A decay-modeled compressed sensing reconstruction approach for non-Cartesian hyperpolarized 129Xe MRI.

PURPOSE: Hyperpolarized 129Xe MRI benefits from non-Cartesian acquisitions that sample k-space efficiently and rapidly. However, their reconstructions are complex and burdened by decay processes unique to hyperpolarized gas. Currently used gridded reconstructions are prone to artifacts caused by magnetization decay and are ill-suited for undersampling. We present a compressed sensing (CS) reconstruction approach that incorporates magnetization decay in the forward model, thereby producing images with increased sharpness and contrast, even in undersampled data. METHODS: Radio-frequency, T1, and T 2 * $$ {\mathrm{T}}_2^{\ast } $$ decay processes were incorporated into the forward model and solved using iterative methods including CS. The decay-modeled reconstruction was validated in simulations and then tested in 2D/3D-spiral ventilation and 3D-radial gas-exchange MRI. Quantitative metrics including apparent-SNR and sharpness were compared between gridded, CS, and twofold undersampled CS reconstructions. Observations were validated in gas-exchange data collected from 15 healthy and 25 post-hematopoietic-stem-cell-transplant participants. RESULTS: CS reconstructions in simulations yielded images with threefold increases in accuracy. CS increased sharpness and contrast for ventilation in vivo imaging and showed greater accuracy for undersampled acquisitions. CS improved gas-exchange imaging, particularly in the dissolved-phase where apparent-SNR improved, and structure was made discernable. Finally, CS showed repeatability in important global gas-exchange metrics including median dissolved-gas signal ratio and median angle between real/imaginary components. CONCLUSION: A non-Cartesian CS reconstruction approach that incorporates hyperpolarized 129Xe decay processes is presented. This approach enables improved image sharpness, contrast, and overall image quality in addition to up-to threefold undersampling. This contribution benefits all hyperpolarized gas MRI through improved accuracy and decreased scan durations.

Finite element simulations of hyperpolarized gas DWI in micro-CT meshes of acinar airways: validating the cylinder and stretched exponential models of lung microstructural length scales.

PURPOSE: This work assesses the accuracy of the stretched exponential (SEM) and cylinder models of lung microstructural length scales that can be derived from hyperpolarized gas DWI. This was achieved by simulating 3 He and 129 Xe DWI signals within two micro-CT-derived realistic acinar airspace meshes that represent healthy and idiopathic pulmonary fibrosis lungs. METHODS: The healthy and idiopathic pulmonary fibrosis acinar airway meshes were derived from segmentations of 3D micro-CT images of excised human lungs and meshed for finite element simulations of the Bloch-Torrey equations. 3 He and 129 Xe multiple b value DWI experiments across a range of diffusion times (3 He Δ = 1.6 ms; 129 Xe Δ = 5 to 20 ms) were simulated in each mesh. Global SEM mean diffusive length scale and cylinder model mean chord length value was derived from each finite element simulation and compared against each mesh's mean linear intercept length, calculated from intercept length measurements within micro-CT segmentation masks. RESULTS: The SEM-derived mean diffusive length scale was within ±10% of the mean linear intercept length for simulations with both 3 He (Δ = 1.6 ms) and 129 Xe (Δ = 7 to 13 ms) in the healthy mesh, and with 129 Xe (Δ = 13 to 20 ms) for the idiopathic pulmonary fibrosis mesh, whereas for the cylinder model-derived mean chord length the closest agreement with mean linear intercept length (11.7% and 22.6% difference) was at 129 Xe Δ = 20 ms for both healthy and IPF meshes, respectively. CONCLUSION: This work validates the use of the SEM for accurate estimation of acinar dimensions and indicates that the SEM is relatively robust across a range of experimental conditions and acinar length scales.

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

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

Regional Ventilation Changes in the Lung: Treatment Response Mapping by Using Hyperpolarized Gas MR Imaging as a Quantitative Biomarker.

