129Xe MRI Research Articles

Simultaneous Imaging of Ventilation and Gas Exchange with Hyperpolarized 129Xe MRI for Monitoring Patients with Endobronchial Valve Interventions.

Simultaneous Imaging of Ventilation and Gas Exchange with Hyperpolarized 129Xe MRI for Monitoring Patients with Endobronchial Valve Interventions.

Improving hyperpolarized 129 Xe ADC mapping in pediatric and adult lungs with uncertainty propagation.

Hyperpolarized (HP) 129 Xe-MRI provides non-invasive methods to quantify lung function and structure, with the 129 Xe apparent diffusion coefficient (ADC) being a well validated measure of alveolar airspace size. However, the experimental factors that impact the precision and accuracy of HP 129 Xe ADC measurements have not been rigorously investigated. Here, we introduce an analytical model to predict the experimental uncertainty of 129 Xe ADC estimates. Additionally, we report ADC dependence on age in healthy pediatric volunteers. An analytical expression for ADC uncertainty was derived from the Stejskal-Tanner equation and simplified Bloch equations appropriate for HP media. Parameters in the model were maximum b-value (bmax ), number of b-values (Nb ), number of phase encoding lines (Nph ), flip angle and the ADC itself. This model was validated by simulations and phantom experiments, and five fitting methods for calculating ADC were investigated. To examine the lower range for 129 Xe ADC, 32 healthy subjects (age 6-40 years) underwent diffusion-weighted 129 Xe MRI. The analytical model provides a lower bound on ADC uncertainty and predicts that decreased signal-to-noise ratio yields increases in relative uncertainty . As such, experimental parameters that impact non-equilibrium 129 Xe magnetization necessarily impact the resulting . The values of diffusion encoding parameters (Nb and bmax ) that minimize strongly depend on the underlying ADC value, resulting in a global minimum for . Bayesian fitting outperformed other methods (error < 5%) for estimating ADC. The whole-lung mean 129 Xe ADC of healthy subjects increased with age at a rate of 1.75 × 10-4 cm2 /s/yr (p= 0.001). HP 129 Xe diffusion MRI can be improved by minimizing the uncertainty of ADC measurements via uncertainty propagation. Doing so will improve experimental accuracy when measuring lung microstructure in vivo and should allow improved monitoring of regional disease progression and assessment of therapy response in a range of lung diseases.

Characterizing Gas Exchange Physiology in Healthy Young Electronic-Cigarette Users with Hyperpolarized 129Xe MRI: A Pilot Study.

Characterizing Gas Exchange Physiology in Healthy Young Electronic-Cigarette Users with Hyperpolarized 129Xe MRI: A Pilot Study.

537: 129Xe MRI is a repeatable measure of regional ventilation in children with stable CF

537: 129Xe MRI is a repeatable measure of regional ventilation in children with stable CF

Protocols for multi-site trials using hyperpolarized 129 Xe MRI for imaging of ventilation, alveolar-airspace size, and gas exchange: A position paper from the 129 Xe MRI clinical trials consortium.

Hyperpolarized (HP) 129 Xe 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 129 Xe MRI as outcome measures in multi-site clinical trials across a range of pulmonary disorders. Until recently, HP 129 Xe 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 129 Xe MRI more widely in translational research, multi-site trials, and ultimately clinical practice, this position paper from the 129 Xe MRI Clinical Trials Consortium (https://cpir.cchmc.org/XeMRICTC) recommends standard protocols to harmonize methods for image acquisition in HP 129 Xe 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 129 Xe dose volumes and breath-hold standardization to further foster consistency of imaging studies. The intention is that sites with HP 129 Xe 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 129 Xe MRI for multi-site pulmonary research.

