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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]

Purpose: In this study, we compared hyperpolarized 3He and 129Xe images from patients with cystic fibrosis using two commonly applied magnetic resonance sequences, standard gradient echo (GRE) and balanced steady-state free precession (TrueFISP) to quantify regional similarities and differences in signal distribution and defect analysis.Materials and Methods: Ten patients (7M/3F) with cystic fibrosis underwent hyperpolarized gas MR imaging with both 3He and 129Xe. Six had MRI with both GRE, and TrueFISP sequences and four patients had only GRE sequence but not TrueFISP. Ventilation defect percentages (VDPs) were calculated as lung voxels with <60% of the whole-lung hyperpolarized gas signal mean and was measured in all datasets. The voxel signal distributions of both 129Xe and 3He gases were visualized and compared using violin plots. VDPs of hyperpolarized 3 He and 129 Xe were compared in Bland-Altman plots; Pearson correlation coefficients were used to evaluate the relationships between inter-gas and inter-scan to assess the reproducibility.Results: A significant correlation was demonstrated between 129Xe VDP and 3He VDP for both GRE and TrueFISP sequences (ρ = 0.78, p<0.0004). The correlation between the GRE and TrueFISP VDP for 3He was ρ = 0.98 and was ρ = 0.91 for 129Xe. Overall, 129Xe (27.2±9.4) VDP was higher than 3He (24.3±6.9) VDP on average on cystic fibrosis patients.Conclusion: In patients with cystic fibrosis, the selection of hyperpolarized 129Xe or 3He gas is most likely inconsequential when it comes to measure the overall lung function by VDP although 129Xe may be more sensitive to starker lung defects, particularly when using a TrueFISP sequence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether chemical shift saturation recovery (CSSR) MR spectroscopy with hyperpolarized xenon- 129 is sensitive to the pulsatile nature of pulmonary blood flow during the cardiac cycle. Methods: A CSSR pulse sequence typically uses radiofrequency (RF) pulses to saturate the magnetization of xenon- 129 dissolved in lung tissue followed, after a variable delay time, by an RF excitation and subsequent acquisition of a free-induction decay. Thereby it is possible to monitor the uptake of xenon-129 by lung tissue and extract physiological parameters of pulmonary gas exchange. In the current studies, the delay time was instead held at a constant value, which permitted observation of xenon-129 gas uptake as a function of breath-hold time. CSSR studies were performed in 13 subjects (10 healthy, 2 chronic obstructive pulmonary disease [COPD], 1 second-hand smoke exposure), holding their breath at total lung capacity. Results: The areas of the tissue/plasma and the red-bloodcell peaks in healthy subjects varied by an average of 1:760:7% and 15:163:8%, respectively, during the cardiac cycle. In 2 subjects with COPD these peak pulsations were not detectable during at least part of the measurement period. Conclusion: CSSR spectroscopy is sufficiently sensitive to detect oscillations in the xenon-129 gas-uptake rate associated with the cardiac cycle. [ABSTRACT FROM AUTHOR]

