Age, sex, and lung volume dependence of dissolved xenon-129 MRI gas exchange metrics.

PURPOSE: To characterize the dependence of Xe-MRI gas transfer metrics upon age, sex, and lung volume in a group of healthy volunteers. METHODS: Sixty-five subjects with no history of chronic lung disease were assessed with 129Xe-MRI using a four-echo 3D radial spectroscopic imaging sequence and a dose of xenon titrated according to subject height that was inhaled from a lung volume of functional residual capacity (FRC). Imaging was repeated in 34 subjects at total lung capacity (TLC). Regional maps of the fractions of dissolved xenon in red blood cells (RBC), membrane (M), and airspace (Gas) were acquired at an isotropic resolution of 2 cm, from which global averages of the ratios RBC:M, RBC:Gas, and M:Gas were computed. RESULTS: Data from 26 males and 36 females with a median age of 43 y (range: 20-69 y) were of sufficient quality to analyze. Age (p = 0.0006) and sex (p < 0.0001) were significant predictors for RBC:M, and a linear regression showed higher values and steeper decline in males: RBC:M(Males) = -0.00362 × Age + 0.60 (p = 0.01, R2 = 0.25); RBC:M(Females) = -0.00170 × Age + 0.44 (p = 0.02, R2 = 0.15). Similarly, age and sex were significant predictors for RBC:Gas but not for M:Gas. RBC:M, M:Gas and RBC:Gas were significantly lower at TLC than at FRC (plus inhaled volume), with an average 9%, 30% and 35% decrease, respectively. CONCLUSION: Expected age and sex dependence of pulmonary function concurs with 129Xe RBC:M imaging results, demonstrating that these variables must be considered when reporting Xe-MRI metrics. Xenon doses and breathing maneuvers should be controlled due to the strong dependence of Xe-MRI metrics upon lung volume.

Image Phenotyping of Preterm-Born Children Using Hyperpolarized 129Xe Lung Magnetic Resonance Imaging and Multiple-Breath Washout.

Rationale: Preterm birth is associated with low lung function in childhood, but little is known about the lung microstructure in childhood. Objectives: We assessed the differential associations between the historical diagnosis of bronchopulmonary dysplasia (BPD) and current lung function phenotypes on lung ventilation and microstructure in preterm-born children using hyperpolarized 129Xe ventilation and diffusion-weighted magnetic resonance imaging (MRI) and multiple-breath washout (MBW). Methods: Data were available from 63 children (aged 9-13 yr), including 44 born preterm (⩽34 weeks' gestation) and 19 term-born control subjects (⩾37 weeks' gestation). Preterm-born children were classified, using spirometry, as prematurity-associated obstructive lung disease (POLD; FEV1 < lower limit of normal [LLN] and FEV1/FVC < LLN), prematurity-associated preserved ratio of impaired spirometry (FEV1 < LLN and FEV1/FVC ⩾ LLN), preterm-(FEV1 ⩾ LLN) and term-born control subjects, and those with and without BPD. Ventilation heterogeneity metrics were derived from 129Xe ventilation MRI and SF6 MBW. Alveolar microstructural dimensions were derived from 129Xe diffusion-weighted MRI. Measurements and Main Results: 129Xe ventilation defect percentage and ventilation heterogeneity index were significantly increased in preterm-born children with POLD. In contrast, mean 129Xe apparent diffusion coefficient, 129Xe apparent diffusion coefficient interquartile range, and 129Xe mean alveolar dimension interquartile range were significantly increased in preterm-born children with BPD, suggesting changes of alveolar dimensions. MBW metrics were all significantly increased in the POLD group compared with preterm- and term-born control subjects. Linear regression confirmed the differential effects of obstructive disease on ventilation defects and BPD on lung microstructure. Conclusion: We show that ventilation abnormalities are associated with POLD, and BPD in infancy is associated with abnormal lung microstructure.

Imaging gas-exchange lung function and brain tissue uptake of hyperpolarized 129 Xe using sampling density-weighted MRSI.

