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Background: Individuals with asthma can vary widely in clinical presentation, severity, and pathobiology. Hyperpolarized xenon‐129 (Xe129) MRI is a novel imaging method to provide 3‐D mapping of both ventilation and gas exchange in the human lung. Purpose: To evaluate the functional changes in adults with asthma as compared to healthy controls using Xe129 MRI. Methods: All subjects (20 controls and 20 asthmatics) underwent lung function measurements and Xe129 MRI on the same day. Outcome measures included the pulmonary ventilation defect and transfer of inspired Xe129 into two soluble compartments: tissue and blood. Ten asthmatics underwent Xe129 MRI before and after bronchodilator to test whether gas transfer measures change with bronchodilator effects. Results: Initial analysis of the results revealed striking differences in gas transfer measures based on age, hence we compared outcomes in younger (n = 24, ≤ 35 years) versus older (n = 16, > 45 years) asthmatics and controls. The younger asthmatics exhibited significantly lower Xe129 gas uptake by lung tissue (Asthmatic: 0.98% ± 0.24%, Control: 1.17% ± 0.12%, P = 0.035), and higher Xe129 gas transfer from tissue to the blood (Asthmatic: 0.40 ± 0.10, Control: 0.31% ± 0.03%, P = 0.035) than the younger controls. No significant difference in Xe129 gas transfer was observed in the older group between asthmatics and controls (P > 0.05). No significant change in Xe129 transfer was observed before and after bronchodilator treatment. Conclusions: By using Xe129 MRI, we discovered heterogeneous alterations of gas transfer that have associations with age. This finding suggests a heretofore unrecognized physiological derangement in the gas/tissue/blood interface in young adults with asthma that deserves further study. [ABSTRACT FROM AUTHOR]

Rationale: Hyperpolarized (HP) 129Xe‐MRI provides non‐invasive methods to quantify lung function and structure, with the 129Xe 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 129Xe ADC measurements have not been rigorously investigated. Here, we introduce an analytical model to predict the experimental uncertainty of 129Xe ADC estimates. Additionally, we report ADC dependence on age in healthy pediatric volunteers. Methods: 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 129Xe ADC, 32 healthy subjects (age 6‐40 years) underwent diffusion‐weighted 129Xe MRI. Results: The analytical model provides a lower bound on ADC uncertainty and predicts that decreased signal‐to‐noise ratio yields increases in relative uncertainty (ϵADC). As such, experimental parameters that impact non‐equilibrium 129Xe magnetization necessarily impact the resulting ϵADC. The values of diffusion encoding parameters (Nb and bmax) that minimize ϵADC strongly depend on the underlying ADC value, resulting in a global minimum for ϵADC. Bayesian fitting outperformed other methods (error < 5%) for estimating ADC. The whole‐lung mean 129Xe ADC of healthy subjects increased with age at a rate of 1.75 × 10−4 cm2/s/yr (p = 0.001). Conclusions: HP 129Xe 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. [ABSTRACT FROM AUTHOR]

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

Purpose: To demonstrate the feasibility of generating red blood cell (RBC) and tissue/plasma (TP)‐specific gas‐phase (GP) depolarization maps using xenon‐polarization transfer contrast (XTC) MR imaging. Methods: Imaging was performed in three healthy subjects, an asymptomatic smoker, and a chronic obstructive pulmonary disease (COPD) patient. Single‐breath XTC data were acquired through a series of three GP images using a 2D multi‐slice GRE during a 12 s breath‐hold. A series of 8 ms Gaussian inversion pulses spaced 30 ms apart were applied in‐between the images to quantify the exchange between the GP and dissolved‐phase (DP) compartments. Inversion pulses were either centered on‐resonance to generate contrast, or off‐resonance to correct for other sources of signal loss. For an alternative scheme, inversions of both RBC and TP resonances were inserted in lieu of off‐resonance pulses. Finally, this technique was extended to a multi‐breath protocol consistent with tidal breathing, involving 30 consecutive acquisitions. Results: Inversion pulses shifted off‐resonance by 20 ppm to mimic the distance between the RBC and TP resonances demonstrated selectivity, and initial GP depolarization maps illustrated stark magnitude and distribution differences between healthy and diseased subjects that were consistent with traditional approaches. Conclusion: The proposed DP‐compartment selective XTC MRI technique provides information on gas exchange between all three detectable states of xenon in the lungs and is sufficiently sensitive to indicate differences in lung function between the study subjects. Investigated extensions of this approach to imaging schemes that either minimize breath‐hold duration or the overall number of breath‐holds open avenues for future research to improve measurement accuracy and patient comfort. [ABSTRACT FROM AUTHOR]

The article describes the case of a 67-year old man with severe emphysema who underwent bronchoscopic lung volume reduction using endobronchial valves monitored with simultaneous imaging of ventilation and gas exchange with hyperpolarized 129XE (HXE) magnetic resonance imaging (MRI). It highlights clinical observations on the patient's lung function, breathing, ventilation and gas exchange. The effectiveness of inhaled HXe functional MRI in measuring lobar ventilation and gas exchange is noted.

