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

Purpose: To measure regional changes in hyperpolarized 129Xe MRI signal and apparent transverse relaxation (T2∗) because of instillation of SPION‐labeled alveolar‐like macrophages (ALMs) in the lungs of rats and compare to histology. Methods: MRI was performed in 6 healthy mechanically ventilated rats before instillation, as well as 5 min and 1 h after instillation of 4 million SPION‐labeled ALMs into either the left or right lung. T2∗ maps were calculated from 2D multi‐echo data at each time point and changes in T2∗ were measured and compared to control rats receiving 4 million unlabeled ALMs. Histology of the ex vivo lungs was used to compare the regional MRI findings with the locations of the SPION‐labeled ALMs. Results: Regions of signal loss were observed immediately after instillation of unlabeled and SPION‐labeled ALMs and persisted at least 1 h in the case of the SPION‐labeled ALMs. This was reflected in the measurements of T2∗. One hour after the instillation of SPION‐labeled ALMs, the T2∗ decreased to 54.0 ± 7.0% of the baseline, compared to a full recovery to baseline after the instillation of unlabeled ALMs. Histology confirmed the co‐localization of SPION‐labeled ALMs with regions of signal loss and T2∗ decreases for each rat. Conclusion: Hyperpolarized 129Xe MRI can detect the presence of SPION‐labeled ALMs in the airways 1 h after instillation. This approach is promising for targeting and tracking of stem cells for the treatment of lung disease. [ABSTRACT FROM AUTHOR]

Hyperpolarized noble gas (HNG) magnetic resonance (MR) imaging is a very promising noninvasive tool for the investigation of animal models of lung disease, particularly to follow longitudinal changes in lung function and anatomy without the accumulated radiation dose associated with x rays. The two most common noble gases for this purpose are 3He (helium 3) and 129Xe (xenon 129), the latter providing a cost-effective approach for clinical applications. Hyperpolarization is typically achieved using spin-exchange optical pumping techniques resulting in ∼10 000-fold improvement in available magnetization compared to conventional Boltzmann polarizations. This substantial increase in polarization allows high spatial resolution (<1 mm) single-slice images of the lung to be obtained with excellent temporal resolution (<1 s). Complete three-dimensional images of the lungs with 1 mm slice thickness can be obtained within reasonable breath-hold intervals (<20 s). This article provides an overview of the current methods used in HNG MR imaging with an emphasis on ventilation studies in animals. Special MR hardware and software considerations are described in order to use the strong but nonrecoverable magnetization as efficiently as possible and avoid depolarization primarily by molecular oxygen. Several applications of HNG MR imaging are presented, including measurement of gross lung anatomy (e.g., airway diameters), microscopic anatomy (e.g., apparent diffusion coefficient), and a variety of functional parameters including dynamic ventilation, alveolar oxygen partial pressure, and xenon diffusing capacity. [ABSTRACT FROM AUTHOR]

Hyperpolarized 129Xe (xenon) gas dissolved in a perfluorooctyl bromide (PFOB) emulsion stabilized with egg yolk phospholipid (EYP) is a possible contrast agent for quantitative blood flow measurements using magnetic resonance imaging. The NMR line shape of xenon dissolved in PFOB emulsion depends strongly on the exchange of spins between PFOB and water. The exchange in this system depends on three factors: the geometrical factors (i.e., droplet size and surrounding water volume), the permeability of the EYP monolayer surrounding the droplet, and the diffusion coefficients of xenon in the two media. A theoretical model which predicts the line shape of xenon in the emulsion based on the Bloch-Torrey equations is presented. Fitting the full width at half maximum (FWHM) of the theoretical line shapes with the FWHM of the experimental spectra obtained from emulsions with different water dilutions allows estimation of the volume-weighted average diameter of the PFOB droplets (3.5±0.8) μm and the permeability of the EYP membrane surrounding the droplet (58±14) μm/s. [ABSTRACT FROM AUTHOR]