Purpose To assess the magnitude of regional response to respiratory therapeutic agents in the lungs by using treatment response mapping (TRM) with hyperpolarized gas magnetic resonance (MR) imaging. TRM was used to quantify regional physiologic response in adults with asthma who underwent a bronchodilator challenge. Materials and Methods This study was approved by the national research ethics committee and was performed with informed consent. Imaging was performed in 20 adult patients with asthma by using hyperpolarized helium 3 (3He) ventilation MR imaging. Two sets of baseline images were acquired before inhalation of a bronchodilating agent (salbutamol 400 µg), and one set was acquired after. All images were registered for voxelwise comparison. Regional treatment response, ΔR(r), was calculated as the difference in regional gas distribution (R[r] = ratio of inhaled gas to total volume of a voxel when normalized for lung inflation volume) before and after intervention. A voxelwise activation threshold from the variability of the baseline images was applied to ΔR(r) maps. The summed global treatment response map (ΔRnet) was then used as a global lung index for comparison with metrics of bronchodilator response measured by using spirometry and the global imaging metric percentage ventilated volume (%VV). Results ΔRnet showed significant correlation (P < .01) with changes in forced expiratory volume in 1 second (r = 0.70), forced vital capacity (r = 0.84), and %VV (r = 0.56). A significant (P < .01) positive treatment effect was detected with all metrics; however, ΔRnet showed a lower intersubject coefficient of variation (64%) than all of the other tests (coefficient of variation, ≥99%). Conclusion TRM provides regional quantitative information on changes in inhaled gas ventilation in response to therapy. This method could be used as a sensitive regional outcome metric for novel respiratory interventions. © RSNA, 2017 Online supplemental material is available for this article.

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

PURPOSE: To demonstrate three-dimensional (3D) multiple b-value diffusion-weighted (DW) MRI of hyperpolarized 3 He gas for whole lung morphometry with compressed sensing (CS). METHODS: A fully-sampled, two b-value, 3D hyperpolarized 3 He DW-MRI dataset was acquired from the lungs of a healthy volunteer and retrospectively undersampled in the ky and kz phase-encoding directions for CS simulations. Optimal k-space undersampling patterns were determined by minimizing the mean absolute error between reconstructed and fully-sampled 3 He apparent diffusion coefficient (ADC) maps. Prospective three-fold, undersampled, 3D multiple b-value 3 He 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 (LmD ) were validated against two-dimensional (2D) and 3D fully-sampled 3 He DW-MRI experiments. RESULTS: Reconstructed 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 LmD values, respectively. These differences were within the standard deviation range and consistent with values reported from healthy and COPD lungs. CONCLUSIONS: Accelerated CS acquisition has facilitated 3D multiple b-value 3 He 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.

Comparison of CT-based Lobar Ventilation with 3He MR Imaging Ventilation Measurements.

