Hyperpolarized Gas Magnetic Resonance Research Articles

Dynamic evaluation of acute lung injury using hyperpolarized 129 Xe magnetic resonance.

Prognosticating acute lung injury (ALI) is challenging, in part because of a lack of sensitive biomarkers. Hyperpolarized gas magnetic resonance (MR) has unique advantages in pulmonary function measurement and can provide promising biomarkers for the assessment of lung injuries. Herein, we employ hyperpolarized 129 Xe MRI and generate a number of imaging biomarkers to detect the pulmonary physiological and morphological changes during the progression of ALI in an animal model. We find the measured ratio of 129 Xe in red blood cells to interstitial tissue/plasma (RBC/TP) is significantly lower in the ALI group on the second (0.32 ± 0.03, p = 0.004), seventh (0.23 ± 0.03, p < 0.001), and 14th (0.29 ± 0.04, p = 0.001) day after lipopolysaccharide treatment compared with that in the control group (0.41 ± 0.04). In addition, significant differences are also observed for RBC/TP measurements between the second and seventh day (p = 0.001) and between the seventh and 14th day (p = 0.018) in the ALI group after treatment. Besides RBC/TP, significant differences are also observed in the measured exchange time constant (T) on the second (p = 0.038) and seventh day (p = 0.009) and in the measured apparent diffusion coefficient (ADC) and alveolar surface-to-volume ratio (SVR) on the 14th day (ADC: p = 0.009 and SVR: p = 0.019) after treatment in the ALI group compared with that in the control group. These findings indicate that the parameters measured with 129 Xe MR can detect the dynamic changes in pulmonary structure and function in an ALI animal model.

Deep Learning Approaches for Quantifying Ventilation Defects in Hyperpolarized Gas Magnetic Resonance Imaging of the Lung: A Review.

This paper provides an in-depth overview of Deep Neural Networks and their application in the segmentation and analysis of lung Magnetic Resonance Imaging (MRI) scans, specifically focusing on hyperpolarized gas MRI and the quantification of lung ventilation defects. An in-depth understanding of Deep Neural Networks is presented, laying the groundwork for the exploration of their use in hyperpolarized gas MRI and the quantification of lung ventilation defects. Five distinct studies are examined, each leveraging unique deep learning architectures and data augmentation techniques to optimize model performance. These studies encompass a range of approaches, including the use of 3D Convolutional Neural Networks, cascaded U-Net models, Generative Adversarial Networks, and nnU-net for hyperpolarized gas MRI segmentation. The findings highlight the potential of deep learning methods in the segmentation and analysis of lung MRI scans, emphasizing the need for consensus on lung ventilation segmentation methods.

Bronchial thermoplasty guided by hyperpolarised gas magnetic resonance imaging in adults with severe asthma: a 1-year pilot randomised trial.

Patient-specific localisation of ventilation defects using hyperpolarised gas magnetic resonance imaging (MRI) introduces the possibility of regionally targeted bronchial thermoplasty (BT) for the treatment of severe asthma. We aimed to demonstrate that BT guided by MRI to ventilation defects reduces the number of radiofrequency activations while resulting in improved asthma quality-of-life and control scores that are non-inferior to standard BT.In a 1-year pilot randomised controlled trial, 14 patients with severe asthma who were clinically eligible to receive BT underwent hyperpolarised gas MRI to characterise ventilation defects and were randomised to MRI-guided or standard BT. End-points were improved Asthma Quality of Life Questionnaire (AQLQ) and Asthma Control Questionnaire (ACQ) scores, the proportion of AQLQ and ACQ responders and the number of radiofrequency activations and bronchoscopy sessions.Participants who underwent MRI-guided BT received 53% fewer radiofrequency activations than those who had standard BT (p=0.003). At 12 months, the mean improvement from baseline was similar between the MRI-guided group (n=5) and the standard group (n=7) for AQLQ score (MRI-guided: 1.8, 95% CI 0.1–3.5, p=0.04; standard: 0.7, 95% CI −0.9–2.3, p=0.30) (p=0.25) and ACQ-5 score (MRI-guided: −1.4, 95% CI −2.6– −0.2, p=0.03; standard: −0.7, 95% CI −1.3–0.0, p=0.04) (p=0.17). A similar proportion of participants in both groups achieved a clinically relevant improvement in AQLQ score (MRI-guided: 80%; standard: 71%) and ACQ-5 score (MRI-guided: 80%; standard: 57%).Hyperpolarised gas MRI-guided BT reduced the number of radiofrequency activations, and resulted in asthma quality of life and control improvements at 12 months that were non-inferior to standard BT.

Novel imaging techniques for cystic fibrosis lung disease.

