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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 hyperpolarised 129Xe ventilation and diffusion-weighted MRI, and multiple breath washout (MBW). Methods: Data were available from 63 children (aged 9-13 years) including 44 born preterm (≤34 weeks’ gestation) and 19 term-born controls (≥37 weeks’ gestation). Preterm-born children were classified, using spirometry, into prematurity-associated obstructive lung disease (POLD, FEV1

Background\ud \ud 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.\ud \ud \ud \ud Methods\ud \ud We developed computer simulations of the ventilation distribution in the lungs to model MBW measurement with 3 parameters: determining the extent of VH; , the lung volume; and , the dead-space volume. These were inferred for each individual from supine MBW data recorded from 25 patients with cystic fibrosis (CF) using approximate Bayesian computation. The fitted models were used to predict the distribution of gas imaged by 3He ventilation MRI measurements collected from the same visit.\ud \ud \ud \ud Results\ud \ud The MRI indices measured (, the fraction of pixels below one-third of the mean intensity and , the coefficient of variation of pixel intensity) correlated strongly with those predicted by the MBW model fits ( respectively). There was also good agreement between predicted and measured MRI indices (mean bias limits of agreement: and Fitted model parameters were robust to truncation of MBW data.\ud \ud \ud \ud Conclusion\ud \ud We 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.

Respiratory diseases are leading causes of mortality and morbidity worldwide. Pulmonary imaging is an essential component of the diagnosis, treatment planning, monitoring, and treatment assessment of respiratory diseases. Insights into numerous pulmonary pathologies can be gleaned from functional lung MRI techniques. These include hyperpolarized gas ventilation MRI, which enables visualization and quantification of regional lung ventilation with high spatial resolution. Segmentation of the ventilated lung is required to calculate clinically relevant biomarkers. Recent research in deep learning (DL) has shown promising results for numerous segmentation problems. Here, we evaluate several 3D convolutional neural networks to segment ventilated lung regions on hyperpolarized gas MRI scans. The dataset consists of 759 helium-3 (3He) or xenon-129 (129Xe) volumetric scans and corresponding expert segmentations from 341 healthy subjects and patients with a wide range of pathologies. We evaluated segmentation performance for several DL experimental methods via overlap, distance and error metrics and compared them to conventional segmentation methods, namely, spatial fuzzy c-means (SFCM) and K-means clustering. We observed that training on combined 3He and 129Xe MRI scans using a 3D nn-UNet outperformed other DL methods, achieving a mean ± SD Dice coefficient of 0.963 ± 0.018, average boundary Hausdorff distance of 1.505 ± 0.969 mm, Hausdorff 95th percentile of 5.754 ± 6.621 mm and relative error of 0.075 ± 0.039. Moreover, limited differences in performance were observed between 129Xe and 3He scans in the testing set. Combined training on 129Xe and 3He yielded statistically significant improvements over the conventional methods (p

Background\ud \ud Post-Covid-19 condition describes symptoms following COVID-19 infection after four weeks. Symptoms are wide-ranging but breathlessness is common.\ud \ud \ud \ud Purpose\ud \ud The purpose of this study was to determine whether the previously described lung abnormalities on Hp-XeMRI in post-hospitalised COVID-19 participants are also present in non-hospitalised participants with Post-Covid-19 condition.\ud \ud \ud \ud Methods\ud \ud In this prospective study, non-hospitalised Post-Covid-19 condition (NHLC) and post-hospitalised COVID-19 (PHC) participants were enrolled from 06/2020 to 08/2021. Participants had chest CT, hyperpolarized pulmonary 129Xenon MRI (Hp-XeMRI), pulmonary function tests, 1-minute sit-to-stand test and breathlessness questionnaires. Control subjects underwent HP-XeMRI only. CT scans were analysed for post COVID interstitial lung disease severity using a previously published scoring system, and Full-scale Airway Network (FAN) modelling. Analysis used group and pair-wise comparisons between participants and controls, and correlations between participant clinical and imaging data.\ud \ud \ud \ud Results\ud \ud A total of 11 NHLC (4:7 Male: Female, 44 ± 11 years, [37-50], (mean ± SD, [95% CI]) and 12 PHC (10:2, Male: Female, 58 ± 10 years, [52-64]) participants were included, with a significant difference in age between groups, p = 0.05. NHLC participants were 287 ± 79, [240-334] and PHC 143 ± 72, [105-190] days from infection, respectively. NHLC and PHC participants had normal or near normal CT scans (0.3/25 ± 0.6, [0-0.63] and 7/25 ± 5, [4-10], respectively). Gas transfer (DLCO (%)) was different between NHLC and PHC participants (76 ± 8%, [73-83] vs 86 ± 8%, [80-91] respectively, p = 0.04) but there was no evidence of other differences in lung function. Red Blood Cell:Tissue Plasma (RBC:TP) mean was different between volunteers vs PHC (0.45 ± 0.07, [0.43-0.47] vs (0.31 ± 0.10, [0.24-0.37], respectively, p = 0.02) and volunteers vs NHLC (0.37 ± 0.10, [0.31-0.44], p = 0.03) participants, but not between NHLC and PHC participants (p = 0.26). FAN results did not correlate with DLCO or Hp- XeMRI.\ud \ud \ud \ud Conclusion\ud \ud NHLC and PHC subjects showed Hp-XeMRI RBC:TP abnormalities, with NHLC participants demonstrating lower DLCO than PHC participants despite having normal CT scans.

Objectives\ud \ud Design and build a portable xenon-129 (129Xe) hyperpolariser for clinically accessible 129Xe lung MRI.\ud \ud \ud \ud Methods\ud \ud 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.\ud \ud \ud \ud Results\ud \ud 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.\ud \ud \ud \ud Conclusion\ud \ud 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.

Hyperpolarized (HP) 129Xe MRI uniquely images pulmonary ventilation, gas exchange, and terminal airway morphology rapidly and safely, providing novel information not possible using conventional imaging modalities or pulmonary function tests. As such, there is mounting interest in expanding the use of biomarkers derived from HP 129Xe MRI as outcome measures in multi-site clinical trials across a range of pulmonary disorders. Until recently, HP 129Xe MRI techniques have been developed largely independently at a limited number of academic centers, without harmonizing acquisition strategies. To promote uniformity and adoption of HP 129Xe MRI more widely in translational research, multi-site trials, and ultimately clinical practice, this position paper from the 129Xe MRI Clinical Trials Consortium (https://cpir.cchmc.org/XeMRICTC) recommends standard protocols to harmonize methods for image acquisition in HP 129Xe MRI. Recommendations are described for the most common HP gas MRI techniques—calibration, ventilation, alveolar-airspace size, and gas exchange—across MRI scanner manufacturers most used for this application. Moreover, recommendations are described for 129Xe dose volumes and breath-hold standardization to further foster consistency of imaging studies. The intention is that sites with HP 129Xe MRI capabilities can readily implement these methods to obtain consistent high-quality images that provide regional insight into lung structure and function. While this document represents consensus at a snapshot in time, a roadmap for technical developments is provided that will further increase image quality and efficiency. These standardized dosing and imaging protocols will facilitate the wider adoption of HP 129Xe MRI for multi-site pulmonary research.

Background: Hyperpolarised gas MRI can be used to assess ventilation patterns. Previous studies have shown the image derived metric of ventilation defect percent (VDP) to correlate with FEV1/FVC and FEV1 in asthma.\ud \ud Objectives: To explore the utility of hyperpolarised xenon-129 (129Xe) ventilation MRI in clinical care and examine its relationship with spirometry and other clinical metrics in people seen in a severe asthma service.\ud \ud Methods: 26 people referred from a severe asthma clinic for MRI scanning were assessed by contemporaneous 129Xe MRI and spirometry. A sub-group of 18 patients also underwent reversibility testing with spirometry and MRI. Quantitative MRI measures of ventilation were calculated; VDP and the ventilation heterogeneity index (VHI), and compared to spirometry, ACQ7 and blood eosinophil count. Images were reviewed by a multidisciplinary team.\ud \ud Results: VDP and VHI correlated with FEV1, FEV1/FVC and FEF25–75% but not with ACQ7 or blood eosinophil count. Discordance of MRI imaging and symptoms and/or pulmonary function tests also occurred, prompting diagnostic re-evaluation in some cases.\ud \ud Conclusion Hyperpolarised gas MRI provides a complementary method of assessment in people with difficult to manage asthma in a clinical setting. When used as a tool supporting clinical care in a severe asthma service, occurrences of discordance between symptoms, spirometry and MRI scanning indicate how MRI scanning may add to a management pathway.

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 3He and 129Xe – 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.

Enlargements of distal airspaces can indicate pathological changes in the lung, but accessible and precise techniques able to measure these regions are lacking. Airspace Dimension Assessment with inhaled nanoparticles (AiDA) is a new method developed for in vivo measurement of distal airspace dimensions. The aim of this study was to benchmark the AiDA method against quantitative measurements of distal airspaces from hyperpolarised 129Xe diffusion-weighted (DW)-lung magnetic resonance imaging (MRI). AiDA and 129Xe DW-MRI measurements were performed in 23 healthy volunteers who spanned an age range of 23–70 years. The relationship between the 129Xe DW-MRI and AiDA metrics was tested using Spearman’s rank correlation coefficient. Significant correlations were observed between AiDA distal airspace radius (rAiDA) and mean 129Xe apparent diffusion coefficient (ADC) (p

This paper introduces a linear operator for the purposes of quantifying the spectral properties of transport within resistive trees, such as airflow in lung airway networks. The operator, which we call the Maury matrix, acts only on the terminal nodes of the tree and is equivalent to the adjacency matrix of a complete graph summarizing the relationships between all pairs of terminal nodes. We show that the eigenmodes of the Maury operator have a direct physical interpretation as the relaxation, or resistive, modes of the network. We apply these findings to both idealized and image-based models of ventilation in lung airway trees and show that the spectral properties of the Maury matrix characterize the flow asymmetry in these networks more concisely than the Laplacian modes, and that eigenvector centrality in the Maury spectrum is closely related to the phenomenon of ventilation heterogeneity caused by airway narrowing or obstruction. This method has applications in dimensionality reduction in simulations of lung mechanics, as well as for characterization of models of the airway tree derived from medical images.

In this study, the effect of lung volume on quantitative measures of lung ventilation was investigated using MRI with hyperpolarized 3He and 129Xe. Six volunteers were imaged with hyperpolarized 3He at five different lung volumes (residual volume (RV), RV+1L, functional residual capacity (FRC), FRC+1L and total lung capacity (TLC)), and three were also imaged with hyperpolarized 129Xe. Imaging at each of the lung volumes was repeated twice on the same day with corresponding 1H lung anatomical images. Percentage lung ventilated volume (%VV) and variation of signal intensity (heterogeneity score, Hscore) were evaluated. Increased ventilation heterogeneity, quantified by reduced %VV and increased Hscore, was observed at lower lung volumes with the least ventilation heterogeneity observed at TLC. For 3He MRI data, the coefficient of variation of %VV was less than 1.5% and less than 5.5% for Hscore at all lung volumes, whilst for 129Xe data the values were 4% and 10% respectively. Generally, %VV generated from 129Xe images was lower than that seen from 3He images. The good repeatability of 3He %VV found here supports prior publications showing that percentage lung ventilated volume is a robust method for assessing global lung ventilation. The greater ventilation heterogeneity observed at lower lung volumes indicates that there may be partial airway closure in healthy lungs and that lung volume should be carefully considered for reliable longitudinal measurements of %VV and Hscore. The results suggest that imaging patients at different lung volumes may help to elucidate obstructive disease pathophysiology and progression.

Purpose\ud To develop and apply an image acquisition and analysis strategy for spatial comparison of CT-ventilation images with hyperpolarized gas MRI.\ud \ud Methods\ud 11 lung cancer patients underwent 129Xe and 3He ventilation MRI and co-registered 1H anatomical MRI. Expiratory and inspiratory breath-hold CTs were used for deformable image registration and calculation of three CT-ventilation metrics: Hounsfield unit (CTHU), Jacobian (CTJac) and specific gas volume change (CTSGV). Inspiration CT and hyperpolarized gas ventilation MRI were registered via same-breath anatomical 1H-MRI. Voxel-wise Spearman correlation coefficients were calculated between each CT-ventilation image and its corresponding 3He/129Xe-MRI, and for the mean values in regions of interest (ROIs) ranging from fine to coarse in-plane dimensions of 5x5, 10x10, 15x15 and 20x20, located within the lungs as defined by the same-breath 1H-MRI lung mask. Correlation of 3He and 129Xe-MRI was also assessed.\ud \ud Results\ud Spatial correlation of CT-ventilation against 3He/129Xe-MRI increased with ROI size. For example, for CTHU, mean±SD Spearman coefficients were 0.37±0.19/0.33±0.17 at the voxel-level and 0.52±0.20/0.51±0.18 for 20x20 ROIs, respectively. Correlations were stronger for CTHU than for CTJac or CTSGV. Correlation of 3He with 129Xe-MRI was consistently higher than either gas against CT-ventilation maps over all ROIs (p

Hyperpolarised helium-3 (3He) ventilation magnetic resonance imaging (MRI) and multiple-breath washout (MBW) are sensitive methods for detecting lung disease in cystic fibrosis (CF). We aimed to explore their relationship across a broad range of CF disease severity and patient age, as well as assess the effect of inhaled lung volume on ventilation distribution.32 children and adults with CF underwent MBW and 3He-MRI at a lung volume of end-inspiratory tidal volume (EIVT). In addition, 28 patients performed 3He-MRI at total lung capacity. 3He-MRI scans were quantitatively analysed for ventilation defect percentage (VDP), ventilation heterogeneity index (VHI) and the number and size of individual contiguous ventilation defects. From MBW, the lung clearance index, convection-dependent ventilation heterogeneity (Scond) and convection-diffusion-dependent ventilation heterogeneity (Sacin) were calculated.VDP and VHI at EIVT strongly correlated with lung clearance index (r=0.89 and r=0.88, respectively), Sacin (r=0.84 and r=0.82, respectively) and forced expiratory volume in 1 s (FEV1) (r=-0.79 and r=-0.78, respectively). Two distinct 3He-MRI patterns were highlighted: patients with abnormal FEV1 had significantly (p

BACKGROUND: 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. PURPOSE: To develop MRI-based methods to study airway flow in realistic 3D-printed models. STUDY TYPE: Case control. PHANTOM: Two 3D-printed lung models. FIELD STRENGTH/SEQUENCE: 1.5-3T, flow MRI. ASSESSMENT: 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. STATISTICAL TESTS: Linear regression analysis to compare both flow velocity fields and local flow rates from CFD simulations and experimental measurement with flow MRI. RESULTS: 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. DATA CONCLUSION: 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. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

BACKGROUND: To support translational lung MRI research with hyperpolarized129Xe gas, comprehensive evaluation of derived quantitative lung function measures against established measures from3He MRI is required. Few comparative studies have been performed to date, only at 3T, and multisession repeatability of129Xe functional metrics have not been reported. PURPOSE/HYPOTHESIS: To compare hyperpolarized129Xe and3He 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 both3He and129Xe. 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 between3He and129Xe VV% was observed (r = 0.860, P

The upper airways play a significant role in the tracheal flow dynamics. Despite many previous studies, however, the effect of the upper airways on the ventilation distribution in distal airways has remained a challenge. The aim of this study is to experimentally and computationally investigate the dynamic behaviour in the intratracheal flow induced by the upper respiratory tract and to assess its influence on the subsequent tributaries. Patient-specific images from 2 different modalities (magnetic resonance imaging of the upper airways and computed tomography of the lower airways) were segmented and combined. An experimental phantom of patient-specific airways (including the oral cavity, larynx, trachea, down to generations 6-8) was generated using 3D printing. The flow velocities in this phantom model were measured by the flow-sensitised phase contrast magnetic resonance imaging technique and compared with the computational fluid dynamics simulations. Both experimental and computational results show a good agreement in the time-averaged velocity fields as well as fluctuating velocity. The flows in the proximal trachea were complex and unsteady under both lower- and higher-flow rate conditions. Computational fluid dynamics simulations were also performed with an airways model without the upper airways. Although the flow near the carina remained unstable only when the inflow rate was high, the influence of the upper airways caused notable changes in distal flow distributions when the 2 airways models were compared with and without the upper airways. The results suggest that the influence of the upper airways should be included in the respiratory flow assessment as the upper airways extensively affect the flows in distal airways and consequent ventilation distribution in the lungs.

INTRODUCTION: Lung Clearance Index (LCI) is recognised as an early marker of cystic fibrosis (CF) lung disease. The effect of posture on LCI however is important when considering longitudinal measurements from infancy and when comparing LCI to imaging studies. METHODS: 35 children with CF and 28 healthy controls (HC) were assessed. Multiple breath washout (MBW) was performed both sitting and supine in triplicate and analysed for LCI, Scond, Sacin, and lung volumes. These values were also corrected for the Fowler dead-space to create 'alveolar' indices. RESULTS: From sitting to supine there was a significant increase in LCI and a significant decrease in FRC for both CF and HC (p

PURPOSE: To obtain whole lung morphometry measurements from (129) Xe in a single breath-hold with 3D multiple b-value (129) Xe 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 (129) Xe 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 (3) He. The empirically optimized (129) Xe diffusion time was then implemented with a four-fold undersampling scheme and was prospectively benchmarked against (3) He 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 (129) Xe and (3) He LmD (mean difference, 2.2%) and Lm (mean difference, 1.1%) values was obtained in all subjects at an empirically optimized (129) Xe Δ = 8.5 ms. CONCLUSION: Compressed sensing has facilitated single-breath 3D multiple b-value (129) Xe DW-MRI acquisitions, and results at (129) Xe Δ = 8.5 ms indicate that (129) Xe provides a viable alternative to (3) He for whole lung morphometry mapping with either the SEM or CM. Magn Reson Med, 2017. © 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.