Hyperpolarized 129Xenon MRI Ventilation Defect Quantification via Thresholding and Linear Binning in Multiple Pulmonary Diseases

There is no agreed upon method for quantifying ventilation defect percentage (VDP) with high sensitivity and specificity from hyperpolarized (HP) gas ventilation MR images in multiple pulmonary diseases for both pediatrics and adults, yet identifying such methods will be necessary for future multi-site trials. Most HP gas MRI ventilation research focuses on a specific pulmonary disease and utilizes one quantification scheme for determining VDP. Here we sought to determine the potential of different methods for quantifying VDP from HP 129Xe images in multiple pulmonary diseases through comparison of the most utilized quantification schemes: linear binning and thresholding. HP 129Xe MRI was performed in a total of 176 subjects (125 pediatrics and 51 adults, age 20.98±16.48 years) who were either healthy controls (n=23) or clinically diagnosed with cystic fibrosis (CF) (n=37), lymphangioleiomyomatosis (LAM) (n=29), asthma (n=22), systemic juvenile idiopathic arthritis (sJIA) (n=11), interstitial lung disease (ILD) (n=7), or were bone marrow transplant (BMT) recipients (n=47). HP 129Xe ventilation images were acquired during a ≤16 second breath-hold using a 2D multi-slice gradient echo sequence on a 3T Philips scanner (TR/TE 8.0/4.0ms, FA 10-12°, FOV 300×300mm, voxel size≈3×3×15mm). Images were analyzed using 5 different methods to quantify VDPs: linear binning (histogram normalization with binning into 6 clusters) following either linear or a variant of a nonparametric nonuniform intensity normalization algorithm(N4ITK) bias-field correction, thresholding ≤60% of the mean signal intensity with linear bias-field correction, and thresholding ≤60% and ≤75% of the mean signal intensity following N4ITK bias-field correction. Spirometry was successfully obtained in 84% of subjects. All quantification schemes were able to label visually identifiable ventilation defects in similar regions within all subjects. The VDPs of control subjects were significantly lower (p<0.05) compared to BMT, CF, LAM, and ILD subjects for most of the quantification methods. No one quantification scheme was better able to differentiate individual disease groups from the control group. Advanced statistical modeling of the VDP quantification schemes revealed that in comparing controls to the combined disease group, N4ITK bias-field corrected 60% thresholding had the highest predictive efficacy, sensitivity, and specificity at the VDP cut-point of 2.3%. However, compared to the thresholding quantification schemes, linear binning was able to capture and label subtle low-ventilation regions in subjects with milder obstruction, such as subjects with asthma. The difference in VDP between healthy controls and patients varied between the different disease states for all quantification methods. Although N4ITK bias-field corrected 60% thresholding was superior in separating the combined diseased group from controls, linear binning is able to better label low-ventilation regions unlike the current, 60% thresholding scheme. For future clinical trials, a consensus will need to be reached on which VDP scheme to utilize, as there are subtle advantages for each for specific disease.

Imaging Dynamic Expiration: Feasibility of MRI Spirometry Using Hyperpolarized Xenon Gas.

To examine the feasibility of imaging-based spirometry using high-temporal-resolution projection MRI and hyperpolarized xenon 129 (129Xe) gas. In this prospective exploratory study, five healthy participants (age range, 25-45 years; three men) underwent an MRI spirometry technique using inhaled hyperpolarized 129Xe and rapid two-dimensional projection MRI. Participants inhaled 129Xe, then performed a forced expiratory maneuver while in an MR imager. Images of the lungs during expiration were captured in time intervals as short as 250 msec. Volume-corrected images of the lungs at expiration commencement (0 second), 1 second after expiration, and 6 seconds after expiration were extracted to generate forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio pulmonary maps. For comparison, participants performed conventional spirometry in the sitting position using room air, in the supine position using room air, and in the supine position using a room air and 129Xe mixture. Paired t tests with Bonferroni corrections for multiple comparisons were used for statistical analyses. The mean MRI-derived FEV1/FVC value was lower in comparison with conventional spirometry (0.52 ± 0.03 vs 0.70 ± 0.05, P < .01), which may reflect selective 129Xe retention. A secondary finding of this study was that 1 L of inhaled 129Xe negatively impacted pulmonary function as measured by conventional spirometry (in supine position), which reduced measured FEV1 (2.70 ± 0.90 vs 3.04 ± 0.85, P < .01) and FEV1/FVC (0.70 ± 0.05 vs 0.79 ± 0.04, P < .01). A forced expiratory maneuver was successfully imaged with hyperpolarized 129Xe and high-temporal-resolution MRI. Derivation of regional lung spirometric maps was feasible.Keywords: MR-Imaging, MR-Dynamic Contrast Enhanced, MR-Functional Imaging, Pulmonary, Thorax, Diaphragm, Lung, Pleura, Physics Supplemental material is available for this article. © RSNA, 2021.

