Highly accelerated dynamic acquisition of 3D grid-tagged hyperpolarized-gas lung images using compressed sensing.

PURPOSE: To develop and test compressed sensing-based multiframe 3D MRI of grid-tagged hyperpolarized gas in the lung. THEORY AND METHODS: Applying grid-tagging RF pulses to inhaled hyperpolarized gas results in images in which signal intensity is predictably and sparsely distributed. In the present work, this phenomenon was used to produce a sampling pattern in which k-space is undersampled by a factor of approximately seven, yet regions of high k-space energy remain densely sampled. Three healthy subjects received multiframe 3D 3 He tagging MRI using this undersampling method. Images were collected during a single exhalation at eight timepoints spanning the breathing cycle from end-of-inhalation to end-of-exhalation. Grid-tagged images were used to generate 3D displacement maps of the lung during exhalation, and time-resolved maps of principal strains and fractional volume change were generated from these displacement maps using finite-element analysis. RESULTS: Tags remained clearly resolvable for 4-6 timepoints (5-8 s) in each subject. Displacement maps revealed noteworthy temporal and spatial nonlinearities in lung motion during exhalation. Compressive normal strains occurred along all three principal directions but were primarily oriented in the head-foot direction. Fractional volume changes displayed clear bilateral symmetry, but with the lower lobes displaying slightly higher change than the upper lobes in 2 of the 3 subjects. CONCLUSION: We developed a compressed sensing-based method for multiframe 3D MRI of grid-tagged hyperpolarized gas in the lung during exhalation. This method successfully overcomes previous challenges for 3D dynamic grid-tagging, allowing time-resolved biomechanical readouts of lung function to be generated.

Image- versus histogram-based considerations in semantic segmentation of pulmonary hyperpolarized gas images.

PURPOSE: To characterize the differences between histogram-based and image-based algorithms for segmentation of hyperpolarized gas lung images. METHODS: Four previously published histogram-based segmentation algorithms (ie, linear binning, hierarchical k-means, fuzzy spatial c-means, and a Gaussian mixture model with a Markov random field prior) and an image-based convolutional neural network were used to segment 2 simulated data sets derived from a public (n = 29 subjects) and a retrospective collection (n = 51 subjects) of hyperpolarized 129Xe gas lung images transformed by common MRI artifacts (noise and nonlinear intensity distortion). The resulting ventilation-based segmentations were used to assess algorithmic performance and characterize optimization domain differences in terms of measurement bias and precision. RESULTS: Although facilitating computational processing and providing discriminating clinically relevant measures of interest, histogram-based segmentation methods discard important contextual spatial information and are consequently less robust in terms of measurement precision in the presence of common MRI artifacts relative to the image-based convolutional neural network. CONCLUSIONS: Direct optimization within the image domain using convolutional neural networks leverages spatial information, which mitigates problematic issues associated with histogram-based approaches and suggests a preferred future research direction. Further, the entire processing and evaluation framework, including the newly reported deep learning functionality, is available as open source through the well-known Advanced Normalization Tools ecosystem.

Protocols for multi-site trials using hyperpolarized 129 Xe MRI for imaging of ventilation, alveolar-airspace size, and gas exchange: A position paper from the 129 Xe MRI clinical trials consortium.

