Highly accelerated dynamic acquisition of 3D grid-tagged hyperpolarized-gas lung images using compressed sensing.

PURPOSE: To develop and test compressed sensing-based multiframe 3D MRI of grid-tagged hyperpolarized gas in the lung. THEORY AND METHODS: Applying grid-tagging RF pulses to inhaled hyperpolarized gas results in images in which signal intensity is predictably and sparsely distributed. In the present work, this phenomenon was used to produce a sampling pattern in which k-space is undersampled by a factor of approximately seven, yet regions of high k-space energy remain densely sampled. Three healthy subjects received multiframe 3D 3 He tagging MRI using this undersampling method. Images were collected during a single exhalation at eight timepoints spanning the breathing cycle from end-of-inhalation to end-of-exhalation. Grid-tagged images were used to generate 3D displacement maps of the lung during exhalation, and time-resolved maps of principal strains and fractional volume change were generated from these displacement maps using finite-element analysis. RESULTS: Tags remained clearly resolvable for 4-6 timepoints (5-8 s) in each subject. Displacement maps revealed noteworthy temporal and spatial nonlinearities in lung motion during exhalation. Compressive normal strains occurred along all three principal directions but were primarily oriented in the head-foot direction. Fractional volume changes displayed clear bilateral symmetry, but with the lower lobes displaying slightly higher change than the upper lobes in 2 of the 3 subjects. CONCLUSION: We developed a compressed sensing-based method for multiframe 3D MRI of grid-tagged hyperpolarized gas in the lung during exhalation. This method successfully overcomes previous challenges for 3D dynamic grid-tagging, allowing time-resolved biomechanical readouts of lung function to be generated.

A Dual-Channel Deep Learning Approach for Lung Cavity Estimation From Hyperpolarized Gas and Proton MRI.

BACKGROUND: 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 (1 H)-MRI. Although acquired at similar lung inflation levels, they are frequently misaligned, requiring a lung cavity estimation (LCE). Recently, single-channel, mono-modal deep learning (DL)-based methods have shown promise for pulmonary image segmentation problems. Multichannel, multimodal approaches may outperform single-channel alternatives. PURPOSE: We hypothesized that a DL-based dual-channel approach, leveraging both 1 H-MRI and Xenon-129-MRI (129 Xe-MRI), can generate LCEs more accurately than single-channel alternatives. STUDY TYPE: Retrospective. POPULATION: A total of 480 corresponding 1 H-MRI and 129 Xe-MRI scans from 26 healthy participants (median age [range]: 11 [8-71]; 50% females) and 289 patients with pulmonary pathologies (median age [range]: 47 [6-83]; 51% females) were split into training (422 scans [88%]; 257 participants [82%]) and testing (58 scans [12%]; 58 participants [18%]) sets. FIELD STRENGTH/SEQUENCE: 1.5-T, three-dimensional (3D) spoiled gradient-recalled 1 H-MRI and 3D steady-state free-precession 129 Xe-MRI. ASSESSMENT: We developed a multimodal DL approach, integrating 129 Xe-MRI and 1 H-MRI, in a dual-channel convolutional neural network. We compared this approach to single-channel alternatives using manually edited LCEs as a benchmark. We further assessed a fully automatic DL-based framework to calculate VDPs and compared it to manually generated VDPs. STATISTICAL TESTS: Friedman 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. RESULTS: 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). DATA CONCLUSION: Our dual-channel approach generated LCEs, which could be integrated with ventilated lung segmentations to produce biomarkers such as the VDP without manual intervention. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 1.

Chest MRI and CT Predictors of 10-Year All-Cause Mortality in COPD.

Pulmonary imaging measurements using magnetic resonance imaging (MRI) and computed tomography (CT) have the potential to deepen our understanding of chronic obstructive pulmonary disease (COPD) by measuring airway and parenchymal pathologic information that cannot be provided by spirometry. Currently, MRI and CT measurements are not included in mortality risk predictions, diagnosis, or COPD staging. We evaluated baseline pulmonary function, MRI and CT measurements alongside imaging texture-features to predict 10-year all-cause mortality in ex-smokers with (n = 93; 31 females; 70 ± 9years) and without (n = 69; 29 females, 69 ± 9years) COPD. CT airway and vessel measurements, helium-3 (3He) MRI ventilation defect percent (VDP) and apparent diffusion coefficients (ADC) were quantified. MRI and CT texture-features were extracted using PyRadiomics (version2.2.0). Associations between 10-year all-cause mortality and all clinical and imaging measurements were evaluated using multivariable regression model odds-ratios. Machine-learning predictive models for 10-year all-cause mortality were evaluated using area-under-receiver-operator-characteristic-curve (AUC), sensitivity and specificity analyses. DLCO (%pred) (HR = 0.955, 95%CI: 0.934-0.976, p < 0.001), MRI ADC (HR = 1.843, 95%CI: 1.260-2.871, p < 0.001), and CT informational-measure-of-correlation (HR = 3.546, 95% CI: 1.660-7.573, p = 0.001) were the strongest predictors of 10-year mortality. A machine-learning model trained on clinical, imaging, and imaging textures was the best predictive model (AUC = 0.82, sensitivity = 83%, specificity = 84%) and outperformed the solely clinical model (AUC = 0.76, sensitivity = 77%, specificity = 79%). In ex-smokers, regardless of COPD status, addition of CT and MR imaging texture measurements to clinical models provided unique prognostic information of mortality risk that can allow for better clinical management.Clinical Trial Registration: www.clinicaltrials.gov NCT02279329.

Peripheral and proximal lung ventilation in asthma: Short-term variation and response to bronchodilator inhalation.

BACKGROUND: The relative involvement of the large and small airways in asthma is not clear. Hyperpolarized gas magnetic resonance imaging (MRI) provides high-resolution 3-dimensional images of ventilation distribution that can be quantified by the ventilated volume percentage (VV%) of the lungs. OBJECTIVE: Our aims were to (1) quantify the baseline reproducibility of VV%, (2) assess the ventilation distribution between the proximal and peripheral lungs, and (3) investigate regional ventilation response to bronchodilator inhalation in a cohort of patients with asthma. METHODS: A total of 33 patients with poorly controlled, moderate-to-severe asthma were scanned with hyperpolarized 3He MRI. Two image data sets were acquired at baseline, and 1 image data set was acquired after bronchodilator inhalation. Images were divided into proximal and peripheral regions for analysis. RESULTS: Bland-Altman analysis showed strong reproducibility of VV% (bias = 0.12%; LOA = -1.86% to 2.10%). VV% variation at baseline was greater in the periphery than in the proximal lung. The proximal lung was better ventilated than the peripheral lung. Ventilation increased significantly in response to bronchodilator inhalation, globally and regionally, and the ventilation increase in response to bronchodilator inhalation was greater in the peripheral lung than in the proximal lung. Hyperpolarized gas MRI was more sensitive to changes in response to bronchodilator inhalation (58%) than spirometry (33%). CONCLUSION: The peripheral lung showed reduced ventilation and a greater response to bronchodilator inhalation than the proximal lung. The high level of baseline reproducibility and sensitivity of hyperpolarized gas MRI to bronchodilator reversibility suggests that it is suitable for low subject number studies of therapy response.

Ventilation heterogeneity imaged by multibreath wash-ins of hyperpolarized 3 He and 129 Xe in healthy rabbits.

KEY POINTS: Multibreath imaging to estimate regional gas mixing efficiency is superior to intensity-based single-breath ventilation markers, as it is capable of revealing minute but essential measures of ventilation heterogeneity which may be sensitive to subclinical alterations in the early stages of both obstructive and restrictive respiratory disorders. Large-scale convective stratification of ventilation in central-to-peripheral directions is the dominant feature of observed ventilation heterogeneity when imaging a heavy/less diffusive xenon gas mixture; smaller-scale patchiness, probably originating from asymmetric lung function at bronchial airway branching due to the interaction of convective and diffusive flows, is the dominant feature when imaging a lighter/more diffusive helium gas mixture. Since detecting low regional ventilation is crucial for characterizing diseased lungs, our results suggest that dilution with natural abundance helium and imaging at higher lung volumes seem advisable when imaging with hyperpolarized 129 Xe; this will allow the imaging gas to reach slow-filling and/or non-dependent lung regions, which might otherwise be impossible to distinguish from total ventilation shunt regions. The ability to differentiate these regions from those of total shunt is worse with typical single-breath imaging techniques. ABSTRACT: The mixing of freshly inhaled gas with gas already present in the lung can be directly assessed with heretofore unachievable precision via magnetic resonance imaging of signal build-up resulting from multiple wash-ins of a hyperpolarized (HP) gas. Here, we used normoxic HP 3 He and 129 Xe mixtures to study regional ventilation at different spatial scales in five healthy mechanically ventilated supine rabbits at two different inspired volumes. To decouple the respective effects of density and diffusion rates on ventilation heterogeneity, two additional studies were performed: one in which 3 He was diluted with an equal fraction of natural abundance xenon, and one in which 129 Xe was diluted with an equal fraction of 4 He. We observed systematic differences in the spatial scale of specific ventilation heterogeneity between HP 3 He and 129 Xe. We found that large-scale, central-to-peripheral convective ventilation inhomogeneity is the dominant cause of observed heterogeneity when breathing a normoxic xenon gas mixture. In contrast, small-scale ventilation heterogeneity in the form of patchiness, probably originating from asymmetric lung function at bronchial airway branching due to interactions between convective and diffusive flows, is the dominant feature when breathing a normoxic helium gas mixture, for which the critical zone occurs more proximally and at an imageable spatial scale. We also showed that the existence of particular underventilated non-dependent lung regions when breathing a heavy gas mixture is the result of the density of that mixture - rather than, for example, its diffusion rate or viscosity. Finally, we showed that gravity-dependent ventilation heterogeneity becomes substantially more uniform at higher inspired volumes for xenon gas mixtures compared to helium mixtures.

Hyperpolarized 129Xe magnetic resonance spectroscopy in a rat model of bronchopulmonary dysplasia.

Premature infants often require mechanical ventilation and oxygen therapy, which can result in bronchopulmonary dysplasia (BPD), characterized by developmental arrest and impaired lung function. Conventional clinical methods for assessing the prenatal lung are not adequate for the detection and assessment of long-term health risks in infants with BPD, highlighting the need for a noninvasive tool for the characterization of lung microstructure and function. Theoretical diffusion models, like the model of xenon exchange (MOXE), interrogate alveolar gas exchange by predicting the uptake of inert hyperpolarized (HP) 129Xe gas measured with HP 129Xe magnetic resonance spectroscopy (MRS). To investigate HP 129Xe MRS as a tool for noninvasive characterization of pulmonary microstructural and functional changes in vivo, HP 129Xe gas exchange data were acquired in an oxygen exposure rat model of BPD that recapitulates the fewer and larger distal airways and pulmonary vascular stunting characteristics of BPD. Gas exchange parameters from MOXE, including airspace mean chord length (Lm), apparent hematocrit in the pulmonary capillaries (HCT), and pulmonary capillary transit time (tx), were compared with airspace mean axis length and area density (MAL and ρA) and percentage area of tissue and air (PTA and PAA) from histology. Lm was significantly larger in the exposed rats (P = 0.003) and correlated with MAL, ρA, PTA, and PAA (0.59<|ρ|<0.66 and P < 0.05). Observed increase in HCT (P = 0.012) and changes in tx are also discussed. These findings support the use of HP 129Xe MRS for detecting fewer, enlarged distal airways in this rat model of BPD, and potentially in humans.

Comparison of single breath hyperpolarized 129 Xe MRI with dynamic 19 F MRI in cystic fibrosis lung disease.

PURPOSE: To quantitatively compare dynamic 19 F and single breath hyperpolarized 129 Xe MRI for the detection of ventilation abnormalities in subjects with mild cystic fibrosis (CF) lung disease. METHODS: Ten participants with stable CF and a baseline FEV1 > 70% completed a single imaging session where dynamic 19 F and single breath 129 Xe lung ventilation images were acquired on a 3T MRI scanner. Ventilation defect percentages (VDP) values between 19 F early-breath, 19 F maximum-ventilation, 129 Xe low-resolution, and 129 Xe high-resolution images were compared. Dynamic 19 F images were used to determine gas wash-in/out rates in regions of ventilation congruency and mismatch between 129 Xe and 19 F. RESULTS: VDP values from high-resolution 129 Xe images were greater than from low-resolution images (P = .001), although these values were significantly correlated (r = 0.68, P = .03). Early-breath 19 F VDP and max-vent 19 F VDP also showed significant correlation (r = 0.75, P = .012), with early-breath 19 F VDP values being significantly greater (P < .001). No correlation in VDP values were detected between either 19 F method or high-res 129 Xe images. In addition, the location and volume of ventilation defects were often different when comparing 129 Xe and 19 F images from the same subject. Areas of ventilation congruence displayed the expected ventilation kinetics, while areas of ventilation mismatch displayed abnormally slow gas wash-in and wash-out. CONCLUSION: In CF subjects, ventilation abnormalities are identified by both 19 F and HP 129 Xe imaging. However, these ventilation abnormalities are not entirely congruent. 19 F and HP 129 Xe imaging provide complementary information that enable differentiation of normally ventilated, slowly ventilated, and non-ventilated regions in the lungs.

Finite element simulations of hyperpolarized gas DWI in micro-CT meshes of acinar airways: validating the cylinder and stretched exponential models of lung microstructural length scales.

PURPOSE: This work assesses the accuracy of the stretched exponential (SEM) and cylinder models of lung microstructural length scales that can be derived from hyperpolarized gas DWI. This was achieved by simulating 3 He and 129 Xe DWI signals within two micro-CT-derived realistic acinar airspace meshes that represent healthy and idiopathic pulmonary fibrosis lungs. METHODS: The healthy and idiopathic pulmonary fibrosis acinar airway meshes were derived from segmentations of 3D micro-CT images of excised human lungs and meshed for finite element simulations of the Bloch-Torrey equations. 3 He and 129 Xe multiple b value DWI experiments across a range of diffusion times (3 He Δ = 1.6 ms; 129 Xe Δ = 5 to 20 ms) were simulated in each mesh. Global SEM mean diffusive length scale and cylinder model mean chord length value was derived from each finite element simulation and compared against each mesh's mean linear intercept length, calculated from intercept length measurements within micro-CT segmentation masks. RESULTS: The SEM-derived mean diffusive length scale was within ±10% of the mean linear intercept length for simulations with both 3 He (Δ = 1.6 ms) and 129 Xe (Δ = 7 to 13 ms) in the healthy mesh, and with 129 Xe (Δ = 13 to 20 ms) for the idiopathic pulmonary fibrosis mesh, whereas for the cylinder model-derived mean chord length the closest agreement with mean linear intercept length (11.7% and 22.6% difference) was at 129 Xe Δ = 20 ms for both healthy and IPF meshes, respectively. CONCLUSION: This work validates the use of the SEM for accurate estimation of acinar dimensions and indicates that the SEM is relatively robust across a range of experimental conditions and acinar length scales.

Novel Thoracic MRI Approaches for the Assessment of Pulmonary Physiology and Inflammation.

