Hyperpolarized Gas Research Articles

Stimulated echo double diffusion encoded imaging of closed pores: Influence and removal of unbalanced terms.

Nuclear magnetic resonance (NMR) diffusion pore imaging has been proposed to study the shape of arbitrary closed pores filled with an NMR-detectable medium by use of nonclassical diffusion encoding schemes. Potential applications can be found in biomedical imaging and porous media research. When studying non-point-symmetric pores, NMR signals with nonvanishing imaginary parts arise containing the pore shape information, which is lost for classical diffusion encoding schemes. Key limitations are the required high magnetic field gradient amplitudes and T2 relaxation while approaching the diffusion long-time limit. To benefit from the slower T1 decay, we demonstrate the feasibility of diffusion pore imaging with stimulated echoes using Monte Carlo simulations and experiments with hyperpolarized xenon-129 gas in well-defined geometries and show that the necessary complex-valued signals can be acquired. Analytical derivation of the stimulated echo double diffusion encoded signal was performed to investigate the effect of the additionally arising undesired terms on the complex phase information. These terms correspond to signals arising for spin-echo sequences with unbalanced gradients. For most possible applications, the unbalanced terms can be neglected. If non-negligible, selection of the appropriate signal component using a phase cycling scheme was demonstrated experimentally. Using stimulated echoes may be a step towards application of diffusion pore imaging to larger pores with gradient amplitudes available today in preclinical systems.

$k$ -Space-Based Enhancement of Pulmonary Hyperpolarized 129Xe Ventilation Images

Hyperpolarized (HP) noble gas (e.g., 3He/129Xe) MR images are susceptible to noise and artifacts due to the rapid attenuation of nonrenewable HP magnetization along with the scan time. However, a little attention is paid to this issue through postprocessing techniques. Here, a $k$ -space-based analysis method is proposed to improve the overall signal-to-noise ratio (SNR) and lessen the blurring of pulmonary HP 129Xe ventilation images. This method performs $k$ -space weighting using low-frequency boost and a high-frequency modulation which offsets the magnetization loss per excitation, and then integrates two outputs in image domain through a convex combination model. Furthermore, a nonreference quality metric, called second-derivative measure of improvement by entropy (SMIE), is introduced to assess the image quality of HP gas MRI. The simulation results demonstrate that the enhanced images are statistically significantly different to the original ones regarding the SNR, peak SNR, structural similarity, and SMIE (each $P$ -value is less than 0.0001). In vivo results indicate that the proposed method significantly upsets the SNR and SMIE in human pulmonary HP 129Xe ventilation images (all $P$ -values are less than 0.05), while maintaining the appearance of ventilation defects or fine structures. In this case, the proposed scheme has potential for improving the understandability and/or differentiation of regions of interest in the lung.

Hyperpolarized 129xe Gas MRI Pulmonary Ventilation Imaging-Based Functional Avoidance for Lung Cancer Radiotherapy

For patients undergoing lung cancer radiotherapy, functional lung imaging can be incorporated into treatment planning to achieve differential sparing between the viable and defective non-target lung regions. Hyperpolarized 129Xe gas MRI is a powerful tool for evaluating the pulmonary function due to the extremely high enhancement in spin polarization using spin-exchange optical pumping. As the first implementation of hyperpolarized 129Xe gas MRI pulmonary ventilation imaging-guided functional treatment planning in China, this study aimed to quantify its dosimetric impact on sparing the high-functional lung regions. Ten locally advanced lung cancer patients with a median PTV volume of 233.2 cm3 (range: 119.2-667.9 cm3) were included in this study. Before radiotherapy, each patient underwent an MRI scan with 1 liter (L) xenon-inhalation and a simulation CT scan with 1L air-ventilation. The CT and MRI was then registered in a commercially available deformable registration algorithm where the GTV, CTV, and regular OARs were contoured on the CT and the high-functional lungs contoured on the MRI. Two IMRT plans (64Gy/35fractions) were designed for each patient: an anatomic plan (Plan-A) using the simulation CT alone and a functional plan (Plan-F) using the hyperpolarized 129Xe gas MRI in addition. The two plans were created using a treatment planning system with the same dose optimization objectives except that the lung dose objectives in Plan-A were placed on the high-functional lung instead in Plan-F. These lung dose goals focused on V20Gy, V5Gy and the mean dose. Finally, the dose-volume histograms were compared between the two plans for the PTV and OARs using the Wilcoxon signed-rank test. All plans were judged as clinically acceptable. Plan-A and Plan-F showed similar PTV dose homogeneity index and conformity index. Similarly, the doses to all OARs except the high-functional lungs showed no statistical difference. Compared with Plan-A, the V5Gy, V10Gy, V15Gy, V20Gy, V25Gy, V30Gy, and Dmean of high-functional lungs were significantly reduced in Plan-F (P＜0.05 for all indices), from 34.0±13.5%, 24.2±10.8%, 16.7±7.6%, 12.8±6.2%, 9.5±4.8%, 6.4±3.8%, and 7.4±3.0Gy in Plan-A, to 31.8±12.3%, 21.7±8.6%, 14.9±6.2%, 11.1±4.8%, 8.2±4.0%, 5.7±3.4%, and 6.9±2.6Gy in Plan-F, respectively. The sparing is more significant when the high-functional lung is adjacent to the PTV, with the above indices reduced from 46.8%, 39.2%, 32.2%, 26.5%, 19.7%, 15.2%, and 13.6Gy in Plan-A, to 41.8%, 33.4%, 24.8%, 19.4%, 14.2%, 11.8%, and 10.2Gy in Plan-F, for one patient. An emerging technology, hyperpolarized 129Xe gas MRI has been translated into the clinic and used in functional image-guided radiotherapy in China for the first time. Our findings indicate the potential of functional planning in lung functional avoidance for IMRT, particularly for patients who have high-functional lung adjacent to the PTV.

