Regional Structure-Function in Cystic Fibrosis Lung Disease Using Hyperpolarized 129Xe and Ultrashort Echo Magnetic Resonance Imaging.
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ABSTRACT:
SUBMITTER: Thomen RP
PROVIDER: S-EPMC7365365 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
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Regional Structure-Function in Cystic Fibrosis Lung Disease Using Hyperpolarized <sup>129</sup>Xe and Ultrashort Echo Magnetic Resonance Imaging.
Thomen Robert P RP Walkup Laura L LL Roach David J DJ Higano Nara N Schapiro Andrew A Brody Alan A Clancy John P JP Cleveland Zackary I ZI Woods Jason C JC
American journal of respiratory and critical care medicine 20200701 2
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Project description:BackgroundMRI of hyperpolarized 129 Xenon (HP 129 Xe) is increasingly utilized for investigating pulmonary function. The solubility of HP 129 Xe in lung tissue, blood plasma (Barrier), and red blood cells (RBC), with unique chemical shifts, enables spectroscopic imaging of potential imaging biomarkers of gas exchange and microstructural pulmonary physiology.PurposeTo quantify global average and regional repeatability of Barrier:gas, RBC:gas, and RBC:Barrier ratios derived from dissolved-phase 129 Xe imaging and their dependence on intervisit changes in lung inflation volume.Study typeProspective.PopulationFourteen healthy volunteers. One subject was unable to complete the study resulting in 13 subjects for analysis (eight female, five male, ages 24-69, 53.8 ± 13.9).Field strength1.5T.AssessmentSubjects were imaged using a 3D radial 1-point Dixon method to separate Barrier and RBC component signals, at two different timepoints, with ~1 month between visits. RBC:Gas, Barrier:Gas, and RBC:Barrier measures were compared across time and with pulmonary function tests (PFTs).Statistical testsRepeatablilty was quantified using Bland-Altman plots, coefficient of repeatability, coefficient of variation (CV), and intraclass correlation coefficients (ICCs). Dependence of imaging measures on PFTs and lung volume was evaluated using Spearman and Pearson correlation coefficients, respectively. Statistical significance was determined by F-test for intraclass correlations, and t-test for Spearman correlations and regression.ResultsMean RBC:Gas, Barrier:Gas, and RBC:Barrier had CVs of 19.2%, 20.0%, and 11.5%, respectively, and had significant ICCs, equal to 0.78, 0.79, and 0.92, respectively. Intervisit differences in RBC:Barrier were significantly correlated with intervisit differences in DLCO (r = 0.93, P = 0.007). Significant correlations with intervisit lung volume differences and intervisit differences in mean RBC:Gas (r = -0.73, P = 0.005) and Barrier:Gas (r = -0.69, P = 0.009) were found.Data conclusionThree commonly used 129 Xe MRI-based measures of gas-exchange show good repeatability, particularly the Barrier:RBC ratio, which did not depend on lung inflation volume and was strongly associated with intervisit changes in DLCO .Level of evidence1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1182-1190.
| S-EPMC6750965 | biostudies-literature
Project description:PurposeTo develop and optimize a rapid dynamic hyperpolarized 129 Xe ventilation (DXeV) MRI protocol and investigate the feasibility of capturing pulmonary signal-time curves in human lungs.Theory and methodsSpiral k-space trajectories were designed with the number of interleaves Nint = 1, 2, 4, and 8 corresponding to voxel sizes of 8 mm, 5 mm, 4 mm, and 2.5 mm, respectively, for field of view = 15 cm. DXeV images were acquired from a gas-flow phantom to investigate the ability of Nint = 1, 2, 4, and 8 to capture signal-time curves. A finite element model was constructed to investigate gas-flow dynamics corroborating the experimental signal-time curves. DXeV images were also carried out in six subjects (three healthy and three chronic obstructive pulmonary disease subjects).ResultsDXeV images and numerical modelling of signal-time curves permitted the quantification of temporal and spatial resolutions for different numbers of spiral interleaves. The two-interleaved spiral (Nint = 2) was found to be the most time-efficient to obtain DXeV images and signal-time curves of whole lungs with a temporal resolution of 624 ms for 13 slices. Signal-time curves were well matched in three healthy volunteers. The Spearman's correlations of chronic obstructive pulmonary disease subjects were statistically different from three healthy subjects (P < 0.05).ConclusionThe Nint = 2 spiral demonstrates the successful acquisition of DXeV images and signal-time curves in healthy subjects and chronic obstructive pulmonary disease patients. Magn Reson Med 79:2597-2606, 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.