Excessive pulmonary inflammation can lead to damage of lung tissue, airway remodelling and established structural lung disease. Novel therapeutics that specifically target inflammatory pathways are becoming increasingly common in clinical practice, but there is yet to be a similar stepwise change in pulmonary diagnostic tools. A variety of thoracic magnetic resonance imaging (MRI) tools are currently in development, which may soon fulfil this emerging clinical need for highly sensitive assessments of lung structure and function. Given conventional MRI techniques are poorly suited to lung imaging, alternate strategies have been developed, including the use of inhaled contrast agents, intravenous contrast and specialized lung MR sequences. In this chapter, we discuss technical challenges of performing MRI of the lungs and how they may be overcome. Key thoracic MRI modalities are reviewed, namely, hyperpolarized noble gas MRI, oxygen-enhanced MRI (OE-MRI), ultrashort echo time (UTE) MRI and dynamic contrast-enhanced (DCE) MRI. Finally, we consider potential clinical applications of these techniques including phenotyping of lung disease, evaluation of novel pulmonary therapeutic efficacy and longitudinal assessment of specific patient groups.

Fast and accurate reconstruction of human lung gas MRI with deep learning.

PURPOSE: To fast and accurately reconstruct human lung gas MRI from highly undersampled k-space using deep learning. METHODS: The scheme was comprised of coarse-to-fine nets (C-net and F-net). Zero-filling images from retrospectively undersampled k-space at an acceleration factor of 4 were used as input for C-net, and then output intermediate results which were fed into F-net. During training, a L2 loss function was adopted in C-net, while a function that united L2 loss with proton prior knowledge was used in F-net. The 871 hyperpolarized 129 Xe pulmonary ventilation images from 72 volunteers were randomly arranged as training (90%) and testing (10%) data. Ventilation defect percentage comparisons were implemented using a paired 2-tailed Student's t-test and correlation analysis. Furthermore, prospective acquisitions were demonstrated in 5 healthy subjects and 5 asymptomatic smokers. RESULTS: Each image with size of 96 × 84 could be reconstructed within 31 ms (mean absolute error was 4.35% and structural similarity was 0.7558). Compared with conventional compressed sensing MRI, the mean absolute error decreased by 17.92%, but the structural similarity increased by 6.33%. For ventilation defect percentage, there were no significant differences between the fully sampled and reconstructed images through the proposed algorithm (P = 0.932), but had significant correlations (r = 0.975; P < 0.001). The prospectively undersampled results validated a good agreement with fully sampled images, with no significant differences in ventilation defect percentage but significantly higher signal-to-noise ratio values. CONCLUSION: The proposed algorithm outperformed classical undersampling methods, paving the way for future use of deep learning in real-time and accurate reconstruction of gas MRI.

A protocol for quantifying cardiogenic oscillations in dynamic 129 Xe gas exchange spectroscopy: The effects of idiopathic pulmonary fibrosis.

The spectral parameters of hyperpolarized 129 Xe exchanging between airspaces, interstitial barrier, and red blood cells (RBCs) are sensitive to pulmonary pathophysiology. This study sought to evaluate whether the dynamics of 129 Xe spectroscopy provide additional insight, with particular focus on quantifying cardiogenic oscillations in the RBC resonance. 129 Xe spectra were dynamically acquired in eight healthy volunteers and nine subjects with idiopathic pulmonary fibrosis (IPF). 129 Xe FIDs were collected every 20 ms (TE  = 0.932 ms, 512 points, dwell time = 32 µs, flip angle ≈ 20°) during a 16 s breathing maneuver. The FIDs were pre-processed using the spectral improvement by Fourier thresholding technique (SIFT) and fit in the time domain to determine the airspace, interstitial barrier, and RBC spectral parameters. The RBC and gas resonances were fit to a Lorentzian lineshape, while the barrier was fit to a Voigt lineshape to account for its greater structural heterogeneity. For each complex resonance the amplitude, chemical shift, linewidth(s), and phase were calculated. The time-averaged spectra confirmed that the RBC to barrier amplitude ratio (RBC:barrier ratio) and RBC chemical shift are both reduced in IPF subjects. Their temporal dynamics showed that all three 129 Xe resonances are affected by the breathing maneuver. Most notably, several RBC spectral parameters exhibited prominent oscillations at the cardiac frequency, and their peak-to-peak variation differed between IPF subjects and healthy volunteers. In the IPF cohort, oscillations were more prominent in the RBC amplitude (16.8 ± 5.2 versus 9.7 ± 2.9%; P = 0.008), chemical shift (0.43 ± 0.33 versus 0.083 ± 0.05 ppm; P < 0.001), and phase (7.7 ± 5.6 versus 1.4 ± 0.8°; P < 0.001). Dynamic 129 Xe spectroscopy is a simple and sensitive tool that probes the temporal variability of gas exchange and may prove useful in discerning the underlying causes of its impairment.

Pulmonary MRI morphometry modeling of airspace enlargement in chronic obstructive pulmonary disease and alpha-1 antitrypsin deficiency.

PURPOSE: We generated lung morphometry measurements using single-breath diffusion-weighted MRI and three different acinar duct models in healthy participants and patients with emphysema stemming from chronic obstructive lung disease (COPD) and alpha-1 antitrypsin deficiency (AATD). METHODS: Single-breath-inhaled 3 He MRI with five diffusion sensitizations (b-value = 0, 1.6, 3.2, 4.8, and 6.4 s/cm2 ) was used, and signal intensities were fit using a cylindrical and single-compartment acinar-duct model to estimate MRI-derived mean linear intercept (Lm ) and surface-to-volume ratio (S/V). A stretched exponential model was also developed to estimate the mean airway length and Lm . RESULTS: We evaluated 42 participants, including 15 elderly never-smokers (69 ± 5 years), 12 ex-smokers without COPD (67 ± 11 years), 9 COPD ex-smokers (80 ± 6 years), and 6 AATD patients (59 ± 6 years). In the never- and ex-smokers, the diffusing capacity of the lung for carbon monoxide (DLCO ) and computed tomography relative area of less than -950 Hounsfield units (RA950 ) were normal, but these were abnormal in the COPD and AATD patients, which is reflective of emphysema. Although cylindrical and stretched-exponential-model estimates of Lm and S/V were not significantly different, the single-compartment-model estimates were significantly different (P < 0.05) for the never- and ex-smoker subgroups. All models estimated significantly worse Lm and S/V in the AATD and COPD subgroups compared with the never- and ex-smokers without emphysema. CONCLUSIONS: Differences in airspace enlargement may be estimated using Lm and S/V, generated using MRI and a stretched-exponential or cylindrical model of the acinar ducts. Magn Reson Med 79:439-448, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Spatial fuzzy c-means thresholding for semiautomated calculation of percentage lung ventilated volume from hyperpolarized gas and 1 H MRI.

PURPOSE: 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. MATERIALS AND METHODS: Six patients were imaged with hyperpolarized 3 He and same-breath lung 1 H MRI at 1.5T and six other patients were scanned with hyperpolarized 129 Xe and separate-breath 1 H 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. RESULTS: 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). CONCLUSION: 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. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:640-646.

Comparison of 3 He and 129 Xe MRI for evaluation of lung microstructure and ventilation at 1.5T.

BACKGROUND: To support translational lung MRI research with hyperpolarized 129 Xe gas, comprehensive evaluation of derived quantitative lung function measures against established measures from 3 He MRI is required. Few comparative studies have been performed to date, only at 3T, and multisession repeatability of 129 Xe functional metrics have not been reported. PURPOSE/HYPOTHESIS: To compare hyperpolarized 129 Xe and 3 He 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 3 He and 129 Xe. 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 3 He and 129 Xe VV% was observed (r = 0.860, P < 0.001). VV% was larger for 3 He than 129 Xe (P = 0.001); average bias, 8.79%. A strong correlation between mean 3 He and 129 Xe ADC was obtained (r = 0.922, P < 0.001). MR parameters exhibited good correlations with pulmonary function tests. In COPD patients, mean CV of 3 He and 129 Xe VV% was 4.08% and 13.01%, respectively, with ICC coefficients of 0.541 (P = 0.061) and 0.458 (P = 0.095). Mean 3 He and 129 Xe ADC values were highly repeatable (mean CV: 2.98%, 2.77%, respectively; ICC: 0.995, P < 0.001; 0.936, P < 0.001). DATA CONCLUSION: 129 Xe lung MRI provides near-equivalent information to 3 He for quantitative lung ventilation and microstructural MRI at 1.5T. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2018.

Hyperpolarized gas diffusion MRI of biphasic lung inflation in short- and long-term emphysema models.

During lung inflation, airspace dimensions are affected nonlinearly by both alveolar expansion and recruitment, potentially confounding the identification of emphysematous lung by hyperpolarized helium-3 diffusion magnetic resonance imaging (HP MRI). This study aimed to characterize lung inflation over a broad range of inflation volume and pressure values in two different models of emphysema, as well as in normal lungs. Elastase-treated rats (n = 7) and healthy controls (n = 7) were imaged with HP MRI. Gradual inflation was achieved by incremental changes to both inflation volume and airway pressure. The apparent diffusion coefficient (ADC) was measured at each level of inflation and fitted to the corresponding airway pressures as the second-order response equation, with minimizing residue (χ2 < 0.001). A biphasic ADC response was detected, with an initial ADC increase followed by a decrease at airway pressures >18 cmH2O. Discrimination between treated and control rats was optimal when airway pressure was intermediate (between 10 and 11 cmH2O). Similar findings were confirmed in mice following long-term exposure to cigarette smoke, where optimal discrimination between treated and healthy mice occurred at a similar airway pressure as in the rats. We subsequently explored the evolution of ADC measured at the intermediate inflation level in mice after prolonged smoke exposure and found a significant increase (P < 0.01) in ADC over time. Our results demonstrate that measuring ADC at intermediate inflation enhances the distinction between healthy and diseased lungs, thereby establishing a model that may improve the diagnostic accuracy of future HP gas diffusion studies.

Multiple breath washout of hyperpolarized 129 Xe and 3 He in human lungs with three-dimensional balanced steady-state free-precession imaging.

PURPOSE: To compare quantitative fractional ventilation measurements from multiple breath washout imaging (MBW-I) using hyperpolarized 3 He with both spoiled gradient echo (SPGR) and balanced steady-state free precession (bSSFP) three-dimensional (3D) pulse sequences and to evaluate the feasibility of MBW-I with hyperpolarized 129 Xe. METHODS: Seven healthy subjects were scanned using 3 He MBW-I with 3D SPGR and bSSFP sequences. Five also underwent MBW-I with 129 Xe. A dual-tuned coil was used to acquire MBW-I data from both nuclei in the same subject position, enabling direct comparison of regional information. RESULTS: High-quality MBW images were obtained with bSSFP sequences using a reduced dose (100 mL) of inhaled hyperpolarized 3 He. 3D MBW-I with 129 Xe was also successfully demonstrated with a bSSFP sequence. Regional quantitative ventilation measures derived from 3 He and 129 Xe MBW-I correlated well in all subjects (P < 0.001) with mean Pearson's correlation coefficients of r = 0.61 and r = 0.52 for 3 He SPGR-bSSFP and 129 Xe-3 He (bSSFP) comparisons. The average intersubject mean difference (and standard deviation) in fractional ventilation in SPGR-bSSFP and 129 Xe-3 He comparisons was 15% (28%) and 9% (38%), respectively. CONCLUSIONS: Improved sensitivity in MBW-I can be achieved with polarization-efficient bSSFP sequences. Same scan-session 3D MBW-I with 3 He and 129 Xe has been demonstrated using a dual-tuned coil. Magn Reson Med 77:2288-2295, 2017. © 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.

Diffusion lung imaging with hyperpolarized gas MRI.

Lung imaging using conventional 1 H MRI presents great challenges because of the low density of lung tissue, lung motion and very fast lung tissue transverse relaxation (typical T2 * is about 1-2 ms). MRI with hyperpolarized gases (3 He and 129 Xe) provides a valuable alternative because of the very strong signal originating from inhaled gas residing in the lung airspaces and relatively slow gas T2 * relaxation (typical T2 * is about 20-30 ms). However, in vivo human experiments should be performed very rapidly - usually during a single breath-hold. In this review, we describe the recent developments in diffusion lung MRI with hyperpolarized gases. We show that a combination of the results of modeling of gas diffusion in lung airspaces and diffusion measurements with variable diffusion-sensitizing gradients allows the extraction of quantitative information on the lung microstructure at the alveolar level. From an MRI scan of less than 15 s, this approach, called in vivo lung morphometry, allows the provision of quantitative values and spatial distributions of the same physiological parameters as measured by means of 'standard' invasive stereology (mean linear intercept, surface-to-volume ratio, density of alveoli, etc.). In addition, the approach makes it possible to evaluate some advanced Weibel parameters characterizing lung microstructure: average radii of alveolar sacs and ducts, as well as the depth of their alveolar sleeves. Such measurements, providing in vivo information on the integrity of pulmonary acinar airways and their changes in different diseases, are of great importance and interest to a broad range of physiologists and clinicians. We also discuss a new type of experiment based on the in vivo lung morphometry technique combined with quantitative computed tomography measurements, as well as with gradient echo MRI measurements of hyperpolarized gas transverse relaxation in the lung airspaces. Such experiments provide additional information on the blood vessel volume fraction, specific gas volume and length of the acinar airways, and allow the evaluation of lung parenchymal and non-parenchymal tissue. Copyright © 2015 John Wiley & Sons, Ltd.

What makes a good pediatric transplant lung: Insights from in vivo lung morphometry with hyperpolarized 3 He magnetic resonance imaging.

Obtaining information on transplanted lung microstructure is an important part of the current care for monitoring transplant recipients. However, until now this information was only available from invasive lung biopsy. The objective of this study was to evaluate the use of an innovative non-invasive technique, in vivo lung morphometry with hyperpolarized ³He MRI-to characterize lung microstructure in the pediatric lung transplant population. This technique yields quantitative measurements of acinar airways' (alveolar ducts and sacs) parameters, such as acinar airway radii and alveolar depth. Six pediatric lung transplant recipients with cystic fibrosis underwent in vivo lung morphometry MRI, pulmonary function testing, and quantitative CT. We found a strong correlation between lung lifespan and alveolar depth-patients with more shallow alveoli were likely to have a negative outcome sooner than those with larger alveolar depth. Combining morphometric results with CT, we also determined mean alveolar wall thickness and found substantial increases in this parameter in some patients that negatively correlated with DLCO. In vivo lung morphometry uniquely provides previously unavailable information on lung microstructure that may be predictive of a negative outcome and has a potential to aid in lung selection for transplantation.

High resolution spectroscopy and chemical shift imaging of hyperpolarized (129) Xe dissolved in the human brain in vivo at 1.5 tesla.

PURPOSE: Upon inhalation, xenon diffuses into the bloodstream and is transported to the brain, where it dissolves in various compartments of the brain. Although up to five chemically distinct peaks have been previously observed in (129) Xe rat head spectra, to date only three peaks have been reported in the human head. This study demonstrates high resolution spectroscopy and chemical shift imaging (CSI) of (129) Xe dissolved in the human head at 1.5 Tesla. METHODS: A (129) Xe radiofrequency coil was built in-house and (129) Xe gas was polarized using spin-exchange optical pumping. Following the inhalation of (129) Xe gas, NMR spectroscopy was performed with spectral resolution of 0.033 ppm. Two-dimensional CSI in all three anatomical planes was performed with spectral resolution of 2.1 ppm and voxel size 20 mm × 20 mm. RESULTS: Spectra of hyperpolarized (129) Xe dissolved in the human head showed five distinct peaks at 188 ppm, 192 ppm, 196 ppm, 200 ppm, and 217 ppm. Assignment of these peaks was consistent with earlier studies. CONCLUSION: High resolution spectroscopy and CSI of hyperpolarized (129) Xe dissolved in the human head has been demonstrated. For the first time, five distinct NMR peaks have been observed in (129) Xe spectra from the human head in vivo. Magn Reson Med 75:2227-2234, 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.