Hyperpolarized 129Xe MRI and Spectroscopy of Gas-Exchange Abnormalities in Nonspecific Interstitial Pneumonia.

Background Recent studies demonstrate that antifibrotic drugs previously reserved for idiopathic pulmonary fibrosis (IPF) may slow progression in other interstitial lung diseases (ILDs), creating an urgent need for tools that can sensitively assess disease activity, progression, and therapy response across ILDs. Hyperpolarized xenon 129 (129Xe) MRI and spectroscopy have provided noninvasive measurements of regional gas-exchange abnormalities in IPF. Purpose To assess gas exchange function using 129Xe MRI in a group of study participants with nonspecific interstitial pneumonia (NSIP) compared with healthy control participants. Materials and Methods In this prospective study, participants with NSIP and healthy control participants were enrolled between November 2017 and February 2020 and underwent 129Xe MRI and spectroscopy. Quantitative imaging provided three-dimensional maps of ventilation, interstitial barrier uptake, and transfer into the red blood cell (RBC) compartment. Spectroscopy provided parameters of the static RBC and barrier uptake compartments, as well as cardiogenic oscillations in RBC signal amplitude and chemical shift. Differences between NSIP and healthy control participants were assessed using the Wilcoxon rank-sum test. Results Thirty-six participants with NSIP (mean age, 57 years ± 11 [standard deviation]; 27 women) and 15 healthy control participants (mean age, 39 years ± 18; two women) were evaluated. Participants with NSIP had no difference in ventilation compared with healthy control participants (median, 4.4% [first quartile, 1.5%; third quartile, 8.7%] vs 6.0% [first quartile, 2.8%; third quartile, 6.9%]; P = .91), but they had a higher barrier uptake (median, 6.2% [first quartile, 1.8%; third quartile, 23.9%] vs 0.53% [first quartile, 0.33%; third quartile, 2.9%]; P = .003) and an increased RBC transfer defect (median, 20.6% [first quartile, 11.6%; third quartile, 27.8%] vs 2.8% [first quartile, 2.3%; third quartile, 4.9%]; P < .001). NSIP participants also had a reduced ratio of RBC-to-barrier peaks (median, 0.24 [first quartile, 0.19; third quartile, 0.31] vs 0.57 [first quartile, 0.52; third quartile, 0.67]; P < .001) and a reduced RBC chemical shift (median, 217.5 ppm [first quartile, 217.0 ppm; third quartile, 218.0 ppm] vs 218.2 ppm [first quartile, 217.9 ppm; third quartile, 218.6 ppm]; P = .001). Conclusion Participants with nonspecific interstitial pneumonia had increased barrier uptake and decreased red blood cell (RBC) transfer compared with healthy controls measured using xenon 129 gas-exchange MRI and reduced RBC-to-barrier ratio and RBC chemical shift measured using spectroscopy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Wild in this issue.

Accelerate gas diffusion-weighted MRI for lung morphometry with deep learning.

ObjectivesMultiple b-value gas diffusion-weighted MRI (DW-MRI) enables non-invasive and quantitative assessment of lung morphometry, but its long acquisition time is not well-tolerated by patients. We aimed to accelerate multiple b-value gas DW-MRI for lung morphometry using deep learning.MethodsA deep cascade of residual dense network (DC-RDN) was developed to reconstruct high-quality DW images from highly undersampled k-space data. Hyperpolarized 129Xe lung ventilation images were acquired from 101 participants and were retrospectively collected to generate synthetic DW-MRI data to train the DC-RDN. Afterwards, the performance of the DC-RDN was evaluated on retrospectively and prospectively undersampled multiple b-value 129Xe MRI datasets.ResultsEach slice with size of 64 × 64 × 5 could be reconstructed within 7.2 ms. For the retrospective test data, the DC-RDN showed significant improvement on all quantitative metrics compared with the conventional reconstruction methods (p < 0.05). The apparent diffusion coefficient (ADC) and morphometry parameters were not significantly different between the fully sampled and DC-RDN reconstructed images (p > 0.05). For the prospectively accelerated acquisition, the required breath-holding time was reduced from 17.8 to 4.7 s with an acceleration factor of 4. Meanwhile, the prospectively reconstructed results showed good agreement with the fully sampled images, with a mean difference of −0.72% and −0.74% regarding global mean ADC and mean linear intercept (Lm) values.ConclusionsDC-RDN is effective in accelerating multiple b-value gas DW-MRI while maintaining accurate estimation of lung microstructural morphometry, facilitating the clinical potential of studying lung diseases with hyperpolarized DW-MRI.Key Points• The deep cascade of residual dense network allowed fast and high-quality reconstruction of multiple b-value gas diffusion-weighted MRI at an acceleration factor of 4.• The apparent diffusion coefficient and morphometry parameters were not significantly different between the fully sampled images and the reconstructed results (p > 0.05).• The required breath-holding time was reduced from 17.8 to 4.7 s and each slice with size of 64 × 64 × 5 could be reconstructed within 7.2 ms.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00330-021-08126-y.

