Improved Diffusion-Weighted Hyperpolarized 129Xe Lung MRI with Patch-Based Higher-Order, Singular Value Decomposition Denoising.

RATIONALE AND OBJECTIVES: Hyperpolarized xenon (129Xe) MRI is a noninvasive method to assess pulmonary structure and function. To measure lung microstructure, diffusion-weighted imaging-commonly the apparent diffusion coefficient (ADC)-can be employed to map changes in alveolar-airspace size resulting from normal aging and pulmonary disease. However, low signal-to-noise ratio (SNR) decreases ADC measurement certainty, and biases ADC to spuriously low values. Further, these challenges are most severe in regions of the lung where alveolar simplification or emphysematous remodeling generate abnormally high ADCs. Here, we apply Global Local Higher Order Singular Value Decomposition (GLHOSVD) denoising to enhance image SNR, thereby reducing uncertainty and bias in diffusion measurements. MATERIALS AND METHODS: GLHOSVD denoising was employed in simulated images and gas phantoms with known diffusion coefficients to validate its effectiveness and optimize parameters for analysis of diffusion-weighted 129Xe MRI. GLHOSVD was applied to data from 120 subjects (34 control, 39 cystic fibrosis (CF), 27 lymphangioleiomyomatosis (LAM), and 20 asthma). Image SNR, ADC, and distributed diffusivity coefficient (DDC) were compared before and after denoising using Wilcoxon signed-rank analysis for all images. RESULTS: Denoising significantly increased SNR in simulated, phantom, and in-vivo images, showing a greater than 2-fold increase (p < 0.001) across diffusion-weighted images. Although mean ADC and DDC remained unchanged (p > 0.05), ADC and DDC standard deviation decreased significantly in denoised images (p < 0.001). CONCLUSION: When applied to diffusion-weighted 129Xe images, GLHOSVD improved image quality and allowed airspace size to be quantified in high-diffusion regions of the lungs that were previously inaccessible to measurement due to prohibitively low SNR, thus providing insights into disease pathology.

Pulmonary MRI with hyperpolarized xenon-129 demonstrates novel alterations in gas transfer across the air-blood barrier in asthma.

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.

Sampling pattern discrepancy in the application of compressed sensing hyperpolarized xenon-129 lung MRI.

Although hyperpolarized (HP) 129Xe ventilation MRI can be carried out within a breath hold, it is still challenging for many sick patients. Compressed sensing (CS) is a viable alternative to accelerate this approach. However, undersampled images with identical sampling ratios differ from one another. Twenty subjects (n = 10 healthy and n = 10 patients with asthma) were scanned using a GE MR750 3 T scanner, acquiring fully sampled 2D multi-slice HP 129Xe lung ventilation images (10 s breath hold, 128 × 80 (FE × PE-frequency encoding × phase encoding) and 16 slices). Using fully sampled data, 500 variable-density Cartesian random undersampling patterns were generated, each at eight different sampling ratios from 10% to 80%. The parallel imaging and compressed sensing (PICS) command from BART was employed to reconstruct undersampled data. The signal to noise ratio (SNR), structural similarity index measurement (SSIM) and sidelobe to peak ratio of each were subsequently compared. There was a high degree of variation in both SNR and SSIM results from each of the 500 masks of each sampling rate. As the undersampling increases, there is more variation in the quantifying metrics, for both healthy and asthmatic individuals. Our study shows that random undersampling poses a significant challenge when applied at sampling ratios less than 60%, despite fulfilling CS's incoherency criteria. Such low sampling ratios will result in a large variety of undersampling patterns. Therefore, skipped segments of k-space cannot be allowed to happen randomly at low sampling rates. By optimizing the sampling pattern, CS will reach its full potential and be able to be applied to a highly undersampled 129Xe lung dataset.

Simultaneous quantification of hyperpolarized xenon-129 ventilation and gas exchange with multi-breath xenon-polarization transfer contrast (XTC) MRI.

