Purpose To evaluate the feasibility of directly imaging perfusion of human brain tissue by using magnetic resonance (MR) imaging with inhaled hyperpolarized xenon 129 (Xe). Materials and Methods In vivo imaging with Xe was performed in three healthy participants. The combination of a high-yield spin-exchange optical pumpingXe polarizer, custom-built radiofrequency coils, and an optimized gradient-echo MR imaging protocol was used to achieve signal sensitivity sufficient to directly image hyperpolarized Xe dissolved in the human brain. Conventional T1-weighted proton (hydrogen 1 [H]) images and perfusion images by using arterial spin labeling were obtained for comparison. Results Images of Xe uptake were obtained with a signal-to-noise ratio of 31 ± 9 and demonstrated structural similarities to the gray matter distribution on conventional T1-weightedH images and to perfusion images from arterial spin labeling. Conclusion Hyperpolarized Xe 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.

PurposeTo obtain whole lung morphometry measurements from 129Xe in a single breath‐hold with 3D multiple b‐value 129Xe diffusion‐weighted MRI (DW‐MRI) with an empirically optimized diffusion time and compressed sensing for scan acceleration.MethodsProspective three‐fold undersampled 3D multiple b‐value hyperpolarized 129Xe 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 3He. The empirically optimized 129Xe diffusion time was then implemented with a four‐fold undersampling scheme and was prospectively benchmarked against 3He 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).ResultsGood agreement between the mean 129Xe and 3He LmD (mean difference, 2.2%) and Lm (mean difference, 1.1%) values was obtained in all subjects at an empirically optimized 129Xe Δ = 8.5 ms.ConclusionCompressed sensing has facilitated single‐breath 3D multiple b‐value 129Xe DW‐MRI acquisitions, and results at 129Xe Δ = 8.5 ms indicate that 129Xe provides a viable alternative to 3He 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.

CSSR with hyperpolarized Xe is sensitive to pathology-induced degradation of lung structure/function and shows promise for quantification of disease severity and monitoring treatment response. Magn Reson Med 74:196-207, 2015. © 2014 Wiley Periodicals, Inc.

PurposeUpon 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 129Xe 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 129Xe dissolved in the human head at 1.5 Tesla.MethodsA 129Xe radiofrequency coil was built in‐house and 129Xe gas was polarized using spin‐exchange optical pumping. Following the inhalation of 129Xe 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.ResultsSpectra of hyperpolarized 129Xe 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.ConclusionHigh resolution spectroscopy and CSI of hyperpolarized 129Xe dissolved in the human head has been demonstrated. For the first time, five distinct NMR peaks have been observed in 129Xe 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.

BackgroundTo support translational lung MRI research with hyperpolarized 129Xe gas, comprehensive evaluation of derived quantitative lung function measures against established measures from 3He MRI is required. Few comparative studies have been performed to date, only at 3T, and multisession repeatability of 129Xe functional metrics have not been reported.Purpose/HypothesisTo compare hyperpolarized 129Xe and 3He MRI‐derived quantitative metrics of lung ventilation and microstructure, and their repeatability, at 1.5T.Study TypeRetrospective.PopulationFourteen 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/Sequence1.5T. NSCLC, COPD patients and selected HN subjects underwent 3D balanced steady‐state free‐precession lung ventilation MRI using both 3He and 129Xe. Selected HN, all ES, and COPD patients underwent 2D multislice spoiled gradient‐echo diffusion‐weighted lung MRI using both hyperpolarized gas nuclei.AssessmentVentilated 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 TestsIntermetric correlations: Spearman's coefficient. Intergroup/internuclei differences: analysis of variance / Wilcoxon's signed rank. Repeatability: coefficient of variation (CV), intraclass correlation (ICC) coefficient.ResultsA significant positive correlation between 3He and 129Xe VV% was observed (r = 0.860, P < 0.001). VV% was larger for 3He than 129Xe (P = 0.001); average bias, 8.79%. A strong correlation between mean 3He and 129Xe ADC was obtained (r = 0.922, P < 0.001). MR parameters exhibited good correlations with pulmonary function tests. In COPD patients, mean CV of 3He and 129Xe VV% was 4.08% and 13.01%, respectively, with ICC coefficients of 0.541 (P = 0.061) and 0.458 (P = 0.095). Mean 3He and 129Xe 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 129Xe lung MRI provides near‐equivalent information to 3He for quantitative lung ventilation and microstructural MRI at 1.5T. Level of Evidence: 3 Technical Efficacy Stage 2J. Magn. Reson. Imaging 2018;48:632–642.

In this work, the production rate of a spin-exchange optical pumping 129Xe gas polarizer was optimized for routine generation of hyperpolarized 129Xe for in vivo lung MRI. This system uses a narrow (∼ 0.1 nm linewidth), tuneable external cavity laser (operating at ∼25 W) for SEOP of 3% gas mixtures of Xe inside a mid-pressure (2 bars) cell of 491 cm3 volume. Under this regime, theoretical and experimentally measured 129Xe polarizations were calculated to be 24% and 12%, respectively, for a gas flow rate of 300 sccm and a cell temperature of 373 K. The photon efficiency was evaluated, yielding theoretical and experimental values of 0.039 and 0.046, respectively. The theoretical efficiency was calculated from spin-exchange and spin-destruction cross sections and the experimental photon efficiency was measured under flow for a gas-cell residency time equal to an empirically determined spin-exchange time of 45 s. In addition, details of the Xe freeze-out process were analyzed with a model of polarization decay during Xe accumulation in the frozen phase, where a T1 of 87 ± 2 min was observed. To demonstrate the system's application, in vivo lung magnetic resonance images (signal-to-noise ratio ∼ 50 from a voxel of 15 mm× 4 mm× 4 mm) were acquired using modest volumes (&lt;400 ml) of isotopically enriched (86% 129Xe) Xe gas polarized to &gt;10%. Despite the experimental polarization being a factor of 2 lower than the predicted polarization for typical operating parameters, the system is close to the theoretical photon efficiency and the system has so far produced polarized gas for more than 100 in vivo 129Xe lung imaging studies.

Detection of early subclinical lung disease in children with cystic fibrosis by lung ventilation imaging with hyperpolarised gas MRI ABSTRACT Hyperpolarised 3 He 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) (FEV 1 > −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.

PurposeTo evaluate the dependency of the 129Xe‐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 129Xe NMR.MethodsHyperpolarized 129Xe 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 129Xe.ResultsThe 129Xe chemical shift in RBCs was found to increase nonlinearly with blood oxygenation at 1.5 T and 3 T. During breath hold apnea, the 129Xe 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 129Xe‐RBC signal amplitude showed a modulation with the same frequency as the 129Xe‐RBC chemical shift.ConclusionThe feasibility of using the 129Xe‐RBC chemical shift to measure pulmonary blood oxygenation in vivo has been demonstrated. Correlation between 129Xe‐RBC signal and 129Xe‐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.