With an increasing number of patients with cystic fibrosis (CF) receiving highly effective CFTR (cystic fibrosis transmembrane regulator protein) modulator therapy, particularly at a young age, there is an increasing need to identify imaging tools that can detect and regionally visualize mild CF lung disease and subtle changes in disease state. In this review, we discuss the latest developments in imaging modalities for both structural and functional imaging of the lung available to CF clinicians and researchers, from the widely available, clinically utilized imaging methods for assessing CF lung disease-chest radiography and computed tomography-to newer techniques poised to become the next phase of clinical tools-structural/functional proton and hyperpolarized gas magnetic resonance imaging (MRI). Finally, we provide a brief discussion of several newer lung imaging techniques that are currently available only in selected research settings, including chest tomosynthesis, and fluorinated gas MRI. We provide an update on the clinical and/or research status of each technique, with a focus on sensitivity, early disease detection, and possibilities for monitoring treatment efficacy.

Peripheral and proximal lung ventilation in asthma: Short-term variation and response to bronchodilator inhalation

The relative involvement of the large and small airways in asthma is not clear. Hyperpolarized gas magnetic resonance imaging (MRI) provides high-resolution 3-dimensional images of ventilation distribution that can be quantified by the ventilated volume percentage (VV%) of the lungs. Our aims were to (1) quantify the baseline reproducibility of VV%, (2) assess the ventilation distribution between the proximal and peripheral lungs, and (3) investigate regional ventilation response to bronchodilator inhalation in a cohort of patients with asthma. A total of 33 patients with poorly controlled, moderate-to-severe asthma were scanned with hyperpolarized 3He MRI. Two image data sets were acquired at baseline, and 1 image data set was acquired after bronchodilator inhalation. Images were divided into proximal and peripheral regions for analysis. Bland-Altman analysis showed strong reproducibility of VV% (bias= 0.12%; LOA= -1.86% to 2.10%). VV% variation at baseline was greater in the periphery than in the proximal lung. The proximal lung was better ventilated than the peripheral lung. Ventilation increased significantly in response to bronchodilator inhalation, globally and regionally, and the ventilation increase in response to bronchodilator inhalation was greater in the peripheral lung than in the proximal lung. Hyperpolarized gas MRI was more sensitive to changes in response to bronchodilator inhalation (58%) than spirometry (33%). The peripheral lung showed reduced ventilation and a greater response to bronchodilator inhalation than the proximal lung. The high level of baseline reproducibility and sensitivity of hyperpolarized gas MRI to bronchodilator reversibility suggests that it is suitable for low subject number studies of therapy response.

Quantitative evaluation of lung injury caused by PM2.5 using hyperpolarized gas magnetic resonance.

To demonstrate the feasibility of 129 Xe MR in evaluating the pulmonary physiological changes caused by PM2.5 in animal models. Six rats were treated with PM2.5 solution (16.2 mg/kg) by intratracheal instillation twice a week for 4 weeks, and another six rats treated with normal saline served as the control cohort. Pulmonary function tests, hyperpolarized 129 Xe multi-b diffusion-weighted imaging, and chemical shift saturation recovery MR spectroscopywere performed on all rats, and the pulmonary structure and functional parameters were obtained from hyperpolarized 129 Xe MR data. Additionally, histological analysis was performed on all rats to evaluate alveolar septal thickness. Statistical analysis of all the obtained parameters was performed using unpaired 2-tailed t tests. Compared with the control group, the measured exchange time constant increased from 11.74 ± 2.39 to 14.00 ± 2.84 ms (P < .05), and the septal wall thickness increased from 6.17 ± 0.48 to 6.74 ± 0.52 μm (P < .05) in the PM2.5 cohort by 129 Xe MR spectroscopy, which correlated well with that obtained using quantitative histology (increased from 5.52 ± 0.32 to 6.20 ± 0.36 μm). Additionally, the mean TP/GAS ratio increased from 0.828 ± 0.115 to 1.019 ± 0.140 in the PM2.5 cohort (P = .021). Hyperpolarized 129 Xe MR could quantify the changes in gas exchange physiology caused by PM2.5 , indicating that the technique has the potential to be a useful tool for evaluation of pulmonary injury caused by air pollution in the future.