PURPOSE: Imaging of the different resonances of hyperpolarized 129 Xe in the brain and lungs was performed using a 3D sampling density-weighted MRSI technique in healthy volunteers. METHODS: Four volunteers underwent dissolved-phase hyperpolarized 129 Xe imaging in the lung with the MRSI technique, which was designed to improve the point-spread function while preserving SNR (1799 phase-encoding steps, 14-s breath hold, 2.1-cm isotropic resolution). A frequency-tailored RF excitation pulse was implemented to reliably excite both the 129 Xe gas and dissolved phase (tissue/blood signal) with 0.1° and 10° flip angles, respectively. Images of xenon gas in the lung airspaces and xenon dissolved in lung tissue/blood were used to generate quantitative signal ratio maps. The method was also optimized and used for imaging dissolved resonances of 129 Xe in the brain in 2 additional volunteers. RESULTS: High-quality regional spectra of hyperpolarized 129 Xe were achieved in both the lung and the brain. Ratio maps of the different xenon resonances were obtained in the lung with sufficient SNR (> 10) at both 1.5 T and 3 T, making a triple Lorentzian fit possible and enabling the measurement of relaxation times and xenon frequency shifts on a voxel-wise basis. The imaging technique was successfully adapted for brain imaging, resulting in the first demonstration of 3D xenon brain images with a 2-cm isotropic resolution. CONCLUSION: Density-weighted MRSI is an SNR and encoding-efficient way to image 129 Xe resonances in the lung and the brain, providing a valuable tool to quantify regional spectroscopic information.

Investigating Rubidium Density and Temperature Distributions in a High-Throughput 129Xe-Rb Spin-Exchange Optical Pumping Polarizer.

Accurate knowledge of the rubidium (Rb) vapor density, [Rb], is necessary to correctly model the spin dynamics of 129Xe-Rb spin-exchange optical pumping (SEOP). Here we present a systematic evaluation of [Rb] within a high-throughput 129Xe-Rb hyperpolarizer during continuous-flow SEOP. Near-infrared (52S1/2→52P1/2 (D1)/52P3/2 (D2)) and violet (52S1/2→62P1/2/62P3/2) atomic absorption spectroscopy was used to measure [Rb] within 3.5 L cylindrical SEOP cells containing different spatial distributions and amounts of Rb metal. We were able to quantify deviation from the Beer-Lambert law at high optical depth for D2 and 62P3/2 absorption by comparison with measurements of the D1 and 62P1/2 absorption lines, respectively. D2 absorption deviates from the Beer-Lambert law at [Rb]D2>4×1017 m−3 whilst 52S1/2→62P3/2 absorption deviates from the Beer-Lambert law at [Rb]6P3/2>(4.16±0.01)×1019 m−3. The measured [Rb] was used to estimate a 129Xe-Rb spin exchange cross section of γ'=(1.2±0.1)×10−21 m3 s−1, consistent with spin-exchange cross sections from the literature. Significant [Rb] heterogeneity was observed in a SEOP cell containing 1 g of Rb localized at the back of the cell. While [Rb] homogeneity was improved for a greater surface area of the Rb source distribution in the cell, or by using a Rb presaturator, the measured [Rb] was consistently lower than that predicted by saturation Rb vapor density curves. Efforts to optimize [Rb] and thermal management within spin polarizer systems are necessary to maximize potential future enhancements of this technology.

Measuring 129 Xe transfer across the blood-brain barrier using MR spectroscopy.

