Hyperpolarized Gas MRI Research Articles

Current state of the art MRI for the longitudinal assessment of cystic fibrosis.

Pulmonary MRI can now provide high-resolution images that are sensitive to early disease and specific to inflammation in cystic fibrosis (CF) lung disease. With specificity and function limited via computed tomography (CT), there are significant advantages to MRI. Many of the modern MRI techniques can be performed throughout life, and can be employed to understand changes over time, in addition to quantification of treatment response. Proton density and T1 /T2 contrast images can be obtained within a single breath-hold, providing depiction of structural abnormalities and active inflammation. Modern radial and/or spiral ultrashort echo-time (UTE) techniques rival CT in resolution for depiction and quantification of structure, for both airway and parenchymal abnormalities. Contrast perfusion MRI techniques are now utilized routinely to visualize changes in pulmonary and bronchial circulation that routinely occur in CF lung disease, and noncontrast techniques are moving closer to clinical translation. Functional information can be obtained from noncontrast proton images alone, using techniques such as Fourier decomposition. Hyperpolarized-gas MRI, increasingly using 129 Xe, is now becoming more widespread and has been demonstrated to have high sensitivity to early airway obstruction in CF via ventilation MRI. The sensitivity of 129 Xe MRI promises future use in personalized medicine, management of early CF lung disease, and in future clinical trials. By combining structural and functional techniques, with or without hyperpolarized gases, regional structure-function relationships can be obtained, giving insight into the pathophysiology of disease and improved clinical management. This article reviews the modern MRI techniques that can routinely be employed for CF lung disease in nearly any large medical center. Level of Evidence: 4 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019.

$k$ -Space-Based Enhancement of Pulmonary Hyperpolarized 129Xe Ventilation Images

Hyperpolarized (HP) noble gas (e.g., 3He/129Xe) MR images are susceptible to noise and artifacts due to the rapid attenuation of nonrenewable HP magnetization along with the scan time. However, a little attention is paid to this issue through postprocessing techniques. Here, a $k$ -space-based analysis method is proposed to improve the overall signal-to-noise ratio (SNR) and lessen the blurring of pulmonary HP 129Xe ventilation images. This method performs $k$ -space weighting using low-frequency boost and a high-frequency modulation which offsets the magnetization loss per excitation, and then integrates two outputs in image domain through a convex combination model. Furthermore, a nonreference quality metric, called second-derivative measure of improvement by entropy (SMIE), is introduced to assess the image quality of HP gas MRI. The simulation results demonstrate that the enhanced images are statistically significantly different to the original ones regarding the SNR, peak SNR, structural similarity, and SMIE (each $P$ -value is less than 0.0001). In vivo results indicate that the proposed method significantly upsets the SNR and SMIE in human pulmonary HP 129Xe ventilation images (all $P$ -values are less than 0.05), while maintaining the appearance of ventilation defects or fine structures. In this case, the proposed scheme has potential for improving the understandability and/or differentiation of regions of interest in the lung.

Hyperpolarized 129xe Gas MRI Pulmonary Ventilation Imaging-Based Functional Avoidance for Lung Cancer Radiotherapy

For patients undergoing lung cancer radiotherapy, functional lung imaging can be incorporated into treatment planning to achieve differential sparing between the viable and defective non-target lung regions. Hyperpolarized 129Xe gas MRI is a powerful tool for evaluating the pulmonary function due to the extremely high enhancement in spin polarization using spin-exchange optical pumping. As the first implementation of hyperpolarized 129Xe gas MRI pulmonary ventilation imaging-guided functional treatment planning in China, this study aimed to quantify its dosimetric impact on sparing the high-functional lung regions. Ten locally advanced lung cancer patients with a median PTV volume of 233.2 cm3 (range: 119.2-667.9 cm3) were included in this study. Before radiotherapy, each patient underwent an MRI scan with 1 liter (L) xenon-inhalation and a simulation CT scan with 1L air-ventilation. The CT and MRI was then registered in a commercially available deformable registration algorithm where the GTV, CTV, and regular OARs were contoured on the CT and the high-functional lungs contoured on the MRI. Two IMRT plans (64Gy/35fractions) were designed for each patient: an anatomic plan (Plan-A) using the simulation CT alone and a functional plan (Plan-F) using the hyperpolarized 129Xe gas MRI in addition. The two plans were created using a treatment planning system with the same dose optimization objectives except that the lung dose objectives in Plan-A were placed on the high-functional lung instead in Plan-F. These lung dose goals focused on V20Gy, V5Gy and the mean dose. Finally, the dose-volume histograms were compared between the two plans for the PTV and OARs using the Wilcoxon signed-rank test. All plans were judged as clinically acceptable. Plan-A and Plan-F showed similar PTV dose homogeneity index and conformity index. Similarly, the doses to all OARs except the high-functional lungs showed no statistical difference. Compared with Plan-A, the V5Gy, V10Gy, V15Gy, V20Gy, V25Gy, V30Gy, and Dmean of high-functional lungs were significantly reduced in Plan-F (P＜0.05 for all indices), from 34.0±13.5%, 24.2±10.8%, 16.7±7.6%, 12.8±6.2%, 9.5±4.8%, 6.4±3.8%, and 7.4±3.0Gy in Plan-A, to 31.8±12.3%, 21.7±8.6%, 14.9±6.2%, 11.1±4.8%, 8.2±4.0%, 5.7±3.4%, and 6.9±2.6Gy in Plan-F, respectively. The sparing is more significant when the high-functional lung is adjacent to the PTV, with the above indices reduced from 46.8%, 39.2%, 32.2%, 26.5%, 19.7%, 15.2%, and 13.6Gy in Plan-A, to 41.8%, 33.4%, 24.8%, 19.4%, 14.2%, 11.8%, and 10.2Gy in Plan-F, for one patient. An emerging technology, hyperpolarized 129Xe gas MRI has been translated into the clinic and used in functional image-guided radiotherapy in China for the first time. Our findings indicate the potential of functional planning in lung functional avoidance for IMRT, particularly for patients who have high-functional lung adjacent to the PTV.

Normalisation of MRI ventilation heterogeneity in severe asthma by dupilumab

Ventilation heterogeneity in asthma could be due to many reasons. Luminal obstruction due to inflammatory cells or mucus, smooth muscle constriction and airway wall thickness could all contribute individually or...

Measuring lung function in airways diseases: current and emerging techniques

Chronic airways diseases, including asthma, COPD and cystic fibrosis, cause significant morbidity and mortality and are associated with high healthcare expenditure, in the UK and worldwide. For patients with these...

Comparison of CT ventilation imaging and hyperpolarised gas MRI: effects of breathing manoeuvre

Image registration of lung CT images acquired at different inflation levels has been proposed as a surrogate method to map lung ‘ventilation’. Prior to clinical use, it is important to understand how this technique compares with direct ventilation imaging modalities such as hyperpolarised gas MRI. However, variations in lung inflation level have been shown to affect regional ventilation distributions. Therefore, the aim of this study was to evaluate the impact of lung inflation levels when comparing CT ventilation imaging to ventilation from 3He-MRI.Seven asthma patients underwent breath-hold CT at total lung capacity (TLC) and functional residual capacity (FRC). 3He-MRI and a same-breath 1H-MRI were acquired at FRC+1L and TLC. Percentage ventilated volumes (%VVs) were calculated for FRC+1L and TLC 3He-MRI. TLC-CT and registered FRC-CT were used to compute a surrogate ventilation map from voxel-wise intensity differences in Hounsfield unit values, which was thresholded at the 10th and 20th percentiles. For direct comparison of CT and 3He-MRI ventilation, FRC+1L and TLC 3He-MRI were registered to TLC-CT indirectly via the corresponding same-breath 1H-MRI data. For 3He-MRI and CT ventilation comparison, Dice similarity coefficients (DSCs) between the binary segmentations were computed.The median (range) of %VVs for FRC+1L and TLC 3He-MRI were 90.5 (54.9–93.6) and 91.8 (67.8–96.2), respectively (p = 0.018). For MRI versus CT ventilation comparison, statistically significant improvements in DSCs were observed for TLC 3He MRI when compared with FRC+1L, with median (range) values of 0.93 (0.86–0.93) and 0.86 (0.68–0.92), respectively (p = 0.017), for the 10–100th percentile and 0.87 (0.83–0.88) and 0.81 (0.66–0.87), respectively (p = 0.027), for the 20–100th percentile.Correlation of CT ventilation imaging and hyperpolarised gas MRI is sensitive to lung inflation level. For ventilation maps derived from CT acquired at FRC and TLC, a higher correlation with gas ventilation MRI can be achieved if the MRI is acquired at TLC.

Advanced pulmonary MRI to quantify alveolar and acinar duct abnormalities: Current status and future clinical applications.

There are serious clinical gaps in our understanding of chronic lung disease that require novel, sensitive, and noninvasive in vivo measurements of the lung parenchyma to measure disease pathogenesis and progressive changes over time as well as response to treatment. Until recently, our knowledge and appreciation of the tissue changes that accompany lung disease has depended on ex vivo biopsy and concomitant histological and stereological measurements. These measurements have revealed the underlying pathologies that drive lung disease and have provided important observations about airway occlusion, obliteration of the terminal bronchioles and airspace enlargement, or fibrosis and their roles in disease initiation and progression. ex vivo tissue stereology and histology are the established gold standards and, more recently, micro-computed tomography (CT) measurements of ex vivo tissue samples has also been employed to reveal new mechanistic findings about the progression of obstructive lung disease in patients. While these approaches have provided important understandings using ex vivo analysis of excised samples, recently developed hyperpolarized noble gas MRI methods provide an opportunity to noninvasively measure acinar duct and terminal airway dimensions and geometry in vivo, and, without radiation burden. Therefore, in this review we summarize emerging pulmonary MRI morphometry methods that provide noninvasive in vivo measurements of the lung in patients with bronchopulmonary dysplasia and chronic obstructive pulmonary disease, among others. We discuss new findings, future research directions, as well as clinical opportunities to address current gaps in patient care and for testing of new therapies. Level of Evidence: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;50:28-40.

Rapid single-breath hyperpolarized noble gas MRI-based biomarkers of airspace enlargement.

Multi-b diffusion-weighted hyperpolarized-gas MRI measures pulmonary airspace-enlargement using apparent diffusion coefficients (ADCs) and mean-linear-intercepts (Lm ). To develop single-breath 3D multi-b diffusion-weighted 3 He and 129 Xe MRI using k-space undersampling. Rapid, cost-efficient, single-breath acquisitions may facilitate clinical translation. Prospective. We evaluated 12 participants, including nine subjects (mean age = 69 ± 9) who were included in the retrospective experiment and three chronic pulmonary obstruction disease (COPD) patients (mean age = 81 ± 6) who participated in the prospective study. A whole-body 3 T 2D/3D fast gradient recall echo (FGRE) sequence. Hyperpolarized 3 He/129 Xe MRI, spirometry, plethysmography computed tomography (CT). We evaluated 129 Xe ADC/morphometry estimates by retrospectively undersampling previously acquired fully sampled multibreath, multi-b diffusion-weighted data. Next, we prospectively evaluated the feasibility of accelerated (AF = 7) 3 He MRI static-ventilation/T2 * (extra short-TE, b = 0 image) and ADC/morphometry (five b-values) maps using a single gas-dose and 16-second breath-hold. To conservatively evaluate cost-improvement, we compared total costs of single vs. multiple 129 Xe doses. Multivariate analysis of variance, independent t-tests and voxel-by-voxel basis difference test. For the retrospectively undersampled 129 Xe data, a nonsignificant mean difference for ADC/Lm of 14%/12%, 12%/8%, and 11%/9% was observed (all, P > 0.4) between the fully sampled and accelerated data for the never-smoker, COPD, and alpha-1 antitrypsin deficiency (AATD) groups, respectively. The control never-smoker group had significantly lower ADC (P < 0.001) and Lm (P < 0.001) than the COPD/AATD group for both fully sampled and accelerated data. For the prospectively acquired 3 He MRI data, static-ventilation, T2 *, ADC, and morphometry maps were acquired using a single 16-second breath-hold scan and single gas dose. Accelerated imaging resulted in cost savings of ~$US 1000/patient, a conservative estimate based on 129 Xe MRI dose savings (single vs. five doses). This is a proof-of-concept demonstration of accelerated (7×) morphometry that shows that less cost- and time-efficient multibreath methods that lead to variability and patient fatigue may be avoided in the future. 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.