| S-EPMC5836876 | biostudies-literature
Project description:G protein-coupled receptors can adopt many different conformational states, each of them exhibiting different restraints towards downstream signaling pathways. One promising strategy to identify and quantify this conformational landscape is to introduce a cysteine at a receptor site sensitive to different states and label this cysteine with a probe for detection. Here, the application of NMR of hyperpolarized 129Xe for the detection of the conformational states of human neuropeptide Y2 receptor is introduced. The xenon trapping cage molecule cryptophane-A attached to a cysteine in extracellular loop 2 of the receptor facilitates chemical exchange saturation transfer experiments without and in the presence of native ligand neuropeptide Y. High-quality spectra indicative of structural states of the receptor-cage conjugate were obtained. Specifically, five signals could be assigned to the conjugate in the apo form. After the addition of NPY, one additional signal and subtle modifications in the persisting signals could be detected. The correlation of the spectroscopic signals and structural states was achieved with molecular dynamics simulations, suggesting frequent contact between the xenon trapping cage and the receptor surface but a preferred interaction with the bound ligand.
| S-EPMC9919357 | biostudies-literature
Project description:PurposeTo perform magnetic resonance imaging (MRI), human lung imaging, and quantification of the gas-transfer dynamics of hyperpolarized xenon-129 (HPX) from the alveoli into the blood plasma.Materials and methodsHPX MRI with iterative decomposition of water and fat with echo asymmetry and least-square estimation (IDEAL) approach were used with multi-interleaved spiral k-space sampling to obtain HPX gas and dissolved phase images. IDEAL time-series images were then obtained from ten subjects including six normal subjects and four patients with pulmonary emphysema to test the feasibility of the proposed technique for capturing xenon-129 gas-transfer dynamics (XGTD). The dynamics of xenon gas diffusion over the entire lung was also investigated by measuring the signal intensity variations between three regions of interest, including the left and right lungs and the heart using Welch's t test.ResultsThe technique enabled the acquisition of HPX gas and dissolved phase compartment images in a single breath-hold interval of 8 s. The y-intersect of the XGTD curves were also found to be statistically lower in the patients with lung emphysema than in the healthy group (p < 0.05).ConclusionThis time-series IDEAL technique enables the visualization and quantification of inhaled xenon from the alveoli to the left ventricle with a clinical gradient strength magnet during a single breath-hold, in healthy and diseased lungs.Key points• The proposed hyperpolarized xenon-129 gas and dissolved magnetic resonance imaging technique can provide regional and temporal measurements of xenon-129 gas-transfer dynamics. • Quantitative measurement of xenon-129 gas-transfer dynamics from the alveolar to the heart was demonstrated in normal subjects and pulmonary emphysema. • Comparison of gas-transfer dynamics in normal subjects and pulmonary emphysema showed that the proposed technique appears sensitive to changes affecting the alveoli, pulmonary interstitium, and capillaries.
| S-EPMC6443604 | biostudies-literature
Project description:Introduction: The ideal contrast agents for ventilation SPECT and MRI are Technegas and 129Xe gas, respectively. Despite increasing interest in the clinical utility of ventilation imaging, these modalities have not been directly compared. Therefore, our objective was to compare the ventilation defect percent (VDP) assessed by Technegas SPECT and hyperpolarized 129Xe MRI in patients scheduled to undergo lung cancer resection with and without pre-existing obstructive lung disease. Methods: Forty-one adults scheduled to undergo lung cancer resection performed same-day Technegas SPECT, hyperpolarized 129Xe MRI, spirometry, and diffusing capacity of the lung for carbon monoxide (DLCO). Ventilation abnormalities were quantified as the VDP using two different methods: adaptive thresholding (VDPT) and k-means clustering (VDPK). Correlation and agreement between VDP quantified by Technegas SPECT and 129Xe MRI were determined by Spearman correlation and Bland-Altman analysis, respectively. Results: VDP measured by Technegas SPECT and 129Xe MRI were correlated (VDPT: r = 0.48, p = 0.001; VDPK: r = 0.63, p < 0.0001). A 2.0% and 1.6% bias towards higher Technegas SPECT VDP was measured using the adaptive threshold method (VDPT: 23.0% ± 14.0% vs. 21.0% ± 5.2%, p = 0.81) and k-means method (VDPK: 9.4% ± 9.4% vs. 7.8% ± 10.0%, p = 0.02), respectively. For both modalities, higher VDP was correlated with lower FEV1/FVC (SPECT VDPT: r = -0.38, p = 0.01; MRI VDPK: r = -0.46, p = 0.002) and DLCO (SPECT VDPT: r = -0.61, p < 0.0001; MRI VDPK: r = -0.68, p < 0.0001). Subgroup analysis revealed that VDP measured by both modalities was significantly higher for participants with COPD (n = 13) than those with asthma (n = 6; SPECT VDPT: p = 0.007, MRI VDPK: p = 0.006) and those with no history of obstructive lung disease (n = 21; SPECT VDPT: p = 0.0003, MRI VDPK: p = 0.0003). Discussion: The burden of ventilation defects quantified by Technegas SPECT and 129Xe MRI VDP was correlated and greater in participants with COPD when compared to those without. Our observations indicate that, despite substantial differences between the imaging modalities, quantitative assessment of ventilation defects by Technegas SPECT and 129Xe MRI is comparable.
| S-EPMC10206636 | biostudies-literature
Project description:Fast apparent transverse relaxation (short T2 *) is a common obstacle when attempting to perform quantitative 1 H MRI of the lungs. While T2 * times are longer for pulmonary hyperpolarized (HP) gas functional imaging (in particular for gaseous 129 Xe), T2 * can still lead to quantitative inaccuracies for sequences requiring longer echo times (such as diffusion weighted images) or longer readout duration (such as spiral sequences). This is especially true in preclinical studies, where high magnetic fields lead to shorter relaxation times than are typically seen in human studies. However, the T2 * of HP 129 Xe in the most common animal model of human disease (mice) has not been reported. Herein, we present a multi-echo radial flyback imaging sequence and use it to measure HP 129 Xe T2 * at 7 T under a variety of respiratory conditions. This sequence mitigates the impact of T1 relaxation outside the animal by using multiple gradient-refocused echoes to acquire images at a number of effective echo times for each RF excitation. After validating the sequence using a phantom containing water doped with superparamagnetic iron oxide nanoparticles, we measured the 129 Xe T2 * in vivo for 10 healthy C57Bl/6 J mice and found T2 * ~ 5 ms in the lung airspaces. Interestingly, T2 * was relatively constant over all experimental conditions, and varied significantly with sex, but not age, mass, or the O2 content of the inhaled gas mixture. These results are discussed in the context of T2 * relaxation within porous media.
| S-EPMC7702724 | biostudies-literature
Project description:PurposeThe MR properties (chemical shifts and R2∗ decay rates) of dissolved-phase hyperpolarized (HP) 129 Xe are confounded by the large magnetic field inhomogeneity present in the lung. This work improves measurements of these properties using a model-based image reconstruction to characterize the R2∗ decay rates of dissolved-phase HP 129 Xe in healthy subjects and patients with idiopathic pulmonary fibrosis (IPF).MethodsWhole-lung MRS and 3D radial MRI with four gradient echoes were performed after inhalation of HP 129 Xe in healthy subjects and patients with IPF. A model-based image reconstruction formulated as a regularized optimization problem was solved iteratively to measure regional signal intensity in the gas, barrier, and red blood cell (RBC) compartments, while simultaneously measuring their chemical shifts and R2∗ decay rates.ResultsThe estimation of spectral properties reduced artifacts in images of HP 129 Xe in the gas, barrier, and RBC compartments and improved image SNR by over 20%. R2∗ decay rates of the RBC and barrier compartments were lower in patients with IPF compared to healthy subjects (P < 0.001 and P = 0.005, respectively) and correlated to DLCO (R = 0.71 and 0.64, respectively). Chemical shift of the RBC component measured with whole-lung spectroscopy was significantly different between IPF and normal subjects (P = 0.022).ConclusionEstimates for R2∗ in both barrier and RBC dissolved-phase HP 129 Xe compartments using a regional signal model improved image quality for dissolved-phase images and provided additional biomarkers of lung injury in IPF.