PURPOSE: To compare lobar lung ventilation computed from expiratory and inspiratory computed tomographic (CT) data with direct measurements of ventilation at hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging by using same-breath hydrogen 1 ((1)H) MR imaging examinations to coregister the multimodality images. MATERIALS AND METHODS: The study was approved by the national research ethics committee, and written patient consent was obtained. Thirty patients with asthma underwent breath-hold CT at total lung capacity and functional residual capacity. (3)He and (1)H MR images were acquired during the same breath hold at a lung volume of functional residual capacity plus 1 L. Lobar segmentations delineated by major fissures on both CT scans were used to calculate the percentage of ventilation per lobe from the change in inspiratory and expiratory lobar volumes. CT-based ventilation was compared with (3)He MR imaging ventilation by using diffeomorphic image registration of (1)H MR imaging to CT, which enabled indirect registration of (3)He MR imaging to CT. Statistical analysis was performed by using the Wilcoxon signed-rank test, Pearson correlation coefficient, and Bland-Altman analysis. RESULTS: The mean ± standard deviation absolute difference between the CT and (3)He MR imaging percentage of ventilation volume in all lobes was 4.0% (right upper and right middle lobes, 5.4% ± 3.3; right lower lobe, 3.7% ± 3.9; left upper lobe, 2.8% ± 2.7; left lower lobe, 3.9% ± 2.6; Wilcoxon signed-rank test, P < .05). The Pearson correlation coefficient between the two techniques in all lobes was 0.65 (P < .001). Greater percentage of ventilation was seen in the upper lobes with (3)He MR imaging and in the lower lobes with CT. This was confirmed with Bland-Altman analysis, with 95% limits of agreement for right upper and middle lobes, -2.4, 12.7; right lower lobe, -11.7, 4.6; left upper lobe, -4.9, 8.7; and left lower lobe, -9.8, 2.8. CONCLUSION: The percentage of regional ventilation per lobe calculated at CT was comparable to a direct measurement of lung ventilation at hyperpolarized (3)He MR imaging. This work provides evidence for the validity of the CT model, and same-breath (1)H MR imaging enables regional interpretation of (3)He ventilation MR imaging on the underlying lung anatomy at thin-section CT.

Experimental validation of the hyperpolarized 129 Xe chemical shift saturation recovery technique in healthy volunteers and subjects with interstitial lung disease.

PURPOSE: To assess the sensitivity of the hyperpolarized 129 Xe chemical shift saturation recovery (CSSR) technique for noninvasive quantification of changes to lung microstructure and function in idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). METHODS: Ten healthy volunteers, four subjects with SSc and four with IPF were scanned at 1.5 T. A CSSR pulse sequence was implemented using binomial-composite radiofrequency pulses to monitor 129 Xe magnetization in tissues and blood plasma (T/P) and red blood cells (RBCs). The dynamics of 129 Xe uptake into these compartments were fitted with three existing analytical models of gas diffusion to extract parameters of lung physiology. These parameters were quantitatively compared between models. RESULTS: Uptake of xenon into the pulmonary capillaries was impaired in subjects with IPF and SSc. Statistically significant septal thickening was measured by 129 Xe CSSR in IPF patients. Preliminary data suggests age-dependent alterations to septal thickness in healthy volunteers. These findings were reproduced using each of the literature models. CSSR-derived parameters were compared with gold-standard indicators of pulmonary function; diffusing capacity of carbon monoxide and pulmonary transit-time. CONCLUSIONS: CSSR with hyperpolarized 129 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.

(3)He pO2 mapping is limited by delayed-ventilation and diffusion in chronic obstructive pulmonary disease.

PURPOSE: Lung pO2 mapping with (3)He MRI assumes that the sources of signal decay with time during a breath-hold are radiofrequency depolarization and oxygen-dependent T1 relaxation, but the method is sensitive to other sources of spatio-temporal signal change such as diffusion. The purpose of this work was to assess the use of (3)He pO2 mapping in patients with chronic obstructive pulmonary disease. METHODS: Ten patients with moderate to severe chronic obstructive pulmonary disease were scanned with a 3D single breath-hold pO2 mapping sequence. RESULTS: Images showed signal increasing over time in some lung regions due to delayed ventilation during breath-hold. Regions of physically unrealistic negative pO2 values were seen in all patients, and regional mean pO2 values of -0.3 bar were measured in the two patients most affected by delayed ventilation (where mean time to signal onset was 3-4 s). CONCLUSIONS: Movement of gas within the lungs during breath-hold causes regional changes in signal over time that are not related to oxygen concentration, leading to erroneous pO2 measurements using the linear oxygen-dependent signal decay model. These spatio-temporal sources of signal change cannot be reliably separated at present, making pO2 mapping using this methodology unreliable in chronic obstructive pulmonary disease patients with significant bullous emphysema or delayed ventilation.

Simultaneous imaging of lung structure and function with triple-nuclear hybrid MR imaging.

PURPOSE: To re-engineer a standard clinical magnetic resonance (MR) imaging system to enable the acquisition, in the same breath hold, of lung images from two hyperpolarized gases (helium 3 [(3)He] and xenon 129 [(129)Xe]) with simultaneous registered anatomic proton (hydrogen 1 [(1)H]) MR images of lung structure. MATERIALS AND METHODS: Studies with (3)He and (129)Xe were performed with National Research Ethics Committee approval, with informed consent from the volunteer. (1)H-(3)He-(129)Xe MR imaging was achieved in the same breath by using mutually decoupled nested radiofrequency coil hardware capable of transmit and receive on each respective nucleus without power cross talk. MR pulse sequences were also developed for rapid switching between each nucleus. The system is demonstrated with triple-nuclear lung images in a healthy individual following inhalation of a mixture of (3)He and (129)Xe gases. RESULTS: Spatially and temporally registered images of all three nuclei were obtained with high signal to noise ratio and high spatial resolution in the same breath. CONCLUSION: The multinuclear technique is capable of providing registered lung images with mutually complementary functional and structural spatial information.

Direct visualisation of collateral ventilation in COPD with hyperpolarised gas MRI.

BACKGROUND: Collateral ventilation has been proposed as a mechanism of compensation of respiratory function in obstructive lung diseases but observations of it in vivo are limited. The assessment of collateral ventilation with an imaging technique might help to gain insight into lung physiology and assist the planning of new bronchoscopic techniques for treating emphysema. OBJECTIVE: To obtain images of delayed ventilation that might be related to collateral ventilation over the period of a single breath-hold in patients with chronic obstructive pulmonary disease (COPD). METHODS: Time-resolved breath-hold hyperpolarised (3)He MRI was used to obtain images of the progressive influx of polarised gas into initially non-ventilated defects. RESULTS: A time-series of images showed that (3)He moves into lung regions which were initially non-ventilated. Ventilation defects with delayed filling were observed in 8 of the 10 patients scanned. CONCLUSIONS: A method for direct imaging of delayed ventilation within a single breath-hold has been demonstrated in patients with COPD. Images of what is believed to be collateral ventilation and slow filling of peripheral airspaces due to increased flow resistance are presented. The technique provides 3D whole-lung coverage with sensitivity to regional information, and is non-invasive and non-ionising.

Hyperpolarized 129Xe gas lung MRI-SNR and T2* comparisons at 1.5 T and 3 T.

In this study, the signal-to-noise ratio of hyperpolarized (129)Xe human lung magnetic resonance imaging was compared at 1.5 T and 3 T. Experiments were performed at both B(0) fields with quadrature double Helmholtz transmit-receive chest coils of the same geometry with the same subject loads. Differences in sensitivity between the two field strengths were assessed from the signal-to-noise ratio of multi-slice 2D (129)Xe ventilation lung images obtained at the two field strengths with a spatial resolution of 15 mm × 4 mm × 4 mm. There was a systematically higher signal-to-noise ratio observed at 3 T than at 1.5 T by a factor of 1.25. Mean image signal-to-noise ratio was in the range 27-44 at 1.5 T and 36-51 at 3 T. T 2* of (129)Xe gas in the partially inflated lungs was measured to be 25 ms and 18 ms at 1.5 T and 3 T, respectively. T 2* of (129)Xe gas in fully inflated lungs was measured to be 52 ms and 24 ms at 1.5 T and 3 T, respectively.

K-space filter deconvolution and flip angle self-calibration in 2D radial hyperpolarised 3He lung MRI.