Purpose: To assess the magnitude of regional response to respiratory therapeutics in the lungs using Treatment Response Mapping (TRM) with hyperpolarized gas MRI. TRM is used to quantify regional physiological response in asthmatic adults using a bronchodilator challenge.\ud \ud Methods: The study was approved by the national research ethics committee and performed with informed consent. Imaging was performed in 20 adult asthmatic patients using hyperpolarized 3He ventilation MRI. Two sets of baseline images were acquired before inhalation of a bronchodilator (Inhaled Salbutamol 400 mcg) and one set was acquired after. All images were registered for voxelwise comparison. Regional treatment response, ΔR(r), is calculated as the difference in regional gas distribution (R(r) = ratio of inhaled gas to total volume of a voxel when normalized for lung inflation volume) before and after intervention. A voxelwise activation threshold from the variability of the baseline images was applied to ΔR(r) maps. The summed global TRM (ΔRnet) was then used as global lung index for comparison with metrics of bronchodilator response measured using spirometry and the global imaging metric, percentage ventilated volume (%VV).\ud \ud Results: ΔRnet showed significant correlation (p

Purpose\ud \ud 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.\ud \ud Materials and Methods\ud \ud Six patients were imaged with hyperpolarized 3He and same-breath lung 1H MRI at 1.5T and six other patients were scanned with hyperpolarized 129Xe and separate-breath 1H MRI. One expert observer and two users with experience in lung image segmentation carried out the image analysis. Spearman (R), Intraclass (ICC) correlations, Bland–Altman limits of agreement (LOA), and Dice Similarity Coefficients (DSC) between output lung volumes were calculated.\ud \ud Results\ud \ud When 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 (pR = 0.25, pICC = 0.25, and pLOA = 0.50 respectively). DSC of VV and TLV masks significantly improved (P < 0.01) using the SA method (mean; DSCVV = 0.973, DSCTLV = 0.980) when compared to the basic method (mean; DSCVV = 0.947, DSCTLV = 0.957). K-means systematically overestimated %VV when compared to both basic (mean overestimation = 5.0%) and SA methods (mean overestimation = 9.7%), and had poor agreement with the other methods (mean ICC; K-means vs. basic = 0.685, K-means vs. SA = 0.740).\ud \ud Conclusion\ud \ud A 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.\ud \ud Level of Evidence: 3\ud \ud Technical Efficacy: Stage 2

Purpose\ud 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.\ud \ud Methods\ud 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.\ud \ud Results\ud CSSR-derived alveolar septal thickness (ST) and surface-area-to-volume (S/V) ratio values decreased with lung inflation level (P

PURPOSE: To demonstrate three-dimensional (3D) multiple b-value diffusion-weighted (DW) MRI of hyperpolarized (3) He gas for whole lung morphometry with compressed sensing (CS). METHODS: A fully-sampled, two b-value, 3D hyperpolarized (3) He DW-MRI dataset was acquired from the lungs of a healthy volunteer and retrospectively undersampled in the ky and kz phase-encoding directions for CS simulations. Optimal k-space undersampling patterns were determined by minimizing the mean absolute error between reconstructed and fully-sampled (3) He apparent diffusion coefficient (ADC) maps. Prospective three-fold, undersampled, 3D multiple b-value (3) He DW-MRI datasets were acquired from five healthy volunteers and one chronic obstructive pulmonary disease (COPD) patient, and the mean values of maps of ADC and mean alveolar dimension (LmD ) were validated against two-dimensional (2D) and 3D fully-sampled (3) He DW-MRI experiments. RESULTS: Reconstructed undersampled datasets showed no visual artifacts and good preservation of the main image features and quantitative information. A good agreement between fully-sampled and prospective undersampled datasets was found, with a mean difference of +3.4% and +5.1% observed in mean global ADC and LmD values, respectively. These differences were within the standard deviation range and consistent with values reported from healthy and COPD lungs. CONCLUSIONS: Accelerated CS acquisition has facilitated 3D multiple b-value (3) He DW-MRI scans in a single breath-hold, enabling whole lung morphometry mapping. Magn Reson Med, 2016. © 2016 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.