| S-EPMC7329592 | biostudies-literature
Project description:BackgroundFree-breathing 1 H ventilation MRI shows promise but only single-center validation has yet been performed against methods which directly image lung ventilation in patients with cystic fibrosis (CF).PurposeTo investigate the relationship between 129 Xe and 1 H ventilation images using data acquired at two centers.Study typeSequence comparison.PopulationCenter 1; 24 patients with CF (12 female) aged 9-47 years. Center 2; 7 patients with CF (6 female) aged 13-18 years, and 6 healthy controls (6 female) aged 21-31 years. Data were acquired in different patients at each center.Field strength/sequence1.5 T, 3D steady-state free precession and 2D spoiled gradient echo.AssessmentSubjects were scanned with 129 Xe ventilation and 1 H free-breathing MRI and performed pulmonary function tests. Ventilation defect percent (VDP) was calculated using linear binning and images were visually assessed by H.M., L.J.S., and G.J.C. (10, 5, and 8 years' experience).Statistical testsCorrelations and linear regression analyses were performed between 129 Xe VDP, 1 H VDP, FEV1 , and LCI. Bland-Altman analysis of 129 Xe VDP and 1 H VDP was carried out. Differences in metrics were assessed using one-way ANOVA or Kruskal-Wallis tests.Results129 Xe VDP and 1 H VDP correlated strongly with; each other (r = 0.84), FEV1 z-score (129 Xe VDP r = -0.83, 1 H VDP r = -0.80), and LCI (129 Xe VDP r = 0.91, 1 H VDP r = 0.82). Bland-Altman analysis of 129 Xe VDP and 1 H VDP from both centers had a bias of 0.07% and limits of agreement of -16.1% and 16.2%. Linear regression relationships of VDP with FEV1 were not significantly different between 129 Xe and 1 H VDP (P = 0.08), while 129 Xe VDP had a stronger relationship with LCI than 1 H VDP.Data conclusion1 H ventilation MRI shows large-scale agreement with 129 Xe ventilation MRI in CF patients with established lung disease but may be less sensitive to subtle ventilation changes in patients with early-stage lung disease.Evidence level2 TECHNICAL EFFICACY: Stage 2.
| S-EPMC10946578 | biostudies-literature
Project description:PurposeThe underlying functional and microstructural lung disease in neonates who are born preterm (bronchopulmonary dysplasia, BPD) remains poorly characterized. Moreover, there is a lack of suitable techniques to reliably assess lung function in this population. Here, we report our preliminary experience with hyperpolarized 129 Xe MRI in neonates with BPD.MethodsNeonatal intensive care patients with established BPD were recruited (N = 9) and imaged at a corrected gestational age of median:40.7 (range:37.1, 44.4) wk using a 1.5T neonatal scanner. 2D 129 Xe ventilation and diffusion-weighted images and dissolved phase spectroscopy were acquired, alongside 1 H 3D radial UTE. 129 Xe images were acquired during a series of short apneic breath-holds (˜3 s). 1 H UTE images were acquired during tidal breathing. Ventilation defects were manually identified and qualitatively compared to lung structures on UTE. ADCs were calculated on a voxel-wise basis. The signal ratio of the 129 Xe red blood cell (RBC) and tissue membrane (M) resonances from spectroscopy was determined.ResultsSpiral-based 129 Xe ventilation imaging showed good image quality and sufficient sensitivity to detect mild ventilation abnormalities in patients with BPD. 129 Xe ADC values were elevated above that expected given healthy data in older children and adults (median:0.046 [range:0.041, 0.064] cm2 s-1 ); the highest value obtained from an extremely pre-term patient. 129 Xe spectroscopy revealed a low RBC/M ratio (0.14 [0.06, 0.21]).ConclusionWe have demonstrated initial feasibility of 129 Xe lung MRI in neonates. With further data, the technique may help guide management of infant lung diseases in the neonatal period and beyond.
| S-EPMC10629838 | biostudies-literature
Project description:Low thermal-equilibrium nuclear spin polarizations and the need for sophisticated instrumentation render conventional nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) incompatible with small-scale microfluidic devices. Hyperpolarized 129Xe gas has found use in the study of many materials but has required very large and expensive instrumentation. Recently a microfabricated device with modest instrumentation demonstrated all-optical hyperpolarization and detection of 129Xe gas. This device was limited by 129Xe polarizations less than 1%, 129Xe NMR signals smaller than 20 nT, and transport of hyperpolarized 129Xe over millimeter lengths. Higher polarizations, versatile detection schemes, and flow of 129Xe over larger distances are desirable for wider applications. Here we demonstrate an ultra-sensitive microfabricated platform that achieves 129Xe polarizations reaching 7%, NMR signals exceeding 1 μT, lifetimes up to 6 s, and simultaneous two-mode detection, consisting of a high-sensitivity in situ channel with signal-to-noise of 105 and a lower-sensitivity ex situ detection channel which may be useful in a wider variety of conditions. 129Xe is hyperpolarized and detected in locations more than 1 cm apart. Our versatile device is an optimal platform for microfluidic magnetic resonance in particular, but equally attractive for wider nuclear spin applications benefitting from ultra-sensitive detection, long coherences, and simple instrumentation.
| S-EPMC5339783 | biostudies-literature