Hyperpolarized (HP) 129 Xe MRI uniquely images pulmonary ventilation, gas exchange, and terminal airway morphology rapidly and safely, providing novel information not possible using conventional imaging modalities or pulmonary function tests. As such, there is mounting interest in expanding the use of biomarkers derived from HP 129 Xe MRI as outcome measures in multi-site clinical trials across a range of pulmonary disorders. Until recently, HP 129 Xe MRI techniques have been developed largely independently at a limited number of academic centers, without harmonizing acquisition strategies. To promote uniformity and adoption of HP 129 Xe MRI more widely in translational research, multi-site trials, and ultimately clinical practice, this position paper from the 129 Xe MRI Clinical Trials Consortium (https://cpir.cchmc.org/XeMRICTC) recommends standard protocols to harmonize methods for image acquisition in HP 129 Xe MRI. Recommendations are described for the most common HP gas MRI techniques-calibration, ventilation, alveolar-airspace size, and gas exchange-across MRI scanner manufacturers most used for this application. Moreover, recommendations are described for 129 Xe dose volumes and breath-hold standardization to further foster consistency of imaging studies. The intention is that sites with HP 129 Xe MRI capabilities can readily implement these methods to obtain consistent high-quality images that provide regional insight into lung structure and function. While this document represents consensus at a snapshot in time, a roadmap for technical developments is provided that will further increase image quality and efficiency. These standardized dosing and imaging protocols will facilitate the wider adoption of HP 129 Xe MRI for multi-site pulmonary research.

Emphysema Index Based on Hyperpolarized 3He or 129Xe Diffusion MRI: Performance and Comparison with Quantitative CT and Pulmonary Function Tests.

Background Apparent diffusion coefficient (ADC) maps of inhaled hyperpolarized gases have shown promise in the characterization of emphysema in patients with chronic obstructive pulmonary disease (COPD), yet an easily interpreted quantitative metric beyond mean and standard deviation has not been established. Purpose To introduce a quantitative framework with which to characterize emphysema burden based on hyperpolarized helium 3 (3He) and xenon 129 (129Xe) ADC maps and compare its diagnostic performance with CT-based emphysema metrics and pulmonary function tests (PFTs). Materials and Methods Twenty-seven patients with mild, moderate, or severe COPD and 13 age-matched healthy control subjects participated in this retrospective study. Participants underwent CT and multiple b value diffusion-weighted 3He and 129Xe MRI examinations and standard PFTs between August 2014 and November 2017. ADC-based emphysema index was computed separately for each gas and b value as the fraction of lung voxels with ADC values greater than in the healthy group 99th percentile. The resulting values were compared with quantitative CT results (relative lung area <-950 HU) as the reference standard. Diagnostic performance metrics included area under the receiver operating characteristic curve (AUC). Spearman rank correlations and Wilcoxon rank sum tests were performed between ADC-, CT-, and PFT-based metrics, and intraclass correlation was performed between repeated measurements. Results Thirty-six participants were evaluated (mean age, 60 years ± 6 [standard deviation]; 20 women). ADC-based emphysema index was highly repeatable (intraclass correlation coefficient > 0.99) and strongly correlated with quantitative CT (r = 0.86, P < .001 for 3He; r = 0.85, P < .001 for 129Xe) with high AUC (≥0.93; 95% confidence interval [CI]: 0.85, 1.00). ADC emphysema indices were also correlated with percentage of predicted diffusing capacity of lung for carbon monoxide (r = -0.81, P < .001 for 3He; r = -0.80, P < .001 for 129Xe) and percentage of predicted residual lung volume divided by total lung capacity (r = 0.65, P < .001 for 3He; r = 0.61, P < .001 for 129Xe). Conclusion Emphysema index based on hyperpolarized helium 3 or xenon 129 diffusion MRI provides a repeatable measure of emphysema burden, independent of gas or b value, with similar diagnostic performance as quantitative CT or pulmonary function metrics. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Schiebler and Fain in this issue.

Signal-to-noise ratio, T2 , and T2* for hyperpolarized helium-3 MRI of the human lung at three magnetic field strengths.