PURPOSE: This study develops a tracer kinetic model of xenon uptake in the human brain to determine the transfer rate of inhaled hyperpolarized 129 Xe from cerebral blood to gray matter that accounts for the effects of cerebral physiology, perfusion and magnetization dynamics. The 129 Xe transfer rate is expressed using a tracer transfer coefficient, which estimates the quantity of hyperpolarized 129 Xe dissolved in cerebral blood under exchange with depolarized 129 Xe dissolved in gray matter under equilibrium of concentration. THEORY AND METHODS: Time-resolved MR spectra of hyperpolarized 129 Xe dissolved in the human brain were acquired from three healthy volunteers. Acquired spectra were numerically fitted with five Lorentzian peaks in accordance with known 129 Xe brain spectral peaks. The signal dynamics of spectral peaks for gray matter and red blood cells were quantified, and correction for the 129 Xe T1 dependence upon blood oxygenation was applied. 129 Xe transfer dynamics determined from the ratio of the peaks for gray matter and red blood cells was numerically fitted with the developed tracer kinetic model. RESULTS: For all the acquired NMR spectra, the developed tracer kinetic model fitted the data with tracer transfer coefficients between 0.1 and 0.14. CONCLUSION: In this study, a tracer kinetic model was developed and validated that estimates the transfer rate of HP 129 Xe from cerebral blood to gray matter in the human brain.

MR properties of 19 F C3 F8 gas in the lungs of healthy volunteers: T 2 ∗ and apparent diffusion coefficient at 1.5T and T 2 ∗ at 3T.

PURPOSE: To measure the transverse relaxation time ( T 2 ∗ ) and apparent diffusion coefficient (ADC) of 19 F-C3 F8 gas in vivo in human lungs at 1.5T and 3T, and to determine the representative distribution of values of these parameters in a cohort of healthy volunteers. METHODS: Mapping of ADC at lung inflation levels of functional residual capacity (FRC) and total lung capacity (TLC) was performed with inhaled 19 F-C3 F8 (eight subjects) and 129 Xe (six subjects) at 1.5T. T 2 ∗ mapping with 19 F-C3 F8 was performed at 1.5T (at FRC and TLC) for 8 subjects and at 3T (at TLC for seven subjects). RESULTS: At both FRC and TLC, the 19 F-C3 F8 ADC was smaller than the free diffusion coefficient demonstrating airway microstructural diffusion restriction. From FRC to TLC, the mean ADC significantly increased from 1.56 mm2 /s to 1.83 mm2 /s (P = .0017) for 19 F-C3 F8, and from 2.49 mm2 /s to 3.38 mm2 /s (P = .0015) for 129 Xe. The posterior-to-anterior gradient in ADC for FRC versus TLC in the superior half of the lungs was measured as 0.0308 mm2 /s per cm versus 0.0168 mm2 /s per cm for 19 F-C3 F8 and 0.0871 mm2 /s per cm versus 0.0326 mm2 /s per cm for 129 Xe. A consistent distribution of 19 F-C3 F8 T 2 ∗ values was observed in the lungs, with low values observed near the diaphragm and large pulmonary vessels. The mean T 2 ∗ across volunteers was 4.48 ms at FRC and 5.33 ms at TLC for 1.5T, and 3.78 ms at TLC for 3T. CONCLUSION: In this feasibility study, values of physiologically relevant parameters of lung microstructure measurable by MRI ( T 2 ∗ , and ADC) were established for C3 F8 in vivo lung imaging in healthy volunteers.

Dissolved 129 Xe lung MRI with four-echo 3D radial spectroscopic imaging: Quantification of regional gas transfer in idiopathic pulmonary fibrosis.