Dissolved hyperpolarized xenon-129 MRI in human kidneys.

PurposeTo assess the feasibility of using dissolved hyperpolarized xenon‐129 (129Xe) MRI to study renal physiology in humans at 3 T.MethodsUsing a flexible transceiver RF coil, dynamic and spatially resolved 129Xe spectroscopy was performed in the abdomen after inhalation of hyperpolarized 129Xe gas with 3 healthy male volunteers. A transmit‐only receive‐only RF coil array was purpose‐built to focus RF excitation and enhance sensitivity for dynamic imaging of 129Xe uptake in the kidneys using spoiled gradient echo and balanced steady‐state sequences.ResultsUsing spatially resolved spectroscopy, different magnitudes of signal from 129Xe dissolved in red blood cells and tissue/plasma could be identified in the kidneys and the aorta. The spectra from both kidneys showed peaks with similar amplitudes and chemical shift values. Imaging with the purpose‐built coil array was shown to provide more than a 3‐fold higher SNR in the kidneys when compared with surrounding tissues, while further physiological information from the dissolved 129Xe in the lungs and in transit to the kidneys was provided with the transceiver coil. The signal of dissolved hyperpolarized 129Xe could be imaged with both tested sequences for about 40 seconds after inhalation.ConclusionThe uptake of 129Xe dissolved in the human kidneys was measured with spectroscopic and imaging experiments, demonstrating the potential of hyperpolarized 129Xe MR as a novel, noninvasive technique to image human kidney tissue perfusion.

Normalisation of MRI ventilation heterogeneity in severe asthma by dupilumab

Ventilation heterogeneity in asthma could be due to many reasons. Luminal obstruction due to inflammatory cells or mucus, smooth muscle constriction and airway wall thickness could all contribute individually or...

Localization regime in diffusion NMR: Theory and experiments.

In this work we investigate the emergence of the localization regime for diffusion NMR in various geometries: inside slabs, inside cylinders and outside rods arranged on a square array. At high gradients, the transverse magnetization is strongly attenuated in the bulk, whereas the macroscopic signal is formed by the remaining magnetization localized near boundaries of the sample. As a consequence, the signal is particularly sensitive to the microstructure. The theoretical analysis relies on recent mathematical advances on the study of the Bloch-Torrey equation. Experiments were conducted with hyperpolarized xenon-129 gas in 3D-printed phantoms and show an excellent agreement with numerical simulations and theoretical predictions. Our mathematical arguments and experimental evidence indicate that the localization regime with a stretched-exponential decay of the macroscopic signal is a generic feature of diffusion NMR that can be observed at moderately high gradients in most NMR scanners.