PURPOSE: To demonstrate the feasibility of a multi-breath xenon-polarization transfer contrast (XTC) MR imaging approach for simultaneously evaluating regional ventilation and gas exchange parameters. METHODS: Imaging was performed in five healthy volunteers and six chronic obstructive pulmonary disease (COPD) patients. The multi-breath XTC protocol consisted of three repeated schemes of six wash-in breaths of a xenon mixture and four normoxic wash-out breaths, with and without selective saturation of either the tissue membrane or red blood cell (RBC) resonances. Acquisitions were performed at end-exhalation while subjects maintained tidal breathing throughout the session. The no-saturation, membrane-saturation, and RBC-saturation images were fit to a per-breath gas replacement model for extracting voxelwise tidal volume (TV), functional residual capacity (FRC), and fractional ventilation (FV), as well as tissue- and RBC-gas exchange (fMem and fRBC , respectively). The sensitivity of the derived model was also evaluated via simulations. RESULTS: With the exception of FRC, whole-lung averages for all metrics were decreased in the COPD subjects compared to the healthy cohort, significantly so for FV, fRBC , and fMem . Heterogeneity was higher overall in the COPD subjects, particularly for fRBC , fMem , and fRBC:Mem . The anterior-to-posterior gradient associated with the gravity-dependence of lung function in supine imaging was also evident for FV, fRBC , and fMem values in the healthy subjects, but noticeably absent in the COPD cohort. CONCLUSION: Multi-breath XTC imaging generated high-resolution, co-registered maps of ventilation and gas exchange parameters acquired during tidal breathing and with low per-breath xenon doses. Clear differences between healthy and COPD subjects were apparent and consistent with spirometry.

Dramatic improvement in the "Bulk" hyperpolarization of 131Xe via spin exchange optical pumping probed using in situ low-field NMR.

We report on hyperpolarization of quadrupolar (I=3/2) 131Xe via spin-exchange optical pumping. Observations of the 131Xe polarization dynamics via in situ low-field NMR show that the estimated alkali-metal/131Xe spin-exchange rates can be large enough to compete with 131Xe spin relaxation. 131Xe polarization up to 7.6±1.5% was achieved in ∼8.5×1020 spins-a ∼100-fold improvement in the total spin angular momentum-potentially enabling various applications, including: measurement of spin-dependent neutron-131Xe s-wave scattering; sensitive searches for time-reversal violation in neutron-131Xe interactions beyond the Standard Model; and surface-sensitive pulmonary MRI.

Hyperpolarized Xenon-129: A New Tool to Assess Pulmonary Physiology in Patients with Pulmonary Fibrosis.

PURPOSE: The existing tools to quantify lung function in interstitial lung diseases have significant limitations. Lung MRI imaging using inhaled hyperpolarized xenon-129 gas (129Xe) as a contrast agent is a new technology for measuring regional lung physiology. We sought to assess the utility of the 129Xe MRI in detecting impaired lung physiology in usual interstitial pneumonia (UIP). MATERIALS AND METHODS: After institutional review board approval and informed consent and in compliance with HIPAA regulations, we performed chest CT, pulmonary function tests (PFTs), and 129Xe MRI in 10 UIP subjects and 10 healthy controls. RESULTS: The 129Xe MRI detected highly heterogeneous abnormalities within individual UIP subjects as compared to controls. Subjects with UIP had markedly impaired ventilation (ventilation defect fraction: UIP: 30 ± 9%; healthy: 21 ± 9%; p = 0.026), a greater amount of 129Xe dissolved in the lung interstitium (tissue-to-gas ratio: UIP: 1.45 ± 0.35%; healthy: 1.10 ± 0.17%; p = 0.014), and impaired 129Xe diffusion into the blood (RBC-to-tissue ratio: UIP: 0.20 ± 0.06; healthy: 0.28 ± 0.05; p = 0.004). Most MRI variables had no correlation with the CT and PFT measurements. The elevated level of 129Xe dissolved in the lung interstitium, in particular, was detectable even in subjects with normal or mildly impaired PFTs, suggesting that this measurement may represent a new method for detecting early fibrosis. CONCLUSION: The hyperpolarized 129Xe MRI was highly sensitive to regional functional changes in subjects with UIP and may represent a new tool for understanding the pathophysiology, monitoring the progression, and assessing the effectiveness of treatment in UIP.

Comparison of ventilation defects quantified by Technegas SPECT and hyperpolarized 129Xe MRI.

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.

Towards Probing Conformational States of Y2 Receptor Using Hyperpolarized 129Xe NMR.

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.

Enhanced 129 Xe T1 relaxation in whole blood and in the presence of SPIONs at low magnetic field strengths.

PURPOSE: To compare the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on the T1 of 129 Xe and 1 H and to measure the relaxation of 129 Xe in blood at low and high magnetic field strengths. METHODS: 129 Xe and 1 H T1 relaxometry was performed at low- and high-field strengths in samples containing different SPION concentrations, while imaging was used to compare the contrast obtainable in these two field regimes. In vivo experiments at variable field strengths were performed to determine the depolarization of 129 Xe in blood and the feasibility of in vivo dissolved-phase spectroscopy and imaging at low field. RESULTS: The SPION relaxivity was substantially greater at low field for 1 H, increasing from 0.92 ± 0.06 mM s-1 at 11.7T to 31.5 ± 1.8 mM s-1 at 0.6 mT, and for 129 Xe, which increased from 0.13 ± 0.03 mM s-1 at 11.7T to 7.32 ± 0.71 mM s-1 at 2.1 mT. The additional MR signal loss increased from 0.7% at 9.4T to 20.6 ± 4.2% at 0.6 mT for 1 H and from -0.7 ± 3.4% at 9.4T to 12.7 ± 3.5% at 2.1 mT for 129 Xe. Blood was found to depolarize 129 Xe below 3T in a manner inversely proportional to the field strength. In vitro studies at 2.1 mT suggest 129 Xe relaxation times below 5 s in blood dilutions as low as 0.4% volume. CONCLUSION: SPIONs longitudinal relaxivity increases at low field both for 1 H and 129 Xe. The depolarization of xenon in blood, which is found to increase below 3T, effectively prevents in vivo dissolved-phase spectroscopy and imaging at low-field strengths.

3D Single-Breath Chemical Shift Imaging Hyperpolarized Xe-129 MRI of Healthy, CF, IPF, and COPD Subjects.

3D Single-breath Chemical Shift Imaging (3D-SBCSI) is a hybrid MR-spectroscopic imaging modality that uses hyperpolarized xenon-129 gas (Xe-129) to differentiate lung diseases by probing functional characteristics. This study tests the efficacy of 3D-SBCSI in differentiating physiology among pulmonary diseases. A total of 45 subjects-16 healthy, 11 idiopathic pulmonary fibrosis (IPF), 13 cystic fibrosis (CF), and 5 chronic obstructive pulmonary disease (COPD)-were given 1/3 forced vital capacity (FVC) of hyperpolarized Xe-129, inhaled for a ~7 s MRI acquisition. Proton, Xe-129 ventilation, and 3D-SBCSI images were acquired with separate breath-holds using a radiofrequency chest coil tuned to Xe-129. The Xe-129 spectrum was analyzed in each lung voxel for ratios of spectroscopic peaks, chemical shifts, and T2* relaxation. CF and COPD subjects had significantly more ventilation defects than IPF and healthy subjects, which correlated with FEV1 predicted (R = -0.74). FEV1 predicted correlated well with RBC/Gas ratio (R = 0.67). COPD and IPF had significantly higher Tissue/RBC ratios than other subjects, longer RBC T2* relaxation times, and greater RBC chemical shifts. CF subjects had more ventilation defects than healthy subjects, elevated Tissue/RBC ratio, shorter Tissue T2* relaxation, and greater RBC chemical shift. 3D-SBCSI may be helpful in the detection and characterization of pulmonary disease, following treatment efficacy, and predicting disease outcomes.

Investigating the impact of RF saturation-pulse parameters on compartment-selective gas-phase depolarization with xenon polarization transfer contrast MRI.