PURPOSE: Imaging of the different resonances of dissolved hyperpolarized xenon-129 (129 Xe) in the lung is performed using a four-echo flyback 3D radial spectroscopic imaging technique and is evaluated in healthy volunteers (HV) and subjects with idiopathic pulmonary fibrosis (IPF). THEORY AND METHODS: 10 HV and 25 subjects with IPF underwent dissolved 129 Xe MRI at 1.5T. IPF subjects underwent same day pulmonary function tests to measure forced vital capacity and the diffusion capacity of the lung for carbon monoxide (DLCO ). A four-point echo time technique with k-space chemical-shift modeling of gas, dissolved 129 Xe in lung tissue/plasma (TP) and red blood cells (RBC) combined with a 3D radial trajectory was implemented within a 14-s breath-hold. RESULTS: Results show an excellent chemical shift separation of the dissolved 129 Xe compartments and gas contamination removal, confirmed by a strong agreement between average imaging and global spectroscopy RBC/TP ratio measurements. Subjects with IPF exhibited reduced imaging gas transfer when compared to HV. A significant increase of the amplitude of RBC signal cardiogenic oscillation was also observed. In IPF subjects, DLCO % predicted was significantly correlated with RBC/TP and RBC/GAS ratios and the correlations were stronger in the inferior and periphery sections of the lungs. CONCLUSION: Lung MRI of dissolved 129 Xe was performed with a four-echo spectroscopic imaging method. Subjects with IPF demonstrated reduced xenon imaging gas transfer and increased cardiogenic modulation of dissolved xenon signal in the RBCs when compared to HV.

The assessment of short and long term changes in lung function in CF using 129Xe MRI.

INTRODUCTION: 129Xe ventilation MRI is sensitive to detect early CF lung disease and response to treatment. 129Xe-MRI could play a significant role in clinical trials and patient management. Here we present data on the repeatability of imaging measurements and their sensitivity to longitudinal change. METHODS: 29 children and adults with CF and a range of disease severity were assessed twice, a median [IQR] of 16.0 [14.4,19.5] months apart. Patients performed 129Xe-MRI, lung clearance index (LCI), body plethysmography and spirometry at both visits. Eleven patients repeated 129Xe-MRI in the same session to assess the within-visit repeatability. The ventilation defect percentage (VDP) was the primary metric calculated from 129Xe-MRI. RESULTS: At baseline, mean (sd) age=23.0 (11.1) years and FEV1 z-score=-2.2 (2.0). Median [IQR] VDP=9.5 [3.4,31.6]%, LCI=9.0 [7.7,13.7]. Within-visit and inter-visit repeatability of VDP was high. At 16 months there was no single trend of 129Xe-MRI disease progression. Visible 129Xe-MRI ventilation changes were common, which reflected changes in VDP. Based on the within-visit repeatability, a significant short-term change in VDP is >±1.6%. For longer-term follow up, changes in VDP of up to ±7.7% can be expected, or ±4.1% for patients with normal FEV1. No patient had a significant change in FEV1, however 59% had change in VDP >±1.6%. In patients with normal FEV1, there were significant changes in ventilation and in VDP. CONCLUSIONS: 129Xe-MRI is a highly effective method for assessing longitudinal lung disease in patients with CF. VDP has great potential as a sensitive clinical outcome measure of lung function and endpoint for clinical trials.

Dissolved hyperpolarized xenon-129 MRI in human kidneys.

PURPOSE: To assess the feasibility of using dissolved hyperpolarized xenon-129 (129 Xe) MRI to study renal physiology in humans at 3 T. METHODS: Using a flexible transceiver RF coil, dynamic and spatially resolved 129 Xe spectroscopy was performed in the abdomen after inhalation of hyperpolarized 129 Xe 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 129 Xe uptake in the kidneys using spoiled gradient echo and balanced steady-state sequences. RESULTS: Using spatially resolved spectroscopy, different magnitudes of signal from 129 Xe 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 129 Xe in the lungs and in transit to the kidneys was provided with the transceiver coil. The signal of dissolved hyperpolarized 129 Xe could be imaged with both tested sequences for about 40 seconds after inhalation. CONCLUSION: The uptake of 129 Xe dissolved in the human kidneys was measured with spectroscopic and imaging experiments, demonstrating the potential of hyperpolarized 129 Xe MR as a novel, noninvasive technique to image human kidney tissue perfusion.

Hyperpolarised xenon magnetic resonance spectroscopy for the longitudinal assessment of changes in gas diffusion in IPF.