Hyperpolarized Gas Magnetic Resonance Imaging of Pediatric Cystic Fibrosis Lung Disease

Conventional pulmonary function tests appear normal in early cystic fibrosis (CF) lung disease. Therefore, new diagnostic approaches are required that can detect CF lung disease in children and monitor treatment response. Hyperpolarized (HP) gas (129Xe and 3He) magnetic resonance imaging (MRI) is a powerful, emergent tool for mapping regional lung function and may be well suited for studying pediatric CF. HP gas MRI is well tolerated, reproducible, and it can be performed longitudinally without the need for ionizing radiation. In particular, quantification of the distribution of ventilation, or ventilation defect percent (VDP), has been shown to be a sensitive indicator of CF lung disease and correlates well with pulmonary function tests. This article presents the current state of CF diagnosis and treatment and describes the potential role of HP gas MRI for detection of early CF lung disease and following the effects of interventions. The typical HP gas imaging workflow is described, along with a discussion of image analysis to calculate VDP, dosing considerations, and the reproducibility of VDP. The potential use of VDP as an outcome measure in CF is discussed, by considering the correlation with pulmonary function measures, preliminary interventional studies, and case studies involving longitudinal imaging and pulmonary exacerbations. Finally, emerging HP gas imaging techniques such as multiple breath washout imaging are introduced, followed by a discussion of future directions. Overall, HP gas MRI biomarkers are expected to provide sensitive outcome measures that can be used in disease surveillance as well as interventional studies involving novel CF therapies.

Spatial Comparison of CT-Based Surrogates of Lung Ventilation With Hyperpolarized Helium-3 and Xenon-129 Gas MRI in Patients Undergoing Radiation Therapy

To develop and apply an image acquisition and analysis strategy for spatial comparison of computed tomography (CT)-ventilation images with hyperpolarized gas magnetic resonance imaging (MRI). Eleven lung cancer patients underwent xenon-129 (129Xe) and helium-3 (3He) ventilation MRI and coregistered proton (1H) anatomic MRI. Expiratory and inspiratory breath-hold CTs were used for deformable image registration and calculation of 3 CT-ventilation metrics: Hounsfield unit (CTHU), Jacobian (CTJac), and specific gas volume change (CTSGV). Inspiration CT and hyperpolarized gas ventilation MRI were registered via same-breath anatomic 1H-MRI. Voxel-wise Spearman correlation coefficients were calculated between each CT-ventilation image and its corresponding 3He-/129Xe-MRI, and for the mean values in regions of interest (ROIs) ranging from fine to coarse in-plane dimensions of 5×5, 10×10, 15×15, and 20×20, located within the lungs as defined by the same-breath 1H-MRI lung mask. Correlation of 3He and 129Xe-MRI was also assessed. Spatial correlation of CT-ventilation against 3He/129Xe-MRI increased with ROI size. For example, for CTHU, mean±SD Spearman coefficients were 0.37±0.19/0.33±0.17 at the voxel-level and 0.52±0.20/0.51±0.18 for 20×20 ROIs, respectively. Correlations were stronger for CTHU than for CTJac or CTSGV. Correlation of 3He with 129Xe-MRI was consistently higher than either gas against CT-ventilation maps over all ROIs (P<.05). No significant differences were observed between CT-ventilation versus 3He-MRI and CT-ventilation versus 129Xe-MRI. Comparison of ventilation-related measures from CT and registered hyperpolarized gas MRI is feasible at a voxel level using a dedicated acquisition and analysis protocol. Moderate correlation between CT-ventilation and MRI exists at a regional level. Correlation between MRI and CT is significantly less than that between 3He and 129Xe-MRI, suggesting that CT-ventilation surrogate measures may not be measuring lung ventilation alone.

Airway Inflammation and Inflammatory Biomarkers.

Severe asthma is a complex disease consisting of different endotypes with different inflammatory and clinicopathological characteristics due to the heterogeneity of immune responses and smooth muscle dysfunction. There is an unmet clinical need to develop and to validate biomarkers that can differentiate between the asthma endotypes and guide clinical management, particularly since the availability of biologicals directed against T2 cytokines. The presence of a "Th2 endotype" is currently assessed in clinical practice using markers, such as eosinophil count in sputum or blood, fraction of exhaled nitric oxide, and immunoglobulin E. Individually or in combination, they may help to identify, for example, if the dominant effector protein is interleukin (IL) 5, IL13, or IgE. There is no reliable marker of a "non-Th2 endotype" although sputum neutrophil may provide some indication. The unbiased systems biology approach to severe asthma endotyping which integrates omics signatures and clinical data using large cohort studies may provide more comprehensive information than simple cellular measurements. Novel imaging techniques, such as hyperpolarized noble gas magnetic resonance imaging and computed tomography parametric response maps and metabolomics profiling in breath and other body fluids are also being evaluated as potential biomarkers to guide therapy and to assess prognosis.

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.

Functional Image-guided Radiotherapy Planning for Normal Lung Avoidance

For patients with lung cancer undergoing curative intent radiotherapy, functional lung imaging can be incorporated into treatment planning to modify the dose distribution within non-target volume lung by differentiation of lung regions that are functionally defective or viable. This concept of functional image-guided lung avoidance treatment planning has been investigated with several imaging modalities, primarily single photon emission computed tomography (SPECT), but also hyperpolarised gas magnetic resonance (MR) imaging, positron emission tomography (PET) and computed tomography (CT)-based measures of lung biomechanics. Here, we review the application of each of these modalities, review practical issues of lung avoidance implementation, including image registration and the role of both ventilation and perfusion imaging, and provide guidelines for reporting of future lung avoidance planning studies.

Hyperpolarized Gas Magnetic Resonance Lung Imaging in Children and Young Adults.

The assessment of early pulmonary disease and its severity can be difficult in young children, as procedures such as spirometry cannot be performed on them. Computed tomography provides detailed structural images of the pulmonary parenchyma, but its major drawback is that the patient is exposed to ionizing radiation. In this context, magnetic resonance imaging (MRI) is a promising technique for the evaluation of pediatric lung disease, especially when serial imaging is needed. Traditionally, MRI played a small role in evaluating the pulmonary parenchyma. Because of its low proton density, the lungs display low signal intensity on conventional proton-based MRI. Hyperpolarized (HP) gases are inhaled contrast agents with an excellent safety profile and provide high signal within the lung, allowing for high temporal and spatial resolution imaging of the lung airspaces. Besides morphologic information, HP MR images also offer valuable information about pulmonary physiology. HP gas MRI has already made new contributions to the understanding of pediatric lung diseases and may become a clinically useful tool. In this article, we discuss the HP gas MRI technique, special considerations that need to be made when imaging children, and the role of MRI in 2 of the most common chronic pediatric lung diseases, asthma and cystic fibrosis. We also will discuss how HP gas MRI may be used to evaluate normal lung growth and development and the alterations occurring in chronic lung disease of prematurity and in patients with a congenital diaphragmatic hernia.

A method for quantitative analysis of regional lung ventilation using deformable image registration of CT and hybrid hyperpolarized gas/1H MRI

Hyperpolarized gas magnetic resonance imaging (MRI) generates highly detailed maps of lung ventilation and physiological function while CT provides corresponding anatomical and structural information. Fusion of such complementary images enables quantitative analysis of pulmonary structure-function. However, direct image registration of hyperpolarized gas MRI to CT is problematic, particularly in lungs whose boundaries are difficult to delineate due to ventilation heterogeneity. This study presents a novel indirect method of registering hyperpolarized gas MRI to CT utilizing 1H-structural MR images that are acquired in the same breath-hold as the gas MRI. The feasibility of using this technique for regional quantification of ventilation of specific pulmonary structures is demonstrated for the lobes.The direct and indirect methods of hyperpolarized gas MRI to CT image registration were compared using lung images from 15 asthma patients. Both affine and diffeomorphic image transformations were implemented. Registration accuracy was evaluated using the target registration error (TRE) of anatomical landmarks identified on 1H MRI and CT. The Wilcoxon signed-rank test was used to test statistical significance.For the affine transformation, the indirect method of image registration was significantly more accurate than the direct method (TRE = 14.7 ± 3.2 versus 19.6 ± 12.7 mm, p = 0.036). Using a deformable transformation, the indirect method was also more accurate than the direct method (TRE = 13.5 ± 3.3 versus 20.4 ± 12.8 mm, p = 0.006).Accurate image registration is critical for quantification of regional lung ventilation with hyperpolarized gas MRI within the anatomy delineated by CT. Automatic deformable image registration of hyperpolarized gas MRI to CT via same breath-hold 1H MRI is more accurate than direct registration. Potential applications include improved multi-modality image fusion, functionally weighted radiotherapy planning, and quantification of lobar ventilation in obstructive airways disease.

Putting lung function and physiology into perspective: cystic fibrosis in adults.

Adult cystic fibrosis (CF) is notable for the wide heterogeneity in severity of disease expression, both between patients and within the lungs of individuals. Although CF airways disease appears to start in the small airways, in adults there is typically widespread bronchiectasis, increased airway secretions, and extensive obstruction and inflammation of the small airways. The complexity and heterogeneity of airways disease in CF means that although there are many different methods of assessing and describing lung 'function', none of these single-dimensional tests is able to provide a comprehensive assessment of lung physiology across the spectrum seen in adult CF. The most widely described measure, the forced expiratory volume in 1 s, remains a useful and simple clinical tool, but is insensitive to early changes and may be dissociated from other more detailed assessments of disease severity such as computed tomography. In this review, we also discuss the use of more sensitive novel assessments such as multiple breath washout tests and impulse oscillometry, as well as the role of cardiopulmonary exercise testing. In the future, hyperpolarized gas magnetic resonance imaging techniques that combine regional structural and functional information may help us to better understand these measures, their applications and limitations.

Assessment of Repeatability of Hyperpolarized Gas MR Ventilation Functional Imaging in Cystic Fibrosis

Hyperpolarized (HP) gas magnetic resonance imaging (MRI) is an advanced imaging technique that provides high-resolution regional information on lung function without using ionizing radiation. