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Rationale: 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 129 Xe images in multiple pulmonary diseases through comparison of the most utilized quantification schemes: linear binning and thresholding., Materials and Methods: HP 129 Xe 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 129 Xe 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., Results: 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., Conclusion: 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., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: Hyperpolarized xenon (129Xe) gas‐transfer imaging allows different components of pulmonary gas transfer—alveolar air space, lung interstitium/blood plasma (barrier), and red blood cells (RBCs)—to be assessed separately in a single breath. However, quantitative analysis is challenging because dissolved‐phase 129Xe images are often contaminated by off‐resonant gas‐phase signal generated via imperfectly selective excitation. Although previous methods required additional data for gas‐phase removal, the method reported here requires no/minimal sequence modifications/data acquisitions, allowing many previously acquired images to be corrected retroactively. Methods: 129Xe imaging was implemented at 3.0T via an interleaved three‐dimensional radial acquisition of the gaseous and dissolved phases (using one‐point Dixon reconstruction for the dissolved phase) in 46 human subjects and a phantom. Gas‐phase contamination (9.5% ± 4.8%) was removed from gas‐transfer data using a modified gas‐phase image. The signal‐to‐noise ratio (SNR) and signal distributions were compared before and after contamination removal. Additionally, theoretical gaseous contaminations were simulated at different magnetic field strengths for comparison. Results: Gas‐phase contamination at 3.0T was more diffuse and located predominantly outside the lungs, relative to simulated 1.5T contamination caused by the larger frequency offset. Phantom experiments illustrated a 91% removal efficiency. In human subjects, contamination removal produced significant changes in dissolved signal SNR (+7.8%), mean (–1.4%), and standard deviation (–2.3%) despite low contamination. Repeat measurements showed reduced variance (dissolved mean, –1.0%; standard deviation, –8.4%). Conclusion: Off‐resonance gas‐phase contamination can be removed robustly with no/minimal sequence modifications. Contamination removal permits more accurate quantification, reduces radiofrequency stringency requirements, and increases data consistency, providing improved sensitivity needed for multicenter trials. [ABSTRACT FROM AUTHOR]

Clinical magnetic resonance imaging of the lung is technologically challenging, yet over the past two decades hyperpolarized noble gas (3He and 129Xe) imaging has demonstrated the ability to measure multiple pulmonary functional biomarkers. There is a growing need for non-ionizing, non-invasive imaging techniques due to increased concern about cancer risk from ionizing radiation, but the translation of hyperpolarized gas imaging to the pulmonary clinic has been stunted by limited access to the technology. New developments may open doors to greater access and more translation to clinical studies. Here we briefly review a few translational applications of hyperpolarized gas MRI in the contexts of ventilation, diffusion, and dissolved-phase imaging, as well as comparing and contrasting 3He and 129Xe gases for these applications. Simple static ventilation MRI reveals regions of the lung not participating in normal ventilation, and these defects have been observed in many pulmonary diseases. Biomarkers related to airspace size and connectivity can be quantified by apparent diffusion coefficient measurements of hyperpolarized gas, and have been shown to be more sensitive to small changes in lung morphology than standard clinical pulmonary functional tests and have been validated by quantitative histology. Parameters related to gas uptake and exchange and lung tissue density can be determined using 129Xe dissolved-phase MRI. In most cases functional biomarkers can be determined via MRI of either gas, but for some applications one gas may be preferred, such as 3He for long-range diffusion measurements and 129Xe for dissolved-phase imaging. Greater access to hyperpolarized gas imaging coupled with newly developing therapeutics makes pulmonary medicine poised for a potential revolution, further adding to the prospects of personalized medicine already evidenced by advancements in molecular biology. Hyperpolarized gas researchers have the opportunity to contribute to this revolution, particularly if greater clinical application of hyperpolarized gas imaging is realized. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Here we provide a full report on the construction, components, and capabilities of our consortium’s “open-source” large-scale (~1L/h) 129Xe hyperpolarizer for clinical, pre-clinical, and materials NMR/MRI (Nikolaou et al., Proc. Natl. Acad. Sci. USA, 110, 14150 (2013)). The ‘hyperpolarizer’ is automated and built mostly of off-the-shelf components; moreover, it is designed to be cost-effective and installed in both research laboratories and clinical settings with materials costing less than $125,000. The device runs in the xenon-rich regime (up to 1800Torr Xe in 0.5L) in either stopped-flow or single-batch mode—making cryo-collection of the hyperpolarized gas unnecessary for many applications. In-cell 129Xe nuclear spin polarization values of ~30%–90% have been measured for Xe loadings of ~300–1600Torr. Typical 129Xe polarization build-up and T1 relaxation time constants were ~8.5min and ~1.9h respectively under our spin-exchange optical pumping conditions; such ratios, combined with near-unity Rb electron spin polarizations enabled by the high resonant laser power (up to ~200W), permit such high P Xe values to be achieved despite the high in-cell Xe densities. Importantly, most of the polarization is maintained during efficient HP gas transfer to other containers, and ultra-long 129Xe relaxation times (up to nearly 6h) were observed in Tedlar bags following transport to a clinical 3T scanner for MR spectroscopy and imaging as a prelude to in vivo experiments. The device has received FDA IND approval for a clinical study of chronic obstructive pulmonary disease subjects. The primary focus of this paper is on the technical/engineering development of the polarizer, with the explicit goals of facilitating the adaptation of design features and operative modes into other laboratories, and of spurring the further advancement of HP-gas MR applications in biomedicine. [Copyright &y& Elsevier]