19 F MRI of the Lungs Using Inert Fluorinated Gases: Challenges and New Developments.

Fluorine-19 (19 F) MRI using inhaled inert fluorinated gases is an emerging technique that can provide functional images of the lungs. Inert fluorinated gases are nontoxic, abundant, relatively inexpensive, and the technique can be performed on any MRI scanner with broadband multinuclear imaging capabilities. Pulmonary 19 F MRI has been performed in animals, healthy human volunteers, and in patients with lung disease. In this review, the technical requirements of 19 F MRI are discussed, along with various imaging approaches used to optimize the image quality. Lung imaging is typically performed in humans using a gas mixture containing 79% perfluoropropane (PFP) or sulphur hexafluoride (SF6 ) and 21% oxygen. In lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), ventilation defects are apparent in regions that the inhaled gas cannot access. 19 F lung images are typically acquired in a single breath-hold, or in a time-resolved, multiple breath fashion. The former provides measurements of the ventilation defect percent (VDP), while the latter provides measurements of gas replacement (ie, fractional ventilation). Finally, preliminary comparisons with other functional lung imaging techniques are discussed, such as Fourier decomposition MRI and hyperpolarized gas MRI. Overall, functional 19 F lung MRI is expected to complement existing proton-based structural imaging techniques, and the combination of structural and functional lung MRI will provide useful outcome measures in the future management of pulmonary diseases in the clinic. Level of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:343-354.

Hyperpolarized gas MRI in pulmonology.

Lung diseases have a high prevalence amongst the world population and their early diagnosis has been pointed out to be key for successful treatment. However, there is still a lack of non-invasive examination methods with sensitivity to early, local deterioration of lung function. Proton-based lung MRI is particularly challenging due to short T2* times and low proton density within the lung tissue. Hyperpolarized gas MRI is aan emerging technology providing a richness of methodologies which overcome the aforementioned problems. Unlike proton-based MRI, lung MRI of hyperpolarized gases may rely on imaging of spins in the lung's gas spaces or inside the lung tissue and thereby add substantial value and diagnostic potential to lung MRI. This review article gives an introduction to the MR physics of hyperpolarized media and presents the current state of hyperpolarized gas MRI of 3Headvasd and 129Xe in pulmonology. Key applications, ranging from static and dynamic ventilation imaging as well as oxygen-pressure mapping to 129Xe dissolved-phase imaging and spectroscopy are presented. Hyperpolarized gas MRI is compared to alternative examination methods based on MRI and future directions of hyperpolarized gas MRI are discussed.

High spatial resolution hyperpolarized 3 He MRI of the rodent lung using a single breath X-centric gradient-recalled echo approach.

Hyperpolarized (HP) gas MRI of the rodent lung is of great interest because of the increasing need for novel biomarkers with which to develop new therapies for respiratory diseases. The use of fast gradient-recalled echo (FGRE) for high-resolution HP gas rodent lung MRI is challenging as a result of signal loss caused by significant diffusion weighting, particularly in the larger airways. In this work, a modified FGRE approach is described for HP 3 He rodent lung MRI using a centric-out readout scheme (ie, x-centric), allowing high-resolution, density-weighted imaging. HP 3 He x-centric imaging was performed in a phantom and compared with a conventional partial-echo FGRE acquisition for in-plane spatial resolutions varying between 39 and 312 µm. Partial-echo and x-centric acquisitions were also compared for high spatial-resolution breath-hold (1 s) imaging of rodent lungs. X-centric provided improved signal-to-noise ratio efficiency by a factor of up to 13/1.7 and 6.7/1.8, compared with the partial-echo FGRE for the airways/parenchyma of mouse and rat, respectively, at high spatial resolutions in vivo (<78 µm). In particular, rodent major airways with less restricted diffusion of 3 He could only be visualized with the x-centric method. The x-centric method significantly reduces diffusion weighting, allowing high spatial and temporal resolution HP 3 He gas density-weighted rodent lung MRI. Magn Reson Med 78:2334-2341, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Whole lung morphometry with 3D multiple b-value hyperpolarized gas MRI and compressed sensing.

PurposeTo demonstrate three‐dimensional (3D) multiple b‐value diffusion‐weighted (DW) MRI of hyperpolarized 3He gas for whole lung morphometry with compressed sensing (CS).MethodsA fully‐sampled, two b‐value, 3D hyperpolarized 3He DW‐MRI dataset was acquired from the lungs of a healthy volunteer and retrospectively undersampled in the k y and k z phase‐encoding directions for CS simulations. Optimal k‐space undersampling patterns were determined by minimizing the mean absolute error between reconstructed and fully‐sampled 3He apparent diffusion coefficient (ADC) maps. Prospective three‐fold, undersampled, 3D multiple b‐value 3He DW‐MRI datasets were acquired from five healthy volunteers and one chronic obstructive pulmonary disease (COPD) patient, and the mean values of maps of ADC and mean alveolar dimension (Lm D) were validated against two‐dimensional (2D) and 3D fully‐sampled 3He DW‐MRI experiments.ResultsReconstructed undersampled datasets showed no visual artifacts and good preservation of the main image features and quantitative information. A good agreement between fully‐sampled and prospective undersampled datasets was found, with a mean difference of +3.4% and +5.1% observed in mean global ADC and Lm D values, respectively. These differences were within the standard deviation range and consistent with values reported from healthy and COPD lungs.ConclusionsAccelerated CS acquisition has facilitated 3D multiple b‐value 3He DW‐MRI scans in a single breath‐hold, enabling whole lung morphometry mapping. Magn Reson Med 77:1916–1925, 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.

WE‐AB‐202‐07: Ventilation CT: Voxel‐Level Comparison with Hyperpolarized Helium‐3 &amp; Xenon‐129 MRI

Purpose:To compare the spatial correlation of ventilation surrogates computed from inspiratory and expiratory breath‐hold CT with hyperpolarized Helium‐3 &amp; Xenon‐129 MRI in a cohort of lung cancer patients.Methods:5 patients underwent expiration &amp; inspiration breath‐hold CT. Xenon‐129 &amp; 1H MRI were also acquired at the same inflation state as inspiratory CT. This was followed immediately by acquisition of Helium‐3 &amp; 1H MRI in the same breath and at the same inflation state as inspiratory CT. Expiration CT was deformably registered to inspiration CT for calculation of ventilation CT from voxel‐wise differences in Hounsfield units. Inspiration CT and the Xenon‐129's corresponding anatomical 1H MRI were registered to Helium‐3 MRI via the same‐breath anatomical 1H MRI. This enabled direct comparison of CT ventilation with Helium‐3 MRI &amp; Xenon‐129 MRI for the median values in corresponding regions of interest, ranging from finer to coarser in‐plane dimensions of 10 by 10, 20 by 20, 30 by 30 and 40 by 40, located within the lungs as defined by the same‐breath 1H MRI lung mask. Spearman coefficients were used to assess voxel‐level correlation.Results:The median Spearman's coefficients of ventilation CT with Helium‐3 &amp; Xenon‐129 MRI for ROIs of 10 by 10, 20 by 20, 30 by 30 and 40 by 40 were 0.52, 0.56, 0.60 and 0.68 and 0.40, 0.42, 0.52 and 0.70, respectively.Conclusion:This work demonstrates a method of acquiring CT &amp; hyperpolarized gas MRI (Helium‐3 &amp; Xenon‐129 MRI) in similar breath‐holds to enable direct spatial comparison of ventilation maps. Initial results show moderate correlation between ventilation CT &amp; hyperpolarized gas MRI, improving for coarser regions which could be attributable to the inherent noise in CT intensity, non‐ventilatory effects and registration errors at the voxel‐level. Thus, it may be more beneficial to quantify ventilation at a more regional level.

Fast Determination of Flip Angle and T1 in Hyperpolarized Gas MRI During a Single Breath-Hold.

MRI of hyperpolarized media, such as 129Xe and 3He, shows great potential for clinical applications. The optimal use of the available spin polarization requires accurate flip angle calibrations and T1 measurements. Traditional flip angle calibration methods are time-consuming and suffer from polarization losses during T1 relaxation. In this paper, we propose a method to simultaneously calibrate flip angles and measure T1 in vivo during a breath-hold time of less than 4 seconds. We demonstrate the accuracy, robustness and repeatability of this method and contrast it with traditional methods. By measuring the T1 of hyperpolarized gas, the oxygen pressure in vivo can be calibrated during the same breath hold. The results of the calibration have been applied in variable flip angle (VFA) scheme to obtain a stable steady-state transverse magnetization. Coupled with this method, the ultra-short TE (UTE) and constant VFA (CVFA) schemes are expected to give rise to new applications of hyperpolarized media.

Diffusion lung imaging with hyperpolarized gas MRI.