A hybrid proton and hyperpolarized gas tagging MRI technique for lung respiratory motion imaging: a feasibility study

The aim of this work was to develop a novel hybrid 3D hyperpolarized (HP) gas tagging MRI (t-MRI) technique and to evaluate it for lung respiratory motion measurement with comparison to deformable image registrations (DIR) methods.Three healthy subjects underwent a hybrid MRI which combines 3D HP gas t-MRI with a low resolution (Low-R, 4.5 mm isotropic voxels) 3D proton MRI (p-MRI), plus a high resolution (High-R, 2.5 mm isotropic voxels) 3D p-MRI, during breath-holds at the end-of-inhalation (EOI) and the end-of-exhalation (EOE). Displacement vector field (DVF) of the lung motion was determined from the t-MRI images by tracking tagging grids and from the High-R p-MRI using three DIR methods (B-spline based method implemented by Velocity, Free Form Deformation by MIM, and B-spline by an open source software Elastix: denoted as A, B, and C, respectively), labeled as tDVF and dDVF, respectively. The tDVF from the HP gas t-MRI was used as ground-truth reference to evaluate performance of the three DIR methods. Differences in both magnitude and angle between the tDVF and dDVFs were analyzed.The mean lung motion of the three subjects was 37.3 mm, 8.9 mm and 12.9 mm, respectively. Relatively large discrepancies were observed between the tDVF and the dDVFs as compared to previously reported DIR errors. The mean ± standard deviation (SD) DVF magnitude difference was 8.3 ± 5.6 mm, 9.2 ± 4.5 mm, and 9.3 ± 6.1 mm, and the mean ± SD DVF angular difference was 29.1 ± 12.1°, 50.1 ± 28.6°, and 39.0 ± 6.3°, for the DIR Methods A, B, and C, respectively.These preliminary results showed that the hybrid HP gas t-MRI technique revealed different lung motion patterns as compared to the DIR methods. It may provide unique perspectives in developing and evaluating DIR of the lungs.Novelty and SignificanceWe designed a MRI protocol that includes a novel hybrid MRI technique (3D HP gas t-MRI with a low resolution 3D p-MRI) plus a high resolution 3D p-MRI. We tested the novel hybrid MRI technique on three healthy subjects for measuring regional lung respiratory motion with comparison to deformable image registrations (DIR) methods, and observed relatively large discrepancies in lung motion between HP gas t-MRI and DIR methods.

Measuring lung function in airways diseases: current and emerging techniques

Chronic airways diseases, including asthma, COPD and cystic fibrosis, cause significant morbidity and mortality and are associated with high healthcare expenditure, in the UK and worldwide. For patients with these...

Relaxation Dynamics of Nuclear Long-Lived Spin States in Propane and Propane-d6 Hyperpolarized by Parahydrogen.

We report a systematic study of relaxation dynamics of hyperpolarized (HP) propane and HP propane-d6 prepared by heterogeneous pairwise parahydrogen addition to propylene and propylene-d6 respectively. Long-lived spin states (LLS) created for these molecules at the low magnetic field of 0.0475 T were employed for this study. The parahydrogen-induced overpopulation of a HP propane LLS decays exponentially with time constant (TLLS) approximately 3-fold greater than the corresponding T1 values. Both TLLS and T1 increase linearly with propane pressure in the range from 1 atm (the most biomedically relevant conditions for pulmonary MRI) to 5 atm. The TLLS value of HP propane gas at 1 atm is ~3 s. Deuteration of the substrate (propylene-d6) yields hyperpolarized propane-d6 gas with TLLS values approximately 20% shorter than those of hyperpolarized fully protonated propane gas, indicating that deuteration does not benefit the lifetime of the LLS HP state. The use of pH2 or Xe/N2 buffering gas during heterogeneous hydrogenation reaction (leading to production of 100% HP propane (no buffering gas) versus 43% HP propane gas (with 57% buffering gas) composition mixtures) results in (i) no significant changes in T1, (ii) decrease of TLLS values (by 35±7% and 8±7% respectively); and (iii) an increase of the polarization levels of HP propane gas with a propane concentration decrease (by 1.6±0.1-fold and 1.4±0.1-fold respectively despite the decrease in TLLS, which leads to disproportionately greater polarization losses during HP gas transport). Moreover, we demonstrate the feasibility of HP propane cryo-collection (which can be potentially useful for preparing larger amounts of concentrated HP propane, when buffering gas is employed), and TLLS of liquefied HP propane reaches 14.7 seconds, which is greater than the TLLS value of HP propane gas at any pressure studied. Finally, we have explored the utility of using a partial Spin-Lock Induced Crossing (SLIC) radio frequency (RF) pulse sequence for converting the overpopulated LLS into observable 1H nuclear magnetization at low magnetic field. We find that (i) the bulk of the overpopulated LLS is retained even when the optimal or near-optimal values of SLIC pulse duration are employed, and (ii) the overpopulated LLS of propane is also relatively immune to strong RF pulses-thereby, indicating that LLS is highly suitable as a spin-polarization reservoir in the context of NMR/MRI detection applications. The presented findings may be useful for improving the levels of polarization of HP propane produced by HET-PHIP via the use of an inert buffer gas; increasing the lifetime of the HP state during preparation and storage; and developing efficient approaches for ultrafast MR imaging of HP propane in the context of biomedical applications of HP propane gas, including its potential use as an inhalable contrast agent.

Clinical-Scale Batch-Mode Production of Hyperpolarized Propane Gas for MRI.

NMR spectroscopy and imaging (MRI) are two of the most important methods to study structure, function, and dynamics from atom to organism scale. NMR approaches often suffer from an insufficient sensitivity, which, however, can be transiently boosted using hyperpolarization techniques. One of these techniques is parahydrogen-induced polarization, which has been used to produce catalyst-free hyperpolarized propane gas with proton polarization that is 3 orders of magnitude greater than equilibrium thermal polarization at a 1.5 T field of a clinical MRI scanner. Here we show that more than 0.3 L of hyperpolarized propane gas can be produced in 2 s. This production rate is more than an order of magnitude greater than that demonstrated previously, and the reported production rate is comparable to that employed for in-human MRI using HP noble gas (e.g., 129Xe) produced via a spin exchange optical pumping (SEOP) hyperpolarization technique. We show that high polarization values can be retained despite the significant increase in the production rate of hyperpolarized propane. The enhanced signals of produced hyperpolarized propane gas were revealed by stopped-flow MRI visualization at 4.7 T. Achieving this high production rate enables the future use of this compound (already approved for unlimited use in foods by the corresponding regulating agencies, e.g., FDA in the USA, and more broadly as an E944 food additive) as a new inhalable contrast agent for diagnostic detection via MRI.

Comparison of CT ventilation imaging and hyperpolarised gas MRI: effects of breathing manoeuvre

Image registration of lung CT images acquired at different inflation levels has been proposed as a surrogate method to map lung ‘ventilation’. Prior to clinical use, it is important to understand how this technique compares with direct ventilation imaging modalities such as hyperpolarised gas MRI. However, variations in lung inflation level have been shown to affect regional ventilation distributions. Therefore, the aim of this study was to evaluate the impact of lung inflation levels when comparing CT ventilation imaging to ventilation from 3He-MRI.Seven asthma patients underwent breath-hold CT at total lung capacity (TLC) and functional residual capacity (FRC). 3He-MRI and a same-breath 1H-MRI were acquired at FRC+1L and TLC. Percentage ventilated volumes (%VVs) were calculated for FRC+1L and TLC 3He-MRI. TLC-CT and registered FRC-CT were used to compute a surrogate ventilation map from voxel-wise intensity differences in Hounsfield unit values, which was thresholded at the 10th and 20th percentiles. For direct comparison of CT and 3He-MRI ventilation, FRC+1L and TLC 3He-MRI were registered to TLC-CT indirectly via the corresponding same-breath 1H-MRI data. For 3He-MRI and CT ventilation comparison, Dice similarity coefficients (DSCs) between the binary segmentations were computed.The median (range) of %VVs for FRC+1L and TLC 3He-MRI were 90.5 (54.9–93.6) and 91.8 (67.8–96.2), respectively (p = 0.018). For MRI versus CT ventilation comparison, statistically significant improvements in DSCs were observed for TLC 3He MRI when compared with FRC+1L, with median (range) values of 0.93 (0.86–0.93) and 0.86 (0.68–0.92), respectively (p = 0.017), for the 10–100th percentile and 0.87 (0.83–0.88) and 0.81 (0.66–0.87), respectively (p = 0.027), for the 20–100th percentile.Correlation of CT ventilation imaging and hyperpolarised gas MRI is sensitive to lung inflation level. For ventilation maps derived from CT acquired at FRC and TLC, a higher correlation with gas ventilation MRI can be achieved if the MRI is acquired at TLC.

Advanced pulmonary MRI to quantify alveolar and acinar duct abnormalities: Current status and future clinical applications.

There are serious clinical gaps in our understanding of chronic lung disease that require novel, sensitive, and noninvasive in vivo measurements of the lung parenchyma to measure disease pathogenesis and progressive changes over time as well as response to treatment. Until recently, our knowledge and appreciation of the tissue changes that accompany lung disease has depended on ex vivo biopsy and concomitant histological and stereological measurements. These measurements have revealed the underlying pathologies that drive lung disease and have provided important observations about airway occlusion, obliteration of the terminal bronchioles and airspace enlargement, or fibrosis and their roles in disease initiation and progression. ex vivo tissue stereology and histology are the established gold standards and, more recently, micro-computed tomography (CT) measurements of ex vivo tissue samples has also been employed to reveal new mechanistic findings about the progression of obstructive lung disease in patients. While these approaches have provided important understandings using ex vivo analysis of excised samples, recently developed hyperpolarized noble gas MRI methods provide an opportunity to noninvasively measure acinar duct and terminal airway dimensions and geometry in vivo, and, without radiation burden. Therefore, in this review we summarize emerging pulmonary MRI morphometry methods that provide noninvasive in vivo measurements of the lung in patients with bronchopulmonary dysplasia and chronic obstructive pulmonary disease, among others. We discuss new findings, future research directions, as well as clinical opportunities to address current gaps in patient care and for testing of new therapies. Level of Evidence: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;50:28-40.

Ultra-Sensitive Atomic Magnetometers for Studying Spin Precessions of Hyperpolarized Noble Gases Based on System Identification

We reported an efficient approach to analyze spin precessions of different hyperpolarized noble gases with atomic magnetometers based on system identification. Spin evolution of the magnetometer can be robustly approximated as the second order system by referring to the Bloch equation under the negligible self-interaction and its transfer function model can be deduced. We measured the dynamic responses of different atomic pairs, such as cesium magnetometer with a partner of xenon-129, potassium magnetometer with a partner of helium-3, and hybrid of cesium and rubidium magnetometer with a partner of neon-21. By referring to the experimental results, corresponding systematic parameters for the transfer function models have been identified based on least-square method, whose outputs were consistent with experimental results. Based on the models, the system stabilities and their variations with different gains have been analyzed with control theory, both of which are described here. Applying control theory to analyze dynamic responses of spin ensembles plays an important role for the future applications.

Magnetic resonance imaging of the time course of hyperpolarized 129Xe gas exchange in the human lungs and heart

PurposeTo perform magnetic resonance imaging (MRI), human lung imaging, and quantification of the gas-transfer dynamics of hyperpolarized xenon-129 (HPX) from the alveoli into the blood plasma.Materials and methodsHPX MRI with iterative decomposition of water and fat with echo asymmetry and least-square estimation (IDEAL) approach were used with multi-interleaved spiral k-space sampling to obtain HPX gas and dissolved phase images. IDEAL time-series images were then obtained from ten subjects including six normal subjects and four patients with pulmonary emphysema to test the feasibility of the proposed technique for capturing xenon-129 gas-transfer dynamics (XGTD). The dynamics of xenon gas diffusion over the entire lung was also investigated by measuring the signal intensity variations between three regions of interest, including the left and right lungs and the heart using Welch’s t test.ResultsThe technique enabled the acquisition of HPX gas and dissolved phase compartment images in a single breath-hold interval of 8 s. The y-intersect of the XGTD curves were also found to be statistically lower in the patients with lung emphysema than in the healthy group (p < 0.05).ConclusionThis time-series IDEAL technique enables the visualization and quantification of inhaled xenon from the alveoli to the left ventricle with a clinical gradient strength magnet during a single breath-hold, in healthy and diseased lungs.Key Points• The proposed hyperpolarized xenon-129 gas and dissolved magnetic resonance imaging technique can provide regional and temporal measurements of xenon-129 gas-transfer dynamics.• Quantitative measurement of xenon-129 gas-transfer dynamics from the alveolar to the heart was demonstrated in normal subjects and pulmonary emphysema.• Comparison of gas-transfer dynamics in normal subjects and pulmonary emphysema showed that the proposed technique appears sensitive to changes affecting the alveoli, pulmonary interstitium, and capillaries.

Highly and Adaptively Undersampling Pattern for Pulmonary Hyperpolarized 129Xe Dynamic MRI.

Hyperpolarized (HP) gas (e.g., 3He or 129Xe) dynamic MRI could visualize the lung ventilation process, which provides characteristics regarding lung physiology and pathophysiology. Compressed sensing (CS) is generally used to increase the temporal resolution of such dynamic MRI. Nevertheless, the acceleration factor of CS is constant, which results in difficulties in precisely observing and/or measuring dynamic ventilation process due to bifurcating network structure of the lung. Here, an adaptive strategy is proposed to highly undersample pulmonary HP dynamic k-space data, according to the characteristics of both lung structure and gas motion. After that, a valid reconstruction algorithm is developed to reconstruct dynamic MR images, considering the low-rank, global sparsity, gas-inflow effects, and joint sparsity. Both the simulation and the in vivo results verify that the proposed approach outperforms the state-of-the-art methods both in qualitative and quantitative comparisons. In particular, the proposed method acquires 33 frames within 6.67 s (more than double the temporal resolution of the recently proposed strategy), and achieves high-image quality [the improvements are 29.63%, 3.19%, 2.08%, and 13.03% regarding the mean absolute error (MAE), structural similarity index (SSIM), quality index based on local variance (QILV), and contrast-to-noise ratio (CNR) comparisons]. This provides accurate structural and functional information for early detection of obstructive lung diseases.

An initial investigation of hyperpolarized gas tagging magnetic resonance imaging in evaluating deformable image registration-based lung ventilation.

Deformable image registration (DIR)-based lung ventilation mapping is attractive due to its simplicity, and also challenging due to its susceptibility to errors and uncertainties. In this study, we explored the use of 3D Hyperpolarized (HP) gas tagging MRI to evaluate DIR-based lung ventilation. Three healthy volunteers included in this study underwent both 3D HP gas tagging MRI (t-MRI) and 3D proton MRI (p-MRI) using balanced steady-state free precession pulse sequence at end of inhalation and end of exhalation. We first obtained the reference displacement vector fields (DVFs) from the t-MRIs by tracking the motion of each tagging grid between the exhalation and the inhalation phases. Then, we determined DIR-based DVFs from the p-MRIs by registering the images at the two phases with two commercial DIR algorithms. Lung ventilations were calculated from both the reference DVFs and the DIR-based DVFs using the Jacobian method and then compared using cross correlation and mutual information. The DIR-based lung ventilations calculated using p-MRI varied considerably from the reference lung ventilations based on t-MRI among all three subjects. The lung ventilations generated using Velocity AI were preferable for the better spatial homogeneity and accuracy compared to the ones using MIM, with higher average cross correlation (0.328 vs 0.262) and larger average mutual information (0.528 vs 0.323). We demonstrated that different DIR algorithms resulted in different lung ventilation maps due to underlining differences in the DVFs. HP gas tagging MRI provides a unique platform for evaluating DIR-based lung ventilation.

Exploring Local Disorder within CAU-1 Frameworks Using Hyperpolarized 129Xe NMR Spectroscopy.

The sorption properties of metal-organic frameworks (MOFs) can be influenced by introducing covalently attached functional side chains, which make this subclass of porous materials promising for applications as diverse as gas storage and separation, catalysis, and drug delivery. The incorporation of side groups usually comes along with disorder, as the synthesis procedures rarely allow for one specific position among a larger group of equivalent sites to be selected. For a series of isoreticular CAU-1 frameworks, chosen as model compounds, one out of four positions at every linker is modified with equal probability. Here, we investigate the influence of this disorder on Ar sorption and 129Xe nuclear magnetic resonance spectroscopy using hyperpolarized 129Xe gas. Models used for predicting the pore dimensions as well as their distributions were derived from the unfunctionalized framework by replacing one proton at every linker with either an amino, an acetamide, or a methyl urea functionality. The resulting structures were optimized using density functional theory (DFT) calculations. Results from void analyses and Monte Carlo force field simulations suggest that for available Ar nonlocal DFT (NLDFT) kernels, neither the pore dimensions nor the distributions induced by the side-chain disorder are well-reproduced. By contrast, we found the 129Xe chemical shift analysis for the shift observed at high temperature to be well-suited to develop a detailed fingerprint of the porosity and side-chain disorder within the isoreticular CAU-1 series. After calibrating the 129Xe limiting shift of the amino-functionalized framework with DFT calculations, the downfield shifts for the other two derivatives are an excellent measure for the reduction of the accessible pore space and reveal a strong preference for the side chains toward the octahedral voids for both cases. We expect that the strategy presented here can be commonly applied to disorder phenomena within MOFs in the future.

19 F MRI of the Lungs Using Inert Fluorinated Gases: Challenges and New Developments.

Fluorine-19 (19 F) MRI using inhaled inert fluorinated gases is an emerging technique that can provide functional images of the lungs. Inert fluorinated gases are nontoxic, abundant, relatively inexpensive, and the technique can be performed on any MRI scanner with broadband multinuclear imaging capabilities. Pulmonary 19 F MRI has been performed in animals, healthy human volunteers, and in patients with lung disease. In this review, the technical requirements of 19 F MRI are discussed, along with various imaging approaches used to optimize the image quality. Lung imaging is typically performed in humans using a gas mixture containing 79% perfluoropropane (PFP) or sulphur hexafluoride (SF6 ) and 21% oxygen. In lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), ventilation defects are apparent in regions that the inhaled gas cannot access. 19 F lung images are typically acquired in a single breath-hold, or in a time-resolved, multiple breath fashion. The former provides measurements of the ventilation defect percent (VDP), while the latter provides measurements of gas replacement (ie, fractional ventilation). Finally, preliminary comparisons with other functional lung imaging techniques are discussed, such as Fourier decomposition MRI and hyperpolarized gas MRI. Overall, functional 19 F lung MRI is expected to complement existing proton-based structural imaging techniques, and the combination of structural and functional lung MRI will provide useful outcome measures in the future management of pulmonary diseases in the clinic. Level of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:343-354.

Heterogeneous Parahydrogen Pairwise Addition to Cyclopropane.

Hyperpolarized gases revolutionize functional pulmonary imaging. Hyperpolarized propane is a promising emerging contrast agent for pulmonary MRI. Unlike hyperpolarized noble gases, proton-hyperpolarized propane gas can be imaged using conventional MRI scanners with proton imaging capability. Moreover, it is non-toxic odorless anesthetic. Furthermore, propane hyperpolarization can be accomplished by pairwise addition of parahydrogen to propylene. Here, we demonstrate the feasibility of propane hyperpolarization via hydrogenation of cyclopropane with parahydrogen. 1 H propane polarization up to 2.4 % is demonstrated here using 82 % parahydrogen enrichment and heterogeneous Rh/TiO2 hydrogenation catalyst. This level of polarization is several times greater than that obtained with propylene as a precursor under the same conditions despite the fact that direct pairwise addition of parahydrogen to cyclopropane may also lead to formation of propane with NMR-invisible hyperpolarization due to magnetic equivalence of nascent parahydrogen protons in two CH3 groups. NMR-visible hyperpolarized propane demonstrated here can be formed only via a reaction pathway involving cleavage of at least one C-H bond in the reactant molecule. The resulting NMR signal enhancement of hyperpolarized propane was sufficient for 2D gradient echo MRI of ∼5.5 mL phantom with 1×1 mm2 spatial resolution and 64×64 imaging matrix despite relatively low chemical conversion of cyclopropane substrate.

Hyperpolarized Gas Magnetic Resonance Imaging of Pediatric Cystic Fibrosis Lung Disease

Conventional pulmonary function tests appear normal in early cystic fibrosis (CF) lung disease. Therefore, new diagnostic approaches are required that can detect CF lung disease in children and monitor treatment response. Hyperpolarized (HP) gas (129Xe and 3He) magnetic resonance imaging (MRI) is a powerful, emergent tool for mapping regional lung function and may be well suited for studying pediatric CF. HP gas MRI is well tolerated, reproducible, and it can be performed longitudinally without the need for ionizing radiation. In particular, quantification of the distribution of ventilation, or ventilation defect percent (VDP), has been shown to be a sensitive indicator of CF lung disease and correlates well with pulmonary function tests. This article presents the current state of CF diagnosis and treatment and describes the potential role of HP gas MRI for detection of early CF lung disease and following the effects of interventions. The typical HP gas imaging workflow is described, along with a discussion of image analysis to calculate VDP, dosing considerations, and the reproducibility of VDP. The potential use of VDP as an outcome measure in CF is discussed, by considering the correlation with pulmonary function measures, preliminary interventional studies, and case studies involving longitudinal imaging and pulmonary exacerbations. Finally, emerging HP gas imaging techniques such as multiple breath washout imaging are introduced, followed by a discussion of future directions. Overall, HP gas MRI biomarkers are expected to provide sensitive outcome measures that can be used in disease surveillance as well as interventional studies involving novel CF therapies.