In hyperpolarised (3)He lung MRI with constant flip angles, the transverse magnetisation decays with each RF excitation imposing a k-space filter on the acquired data. For radial data acquired in an angularly-sequential order, this filter causes streaking, angular shading and loss of spatial resolution in the images. The main aim of this work was to reduce the effects of the RF depletion k-space filter in radial acquisitions. Two approaches are presented; (i) retrospective deconvolution of the k-space filter for sequentially-acquired data and (ii) golden angle acquisition order. Radial trajectories sample the centre of k-space with every projection, thereby self-tracking signal decay. The inverse of the signal decay function was used to retrospectively deconvolve RF depolarisation k-space filter effects and the method was demonstrated in 2D radial imaging in phantoms and human lungs. A golden angle radial acquisition was shown to effectively suppress artefacts caused by the RF depletion k-space filter. In addition, the average flip angle per slice was calculated from the signal decay and the values were found to correspond with conventional flip angle maps, providing a means of flip angle self-calibration.

Combined measurement of pulmonary inert gas washout and regional ventilation heterogeneity by MR of a single dose of hyperpolarized 3He.

Washout of inert gases is a measure of pulmonary function well-known in lung physiology. This work presents a method combining inert gas washout and spatially resolved imaging using hyperpolarized (3) He, thus providing complementary information on lung function and physiology. The nuclear magnetic resonance signal of intrapulmonary hyperpolarized (3) He is used to track the total amount of gas present within the lungs during multiple-breath washout via tidal breathing. Before the washout phase, 3D ventilation images are acquired using (3) He magnetic resonance imaging from the same dose of inhaled gas. The measured washout signal is corrected for T(1) relaxation and radiofrequency depletion, converting it into a quantity proportional to the apparent amount of gas within the lungs. The use of a pneumotachograph for acquisition of breathing volumes during washout, together with lung volumes derived from the magnetic resonance imaging data, permits assessment of the washout curves against physiological model predictions for healthy lungs. The shape of the resulting washout curves obtained from healthy volunteers matches the predictions, demonstrating the utility of the technique for the quantitative assessment of lung function. The proposed method can be readily integrated with a standard breath-hold (3) He ventilation imaging sequence, thus providing additional information from a single dose of gas.

A flexible 32-channel receive array combined with a homogeneous transmit coil for human lung imaging with hyperpolarized 3He at 1.5 T.

Parallel imaging presents a promising approach for MRI of hyperpolarized nuclei, as the penalty in signal-to-noise ratio typically encountered with (1)H MRI due to a reduction in acquisition time can be offset by an increase in flip angle. The signal-to-noise ratio of hyperpolarized MRI generally exhibits a strong dependence on flip angle, which makes a homogeneous B(1)(+) transmit field desirable. This paper presents a flexible 32-channel receive array for (3) He human lung imaging at 1.5T designed for insertion into an asymmetric birdcage transmit coil. While the 32-channel array allows parallel imaging at high acceleration factors, the birdcage transmit coil provides a homogeneous B(1)(+) field. Decoupling between array elements is achieved by using a concentric shielding approach together with preamplifier decoupling. Coupling between transmit coil and array elements is low by virtue of a low geometric coupling coefficient, which is reduced further by the concentric shields in the array. The combination of the 32-channel array and birdcage transmit coil provides (3)He ventilation images of excellent quality with similar signal-to-noise ratio at acceleration factors R = 2 and R = 4, while maintaining a homogeneous B(1)(+).

Synchronous acquisition of hyperpolarised 3He and 1H MR images of the lungs - maximising mutual anatomical and functional information.

The development of hybrid medical imaging scanners has allowed imaging with different detection modalities at the same time, providing different anatomical and functional information within the same physiological time course with the patient in the same position. Until now, the acquisition of proton MRI of lung anatomy and hyperpolarised gas MRI of lung function required separate breath-hold examinations, meaning that the images were not spatially registered or temporally synchronised. We demonstrate the spatially registered concurrent acquisition of lung images from two different nuclei in vivo. The temporal and spatial registration of these images is demonstrated by a high degree of mutual consistency that is impossible to achieve in separate scans and breath holds.

Measurement of alveolar oxygen partial pressure in the rat lung using Carr-Purcell-Meiboom-Gill spin-spin relaxation times of hyperpolarized 3He and 129Xe at 74 mT.

Regional measurement of alveolar oxygen partial pressure can be obtained from the relaxation rates of hyperpolarized noble gases, (3) He and (129) Xe, in the lungs. Recently, it has been demonstrated that measurements of alveolar oxygen partial pressure can be obtained using the spin-spin relaxation rate (R(2) ) of (3) He at low magnetic field strengths (<0.1 T) in vivo. R(2) measurements can be achieved efficiently using the Carr-Purcell-Meiboom-Gill pulse sequence. In this work, alveolar oxygen partial pressure measurements based on Carr-Purcell-Meiboom-Gill R(2) values of hyperpolarized (3) He and (129) Xe in vitro and in vivo in the rat lung at low magnetic field strength (74 mT) are presented. In vitro spin-spin relaxivity constants for (3) He and (129) Xe were determined to be (5.2 ± 0.6) × 10(-6) Pa(-1) sec(-1) and (7.3 ± 0.4) × 10(-6) Pa(-1) s(-1) compared with spin-lattice relaxivity constants of (4.0 ± 0.4) × 10(-6) Pa(-1) s(-1) and (4.3 ± 1.3) × 10(-6) Pa(-1) s(-1), respectively. In vivo experimental measurements of alveolar oxygen partial pressure using (3) He in whole rat lung show good agreement (r(2) = 0.973) with predictions based on lung volumes and ventilation parameters. For (129) Xe, multicomponent relaxation was observed with one component exhibiting an increase in R(2) with decreasing alveolar oxygen partial pressure.

Compressed sensing in hyperpolarized 3He lung MRI.

In this work, the application of compressed sensing techniques to the acquisition and reconstruction of hyperpolarized (3)He lung MR images was investigated. The sparsity of (3)He lung images in the wavelet domain was investigated through simulations based on fully sampled Cartesian two-dimensional and three-dimensional (3)He lung ventilation images, and the k-spaces of 2D and 3D images were undersampled randomly and reconstructed by minimizing the L1 norm. The simulation results show that temporal resolution can be readily improved by a factor of 2 for two-dimensional and 4 to 5 for three-dimensional ventilation imaging with (3)He with the levels of signal to noise ratio (SNR) (approximately 19) typically obtained. The feasibility of producing accurate functional apparent diffusion coefficient (ADC) maps from undersampled data acquired with fewer radiofrequency pulses was also demonstrated, with the preservation of quantitative information (mean ADC(cs) approximately mean ADC(full) approximately 0.16 cm(2) sec(-1)). Prospective acquisition of 2-fold undersampled two-dimensional (3)He images with a compressed sensing k-space pattern was then demonstrated in a healthy volunteer, and the results were compared to the equivalent fully sampled images (SNR(cs) = 34, SNR(full) = 19).

Theoretical prediction and experimental measurement of the field dependence of the apparent transverse relaxation of hyperpolarized noble gases in lungs.

In this work, computer modeling based on a finite element method is used to simulate the T2* relaxation of hyperpolarized noble gases (HNG) in the lungs. A physical model of lung airways consisting of a phantom constructed from micro-capillary fibers of diameters similar to the size of lung airways with semi-permeable walls is also presented. The fibers are surrounded by a liquid medium (water) of magnetic susceptibility similar to lung tissue. Theoretical predictions of the field strength dependence of T2* for 129Xe in the phantom and in vivo rat lung are presented. These predictions are in good agreement with experimental T2* values obtained from the phantoms and in vivo rat lungs (160, 19 and 8 ms) at three different field strengths (0.074, 1.89 and 3T, respectively) using hyperpolarized 129Xe. The strong dependence of T2* on field strength is consistent with the theoretical prediction that low fields may be optimal for HNG MR imaging of the lungs as the decreased T2* at high fields necessitates an increase in bandwidth for conventional MR imaging.