comparisons between patients and controls, and correlations between patient clinical and imaging data.ResultsNHLC and PHC patients were 287 ± 79 [range 190-437] and 149 ± 68 [range 68-269] days from infection, respectively. All NHLC patients had normal CT scans, and the PHC had normal or near normal CT scans (0.3/25 ± 0.6 [range 0-2] and 7/25 ± 5 [range 4-8], respectively). There was a significant difference in TLco (%) between NHLC and PHC patients (76 ± 8 % vs 86 ± 8%, respectively, p = 0.04) but no differences in other measurements of lung function. There were significant differences in RBC:TP mean between volunteers (0.45 ± 0.07, range [0.33-0.55]) and PHC (0.31 ± 0.11, [range 0.16-0.37]) and NHLC (0.35 ± 0.09, [range 0.26-0.58]) patients, but not between NHLC and PHC (p = 0.26).ConclusionThere are RBC:TP abnormalities in NHLC and PHC patients, with NHLC patients also demonstrating lower TLco than PHC patients despite their having normal CT scans. These abnormalities are present many months after the initial infection.Summary statementHyperpolarized Xenon MRI and TLco demonstrate significantly impaired gas transfer in non-hospitalised long-COVID patients when all other investigations are normal.Key resultsThere are significant differences in RBC:TP mean between healthy controls and PHC/NHLC patients (0.45 ± 0.07, range [0.33-0.55], 0.31 ± 0.11, [range 0.16-0.37], 0.35 ± 0.09, [range 0.26-0.58], respectively, p < 0.05 after correction for multiple comparisons) indicating a change in lung compartment volumes between groups.There was a significant difference in TLco (%) between NHLC and PHC patients (76 ± 8 % vs 86 ± 8%, respectively, p = 0.04), despite normal or near normal FEV (%) (100 ± 13% [range 72-123%] and 88 ± 21% [range 62-113%], p>0.05.There were significant differences in CT abnormalities between NHLC and PHC patients (0.3/25 ± 0.6 [range 0-2] and 7/25 ± 5 [range 4-8], respectively) despite similarly impaired RBC:TP.

Objectives Design and build a portable xenon-129 (129Xe) hyperpolariser for clinically accessible 129Xe lung MRI. Methods The polariser system consists of six main functional components: (i) a laser diode array and optics; (ii) a B0 coil assembly; (iii) an oven containing an optical cell; (iv) NMR and optical spectrometers; (v) a gas-handling manifold; and (vi) a cryostat within a permanent magnet. All components run without external utilities such as compressed air or three-phase electricity, and require just three mains sockets for operation. The system can be manually transported in a lightweight van and rapidly installed on a small estates footprint in a hospital setting. Results The polariser routinely provides polarised 129Xe for routine clinical lung MRI. To test the concept of portability and rapid deployment, it was transported 200 km, installed at a hospital with no previous experience with the technology and 129Xe MR images of a diagnostic quality were acquired the day after system transport and installation. Conclusion This portable 129Xe hyperpolariser system could form the basis of a cost-effective platform for wider clinical dissemination and multicentre evaluation of 129Xe lung MR imaging. Advances in knowledge Our work successfully demonstrates the feasibility of multicentre clinical 129Xe MRI with a portable hyperpolariser system.

Indices of ventilation heterogeneity (VH) from multiple breath washout (MBW) have been shown to correlate well with VH indices derived from hyperpolarised gas ventilation MRI. Here we report the prediction of ventilation distributions from MBW data using a mathematical model, and the comparison of these predictions with imaging data.We developed computer simulations of the ventilation distribution in the lungs to model MBW measurement with 3 parameters: σThe MRI indices measured (IWe have shown that the ventilation distribution in the lung can be inferred from an MBW signal, and verified this using ventilation MRI. The Bayesian method employed extracts this information with fewer breath cycles than required for LCI, reducing acquisition time required, and gives uncertainty bounds, which are important for clinical decision making.

Imaging of the different resonances of dissolved hyperpolarized xenon-129 (10 HV and 25 subjects with IPF underwent dissolvedResults show an excellent chemical shift separation of the dissolvedLung MRI of dissolved

Background MRI with inhaled hyperpolarized helium 3 (

To develop and assess a method for acquiring coregistered proton anatomical and hyperpolarizedRetrospective CS simulations were performed on fully sampled ventilation images acquired from one healthy smoker to optimize reconstruction parameters. Prospective same-breath anatomical and ventilation images were also acquired in five ex-smokers with an acceleration factor of 3 for hyperpolarizedRetrospective simulations showed good agreement between fully sampled and CS-reconstructed (acceleration factor of 3) images with MAE (root mean square error) of 3.9% (4.5%). The prospective same-breath images showed a good match in ventilation distribution with an average RWith CS, high-quality 3D images of hyperpolarized

Two magnetic resonance specific ventilation imaging (SVI) techniques, namely, oxygen-enhanced proton (OE-(1)H) and hyperpolarized (3)He (HP-(3)He), were compared in eight healthy supine subjects [age 32 (6) yr]. An in-house radio frequency coil array for (1)H configured with the (3)He transmit-receive coil in situ enabled acquisition of SVI data from two nuclei from the same slice without repositioning the subjects. After 3 × 3 voxel downsampling to account for spatial registration errors between the two SV images, the voxel-by-voxel correlation coefficient of two SV maps ranged from 0.11 to 0.63 [0.46 mean (0.17 SD); P < 0.05]. Several indexes were analyzed and compared from the tidal volume-matched SV maps: the mean of SV log-normal distribution (SVmean), the standard deviation of the distribution as a measure of SV heterogeneity (SVwidth), and the gravitational gradient (SVslope). There were no significant differences in SVmean [OE-(1)H: 0.28 (0.08) and HP-(3)He: 0.32 (0.14)], SVwidths [OE-(1)H: 0.28 (0.08) and HP-(3)He: 0.27 (0.10)], and SVslopes [OE-(1)H: −0.016 (0.006) cm(−1) and HP-(3)He: −0.013 (0.007) cm(−1)]. Despite the statistical similarities of the population averages, Bland-Altman analysis demonstrated large individual intertechnique variability. SDs of differences in these indexes were 42% (SVmean), 46% (SVwidths), and 62% (SVslopes) of their corresponding overall mean values. The present study showed that two independent, spatially coregistered, SVI techniques presented a moderate positive voxel-by-voxel correlation. Population averages of SVmean, SVwidth, and SVslope were in close agreement. However, the lack of agreement when the data sets were analyzed individually might indicate some fundamental mechanistic differences between the techniques. NEW & NOTEWORTHY To the best of our knowledge, this is the first cross-comparison of two different specific ventilation (SV) MRI techniques in the human lung (i.e., oxygen-enhanced proton and hyperpolarized (3)He). The present study showed that two types of spatially coregistered SV images presented a modest positive correlation. The two techniques also yielded similar population averages of SV indexes such as log-normal mean, SV heterogeneity, and the gravitational slope, albeit with some intersubject variability.

To compare in vivo lung morphometry parameters derived from theoretical gas diffusion models, the cylinder model and stretched exponential model, in a range of acinar microstructural length scales encountered in healthy and diseased lungs withThree-dimensional multiple b-valueFor bothWithin the experimental range of parameters considered here for both

Knowledge of airflow patterns in the large airways is of interest in obstructive airways disease and in the development of inhaled therapies. Computational fluid dynamics (CFD) simulations are used to study airflow in realistic airway models but usually need experimental validation.To develop MRI-based methods to study airway flow in realistic 3D-printed models.Case control.Two 3D-printed lung models.1.5-3T, flow MRI.Two human airway models, respectively including and excluding the oral cavity and upper airways derived from MR and CT imaging, were 3D-printed. 3D flow MRI was performed at different flow conditions corresponding to slow and steady airflow inhalation rates. Water was used as the working fluid to mimic airflow. Dynamic acquisition of 1D velocity profiles was also performed at different locations in the trachea to observe variability during nonsteady conditions.Linear regression analysis to compare both flow velocity fields and local flow rates from CFD simulations and experimental measurement with flow MRI.A good agreement was obtained between 3D velocity maps measured with flow MRI and predicted by CFD simulations, with linear regression R-squared values ranging from 0.39 to 0.94 when performing a pixel-by-pixel comparison of each velocity component. The flow distribution inside the lung models was also similar, with average slope and R-squared values of 0.96 and 0.99, respectively, when comparing local flow rates assessed at different branching locations. In the model including the upper airways, a turbulent laryngeal jet flow was observed with both methods and affected remarkably the velocity profiles in the trachea.We propose flow MRI using water as a surrogate fluid to air, as a validation tool for CFD simulations of airflow in geometrically realistic models of the human airways.3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1400-1409.