PURPOSE: To evaluate T2 , T2*, and signal-to-noise ratio (SNR) for hyperpolarized helium-3 (3 He) MRI of the human lung at three magnetic field strengths ranging from 0.43T to 1.5T. METHODS: Sixteen healthy volunteers were imaged using a commercial whole body scanner at 0.43T, 0.79T, and 1.5T. Whole-lung T2 values were calculated from a Carr-Purcell-Meiboom-Gill spin-echo-train acquisition. T2* maps and SNR were determined from dual-echo and single-echo gradient-echo images, respectively. Mean whole-lung SNR values were normalized by ventilated lung volume and administered 3 He dose. RESULTS: As expected, T2 and T2* values demonstrated a significant inverse relationship to field strength. Hyperpolarized 3 He images acquired at all three field strengths had comparable SNR values and thus appeared visually very similar. Nonetheless, the relatively small SNR differences among field strengths were statistically significant. CONCLUSIONS: Hyperpolarized 3 He images of the human lung with similar image quality were obtained at three field strengths ranging from 0.43T and 1.5T. The decrease in susceptibility effects at lower fields that are reflected in longer T2 and T2* values may be advantageous for optimizing pulse sequences inherently sensitive to such effects. The three-fold increase in T2* at lower field strength would allow lower receiver bandwidths, providing a concomitant decrease in noise and relative increase in SNR. Magn Reson Med 78:1458-1463, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Detecting pulmonary capillary blood pulsations using hyperpolarized xenon-129 chemical shift saturation recovery (CSSR) MR spectroscopy.

PURPOSE: To investigate whether chemical shift saturation recovery (CSSR) MR spectroscopy with hyperpolarized xenon-129 is sensitive to the pulsatile nature of pulmonary blood flow during the cardiac cycle. METHODS: A CSSR pulse sequence typically uses radiofrequency (RF) pulses to saturate the magnetization of xenon-129 dissolved in lung tissue followed, after a variable delay time, by an RF excitation and subsequent acquisition of a free-induction decay. Thereby it is possible to monitor the uptake of xenon-129 by lung tissue and extract physiological parameters of pulmonary gas exchange. In the current studies, the delay time was instead held at a constant value, which permitted observation of xenon-129 gas uptake as a function of breath-hold time. CSSR studies were performed in 13 subjects (10 healthy, 2 chronic obstructive pulmonary disease [COPD], 1 second-hand smoke exposure), holding their breath at total lung capacity. RESULTS: The areas of the tissue/plasma and the red-blood-cell peaks in healthy subjects varied by an average of 1.7±0.7% and 15.1±3.8%, respectively, during the cardiac cycle. In 2 subjects with COPD these peak pulsations were not detectable during at least part of the measurement period. CONCLUSION: CSSR spectroscopy is sufficiently sensitive to detect oscillations in the xenon-129 gas-uptake rate associated with the cardiac cycle.

Rapid acquisition of helium-3 and proton three-dimensional image sets of the human lung in a single breath-hold using compressed sensing.

PURPOSE: To develop and validate a method for acquiring helium-3 ((3) He) and proton ((1) H) three-dimensional (3D) image sets of the human lung with isotropic spatial resolution within a 10-s breath-hold by using compressed sensing (CS) acceleration, and to assess the fidelity of undersampled images compared with fully sampled images. METHODS: The undersampling scheme for CS acceleration was optimized and tested using (3) He ventilation data. Rapid 3D acquisition of both (3) He and (1) H data during one breath-hold was then implemented, based on a balanced steady-state free-precession pulse sequence, by random undersampling of k-space with reconstruction by means of minimizing the L1 norm and total variance. CS-reconstruction fidelity was evaluated quantitatively by comparing fully sampled and retrospectively undersampled image sets. RESULTS: Helium-3 and (1) H 3D image sets of the lung with isotropic 3.9-mm resolution were acquired during a single breath-hold in 12 s and 8 s using acceleration factors of 2 and 3, respectively. Comparison of fully sampled and retrospectively undersampled (3) He and (1) H images yielded mean absolute errors <10% and structural similarity indices >0.9. CONCLUSION: By randomly undersampling k-space and using CS reconstruction, high-quality (3) He and (1) H 3D image sets with isotropic 3.9-mm resolution can be acquired within an 8-s breath-hold.

Regional anisotropy of airspace orientation in the lung as assessed with hyperpolarized helium-3 diffusion MRI.

PURPOSE: To evaluate regional anisotropy of lung-airspace orientation by assessing the dependence of helium-3 ((3) He) apparent diffusion coefficient (ADC) values on the direction of diffusion sensitization at two field strengths. MATERIALS AND METHODS: Hyperpolarized (3) He diffusion-weighted magnetic resonance imaging (MRI) of the lung was performed at 0.43T and 1.5T in 12 healthy volunteers. A gradient-echo pulse sequence was used with a bipolar diffusion-sensitization gradient applied separately along three orthogonal directions. ADC maps, median ADC values, and signal-to-noise ratios were calculated from the diffusion-weighted images. Two readers scored the ADC maps for increased values at lung margins, major fissures, or within focal central regions. RESULTS: ADC values were found to depend on the direction of diffusion sensitization (P < 0.01, except for craniocaudal vs. anteroposterior directions at 1.5T) and were increased at the lateral and medial surfaces for left-right diffusion sensitization (12 of 12 subjects); at the apex and base (9 of 12), and along the major fissure (8 of 12), for craniocaudal diffusion sensitization; and at the most anterior and posterior lung (10 of 12) for anteroposterior diffusion sensitization. Median ADC values at 0.43T (0.201 ± 0.017, left-right; 0.193 ± 0.019, craniocaudal; and 0.187 ± 0.017 cm(2) /s, anteroposterior) were slightly lower than those at 1.5T (0.205 ± 0.017, 0.197 ± 0.017 and 0.194 ± 0.016 cm(2) /s, respectively; P < 0.05). CONCLUSION: These findings indicate that diffusion-weighted hyperpolarized (3) He MRI can detect regional anisotropy of lung-airspace orientation, including that associated with preferential orientation of terminal airways near pleural surfaces.

Assessment of lung function in asthma and COPD using hyperpolarized 129Xe chemical shift saturation recovery spectroscopy and dissolved-phase MRI.

Magnetic-resonance spectroscopy and imaging using hyperpolarized xenon-129 show great potential for evaluation of the most important function of the human lung -- gas exchange. In particular, chemical shift saturation recovery (CSSR) xenon-129 spectroscopy provides important physiological information for the lung as a whole by characterizing the dynamic process of gas exchange, while dissolved-phase (DP) xenon-129 imaging captures the time-averaged regional distribution of gas uptake by lung tissue and blood. Herein, we present recent advances in assessing lung function using CSSR spectroscopy and DP imaging in a total of 45 subjects (23 healthy, 13 chronic obstructive pulmonary disease (COPD) and 9 asthma). From CSSR acquisitions, the COPD subjects showed red blood cell to tissue-plasma (RBC-to-TP) ratios below the average for the healthy subjects (p < 0.001), but significantly higher septal wall thicknesses as compared with the healthy subjects (p < 0.005); the RBC-to-TP ratios for the asthmatic subjects fell outside two standard deviations (either higher or lower) from the mean of the healthy subjects, although there was no statistically significant difference for the average ratio of the study group as a whole. Similarly, from the 3D DP imaging acquisitions, we found that all the ratios (TP to gas phase (GP), RBC to GP, RBC to TP) measured in the COPD subjects were lower than those from the healthy subjects (p < 0.05 for all ratios), while these ratios in the asthmatic subjects differed considerably between subjects. Despite having been performed at different lung inflation levels, the RBC-to-TP ratios measured by CSSR and 3D DP imaging were fairly consistent with each other, with a mean difference of 0.037 (ratios from 3D DP imaging larger). In ten subjects the RBC-to-GP ratios obtained from the 3D DP imaging acquisitions were also highly correlated with their diffusing capacity of the lung for carbon monoxide per unit alveolar volume ratios measured by pulmonary function testing (R = 0.91).

Lung injury induced by secondhand smoke exposure detected with hyperpolarized helium-3 diffusion MR.