PURPOSE: To demonstrate the utility of continuous-wave (CW) saturation pulses in xenon-polarization transfer contrast (XTC) MRI and MRS, to investigate the selectivity of CW pulses applied to dissolved-phase resonances, and to develop a correction method for measurement biases from saturation of the nontargeted dissolved-phase compartment. METHODS: Studies were performed in six healthy Sprague-Dawley rats over a series of end-exhale breath holds. Discrete saturation schemes included a series of 30 Gaussian pulses (8 ms FWHM), spaced 25 ms apart; CW saturation schemes included single block pulses, with variable flip angle and duration. In XTC imaging, saturation pulses were applied on both dissolved-phase resonance frequencies and off-resonance, to correct for other sources of signal loss and compromised selectivity. In spectroscopy experiments, saturation pulses were applied at a set of 19 frequencies spread out between 185 and 200 ppm to map out modified z-spectra. RESULTS: Both modified z-spectra and imaging results showed that CW RF pulses offer sufficient depolarization and improved selectivity for generating contrast between presaturation and postsaturation acquisitions. A comparison of results obtained using a variety of saturation parameters confirms that saturation pulses applied at higher powers exhibit increased cross-contamination between dissolved-phase resonances. CONCLUSION: Using CW RF saturation pulses in XTC contrast preparation, with the proposed correction method, offers a potentially more selective alternative to traditional discrete saturation. The suppression of the red blood cell contribution to the gas-phase depolarization opens the door to a novel way of quantifying exchange time between alveolar volume and hemoglobin.

Longitudinal nuclear spin relaxation of 129 Xe in solution and in hollow fiber membranes at low and high magnetic field strengths.

PURPOSE: To measure dissolved-phase 129 Xe T1 values at high and low magnetic fields and the field dependence of 129 Xe depolarization by hollow fiber membranes used to infuse hyperpolarized xenon in solution. METHODS: Dissolved-phase T1 measurements were made at 11.7T and 2.1 mT by bubbling xenon in solution and by using a variable delay to allow spins to partially relax back to thermal equilibrium before probing their magnetization. At high field, relaxation values were compared to those obtained by using the small flip angle method. For depolarization studies, we probed the magnetization of the polarized gas diffusing through an exchange membrane module placed at different field strengths. RESULTS: Total loss of polarization was observed for xenon diffusing through hollow fiber membranes at low field, while significant polarization loss (>20%) was observed at magnetic fields up to 2T. Dissolved-phase 129 Xe T1 values were found consistently shorter at 2.1 mT compared to 11.7T. In addition, both O2 and Xe gas concentrations in solution were found to significantly affect dissolved-phase 129 Xe T1 values. CONCLUSION: Dissolved-phase 129 Xe measurements are feasible at low field, but to assess the feasibility of in vivo dissolved-phase imaging and spectroscopy the T1 of xenon in blood will need to be measured. Both O2 and Xe concentrations in solution are found to greatly affect  dissolved-phase 129 Xe T1 values and may explain, along with RF miscalibration, the large discrepancy in previously reported results.

Hyperpolarized 129 Xe imaging of the brain: Achievements and future challenges.

Hyperpolarized (HP) xenon-129 (129 Xe) brain MRI is a promising imaging modality currently under extensive development. HP 129 Xe is nontoxic, capable of dissolving in pulmonary blood, and is extremely sensitive to the local environment. After dissolution in the pulmonary blood, HP 129 Xe travels with the blood flow to the brain and can be used for functional imaging such as perfusion imaging, hemodynamic response detection, and blood-brain barrier permeability assessment. HP 129 Xe MRI imaging of the brain has been performed in animals, healthy human subjects, and in patients with Alzheimer's disease and stroke. In this review, the overall progress in the field of HP 129 Xe brain imaging is discussed, along with various imaging approaches and pulse sequences used to optimize HP 129 Xe brain MRI. In addition, current challenges and limitations of HP 129 Xe brain imaging are discussed, as well as possible methods for their mitigation. Finally, potential pathways for further development are also discussed. HP 129 Xe MRI of the brain has the potential to become a valuable novel perfusion imaging technique and has the potential to be used in the clinical setting in the future.

A pilot study of function-based radiation therapy planning for lung cancer using hyperpolarized xenon-129 ventilation MRI.

PURPOSE: Radiation-induced lung injury (RILI) is a common side effect in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy. Minimizing irradiation into highly functional areas of the lung may reduce the occurrence of RILI. The aim of this study is to evaluate the feasibility and utility of hyperpolarized xenon-129 magnetic resonance imaging (MRI), an imaging tool for evaluation of the pulmonary function, to guide radiotherapy planning. METHODS: Ten locally advanced NSCLC patients were recruited. Each patient underwent a simulation computed tomography (CT) scan and hyperpolarized xenon-129 MRI, then received 64 Gyin 32 fractions for radiotherapy. Clinical contours were drawn on CT. Lung regions with good ventilation were contoured based on the MRI. Two intensity-modulated radiation therapy plans were made for each patient: an anatomic plan (Plan-A) based on CT alone and a function-based plan (Plan-F) based on CT and MRI results. Compared to Plan-A, Plan-F was generated with two additional steps: (1) beam angles were carefully chosen to minimize direct radiation entering well-ventilated areas, and (2) additional optimization criteria were applied to well-ventilated areas to minimize dose exposure. V20Gy , V10Gy , V5Gy , and the mean dose in the lung were compared between the two plans. RESULTS: Plan-A and Plan-F were both clinically acceptable and met similar target coverage and organ-at-risk constraints (p > 0.05) except for the ventilated lungs. Compared with Plan-A, V5Gy (Plan-A: 30.7 ± 11.0%, Plan-F: 27.2 ± 9.3%), V10Gy (Plan-A: 22.0 ± 8.6%, Plan-F: 19.3 ± 7.0%), and V20Gy (Plan-A: 12.5 ± 5.6%, Plan-F: 11.0 ± 4.1%) for well-ventilated lung areas were significantly reduced in Plan-F (p < 0.05). CONCLUSION: In this pilot study, function-based radiotherapy planning using hyperpolarized xenon-129 MRI is demonstrated to be feasible in 10 patients with NSCLC with the potential to reduce radiation exposure in well-ventilated areas of the lung defined by hyperpolarized xenon-129 MRI.

Evaluation of Regional Lung Function in Pulmonary Fibrosis with Xenon-129 MRI.

Idiopathic pulmonary fibrosis, a pattern of interstitial lung disease, is often clinically unpredictable in its progression. This paper presents hyperpolarized Xenon-129 chemical shift imaging as a noninvasive, nonradioactive method of probing lung physiology as well as anatomy to monitor subtle changes in subjects with IPF. Twenty subjects, nine healthy and eleven IPF, underwent HP Xe-129 ventilation MRI and 3D-SBCSI. Spirometry was performed on all subjects before imaging, and DLCO and hematocrit were measured in IPF subjects after imaging. Images were post-processed in MATLAB and segmented using ANTs. IPF subjects exhibited, on average, higher Tissue/Gas ratios and lower RBC/Gas ratios compared with healthy subjects, and quantitative maps were more heterogeneous in IPF subjects. The higher ratios are likely due to fibrosis and thickening of the pulmonary interstitium. T2* relaxation was longer in IPF subjects and corresponded with hematocrit scores, although the mechanism is not well understood. A lower chemical shift in the red blood cell spectroscopic peak correlated well with a higher Tissue/RBC ratio and may be explained by reduced blood oxygenation. Tissue/RBC also correlated well, spatially, with areas of fibrosis in HRCT images. These results may help us understand the underlying mechanism behind gas exchange impairment and disease progression.

The effects of an initial depolarization pulse on dissolved phase hyperpolarized 129 Xe brain MRI.

PURPOSE: To evaluate the effect of an initial 90° depolarization RF pulse on the dissolved-phase hyperpolarized (HP) xenon-129 (129 Xe) brain imaging and to compare the SNR variability of HP 129 Xe images acquired without an initial depolarization RF pulse to those following the initial depolarization pulse. METHODS: Five cognitive normal healthy volunteers were imaged using a Philips Achieva 3.0T MRI scanner during a single breath-hold following inhalation of 1 L of HP 129 Xe. Each participant underwent six HP 129 Xe scans. Three scans were performed using conventional single-slice projection HP 129 Xe brain imaging, and the other three scans were performed using the HP 129 Xe time-of-flight imaging with an initial rectangular depolarization pulse. RESULTS: Although the utilization of an initial depolarization results in the reduction of the mean image SNR, the presence of an initial depolarization RF pulse reduces the SNR variability of the HP 129 Xe brain image by a factor of 2.26. The highest SNR variability was observed from the posterior brain region, where the anterior region possessed the lower level of signal variability. CONCLUSION: An initial 90° depolarization RF pulse, applied prior to the HP 129 Xe image acquisition, reduced the HP 129 Xe signal variability more than two times between the different breath-hold images.

An asymmetrical whole-body birdcage RF coil without RF shield for hyperpolarized 129 Xe lung MR imaging at 1.5 T.

PURPOSE: This study describes the development and testing of an asymmetrical xenon-129 (129 Xe) birdcage radiofrequency (RF) coil for 129 Xe lung ventilation imaging at 1.5 Tesla, which allows proton (1 H) system body coil transmit-receive functionality. METHODS: The 129 Xe RF coil is a whole-body asymmetrical elliptical birdcage constructed without an outer RF shield to enable 1 H imaging. B1+ field homogeneity and flip angle mapping of the 129 Xe birdcage RF coil and 1 H system body RF coil with the 129 Xe RF coil in situ were evaluated in the MR scanner. The functionality of the 129 Xe birdcage RF coil was demonstrated through hyperpolarized 129 Xe lung ventilation imaging with the birdcage in both transceiver configuration and transmit-only configuration when combined with an 8-channel 129 Xe receive-only RF coil array. The functionality of 1 H system body coil with the 129 Xe RF coil in situ was demonstrated by acquiring coregistered 1 H lung anatomical MR images. RESULTS: The asymmetrical birdcage produced a homogeneous B1+ field (±10%) in agreement with electromagnetic simulations. Simulations indicated an optimal detuning configuration with 4 diodes. The obtained g-factor of 1.4 for acceleration factor of R = 2 indicates optimal array configuration. Coregistered 1 H anatomical images from the system body coil along with 129 Xe lung images demonstrated concurrent and compatible arrangement of the RF coils. CONCLUSION: A large asymmetrical birdcage for homogenous B1+ transmission with high sensitivity reception for 129 Xe lung MRI at 1.5 Tesla has been demonstrated. The unshielded asymmetrical birdcage design enables 1 H structural lung MR imaging in the same exam.

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.

129Xe MRI as a measure of clinical disease severity for pediatric asthma.

BACKGROUND: Measurement of regional lung ventilation with hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI) in pediatric asthma is poised to advance our understanding of disease mechanisms and pathophysiology in a disorder with diverse clinical phenotypes. 129Xe MRI has not been investigated in a pediatric asthma cohort. OBJECTIVE: We hypothesized that 129Xe MRI is feasible and can demonstrate ventilation defects that relate to and predict clinical severity in a pediatric asthma cohort. METHODS: Thirty-seven children (13 with severe asthma, 8 with mild/moderate asthma, 16 age-matched healthy controls) aged 6 to 17 years old were imaged with 129Xe MRI. Ventilation defect percentage (VDP) and image reader score were calculated and compared with clinical measures at baseline and at follow-up. RESULTS: Children with asthma had higher VDP (P = .002) and number of defects per image slice (defects/slice) (P = .0001) than children without asthma. Children with clinically severe asthma had significantly higher VDP and number of defects/slice than healthy controls. Children with asthma who had a higher number of defects/slice had a higher rate of health care utilization (r = 0.48; P = .03) and oral corticosteroid use (r = 0.43; P = .05) at baseline. Receiver-operating characteristic analysis demonstrated that the VDP and number of defects/slice were predictive of increased health care utilization, asthma, and severe asthma. VDP correlated with FEV1 (r = -0.35; P = .04) and FEV1/forced vital capacity ratio (r = -0.41; P = .01). CONCLUSIONS: 129Xe MRI correlates with asthma severity, health care utilization, and oral corticosteroid use. Because delineation of clinical severity is often difficult in children, 129Xe MRI may be an important biomarker for severity, with potential to identify children at higher risk for exacerbations and improve outcomes.

Measuring pulmonary gas exchange using compartment-selective xenon-polarization transfer contrast (XTC) MRI.

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.