Inflammation during Lung Cancer Progression and Ethyl Pyruvate Treatment Observed by Pulmonary Functional Hyperpolarized 129Xe MRI in Mice.

This study aimed to assess the suitability of hyperpolarized 129Xe (HPXe) MRI for noninvasive longitudinal evaluation of pulmonary function in preclinical lung cancer models. A mouse model of lung cancer (LC) was induced in 5 mice by intraperitoneal injection of urethane, while a negative-control (NC) mice (N = 5) was prepared by injection of saline solution. Longitudinal HPXe MRI was performed over a 5-month period to monitor lung ventilation and gas exchange. The treatment efficacy of ethyl pyruvate (EP), an anti-inflammatory drug, to the mouse LC model was monitored using HPXe MRI by commencing administration of EP pre (early-phase) and 1-month post (late-phase) injection of urethane (N = 5 mice for each group). Gas-exchange function in LC mice was significantly reduced at 1-month after urethane injection compared with NC mice administered with saline (P < 0.01). Thereafter, it remained consistently lower than that of the NC group for the full 5-month measurement period. In contrast, the ventilation function of the LC model mice was not significantly different to that of the NC mice. Histological analysis revealed alveolar epithelial hyperplasia in LC mice alveoli at 1 month after urethane injection, and adenoma was confirmed 3 months after the injection. The early- and late-phase EP interventions were found to improve HPXe MRI metrics (reduced at 1 month postinjection of urethane) and significantly inhibit tumor growth. These results suggest that HPXe MRI gas-exchange metrics can be used to quantitatively assess changes in the precancerous lesion microenvironment and to evaluate therapeutic efficacy in cancer. Thus, HPXe MRI can be utilized to noninvasively monitor pulmonary pathology during LC progression and can visualize functional changes during therapy.

Hyperpolarized 129Xe MRI Abnormalities in Dyspneic Patients 3 Months after COVID-19 Pneumonia: Preliminary Results.

BackgroundSARS-CoV-2 targets angiotensin-converting enzyme 2 (ACE2) expressing cells in the respiratory tract. There are reports of breathlessness in patients many months post-infection.PurposeThis study aimed to determine if hyperpolarized 129Xe MRI (XeMRI) imaging could identify the possible cause of breathlessness in patients three months after hospital discharge following COVID-19 infection.Materials and MethodsThis prospective study was undertaken between August and December 2020, with patients and healthy control volunteers enrolled. All patients underwent: lung function tests; ventilation and dissolved phase XeMRI, with the mean Red Blood Cell (RBC):Tissue Plasma (TP) ratio to be calculated; and a low dose chest CT scored for the degree of post-COVID-19 abnormalities. Healthy controls underwent XeMRI. The intraclass correlation coefficient was calculated for volunteer and patient scans, to assess repeatability. A Wilcoxon rank-sum test and Cohen's effect size calculated to assess for differences between RBC:TP in patient and controls.Results9 patients (mean age 57±7 years, Male = 6) and 5 volunteers (29 ± 3 years, Female = 5) were enrolled. Patient mean time from hospital discharge was 169, range 116-254 days. There was a difference in RBC:TP between patients and controls (0.3 ± 0.1 versus 0.5 ± 0.1, respectively, p = 0.001, effect size = 1.36). There was significant difference between the RBC and gas phase spectral full width at half maximum (FWHM) between volunteers and patients (median ± 95 % confidence interval, 567 ± 1 vs 507 ± 81, p = 0.002 and 104 ± 2 vs 122 ± 17, p = 0.004, respectively). Results were reproducible with Intraclass Correlation Coefficients of 0.82 and 0.88 for patients and volunteers respectively. Participants had normal or near normal CT scans, mean 7/25, range 0-10/25.ConclusionXe MRI showed alveolar-capillary diffusion limitation in all 9 post COVID-19 pneumonia patients despite normal or nearly normal CT scans.See also the editorial by Dietrich.

Using hyperpolarized 129Xe gas-exchange MRI to model the regional airspace, membrane, and capillary contributions to diffusing capacity.

Hyperpolarized 129Xe MRI has emerged as a novel means to evaluate pulmonary function via 3D mapping of ventilation, interstitial barrier uptake, and RBC transfer. However, the physiological interpretation of these measurements has yet to be firmly established. Here, we propose a model that uses the three components of 129Xe gas-exchange MRI to estimate accessible alveolar volume (VA), membrane conductance, and capillary blood volume contributions to DLCO. 129Xe ventilated volume (VV) was related to VA by a scaling factor kV = 1.47 with 95% confidence interval [1.42, 1.52], relative 129Xe barrier uptake (normalized by the healthy reference value) was used to estimate the membrane-specific conductance coefficient kB = 10.6 [8.6, 13.6] mL/min/mmHg/L, whereas normalized RBC transfer was used to calculate the capillary blood volume-specific conductance coefficient kR = 13.6 [11.4, 16.7] mL/min/mmHg/L. In this way, the barrier and RBC transfer per unit volume determined the transfer coefficient KCO, which was then multiplied by image-estimated VA to obtain DLCO. The model was built on a cohort of 41 healthy subjects and 101 patients with pulmonary disorders. The resulting 129Xe-derived DLCO correlated strongly (R2 = 0.75, P < 0.001) with the measured values, a finding that was preserved within each individual disease cohort. The ability to use 129Xe MRI measures of ventilation, barrier uptake, and RBC transfer to estimate each of the underlying constituents of DLCO clarifies the interpretation of these images while enabling their use to monitor these aspects of gas exchange independently and regionally.NEW & NOTEWORTHY The diffusing capacity for carbon monoxide (DLCO) is perhaps one of the most comprehensive physiological measures used in pulmonary medicine. Here, we spatially resolve and estimate its key components-accessible alveolar volume, membrane, and capillary blood volume conductances-using hyperpolarized 129Xe MRI of ventilation, interstitial barrier uptake, and red blood cell transfer. This image-derived DLCO correlates strongly with measured values in 142 subjects with a broad range of pulmonary disorders.

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

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

Improved preclinical hyperpolarized 129 Xe ventilation imaging with constant flip angle 3D radial golden means acquisition and keyhole reconstruction.

Hyperpolarized (HP) 129 Xe MRI is increasingly used to noninvasively probe regional lung structure and function in the preclinical setting. As in human imaging, the primary barrier to quantitative imaging with HP gases is nonequilibrium magnetization, which is depleted by T1 relaxation and radio frequency excitation. Preclinical HP gas imaging commonly involves mechanically ventilating small animals and encoding k-space over tens or hundreds of breaths, with small subsets of k-space data collected within each breath. Breath-to-breath magnetization renewal enables the use of large flip angles, but the resulting magnetization decay generates large view-to-view differences in within-breath signal intensity, leading to artifacts and degraded image quality. This deleterious signal decay has motivated the use of variable flip angle (VFA) sampling schemes, in which the flip angle is progressively increased to maintain constant view-to-view signal intensity. However, VFA imaging complicates data acquisition and provides only a global correction that fails to compensate for regional differences in signal dynamics. When constant flip angle (CFA) imaging is used alongside 3D radial golden means acquisition, the center of k-space is sampled with every excitation, thereby encoding signal dynamics alongside imaging data. Here, keyhole reconstruction is used to generate multiple images to capture in-breath HP 129 Xe signal dynamics in mice and thus provide flip angle maps to quantitatively correct images without extra data collection. These CFA images display SNR that is not significantly different from VFA images, and further, high frequency k-space scaling can be used to mitigate decay-induced image artifacts. Results are supported by point spread function calculations and simulations of radial imaging with preclinical signal dynamics. Together, these results show that CFA 3D radial golden means ventilation imaging provides comparable image quality with VFA in small animals and allows for keyhole reconstruction, which can be used to generate flip angle maps and correct images for signal depletion.

Sensitive structural and functional measurements and 1-year pulmonary outcomes in pediatric cystic fibrosis

BackgroundTwo functional measurements (multiple breath washout [MBW] and hyperpolarized 129Xe ventilation magnetic resonance imaging [129Xe MRI]) have been shown to be more sensitive to cystic fibrosis (CF) lung obstruction than traditional spirometry. However, functional techniques may be sensitive to different underlying structural abnormalities. The purpose of this study was to determine relationships between these functional markers, their pathophysiology, and 1-year clinical outcomes. MethodsSpirometry, MBW, 129Xe MRI, and ultrashort echo-time (UTE) MRI were obtained in a same-day assessment of 27 pediatric CF patients (ages 11.5±5.0) who had not begun CFTR modulator therapies. UTE MRI was scored for structural abnormalities and functional metrics obtained via spirometry, MBW and 129Xe MRI. 1-year outcomes (ΔFEV1 and pulmonary exacerbations), during which ≈50% initiated modulator therapy, were obtained from the electronic medical record. ResultsMBW, 129Xe MRI, and UTE MRI detected clinically significant disease in more subjects (>78%) compared to spirometry (<30%). UTE MRI suggests increased odds of bronchial changes when mucus plugging is present in the same lobe. MBW and 129Xe MRI correlated best with mucus plugging, while spirometry correlated best with consolidations. Bronchial abnormalities were associated with future pulmonary exacerbations. ConclusionsMBW, 129Xe MRI, and UTE MRI are more sensitive for detection of pediatric CF lung disease when compared to spirometry. MBW and 129Xe MRI correlated with structural abnormalities which occur in early CF disease, suggesting MBW and 129Xe MRI are valuable tools in mild CF lung disease that can guide clinical decision making.

Dissolved 129 Xe lung MRI with four-echo 3D radial spectroscopic imaging: Quantification of regional gas transfer in idiopathic pulmonary fibrosis.

Imaging of the different resonances of dissolved hyperpolarized xenon-129 (129 Xe) in the lung is performed using a four-echo flyback 3D radial spectroscopic imaging technique and is evaluated in healthy volunteers (HV) and subjects with idiopathic pulmonary fibrosis (IPF). 10 HV and 25 subjects with IPF underwent dissolved 129 Xe MRI at 1.5T. IPF subjects underwent same day pulmonary function tests to measure forced vital capacity and the diffusion capacity of the lung for carbon monoxide (DLCO ). A four-point echo time technique with k-space chemical-shift modeling of gas, dissolved 129 Xe in lung tissue/plasma (TP) and red blood cells (RBC) combined with a 3D radial trajectory was implemented within a 14-s breath-hold. Results show an excellent chemical shift separation of the dissolved 129 Xe compartments and gas contamination removal, confirmed by a strong agreement between average imaging and global spectroscopy RBC/TP ratio measurements. Subjects with IPF exhibited reduced imaging gas transfer when compared to HV. A significant increase of the amplitude of RBC signal cardiogenic oscillation was also observed. In IPF subjects, DLCO % predicted was significantly correlated with RBC/TP and RBC/GAS ratios and the correlations were stronger in the inferior and periphery sections of the lungs. Lung MRI of dissolved 129 Xe was performed with a four-echo spectroscopic imaging method. Subjects with IPF demonstrated reduced xenon imaging gas transfer and increased cardiogenic modulation of dissolved xenon signal in the RBCs when compared to HV.

129Xe MRI as a measure of clinical disease severity for pediatric asthma

Measurement of regional lung ventilation with hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI) in pediatric asthma is poised to advance our understanding of disease mechanisms and pathophysiology in a disorder with diverse clinical phenotypes. 129Xe MRI has not been investigated in a pediatric asthma cohort. We hypothesized that 129Xe MRI is feasible and can demonstrate ventilation defects that relate to and predict clinical severity in a pediatric asthma cohort. Thirty-seven children (13 with severe asthma, 8 with mild/moderate asthma, 16 age-matched healthy controls) aged 6 to 17 years old were imaged with 129Xe MRI. Ventilation defect percentage (VDP) and image reader score were calculated and compared with clinical measures at baseline and at follow-up. Children with asthma had higher VDP (P= .002) and number of defects per image slice (defects/slice) (P= .0001) than children without asthma. Children with clinically severe asthma had significantly higher VDP and number of defects/slice than healthy controls. Children with asthma who had a higher number of defects/slice had a higher rate of health care utilization (r= 0.48; P= .03) and oral corticosteroid use (r= 0.43; P= .05) at baseline. Receiver-operating characteristic analysis demonstrated that the VDP and number of defects/slice were predictive of increased health care utilization, asthma, and severe asthma. VDP correlated with FEV1 (r= -0.35; P= .04) and FEV1/forced vital capacity ratio (r= -0.41; P= .01). 129Xe MRI correlates with asthma severity, health care utilization, and oral corticosteroid use. Because delineation of clinical severity is often difficult in children, 129Xe MRI may be an important biomarker for severity, with potential to identify children at higher risk for exacerbations and improve outcomes.

Damaged lung gas exchange function of discharged COVID-19 patients detected by hyperpolarized 129Xe MRI.

The recovery process of COVID-19 patients is unclear. Some recovered patients complain of continued shortness of breath. Vasculopathy has been reported in COVID-19, stressing the importance of probing pulmonary microstructure and function at the alveolar-capillary interface. While computed tomography (CT) detects structural abnormalities, little is known about the impact of disease on lung function. 129Xe magnetic resonance imaging (MRI) is a technique uniquely capable of assessing ventilation, microstructure, and gas exchange. Using 129Xe MRI, we found that COVID-19 patients show a higher rate of ventilation defects (5.9% versus 3.7%), unchanged microstructure, and longer gas-blood exchange time (43.5 ms versus 32.5 ms) compared with healthy individuals. These findings suggest that regional ventilation and alveolar airspace dimensions are relatively normal around the time of discharge, while gas-blood exchange function is diminished. This study establishes the feasibility of localized lung function measurements in COVID-19 patients and their potential usefulness as a supplement to structural imaging.

Decacationic Pillar[5]arene: A New Scaffold for the Development of 129Xe MRI Imaging Agents.

A decacationic water-soluble pillar[5]arene possessing a nonsolvated hydrophobic core has been designed and synthesized. This supramolecular host is capable of binding xenon, as evidenced by hyperCEST depletion experiments. Fluorescence-based studies also demonstrate that xenon binds into the cavity of the pillararene with an association constant of 4.6 × 103 M–1. These data indicate that the water-soluble pillararene is a potential scaffold for building contrast agents that can be detected by xenon-129 magnetic resonance imaging.

Single-Session Bronchial Thermoplasty Guided by 129Xe Magnetic Resonance Imaging. A Pilot Randomized Controlled Clinical Trial.

Rationale: Adverse events have limited the use of bronchial thermoplasty (BT) in severe asthma.Objectives: We sought to evaluate the effectiveness and safety of using 129Xe magnetic resonance imaging (129Xe MRI) to prioritize the most involved airways for guided BT.Methods: Thirty subjects with severe asthma were imaged with volumetric computed tomography and 129Xe MRI to quantitate segmental ventilation defects. Subjects were randomized to treatment of the six most involved airways in the first session (guided group) or a standard three-session BT (unguided). The primary outcome was the change in Asthma Quality of Life Questionnaire score from baseline to 12 weeks after the first BT for the guided group compared with after three treatments for the unguided group.Measurements and Main Results: There was no significant difference in quality of life after one guided compared with three unguided BTs (change in Asthma Quality of Life Questionnaire guided = 0.91 [95% confidence interval, 0.28-1.53]; unguided = 1.49 [95% confidence interval, 0.84-2.14]; P = 0.201). After one BT, the guided group had a greater reduction in the percentage of poorly and nonventilated lung from baseline when compared with unguided (-17.2%; P = 0.009). Thirty-three percent experienced asthma exacerbations after one guided BT compared with 73% after three unguided BTs (P = 0.028).Conclusions: Results of this pilot study suggest that similar short-term improvements can be achieved with one BT treatment guided by 129Xe MRI when compared with standard three-treatment-session BT with fewer periprocedure adverse events.