Three-dimensional printing with high-temperature plastic is used to enable spin exchange optical pumping (SEOP) and hyperpolarization of xenon-129 gas. The use of 3D printed structures increases the simplicity of integration of the following key components with a variable temperature SEOP probe: (i) in situ NMR circuit operating at 84 kHz (Larmor frequencies of 129Xe and 1H nuclear spins), (ii) <0.3 nm narrowed 200 W laser source, (iii) in situ high-resolution near-IR spectroscopy, (iv) thermoelectric temperature control, (v) retroreflection optics, and (vi) optomechanical alignment system. The rapid prototyping endowed by 3D printing dramatically reduces production time and expenses while allowing reproducibility and integration of "off-the-shelf" components and enables the concept of printing on demand. The utility of this SEOP setup is demonstrated here to obtain near-unity 129Xe polarization values in a 0.5 L optical pumping cell, including ~74 ± 7% at 1000 Torr xenon partial pressure, a record value at such high Xe density. Values for the 129Xe polarization exponential build-up rate [(3.63 ± 0.15) × 10-2 min-1] and in-cell 129Xe spin-lattice relaxation time (T1 = 2.19 ± 0.06 h) for 1000 Torr Xe were in excellent agreement with the ratio of the gas-phase polarizations for 129Xe and Rb (PRb ~ 96%). Hyperpolarization-enhanced 129Xe gas imaging was demonstrated with a spherical phantom following automated gas transfer from the polarizer. Taken together, these results support the development of a wide range of chemical, biochemical, material science, and biomedical applications. [ABSTRACT FROM AUTHOR]

• LCI 2.5 , 129Xe VDP, and UTE more sensitive to pediatric CF disease than spirometry. • 1H MRI suggests increased odds for airway damage in lobes with mucus plugging. • Most spirometry measures correlated with consolidations and ground glass. • LCI 2.5 and 129Xe VDP correlated with mucus plugging. • Increased exacerbations most strongly correlated with mucus plugs and airway damage. Two 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. Spirometry, 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 (ΔFEV 1 and pulmonary exacerbations), during which ≈50% initiated modulator therapy, were obtained from the electronic medical record. MBW, 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. MBW, 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. [ABSTRACT FROM AUTHOR]

We present a systematic, multiparameterstudy of Rb/129Xe spin-exchange optical pumping (SEOP)in the regimes of high xenonpressure and photon flux using a 3D-printed, clinical-scale stopped-flowhyperpolarizer. In situ NMR detection was used to study the dynamicsof 129Xe polarization as a function of SEOP-cell operatingtemperature, photon flux, and xenon partial pressure to maximize 129Xe polarization (PXe). PXevalues of 95 ± 9%, 73 ± 4%, 60± 2%, 41 ± 1%, and 31 ± 1% at 275, 515, 1000, 1500,and 2000 Torr Xe partial pressure were achieved. These PXepolarization values were separately validated by ejectingthe hyperpolarized 129Xe gas and performing low-field MRIat 47.5 mT. It is shown that PXein thishigh-pressure regime can be increased beyond already record levelswith higher photon flux and better SEOP thermal management, as wellas optimization of the polarization dynamics, pointing the way tofurther improvements in hyperpolarized 129Xe productionefficiency. [ABSTRACT FROM AUTHOR]