Background To support translational lung MRI research with hyperpolarized 129Xe gas, comprehensive evaluation of derived quantitative lung function measures against established measures from 3He MRI is required. Few comparative studies have been performed to date, only at 3T, and multisession repeatability of 129Xe functional metrics have not been reported. Purpose/Hypothesis To compare hyperpolarized 129Xe and 3He MRI‐derived quantitative metrics of lung ventilation and microstructure, and their repeatability, at 1.5T. Study Type Retrospective. Population Fourteen healthy nonsmokers (HN), five exsmokers (ES), five patients with chronic obstructive pulmonary disease (COPD), and 16 patients with nonsmall‐cell lung cancer (NSCLC). Field Strength/Sequence 1.5T. NSCLC, COPD patients and selected HN subjects underwent 3D balanced steady‐state free‐precession lung ventilation MRI using both 3He and 129Xe. Selected HN, all ES, and COPD patients underwent 2D multislice spoiled gradient‐echo diffusion‐weighted lung MRI using both hyperpolarized gas nuclei. Assessment Ventilated volume percentages (VV%) and mean apparent diffusion coefficients (ADC) were derived from imaging. COPD patients performed the whole MR protocol in four separate scan sessions to assess repeatability. Same‐day pulmonary function tests were performed. Statistical Tests Intermetric correlations: Spearman's coefficient. Intergroup/internuclei differences: analysis of variance / Wilcoxon's signed rank. Repeatability: coefficient of variation (CV), intraclass correlation (ICC) coefficient. Results A significant positive correlation between 3He and 129Xe VV% was observed (r = 0.860, P

Purpose To obtain whole lung morphometry measurements from 129Xe in a single breath‐hold with 3D multiple b‐value 129Xe diffusion‐weighted MRI (DW‐MRI) with an empirically optimized diffusion time and compressed sensing for scan acceleration. Methods Prospective three‐fold undersampled 3D multiple b‐value hyperpolarized 129Xe DW‐MRI datasets were acquired, and the diffusion time (Δ) was iterated so as to provide diffusive length scale (LmD) estimates from the stretched exponential model (SEM) that are comparable to those from 3He. The empirically optimized 129Xe diffusion time was then implemented with a four‐fold undersampling scheme and was prospectively benchmarked against 3He measurements in a cohort of five healthy volunteers, six ex‐smokers, and two chronic obstructive pulmonary disease patients using both SEM‐derived LmD and cylinder model (CM)‐derived mean chord length (Lm). Results Good agreement between the mean 129Xe and 3He LmD (mean difference, 2.2%) and Lm (mean difference, 1.1%) values was obtained in all subjects at an empirically optimized 129Xe Δ = 8.5 ms. Conclusion Compressed sensing has facilitated single‐breath 3D multiple b‐value 129Xe DW‐MRI acquisitions, and results at 129Xe Δ = 8.5 ms indicate that 129Xe provides a viable alternative to 3He for whole lung morphometry mapping with either the SEM or CM. Magn Reson Med 79:2986–2995, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

To develop an image-processing pipeline for semiautomated (SA) and reproducible analysis of hyperpolarized gas lung ventilation and proton anatomical magnetic resonance imaging (MRI) scan pairs. To compare results from the software for total lung volume (TLV), ventilated volume (VV), and percentage lung ventilated volume (%VV) calculation to the current manual "basic" method and a K-means segmentation method.Six patients were imaged with hyperpolarizedWhen comparing values of %VV, agreement between observers improved using the SA method (mean; R = 0.984, ICC = 0.980, LOA = 7.5%) when compared to the basic method (mean; R = 0.863, ICC = 0.873, LOA = 14.2%) nonsignificantly (pA semiautomated image processing software was developed that improves interobserver agreement and correlation of lung ventilation volume percentage when compared to the currently used basic method and provides more consistent segmentations than the K-means method.3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:640-646.

Purpose To evaluate the reproducibility of indices of lung microstructure and function derived from 129Xe chemical shift saturation recovery (CSSR) spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD), and to study the sensitivity of CSSR‐derived parameters to pulse sequence design and lung inflation level. Methods Preliminary data were collected from five volunteers on three occasions, using two implementations of the CSSR sequence. Separately, three volunteers each underwent CSSR at three different lung inflation levels. After analysis of these preliminary data, five COPD patients were scanned on three separate days, and nine age‐matched volunteers were scanned three times on one day, to assess reproducibility. Results CSSR‐derived alveolar septal thickness (ST) and surface‐area‐to‐volume (S/V) ratio values decreased with lung inflation level (P

Hyperpolarized (HP) (3) He and (129) Xe are two gases with different fluid dynamic properties, which can be used as tracers for airflow measurement in the lungs with phase contrast velocimetry MRI sequences. In this work, in vivo measurements of velocity maps of airflow in the upper airways and first bronchi of healthy volunteers were obtained with both gases and compared.To reduce the acquisition time, a Compressed Sensing (CS) based acquisition and reconstruction algorithm was developed and optimized for flow measurement in three directions by including the sparsity of the complex difference images as prior knowledge.CS simulations on retrospectively under-sampled images demonstrated a better reconstruction with the inclusion of the complex difference terms in the cost function. The technique was then validated with a prospective acquisition study providing artifact free maps with acceleration factors up to 3.The presented technique opens up the possibility to map velocity inside human lungs. The results are of interest for the validation of computational fluid dynamics flow simulations and for understanding the spatio-temporal evolution of airflow patterns in the airways in vivo with different gas mixtures.