Increased pulmonary lactate production is correlated with severity of lung injury and outcome in acute respiratory distress syndrome (ARDS) patients. This study was conducted to investigate the relative contributions of inflammation and hypoxia to the lung's metabolic shift to glycolysis in an experimental animal model of ARDS using hyperpolarized (HP) 13C MRI. Fifty‐three intubated and mechanically ventilated male rats were imaged using HP 13C MRI before, and 1, 2.5 and 4 hours after saline (sham) or hydrochloric acid (HCl; 0.5 ml/kg) instillation in the trachea, followed by protective and nonprotective mechanical ventilation (HCl‐PEEP and HCl‐ZEEP) or the start of moderate or severe hypoxia (Hyp90 and Hyp75 groups). Pulmonary and cardiac HP lactate‐to‐pyruvate ratios were compared among groups for different time points. Postmortem histology and immunofluorescence were used to assess lung injury severity and quantify the expression of innate inflammatory markers and local tissue hypoxia. HP pulmonary lactate‐to‐pyruvate ratio progressively increased in rats with lung injury and moderate hypoxia (HCl‐ZEEP), with no significant change in pulmonary lactate‐to‐pyruvate ratio in noninjured but moderately hypoxic rats (Hyp90). Pulmonary lactate‐to‐pyruvate ratio was elevated in otherwise healthy lung tissue only in severe systemic hypoxia (Hyp75 group). ex vivo histological and immunopathological assessment further confirmed the link between elevated glycolysis and the recruitment into and presence of activated neutrophils in injured lungs. HP lactate‐to‐pyruvate ratio is elevated in injured lungs predominantly as a result of increased glycolysis in activated inflammatory cells, but can also increase due to severe inflammation‐induced hypoxia. [ABSTRACT FROM AUTHOR]

Hyperpolarized 129Xe magnetic resonance imaging is a powerful modality capable of assessing lung structure and function. While it has shown promise as a clinical tool for the longitudinal assessment of lung function, its utility as an investigative tool for animal models of pulmonary diseases is limited by the necessity of invasive intubation and mechanical ventilation procedures. In this paper, we overcame this limitation by developing a gas delivery system and implementing a set of imaging schemes to acquire high-resolution gas- and dissolved-phase images in free-breathing mice. Gradient echo pulse sequences were used to acquire both high- and low-resolution gas-phase images, and regional fractional ventilation was quantified by comparing signal buildup among low-resolution gas-phase images acquired at two flip-angles. Dissolved-phase images were acquired using both ultra-short echo time and chemical shift imaging sequences with discrete sets of flip-angle/repetition time combinations to visualize gas uptake and distribution throughout the body. Spectral features distinct to various anatomical regions were identified in images acquired using the latter sequence and were used for the quantification of gas arrival times for respective compartments. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: In this study, we compared a newly developed multibreath simultaneous alveolar oxygen tension and apparent diffusion coefficient (PAO2-ADC) imaging sequence to a single-breath acquisition, with the aim of mitigating the compromising effects of intervoxel flow and slow-filling regions on single-breath measurements, especially in chronic obstructive pulmonary disease (COPD) subjects.Materials and Methods: Both single-breath and multibreath simultaneous PAO2-ADC imaging schemes were performed on a total of 10 human subjects (five asymptomatic smokers and five COPD subjects). Estimated PAO2 and ADC values derived from the different sequences were compared both globally and regionally. The distribution of voxels with nonphysiological values was also compared between the two schemes.Results: The multibreath protocol decreased the ventilation defect volumes by an average of 12.9 ± 6.6%. The multibreath sequence generated nonphysiological PAO2 values in 11.0 ± 8.5% fewer voxels than the single-breath sequence. Single-breath PAO2 maps also showed more regions with gas-flow artifacts and general signal heterogeneity. On average, the standard deviation of the PAO2 distribution was 16.5 ± 7.0% lower using multibreath PAO2-ADC imaging, suggesting a more homogeneous gas distribution. Both mean and standard deviation of the ADC increased significantly from single- to multibreath imaging (p = 0.048 and p = 0.070, respectively), suggesting more emphysematous regions in the slow-filling lung.Conclusion: Multibreath PAO2-ADC imaging provides superior accuracy and efficiency compared to previous imaging protocols. PAO2 and ADC maps generated by multibreath imaging allowed for the qualification of various regions as emphysematous or obstructed, which single-breath PAO2 maps can only identify as defects. The simultaneous PAO2 and ADC measurements generated by the presented multibreath method were also more physiologically realistic, and allowed for more detailed analysis of the slow-filling regions characteristic of COPD subjects. [ABSTRACT FROM AUTHOR]