Prognosticating idiopathic pulmonary fibrosis (IPF) is challenging, in part due to a lack of sensitive biomarkers. A recent article in Thorax described how hyperpolarised xenon magnetic resonance spectroscopy may quantify regional gas exchange in IPF lungs. In a population of patients with IPF, we find that the xenon signal from red blood cells diminishes relative to the tissue/plasma signal over a 12-month time period, even when the diffusion factor for carbon monoxide is static over the same time period. We conclude that hyperpolarised 129Xe MR spectroscopy may be sensitive to short-term changes in interstitial gas diffusion in IPF.

Single breath-held acquisition of coregistered 3D 129 Xe lung ventilation and anatomical proton images of the human lung with compressed sensing.

PURPOSE: To develop and assess a method for acquiring coregistered proton anatomical and hyperpolarized 129 Xe ventilation MR images of the lungs with compressed sensing (CS) in a single breath hold. METHODS: Retrospective CS simulations were performed on fully sampled ventilation images acquired from one healthy smoker to optimize reconstruction parameters. Prospective same-breath anatomical and ventilation images were also acquired in five ex-smokers with an acceleration factor of 3 for hyperpolarized 129 Xe images, and were compared to fully sampled images acquired during the same session. The following metrics were used to assess data fidelity: mean absolute error (MAE), root mean square error, and linear regression of the signal intensity between fully sampled and undersampled images. The effect of CS reconstruction on two quantitative imaging metrics routinely reported [percentage ventilated volume (%VV) and heterogeneity score] was also investigated. RESULTS: Retrospective simulations showed good agreement between fully sampled and CS-reconstructed (acceleration factor of 3) images with MAE (root mean square error) of 3.9% (4.5%). The prospective same-breath images showed a good match in ventilation distribution with an average R2 of 0.76 from signal intensity linear regression and a negligible systematic bias of +0.1% in %VV calculation. A bias of -1.8% in the heterogeneity score was obtained. CONCLUSION: With CS, high-quality 3D images of hyperpolarized 129 Xe ventilation (resolution 4.2 × 4.2 × 7.5 mm3 ) can be acquired with coregistered 1 H anatomical MRI in a 15-s breath hold. The accelerated acquisition time dispenses with the need for registration between separate breath-hold 129 Xe and 1 H MRI, enabling more accurate %VV calculation.

Imaging Human Brain Perfusion with Inhaled Hyperpolarized 129Xe MR Imaging.

Purpose To evaluate the feasibility of directly imaging perfusion of human brain tissue by using magnetic resonance (MR) imaging with inhaled hyperpolarized xenon 129 (129Xe). Materials and Methods In vivo imaging with 129Xe was performed in three healthy participants. The combination of a high-yield spin-exchange optical pumping 129Xe polarizer, custom-built radiofrequency coils, and an optimized gradient-echo MR imaging protocol was used to achieve signal sensitivity sufficient to directly image hyperpolarized 129Xe dissolved in the human brain. Conventional T1-weighted proton (hydrogen 1 [1H]) images and perfusion images by using arterial spin labeling were obtained for comparison. Results Images of 129Xe uptake were obtained with a signal-to-noise ratio of 31 ± 9 and demonstrated structural similarities to the gray matter distribution on conventional T1-weighted 1H images and to perfusion images from arterial spin labeling. Conclusion Hyperpolarized 129Xe MR imaging is an injection-free means of imaging the perfusion of cerebral tissue. The proposed method images the uptake of inhaled xenon gas to the extravascular brain tissue compartment across the intact blood-brain barrier. This level of sensitivity is not readily available with contemporary MR imaging methods. ©RSNA, 2017.

3D diffusion-weighted 129 Xe MRI for whole lung morphometry.

PURPOSE: To obtain whole lung morphometry measurements from 129 Xe in a single breath-hold with 3D multiple b-value 129 Xe diffusion-weighted MRI (DW-MRI) with an empirically optimized diffusion time and compressed sensing for scan acceleration. METHODS: Prospective three-fold undersampled 3D multiple b-value hyperpolarized 129 Xe DW-MRI datasets were acquired, and the diffusion time (Δ) was iterated so as to provide diffusive length scale (LmD ) estimates from the stretched exponential model (SEM) that are comparable to those from 3 He. The empirically optimized 129 Xe diffusion time was then implemented with a four-fold undersampling scheme and was prospectively benchmarked against 3 He measurements in a cohort of five healthy volunteers, six ex-smokers, and two chronic obstructive pulmonary disease patients using both SEM-derived LmD and cylinder model (CM)-derived mean chord length (Lm). RESULTS: Good agreement between the mean 129 Xe and 3 He LmD (mean difference, 2.2%) and Lm (mean difference, 1.1%) values was obtained in all subjects at an empirically optimized 129 Xe Δ = 8.5 ms. CONCLUSION: Compressed sensing has facilitated single-breath 3D multiple b-value 129 Xe DW-MRI acquisitions, and results at 129 Xe Δ = 8.5 ms indicate that 129 Xe provides a viable alternative to 3 He for whole lung morphometry mapping with either the SEM or CM. Magn Reson Med 79:2986-2995, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Comparison of 3 He and 129 Xe MRI for evaluation of lung microstructure and ventilation at 1.5T.

BACKGROUND: To support translational lung MRI research with hyperpolarized 129 Xe gas, comprehensive evaluation of derived quantitative lung function measures against established measures from 3 He MRI is required. Few comparative studies have been performed to date, only at 3T, and multisession repeatability of 129 Xe functional metrics have not been reported. PURPOSE/HYPOTHESIS: To compare hyperpolarized 129 Xe and 3 He MRI-derived quantitative metrics of lung ventilation and microstructure, and their repeatability, at 1.5T. STUDY TYPE: Retrospective. POPULATION: Fourteen healthy nonsmokers (HN), five exsmokers (ES), five patients with chronic obstructive pulmonary disease (COPD), and 16 patients with nonsmall-cell lung cancer (NSCLC). FIELD STRENGTH/SEQUENCE: 1.5T. NSCLC, COPD patients and selected HN subjects underwent 3D balanced steady-state free-precession lung ventilation MRI using both 3 He and 129 Xe. Selected HN, all ES, and COPD patients underwent 2D multislice spoiled gradient-echo diffusion-weighted lung MRI using both hyperpolarized gas nuclei. ASSESSMENT: Ventilated volume percentages (VV%) and mean apparent diffusion coefficients (ADC) were derived from imaging. COPD patients performed the whole MR protocol in four separate scan sessions to assess repeatability. Same-day pulmonary function tests were performed. STATISTICAL TESTS: Intermetric correlations: Spearman's coefficient. Intergroup/internuclei differences: analysis of variance / Wilcoxon's signed rank. Repeatability: coefficient of variation (CV), intraclass correlation (ICC) coefficient. RESULTS: A significant positive correlation between 3 He and 129 Xe VV% was observed (r = 0.860, P < 0.001). VV% was larger for 3 He than 129 Xe (P = 0.001); average bias, 8.79%. A strong correlation between mean 3 He and 129 Xe ADC was obtained (r = 0.922, P < 0.001). MR parameters exhibited good correlations with pulmonary function tests. In COPD patients, mean CV of 3 He and 129 Xe VV% was 4.08% and 13.01%, respectively, with ICC coefficients of 0.541 (P = 0.061) and 0.458 (P = 0.095). Mean 3 He and 129 Xe ADC values were highly repeatable (mean CV: 2.98%, 2.77%, respectively; ICC: 0.995, P < 0.001; 0.936, P < 0.001). DATA CONCLUSION: 129 Xe lung MRI provides near-equivalent information to 3 He for quantitative lung ventilation and microstructural MRI at 1.5T. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2018.

Detection of early subclinical lung disease in children with cystic fibrosis by lung ventilation imaging with hyperpolarised gas MRI.

Hyperpolarised 3He ventilation-MRI, anatomical lung MRI, lung clearance index (LCI), low-dose CT and spirometry were performed on 19 children (6-16 years) with clinically stable mild cystic fibrosis (CF) (FEV1>-1.96), and 10 controls. All controls had normal spirometry, MRI and LCI. Ventilation-MRI was the most sensitive method of detecting abnormalities, present in 89% of patients with CF, compared with CT abnormalities in 68%, LCI 47% and conventional MRI 22%. Ventilation defects were present in the absence of CT abnormalities and in patients with normal physiology, including LCI. Ventilation-MRI is thus feasible in young children, highly sensitive and provides additional information about lung structure-function relationships.

129 Xe chemical shift in human blood and pulmonary blood oxygenation measurement in humans using hyperpolarized 129 Xe NMR.

PURPOSE: To evaluate the dependency of the 129 Xe-red blood cell (RBC) chemical shift on blood oxygenation, and to use this relation for noninvasive measurement of pulmonary blood oxygenation in vivo with hyperpolarized 129 Xe NMR. METHODS: Hyperpolarized 129 Xe was equilibrated with blood samples of varying oxygenation in vitro, and NMR was performed at 1.5 T and 3 T. Dynamic in vivo NMR during breath hold apnea was performed at 3 T on two healthy volunteers following inhalation of hyperpolarized 129 Xe. RESULTS: The 129 Xe chemical shift in RBCs was found to increase nonlinearly with blood oxygenation at 1.5 T and 3 T. During breath hold apnea, the 129 Xe chemical shift in RBCs exhibited a periodic time modulation and showed a net decrease in chemical shift of ∼1 ppm over a 35 s breath hold, corresponding to a decrease of 7-10 % in RBC oxygenation. The 129 Xe-RBC signal amplitude showed a modulation with the same frequency as the 129 Xe-RBC chemical shift. CONCLUSION: The feasibility of using the 129 Xe-RBC chemical shift to measure pulmonary blood oxygenation in vivo has been demonstrated. Correlation between 129 Xe-RBC signal and 129 Xe-RBC chemical shift modulations in the lung warrants further investigation, with the aim to better quantify temporal blood oxygenation changes in the cardiopulmonary vascular circuit. Magn Reson Med 77:1399-1408, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Reproducibility of quantitative indices of lung function and microstructure from 129 Xe chemical shift saturation recovery (CSSR) MR spectroscopy.

PURPOSE: To evaluate the reproducibility of indices of lung microstructure and function derived from 129 Xe chemical shift saturation recovery (CSSR) spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD), and to study the sensitivity of CSSR-derived parameters to pulse sequence design and lung inflation level. METHODS: Preliminary data were collected from five volunteers on three occasions, using two implementations of the CSSR sequence. Separately, three volunteers each underwent CSSR at three different lung inflation levels. After analysis of these preliminary data, five COPD patients were scanned on three separate days, and nine age-matched volunteers were scanned three times on one day, to assess reproducibility. RESULTS: CSSR-derived alveolar septal thickness (ST) and surface-area-to-volume (S/V) ratio values decreased with lung inflation level (P < 0.001; P = 0.057, respectively). Intra-subject standard deviations of ST were lower than the previously measured differences between volunteers and subjects with interstitial lung disease. The mean coefficient of variation (CV) values of ST were 3.9 ± 1.9% and 6.0 ± 4.5% in volunteers and COPD patients, respectively, similar to CV values for whole-lung carbon monoxide diffusing capacity. The mean CV of S/V in volunteers and patients was 14.1 ± 8.0% and 18.0 ± 19.3%, respectively. CONCLUSION: 129 Xe CSSR presents a reproducible method for estimation of alveolar septal thickness. Magn Reson Med 77:2107-2113, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

High resolution spectroscopy and chemical shift imaging of hyperpolarized (129) Xe dissolved in the human brain in vivo at 1.5 tesla.

PURPOSE: Upon inhalation, xenon diffuses into the bloodstream and is transported to the brain, where it dissolves in various compartments of the brain. Although up to five chemically distinct peaks have been previously observed in (129) Xe rat head spectra, to date only three peaks have been reported in the human head. This study demonstrates high resolution spectroscopy and chemical shift imaging (CSI) of (129) Xe dissolved in the human head at 1.5 Tesla. METHODS: A (129) Xe radiofrequency coil was built in-house and (129) Xe gas was polarized using spin-exchange optical pumping. Following the inhalation of (129) Xe gas, NMR spectroscopy was performed with spectral resolution of 0.033 ppm. Two-dimensional CSI in all three anatomical planes was performed with spectral resolution of 2.1 ppm and voxel size 20 mm × 20 mm. RESULTS: Spectra of hyperpolarized (129) Xe dissolved in the human head showed five distinct peaks at 188 ppm, 192 ppm, 196 ppm, 200 ppm, and 217 ppm. Assignment of these peaks was consistent with earlier studies. CONCLUSION: High resolution spectroscopy and CSI of hyperpolarized (129) Xe dissolved in the human head has been demonstrated. For the first time, five distinct NMR peaks have been observed in (129) Xe spectra from the human head in vivo. Magn Reson Med 75:2227-2234, 2016. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Radiofrequency pulse design for the selective excitation of dissolved 129Xe.

PURPOSE: To optimize radiofrequency (RF) pulses for the selective excitation of dissolved phase (129)Xe that take into account the very short T2*, while simultaneously, minimally exciting the much larger gas signal. METHODS: Numerical simulations of Shinnar le-Roux pulses and binomial coefficient composite-element pulses were performed and experimentally implemented on a 1.5 Tesla (T) clinical scanner. These were compared with pulses commonly used for short T2* imaging from the literature. The pulses were then experimentally tested in vivo with healthy volunteers inhaling hyperpolarized (129)Xe using nuclear MR spectroscopy on a 1.5T clinical scanner. RESULTS: Standard RF excitation pulses inadvertently excite the gas compartment, or are long enough that the T2* of the dissolved compartment deteriorates the received signal. Amplitude modulated binomial composite pulses perform well being short and having high selectivity, however, deteriorate at high amplifier gain setting. Composite pulses using pulse width modulation provide the desired frequency response even in these nonlinear, high gain regimes. CONCLUSION: Composite pulses provide a means of very narrow band frequency selectivity in a short duration pulse that is well suited to dissolved (129)Xe imaging. Pulse width modulation maintains the desired frequency response even in the presence of amplitude distortion.

Feasibility of human lung ventilation imaging using highly polarized naturally abundant xenon and optimized three-dimensional steady-state free precession.

PURPOSE: To demonstrate the potential for high quality MRI of pulmonary ventilation using naturally abundant xenon (NAXe) gas. METHODS: MRI was performed at 1.5 Tesla (T) and 3 T on one healthy smoker and two healthy never-smokers. 129Xe gas was polarized to ∼25% using an in-house spin-exchange optical pumping polarizer fitted with a laser diode array with integrated volume holographic grating and optical train system. Volunteers inhaled 1 L of NAXe for an 8 to 15 s breathhold while MR images were acquired with full-lung coverage using a three-dimensional steady-state free precession sequence, optimized for maximum signal-to-noise ratio (SNR) at a given spatial resolution. For the purpose of image quality comparison, the MR acquisition was repeated at 1.5 T with 400 mL enriched xenon and 200 mL 3He. RESULTS: All NAXe lung images were of high quality, with mean SNRs of 25-40 (voxel 4.2 × 4.2 × 8/10 mm3) and ∼30% improvement at 3 T versus 1.5 T. The high SNR permitted identification of minor ventilation defects in the healthy smoker's lungs. NAXe images were of comparable SNR to those obtained with enriched xenon and 3He. CONCLUSION: Optimization of MR pulse sequences and advances in polarization technology have facilitated high quality pulmonary ventilation imaging with inexpensive NAXe gas.