Magnetic-resonance spectroscopy and imaging using hyperpolarized xenon-129 show great potential for evaluation of the most important function of the human lung -- gas exchange. In particular, chemical shift saturation recovery (CSSR) xenon-129 spectroscopy provides important physiological information for the lung as a whole by characterizing the dynamic process of gas exchange, while dissolved-phase (DP) xenon-129 imaging captures the time-averaged regional distribution of gas uptake by lung tissue and blood. Herein, we present recent advances in assessing lung function using CSSR spectroscopy and DP imaging in a total of 45 subjects (23 healthy, 13 chronic obstructive pulmonary disease (COPD) and 9 asthma). From CSSR acquisitions, the COPD subjects showed red blood cell to tissue-plasma (RBC-to-TP) ratios below the average for the healthy subjects ( p < 0.001), but significantly higher septal wall thicknesses as compared with the healthy subjects ( p < 0.005); the RBC-to-TP ratios for the asthmatic subjects fell outside two standard deviations (either higher or lower) from the mean of the healthy subjects, although there was no statistically significant difference for the average ratio of the study group as a whole. Similarly, from the 3D DP imaging acquisitions, we found that all the ratios (TP to gas phase (GP), RBC to GP, RBC to TP) measured in the COPD subjects were lower than those from the healthy subjects ( p < 0.05 for all ratios), while these ratios in the asthmatic subjects differed considerably between subjects. Despite having been performed at different lung inflation levels, the RBC-to-TP ratios measured by CSSR and 3D DP imaging were fairly consistent with each other, with a mean difference of 0.037 (ratios from 3D DP imaging larger). In ten subjects the RBC-to-GP ratios obtained from the 3D DP imaging acquisitions were also highly correlated with their diffusing capacity of the lung for carbon monoxide per unit alveolar volume ratios measured by pulmonary function testing ( R = 0.91). Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose To develop a breathhold acquisition for regional mapping of ventilation and the fractions of hyperpolarized xenon-129 (Xe129) dissolved in tissue (lung parenchyma and plasma) and red blood cells (RBCs), and to perform an exploratory study to characterize data obtained in human subjects. Materials and Methods A three-dimensional, multi-echo, radial-trajectory pulse sequence was developed to obtain ventilation (gaseous Xe129), tissue, and RBC images in healthy subjects, smokers, and asthmatics. Signal ratios (total dissolved Xe129 to gas, tissue-to-gas, RBC-to-gas, and RBC-to-tissue) were calculated from the images for quantitative comparison. Results Healthy subjects demonstrated generally uniform values within coronal slices, and a gradient in values along the anterior-to-posterior direction. In contrast, images and associated ratio maps in smokers and asthmatics were generally heterogeneous and exhibited values mostly lower than those in healthy subjects. Whole-lung values of total dissolved Xe129 to gas, tissue-to-gas, and RBC-to-gas ratios in healthy subjects were significantly larger than those in diseased subjects. Conclusion Regional maps of tissue and RBC fractions of dissolved Xe129 were obtained from a short breathhold acquisition, well tolerated by healthy volunteers and subjects with obstructive lung disease. Marked differences were observed in spatial distributions and overall amounts of Xe129 dissolved in tissue and RBCs among healthy subjects, smokers and asthmatics. J. Magn. Reson. Imaging 2014;39:346-359. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose To present in vivo, human validation of a previously proposed method to measure key pulmonary parameters related to lung microstructure and physiology. Some parameters, such as blood-air barrier thickness, cannot be measured readily by any other noninvasive modality. Methods Healthy volunteers (n = 12) were studied in 1.5T and 3T whole body human scanners using hyperpolarized xenon. Xenon uptake by lung parenchyma and blood was measured using a chemical shift saturation recovery sequence. Both dissolved-xenon peaks at 197 ppm and 217-218 ppm were fitted against a model of xenon exchange (MOXE) as functions of exchange time. Parameters related to lung function and structure can be obtained by fitting to this model. Results The following results were obtained from xenon uptake (averaged over all healthy volunteers): surface-area-to-volume ratio = 210 ± 50 cm−1; total septal wall thickness = 9.2 ± 6.5 μm; blood-air barrier thickness = 1.0 ± 0.3 μm; hematocrit = 27 ± 4%; pulmonary capillary blood transit time = 1.3 ± 0.3 s, in good agreement with literature values from invasive experiments. More detailed fitting results are listed in the text. Conclusion The initial in vivo human results demonstrate that our proposed methods can be used to noninvasively determine lung physiology by simultaneous quantification of a few important pulmonary parameters. This method is highly promising to become a versatile screening method for lung diseases. Magn Reson Med 71:339-344, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Hyperpolarized xenon-129 has the potential to become a noninvasive contrast agent for lung MRI. In addition to its utility for imaging of ventilated airspaces, the property of xenon to dissolve in lung tissue and blood upon inhalation provides the opportunity to study gas exchange. Implementations of imaging protocols for obtaining regional parameters that exploit the dissolved phase are limited by the available signal-to-noise ratio, excitation homogeneity, and length of acquisition times. To address these challenges, a 32-channel receive-array coil complemented by an asymmetric birdcage transmit coil tuned to the hyperpolarized xenon-129 resonance at 3 T was developed. First results of spin-density imaging in healthy subjects and subjects with obstructive lung disease demonstrated the improvements in image quality by high-resolution ventilation images with high signal-to-noise ratio. Parallel imaging performance of the phased-array coil was demonstrated by acceleration factors up to three in 2D acquisitions and up to six in 3D acquisitions. Transmit-field maps showed a regional variation of only 8% across the whole lung. The newly developed phased-array receive coil with the birdcage transmit coil will lead to an improvement in existing imaging protocols, but moreover enable the development of new, functional lung imaging protocols based on the improvements in excitation homogeneity, signal-to-noise ratio, and acquisition speed. Magn Reson Med 70:576-583, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Hyperpolarized gases such as 129Xe and 3He have high potential as imaging agents for functional lung magnetic resonance imaging (MRI). We present new technology offering 129Xe production rates with order-of-magnitude improvement over existing systems, to liter per hour at 50% polarization. Human lung imaging studies with xenon, initially limited by the modest quantity and quality of hyperpolarized gas available, can now be performed with multiliter quantities several times daily. Materials and Methods: The polarizer is a continuous-flow system capable of producing large quantities of highly-polarized 129Xe through rubidium spin-exchange optical pumping. The low-pressure, high-velocity operating regime takes advantage of the enhancement in the spin exchange rate provided by van der Waals molecules dominating the atomic interactions. The long polarizing column moves the flow of the gas opposite to the laser direction, allowing efficient extraction of the laser light. Separate sections of the system assure full rubidium vapor saturation and removal. Results: The system is capable of producing 64% polarization at 0.3 L/hour Xe production rate. Increasing xenon flow reduces output polarization. Xenon polarization was studied as a function of different system operating parameters. A novel xenon trapping design was demonstrated to allow full recovery of the xenon polarization after the freeze-thaw cycle. Delivery methods of the gas to an offsite MRI facility were demonstrated in both frozen and gas states. Conclusions: We demonstrated a new concept for producing large quantities of highly polarized xenon. The system is operating in an MRI facility producing liters of hyperpolarized gas for human lung imaging studies. [Copyright &y& Elsevier]