PURPOSE: To determine whether helium-3 diffusion MR can detect the changes in the lungs of healthy nonsmoking individuals who were regularly exposed to secondhand smoke. MATERIALS AND METHODS: Three groups were studied (age: 59 ± 9 years): 23 smokers, 37 exposure-to-secondhand-smoke subjects, and 29 control subjects. We measured helium-3 diffusion values at diffusion times from 0.23 to 1.97 s. RESULTS: One-way analysis of variance revealed that the mean area under the helium-3 diffusion curves (ADC AUC) of the smokers was significantly elevated compared with the controls and to the exposure-to-secondhand-smoke subjects (P < 0.001 both). No difference between the mean ADC AUC of the exposure-to-secondhand-smoke subjects and that of the controls was found (P = 0.115). However, application of a receiver operator characteristic-derived rule to classify subjects as either a "control" or a "smoker," based on ADC AUC, revealed that 30% (11/37) of the exposure-to-secondhand subjects were classified as "smokers" indicating an elevation of the ADC AUC. CONCLUSION: Using helium-3 diffusion MR, elevated ADC values were detected in 30% of nonsmoking healthy subjects who had been regularly exposed to secondhand smoke, supporting the concept that, in susceptible individuals, secondhand smoke causes mild lung damage.

Regional mapping of gas uptake by blood and tissue in the human lung using hyperpolarized xenon-129 MRI.

PURPOSE: To develop a breathhold acquisition for regional mapping of ventilation and the fractions of hyperpolarized xenon-129 (Xe129) dissolved in tissue (lung parenchyma and plasma) and red blood cells (RBCs), and to perform an exploratory study to characterize data obtained in human subjects. MATERIALS AND METHODS: A three-dimensional, multi-echo, radial-trajectory pulse sequence was developed to obtain ventilation (gaseous Xe129), tissue, and RBC images in healthy subjects, smokers, and asthmatics. Signal ratios (total dissolved Xe129 to gas, tissue-to-gas, RBC-to-gas, and RBC-to-tissue) were calculated from the images for quantitative comparison. RESULTS: Healthy subjects demonstrated generally uniform values within coronal slices, and a gradient in values along the anterior-to-posterior direction. In contrast, images and associated ratio maps in smokers and asthmatics were generally heterogeneous and exhibited values mostly lower than those in healthy subjects. Whole-lung values of total dissolved Xe129 to gas, tissue-to-gas, and RBC-to-gas ratios in healthy subjects were significantly larger than those in diseased subjects. CONCLUSION: Regional maps of tissue and RBC fractions of dissolved Xe129 were obtained from a short breathhold acquisition, well tolerated by healthy volunteers and subjects with obstructive lung disease. Marked differences were observed in spatial distributions and overall amounts of Xe129 dissolved in tissue and RBCs among healthy subjects, smokers and asthmatics.

Simultaneous magnetic resonance imaging of ventilation distribution and gas uptake in the human lung using hyperpolarized xenon-129.

Despite a myriad of technical advances in medical imaging, as well as the growing need to address the global impact of pulmonary diseases, such as asthma and chronic obstructive pulmonary disease, on health and quality of life, it remains challenging to obtain in vivo regional depiction and quantification of the most basic physiological functions of the lung-gas delivery to the airspaces and gas uptake by the lung parenchyma and blood-in a manner suitable for routine application in humans. We report a method based on MRI of hyperpolarized xenon-129 that permits simultaneous observation of the 3D distributions of ventilation (gas delivery) and gas uptake, as well as quantification of regional gas uptake based on the associated ventilation. Subjects with lung disease showed variations in gas uptake that differed from those in ventilation in many regions, suggesting that gas uptake as measured by this technique reflects such features as underlying pathological alterations of lung tissue or of local blood flow. Furthermore, the ratio of the signal associated with gas uptake to that associated with ventilation was substantially altered in subjects with lung disease compared with healthy subjects. This MRI-based method provides a way to quantify relationships among gas delivery, exchange, and transport, and appears to have significant potential to provide more insight into lung disease.