Purpose Hyperpolarized (HP) gas MRI of the rodent lung is of great interest because of the increasing need for novel biomarkers with which to develop new therapies for respiratory diseases. The use of fast gradient-recalled echo (FGRE) for high-resolution HP gas rodent lung MRI is challenging as a result of signal loss caused by significant diffusion weighting, particularly in the larger airways. In this work, a modified FGRE approach is described for HP 3He rodent lung MRI using a centric-out readout scheme (ie, x-centric), allowing high-resolution, density-weighted imaging. Methods HP 3He x-centric imaging was performed in a phantom and compared with a conventional partial-echo FGRE acquisition for in-plane spatial resolutions varying between 39 and 312 µm. Partial-echo and x-centric acquisitions were also compared for high spatial-resolution breath-hold (1 s) imaging of rodent lungs. Results X-centric provided improved signal-to-noise ratio efficiency by a factor of up to 13/1.7 and 6.7/1.8, compared with the partial-echo FGRE for the airways/parenchyma of mouse and rat, respectively, at high spatial resolutions in vivo (<78 µm). In particular, rodent major airways with less restricted diffusion of 3He could only be visualized with the x-centric method. Conclusions The x-centric method significantly reduces diffusion weighting, allowing high spatial and temporal resolution HP 3He gas density-weighted rodent lung MRI. Magn Reson Med 78:2334-2341, 2017. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Purpose To implement and optimize a single-shot spiral encoding strategy for rapid 2D IDEAL projection imaging of hyperpolarized (Hp) 129Xe in the gas phase, and in the pulmonary tissue (PT) and red blood cells (RBCs) compartments of the rat lung, respectively. Theory and Methods A theoretical and experimental point spread function analysis was used to optimize the spiral k-space read-out time in a phantom. Hp 129Xe IDEAL images from five healthy rats were used to: (i) optimize flip angles by a Bloch equation analysis using measured kinetics of gas exchange and (ii) investigate the feasibility of the approach to characterize the exchange of Hp 129Xe. Results A read-out time equal to approximately 1.8 × [ABSTRACT FROM AUTHOR]

Purpose Radiation-induced lung injury (RILI) is still the major dose-limiting toxicity related to lung cancer radiation therapy, and it is difficult to predict and detect patients who are at early risk of severe pneumonitis and fibrosis. The goal of this proof-of-concept preclinical demonstration was to investigate the potential of hyperpolarized 129Xe diffusion-weighted MRI to detect the lung morphological changes associated with early stage RILI. Methods Hyperpolarized 129Xe MRI was performed using eight different diffusion sensitizations (0.0-115 s/cm2) in a small group of control rats (n = 4) and rats 2 wk after radiation exposure (n = 5). The diffusion-weighted images were used to obtain morphological estimates of the pulmonary parenchyma including external radius ( R), internal radius ( r), alveolar sleeve depth ( h), and mean airspace chord length ( Lm). The histological mean linear intercept ( MLI) were obtained for five control and five irradiated animals. Results Mean R, r, and Lm were both significantly different ( P < 0.02) in the irradiated rats (74 ± 17 µm, 43 ± 12 µm, and 54 ± 17 µm, respectively) compared with the control rats (100 ± 12 µm, 67 ± 10 µm, and 79 ± 12 µm, respectively). Changes in measured Lm values were consistent with changes in MLI values observed by histology. Conclusions Hyperpolarized 129Xe MRI provides a way to detect and measure regional microanatomical changes in lung parenchyma in a preclinical model of RILI. Magn Reson Med 75:2421-2431, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To assess the feasibility of hyperpolarized (HP) 129Xe MRI for detection of early stage radiation-induced lung injury (RILI) in a rat model involving unilateral irradiation by assessing differences in gas exchange dynamics between irradiated and unirradiated lungs. Methods: The dynamics of gas exchange between alveolar air space and pulmonary tissue (PT), PT and red blood cells (RBCs) was measured using single-shot spiral iterative decomposition of water and fat with echo asymmetry and least-squares estimation images of the right and left lungs of two age-matched cohorts of Sprague Dawley rats. The first cohort (n = 5) received 18 Gy irradiation to the right lung using a 60Co source and the second cohort (n = 5) was not irradiated and served as the healthy control. Both groups were imaged two weeks following irradiation when radiation pneumonitis (RP) was expected to be present. The gas exchange data were fit to a theoretical gas exchange model to extract measurements of pulmonary tissue thickness (LPT) and relative blood volume (VRBC) from each of the right and left lungs of both cohorts. Following imaging, lung specimens were retrieved and percent tissue area (PTA) was assessed histologically to confirm RP and correlate with MRI measurements. Results: Statistically significant differences in LPT and VRBC were observed between the irradiated and non-irradiated cohorts. In particular, LPT of the right and left lungs was increased approximately 8.2% and 5.0% respectively in the irradiated cohort. Additionally, VRBC of the right and left lungs was decreased approximately 36.1% and 11.7% respectively for the irradiated cohort compared to the non-irradiated cohort. PTA measurements in both right and left lungs were increased in the irradiated group compared to the non-irradiated cohort for both the left (P < 0.05) and right lungs (P < 0.01) confirming the presence of RP. PTA measurements also correlated with the MRI measurements for both the non-irradiated (r = 0.79, P < 0.01) and irradiated groups (r = 0.91, P < 0.01). Conclusions: Regional RILI can be detected two weeks post-irradiation using HP 129Xe MRI and analysis of gas exchange curves. This approach correlates well with histology and can potentially be used clinically to assess radiation pneumonitis associated with early RILI to improve radiation therapy outcomes. [ABSTRACT FROM AUTHOR]