Abstract: The majority of researchers investigating hyperpolarized gas MRI as a candidate functional lung imaging modality have used 3He as their imaging agent of choice rather than 129Xe. This preference has been predominantly due to, 3He providing stronger signals due to higher levels of polarization and higher gyromagnetic ratio, as well as its being easily available to more researchers due to availability of polarizers (USA) or ease of gas transport (Europe). Most researchers agree, however, that hyperpolarized 129Xe will ultimately emerge as the imaging agent of choice due to its unlimited supply in nature and its falling cost. Our recent polarizer technology delivers vast improvements in hyperpolarized 129Xe output. Using this polarizer, we have demonstrated the unique property of xenon to measure alveolar surface area noninvasively. In this article, we describe our human protocols and their safety, and our results for the measurement of the partial pressure of pulmonary oxygen (pO2) by observation of 129Xe signal decay. We note that the measurement of pO2 by observation of 129Xe signal decay is more complex than that for 3He because of an additional signal loss mechanism due to interphase diffusion of 129Xe from alveolar gas spaces to septal tissue. This results in measurements of an equivalent pO2 that accounts for both traditional T 1 decay from pO2 and that from interphase diffusion. We also provide an update on new technological advancements that form the foundation for an improved compact design polarizer as well as improvements that provide another order-of-magnitude scale-up in xenon polarizer output. [Copyright &y& Elsevier]

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 129 Xe magnetic resonance imaging ( 129 Xe MRI) to prioritize the most involved airways for guided BT. Methods: Thirty subjects with severe asthma were imaged with volumetric computed tomography and 129 Xe 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 129 Xe MRI when compared with standard three-treatment-session BT with fewer periprocedure adverse events.

Magnetic-resonance spectroscopy and imaging using hyperpolarized xenon-129 show great potential for evaluation of the most important function of the human lung -- gas exchange. In particular, chemical shift saturation recovery (CSSR) xenon-129 spectroscopy provides important physiological information for the lung as a whole by characterizing the dynamic process of gas exchange, while dissolved-phase (DP) xenon-129 imaging captures the time-averaged regional distribution of gas uptake by lung tissue and blood. Herein, we present recent advances in assessing lung function using CSSR spectroscopy and DP imaging in a total of 45 subjects (23 healthy, 13 chronic obstructive pulmonary disease (COPD) and 9 asthma). From CSSR acquisitions, the COPD subjects showed red blood cell to tissue-plasma (RBC-to-TP) ratios below the average for the healthy subjects (p < 0.001), but significantly higher septal wall thicknesses as compared with the healthy subjects (p < 0.005); the RBC-to-TP ratios for the asthmatic subjects fell outside two standard deviations (either higher or lower) from the mean of the healthy subjects, although there was no statistically significant difference for the average ratio of the study group as a whole. Similarly, from the 3D DP imaging acquisitions, we found that all the ratios (TP to gas phase (GP), RBC to GP, RBC to TP) measured in the COPD subjects were lower than those from the healthy subjects (p < 0.05 for all ratios), while these ratios in the asthmatic subjects differed considerably between subjects. Despite having been performed at different lung inflation levels, the RBC-to-TP ratios measured by CSSR and 3D DP imaging were fairly consistent with each other, with a mean difference of 0.037 (ratios from 3D DP imaging larger). In ten subjects the RBC-to-GP ratios obtained from the 3D DP imaging acquisitions were also highly correlated with their diffusing capacity of the lung for carbon monoxide per unit alveolar volume ratios measured by pulmonary function testing (R = 0.91)., (Copyright © 2014 John Wiley & Sons, Ltd.)

Purpose: To present in vivo, human validation of a previously proposed method to measure key pulmonary parameters related to lung microstructure and physiology. Some parameters, such as blood-air barrier thickness, cannot be measured readily by any other noninvasive modality., Methods: Healthy volunteers (n = 12) were studied in 1.5T and 3T whole body human scanners using hyperpolarized xenon. Xenon uptake by lung parenchyma and blood was measured using a chemical shift saturation recovery sequence. Both dissolved-xenon peaks at 197 ppm and 217-218 ppm were fitted against a model of xenon exchange (MOXE) as functions of exchange time. Parameters related to lung function and structure can be obtained by fitting to this model., Results: The following results were obtained from xenon uptake (averaged over all healthy volunteers): surface-area-to-volume ratio = 210 ± 50 cm(-1) ; total septal wall thickness = 9.2 ± 6.5 μm; blood-air barrier thickness = 1.0 ± 0.3 μm; hematocrit = 27 ± 4%; pulmonary capillary blood transit time = 1.3 ± 0.3 s, in good agreement with literature values from invasive experiments. More detailed fitting results are listed in the text., Conclusion: The initial in vivo human results demonstrate that our proposed methods can be used to noninvasively determine lung physiology by simultaneous quantification of a few important pulmonary parameters. This method is highly promising to become a versatile screening method for lung diseases., (Copyright © 2013 Wiley Periodicals, Inc.)