Acquiring Hyperpolarized 129Xe Magnetic Resonance Images of Lung Ventilation.

Hyperpolarized 129Xe MRI comprises a unique array of structural and functional lung imaging techniques. Technique standardization across sites is increasingly important given the recent FDA approval of 129Xe as an MR contrast agent and as interest in 129Xe MRI increases among research and clinical institutions. Members of the 129Xe MRI Clinical Trials Consortium (Xe MRI CTC) have agreed upon best practices for each of the key aspects of the 129Xe MRI workflow, and these recommendations are summarized in a recent publication. This work provides practical information to develop an end-to-end workflow for collecting 129Xe MR images of lung ventilation according to the Xe MRI CTC recommendations. Preparation and administration of 129Xe for MR studies will be discussed and demonstrated, with specific topics including choice of appropriate gas volumes for entire studies and for individual MR scans, preparation and delivery of individual 129Xe doses, and best practices for monitoring subject safety and 129Xe tolerability during studies. Key MR technical considerations will also be covered, including pulse sequence types and optimized parameters, calibration of 129Xe flip angle and center frequency, and 129Xe MRI ventilation image analysis.

Lung Volume Dependence and Repeatability of Hyperpolarized 129Xe MRI Gas Uptake Metrics in Healthy Volunteers and Participants with COPD.

Purpose: To assess the effect of lung volume on measured values and repeatability of xenon 129 (129Xe) gas uptake metrics in healthy volunteers and participants with chronic obstructive pulmonary disease (COPD). Materials and Methods: This Health Insurance Portability and Accountability Act-compliant prospective study included data (March 2014-December 2015) from 49 participants (19 with COPD [mean age, 67 years ± 9 (SD)]; nine women]; 25 older healthy volunteers [mean age, 59 years ± 10; 20 women]; and five young healthy women [mean age, 23 years ± 3]). Thirty-two participants underwent repeated 129Xe and same-breath-hold proton MRI at residual volume plus one-third forced vital capacity (RV+FVC/3), with 29 also undergoing one examination at total lung capacity (TLC). The remaining 17 participants underwent imaging at TLC, RV+FVC/3, and residual volume (RV). Signal ratios between membrane, red blood cell (RBC), and gas-phase compartments were calculated using hierarchical iterative decomposition of water and fat with echo asymmetry and least-squares estimation (ie, IDEAL). Repeatability was assessed using coefficient of variation and intraclass correlation coefficient, and volume relationships were assessed using Spearman correlation and Wilcoxon rank sum tests. Results: Gas uptake metrics were repeatable at RV+FVC/3 (intraclass correlation coefficient = 0.88 for membrane/gas; 0.71 for RBC/gas, and 0.88 for RBC/membrane). Relative ratio changes were highly correlated with relative volume changes for membrane/gas (r = -0.97) and RBC/gas (r = -0.93). Membrane/gas and RBC/gas measured at RV+FVC/3 were significantly lower in the COPD group than the corresponding healthy group (P ≤ .001). However, these differences lessened upon correction for individual volume differences (P = .23 for membrane/gas; P = .09 for RBC/gas). Conclusion: Dissolved-phase 129Xe MRI-derived gas uptake metrics were repeatable but highly dependent on lung volume during measurement.Keywords: Blood-Air Barrier, MRI, Chronic Obstructive Pulmonary Disease, Pulmonary Gas Exchange, Xenon Supplemental material is available for this article © RSNA, 2023.

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.

Multiple-exchange-time xenon polarization transfer contrast (MXTC) MRI: initial results in animals and healthy volunteers.

Hyperpolarized xenon-129 is a noninvasive contrast agent for lung MRI, which upon inhalation dissolves in parenchymal structures, thus mirroring the gas-exchange process for oxygen in the lung. Multiple-exchange-time xenon polarization transfer contrast (MXTC) MRI is an implementation of the XTC MRI technique in four dimensions (three spatial dimensions plus exchange time). The aim of this study was to evaluate the sensitivity of MXTC MRI for the detection of microstructural deformations of the healthy lung in response to gravity-induced tissue compression and the degree of lung inflation. MXTC MRI was performed in four rabbits and in three healthy human volunteers. Two lung function parameters, one related to tissue- to alveolar-volume ratio and the other to average septal-wall thickness, were determined regionally. A significant gradient in MXTC MRI parameters, consistent with gravity-induced lung tissue deformation in the supine imaging position, was found at low lung volumes. At high lung volumes, parameters were generally lower and the gradient in parameter values was less pronounced. Results show that MXTC MRI permits the quantification of subtle changes in healthy lung microstructure. Further, only structures participating in gas exchange are represented in MXTC MRI data, which potentially makes the technique especially sensitive to pathological changes in lung microstructure affecting gas exchange.

Hyperpolarized Xenon-129 gas-exchange imaging of lung microstructure: first case studies in subjects with obstructive lung disease.

PURPOSE: To develop and test a method to noninvasively assess the functional lung microstructure. MATERIALS AND METHODS: The Multiple exchange time Xenon polarization Transfer Contrast technique (MXTC) encodes xenon gas-exchange contrast at multiple delay times permitting two lung-function parameters to be derived: (i) MXTC-F, the long exchange-time depolarization value, which is proportional to the tissue to alveolar-volume ratio and (ii) MXTC-S, the square root of the xenon exchange-time constant, which characterizes thickness and composition of alveolar septa. Three healthy volunteers, one asthmatic, and two chronic obstructive pulmonary disease (COPD) (GOLD stage I and II) subjects were imaged with MXTC MRI. In a subset of subjects, hyperpolarized xenon-129 ADC MRI and CT imaging were also performed. RESULTS: The MXTC-S parameter was found to be elevated in subjects with lung disease (P-value = 0.018). In the MXTC-F parameter map it was feasible to identify regional loss of functional tissue in a COPD patient. MXTC-F maps showed excellent regional correlation with CT and ADC (P ≥ 0.90) in one COPD subject. CONCLUSION: The functional tissue-density parameter MXTC-F showed regional agreement with other imaging techniques. The newly developed parameter MXTC-S, which characterizes the functional thickness of alveolar septa, has potential as a novel biomarker for regional parenchymal inflammation or thickening.

A short-breath-hold technique for lung pO2 mapping with 3He MRI.

A pulse-sequence strategy was developed for generating regional maps of alveolar oxygen partial pressure (pO2) in a single 6-sec breath hold, for use in human subjects with impaired lung function. Like previously described methods, pO2 values are obtained by measuring the oxygen-induced T1 relaxation of inhaled hyperpolarized 3He. Unlike other methods, only two 3He images are acquired: one with reverse-centric and the other with centric phase-encoding order. This phase-encoding arrangement minimizes the effects of regional flip-angle variations, so that an accurate map of instantaneous pO2 can be calculated from two images acquired a few seconds apart. By combining this phase-encoding strategy with variable flip angles, the vast majority of the hyperpolarized magnetization goes directly into the T1 measurement, minimizing noise in the resulting pO2 map. The short-breath-hold pulse sequence was tested in phantoms containing known O2 concentrations. The mean difference between measured and prepared pO2 values was 1 mm Hg. The method was also tested in four healthy volunteers and three lung-transplant patients. Maps of healthy subjects were largely uniform, whereas focal regions of abnormal pO2 were observed in diseased subjects. Mean pO2 values varied with inhaled O2 concentration. Mean pO2 was consistent with normal steady-state values in subjects who inhaled 3He diluted only with room air.

Convolutional Neural Networks with Template-Based Data Augmentation for Functional Lung Image Quantification.