Lung imaging using conventional 1 H MRI presents great challenges because of the low density of lung tissue, lung motion and very fast lung tissue transverse relaxation (typical T2 * is about 1-2 ms). MRI with hyperpolarized gases (3 He and 129 Xe) provides a valuable alternative because of the very strong signal originating from inhaled gas residing in the lung airspaces and relatively slow gas T2 * relaxation (typical T2 * is about 20-30 ms). However, in vivo human experiments should be performed very rapidly - usually during a single breath-hold. In this review, we describe the recent developments in diffusion lung MRI with hyperpolarized gases. We show that a combination of the results of modeling of gas diffusion in lung airspaces and diffusion measurements with variable diffusion-sensitizing gradients allows the extraction of quantitative information on the lung microstructure at the alveolar level. From an MRI scan of less than 15 s, this approach, called in vivo lung morphometry, allows the provision of quantitative values and spatial distributions of the same physiological parameters as measured by means of 'standard' invasive stereology (mean linear intercept, surface-to-volume ratio, density of alveoli, etc.). In addition, the approach makes it possible to evaluate some advanced Weibel parameters characterizing lung microstructure: average radii of alveolar sacs and ducts, as well as the depth of their alveolar sleeves. Such measurements, providing in vivo information on the integrity of pulmonary acinar airways and their changes in different diseases, are of great importance and interest to a broad range of physiologists and clinicians. We also discuss a new type of experiment based on the in vivo lung morphometry technique combined with quantitative computed tomography measurements, as well as with gradient echo MRI measurements of hyperpolarized gas transverse relaxation in the lung airspaces. Such experiments provide additional information on the blood vessel volume fraction, specific gas volume and length of the acinar airways, and allow the evaluation of lung parenchymal and non-parenchymal tissue. Copyright © 2015 John Wiley & Sons, Ltd.

Mild loss of lung aeration augments stretch in healthy lung regions.

Inspiratory stretch by mechanical ventilation worsens lung injury. However, it is not clear whether and how the ventilator damages lungs in the absence of preexisting injury. We hypothesized that subtle loss of lung aeration during general anesthesia regionally augments ventilation and distension of ventilated air spaces. In eight supine anesthetized and intubated rats, hyperpolarized gas MRI was performed after a recruitment maneuver following 1 h of volume-controlled ventilation with zero positive end-expiratory pressure (ZEEP), FiO2 0.5, and tidal volume 10 ml/kg, and after a second recruitment maneuver. Regional fractional ventilation (FV), apparent diffusion coefficient (ADC) of (3)He (a measurement of ventilated peripheral air space dimensions), and gas volume were measured in lung quadrants of ventral and dorsal regions of the lungs. In six additional rats, computed tomography (CT) images were obtained at each time point. Ventilation with ZEEP decreased total lung gas volume and increased both FV and ADC in all studied regions. Increases in FV were more evident in the dorsal slices. In each lung quadrant, higher ADC was predicted by lower gas volume and by increased mean values (and heterogeneity) of FV distribution. CT scans documented 10% loss of whole-lung aeration and increased density in the dorsal lung, but no macroscopic atelectasis. Loss of pulmonary gas at ZEEP increased fractional ventilation and inspiratory dimensions of ventilated peripheral air spaces. Such regional changes could help explain a propensity for mechanical ventilation to contribute to lung injury in previously uninjured lungs.

Optimizing 3D noncartesian gridding reconstruction for hyperpolarized 129Xe MRI—focus on preclinical applications

The goal of this work is to characterize and optimize gridding reconstruction of 3D radial hyperpolarized (HP) 129Xe MRI. In support of this objective, we developed a flexible, open source reconstruction software package in MATLAB to optimally reconstruct radially acquired, undersampled HP 129Xe MRI. Using this framework, we demonstrate the effects of 5 key reconstruction parameters: overgridding, gridding kernel function, kernel sharpness, kernel extent, and the density compensation algorithm. We further demonstrate how each parameter can be tuned to optimize a high‐resolution 3D radially acquired HP 129Xe image of a ventilated mouse. Specifically, wrap‐around artifact, caused by non‐selective RF excitation of signal in the trachea, was eliminated by overgridding onto a finely spaced k‐space grid; high‐frequency aliasing was reduced using iterative density compensation; image SNR and sharpness were optimized by tuning kernel sharpness; and computational burden was minimized by defining an appropriate kernel extent. Compared to our previous reconstruction methods, this optimized method extended visualization from the 5th to 6th generation of mouse airway, while maintaining comparable SNR. Although optimized here for preclinical mouse MRI, this work suggests that 3D radial acquisition offers many broader advantages to undersampled HP gas MRI. Using the methods presented here, we maintained image quality across datasets acquired with various degrees of undersampling and differing SNR by adjusting only a single parameter. These methods are now available to optimize radially acquired hyperpolarized gas images in both the clinical and preclinical arena. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part A 44A: 190–202, 2015.

Detection of brown adipose tissue and thermogenic activity in mice by hyperpolarized xenon MRI

The study of brown adipose tissue (BAT) in human weight regulation has been constrained by the lack of a noninvasive tool for measuring this tissue and its function in vivo. Existing imaging modalities are nonspecific and intrinsically insensitive to the less active, lipid-rich BAT of obese subjects, the target population for BAT studies. We demonstrate noninvasive imaging of BAT in mice by hyperpolarized xenon gas MRI. We detect a greater than 15-fold increase in xenon uptake by BAT during stimulation of BAT thermogenesis, which enables us to acquire background-free maps of the tissue in both lean and obese mouse phenotypes. We also demonstrate in vivo MR thermometry of BAT by hyperpolarized xenon gas. Finally, we use the linear temperature dependence of the chemical shift of xenon dissolved in adipose tissue to directly measure BAT temperature and to track thermogenic activity in vivo.

Long-lived spin States for low-field hyperpolarized gas MRI.

Parahydrogen induced polarization was employed to prepare a relatively long-lived correlated nuclear spin state between methylene and methyl protons in propane gas. Conventionally, such states are converted into a strong NMR signal enhancement by transferring the reaction product to a high magnetic field in an adiabatic longitudinal transport after dissociation engenders net alignment (ALTADENA) experiment. However, the relaxation time T1 of ∼0.6 s of the resulting hyperpolarized propane is too short for potential biomedical applications. The presented alternative approach employs low-field MRI to preserve the initial correlated state with a much longer decay time TLLSS =(4.7±0.5) s. While the direct detection at low-magnetic fields (e.g. 0.0475 T) is challenging, we demonstrate here that spin-lock induced crossing (SLIC) at this low magnetic field transforms the long-lived correlated state into an observable nuclear magnetization suitable for MRI with sub-millimeter and sub-second spatial and temporal resolution, respectively. Propane is a non-toxic gas, and therefore, these results potentially enable low-cost high-resolution high-speed MRI of gases for functional imaging of lungs and other applications.

Lung ventilation volumetry with same-breath acquisition of hyperpolarized gas and proton MRI.

The purpose of this work was to assess the reproducibility of percentage of ventilated lung volume (PV) measured from hyperpolarized (HP) (3)He and (1)H anatomical images acquired in the same breath-hold when compared with PV measured from (3)He and (1)H images from separate breath-holds. Volumetric (3)He ventilation and (1)H anatomical images of the same resolution were acquired during the same breath-hold. To assess reproducibility, this procedure was performed twice with a short gap between acquisitions. In addition, (1)H images were also acquired in a separate breath for comparison. PV ((3)He ventilated volume divided by (1)H total lung volume) was calculated using the single-breath-hold images (PV(single)) and the separate-breath-hold images (PV(separate)). Short-term reproducibility of PV measurement was assessed for both single- and separate-breath acquisitions. Dice similarity coefficients (DSCs) were calculated to quantify spatial overlap between (3)He and (1)H segmentations for the single- and separate-breath-hold acquisitions. The efficacy of using the separate-breath method combined with image registration was also assessed. The mean magnitude difference between the two sets of PV values (±standard deviation) was 1.49 ± 1.32% for PV(single) and 4.19 ± 4.10% for PV(separate), with a significant difference (p < 0.01). The mean magnitude difference between the two PV values for the registered separate-breath technique (PV(sep-registered)) was 2.27 ± 2.23%. Bland-Altman analysis showed that PV measured with single-breath acquisitions was more repeatable than PV measured with separate-breath acquisitions, regardless of image registration. DSC values were significantly greater (p < 0.01) for single-breath acquisition than for separate-breath acquisition. Acquisition of HP gas ventilation and (1)H anatomical images in a single breath-hold provides a more reproducible means of percentage lung ventilation volume measurement than the previously used separate-breath-hold scan approach, and reduces errors.