RATIONALE AND OBJECTIVES: We propose an automated segmentation pipeline based on deep learning for proton lung MRI segmentation and ventilation-based quantification which improves on our previously reported methodologies in terms of computational efficiency while demonstrating accuracy and robustness. The large data requirement for the proposed framework is made possible by a novel template-based data augmentation strategy. Supporting this work is the open-source ANTsRNet-a growing repository of well-known deep learning architectures first introduced here. MATERIALS AND METHODS: Deep convolutional neural network (CNN) models were constructed and trained using a custom multilabel Dice metric loss function and a novel template-based data augmentation strategy. Training (including template generation and data augmentation) employed 205 proton MR images and 73 functional lung MRI. Evaluation was performed using data sets of size 63 and 40 images, respectively. RESULTS: Accuracy for CNN-based proton lung MRI segmentation (in terms of Dice overlap) was left lung: 0.93 ± 0.03, right lung: 0.94 ± 0.02, and whole lung: 0.94 ± 0.02. Although slightly less accurate than our previously reported joint label fusion approach (left lung: 0.95 ± 0.02, right lung: 0.96 ± 0.01, and whole lung: 0.96 ± 0.01), processing time is <1 second per subject for the proposed approach versus ∼30 minutes per subject using joint label fusion. Accuracy for quantifying ventilation defects was determined based on a consensus labeling where average accuracy (Dice multilabel overlap of ventilation defect regions plus normal region) was 0.94 for the CNN method; 0.92 for our previously reported method; and 0.90, 0.92, and 0.94 for expert readers. CONCLUSION: The proposed framework yields accurate automated quantification in near real time. CNNs drastically reduce processing time after offline model construction and demonstrate significant future potential for facilitating quantitative analysis of functional lung MRI.

A hybrid proton and hyperpolarized gas tagging MRI technique for lung respiratory motion imaging: a feasibility study.

The aim of this work was to develop a novel hybrid 3D hyperpolarized (HP) gas tagging MRI (t-MRI) technique and to evaluate it for lung respiratory motion measurement with comparison to deformable image registrations (DIR) methods. Three healthy subjects underwent a hybrid MRI which combines 3D HP gas t-MRI with a low resolution (Low-R, 4.5 mm isotropic voxels) 3D proton MRI (p-MRI), plus a high resolution (High-R, 2.5 mm isotropic voxels) 3D p-MRI, during breath-holds at the end-of-inhalation (EOI) and the end-of-exhalation (EOE). Displacement vector field (DVF) of the lung motion was determined from the t-MRI images by tracking tagging grids and from the High-R p-MRI using three DIR methods (B-spline based method implemented by Velocity, Free Form Deformation by MIM, and B-spline by an open source software Elastix: denoted as A, B, and C, respectively), labeled as tDVF and dDVF, respectively. The tDVF from the HP gas t-MRI was used as ground-truth reference to evaluate performance of the three DIR methods. Differences in both magnitude and angle between the tDVF and dDVFs were analyzed. The mean lung motion of the three subjects was 37.3 mm, 8.9 mm and 12.9 mm, respectively. Relatively large discrepancies were observed between the tDVF and the dDVFs as compared to previously reported DIR errors. The mean ± standard deviation (SD) DVF magnitude difference was 8.3 ± 5.6 mm, 9.2 ± 4.5 mm, and 9.3 ± 6.1 mm, and the mean ± SD DVF angular difference was 29.1 ± 12.1°, 50.1 ± 28.6°, and 39.0 ± 6.3°, for the DIR Methods A, B, and C, respectively. These preliminary results showed that the hybrid HP gas t-MRI technique revealed different lung motion patterns as compared to the DIR methods. It may provide unique perspectives in developing and evaluating DIR of the lungs. Novelty and Significance We designed a MRI protocol that includes a novel hybrid MRI technique (3D HP gas t-MRI with a low resolution 3D p-MRI) plus a high resolution 3D p-MRI. We tested the novel hybrid MRI technique on three healthy subjects for measuring regional lung respiratory motion with comparison to deformable image registrations (DIR) methods, and observed relatively large discrepancies in lung motion between HP gas t-MRI and DIR methods.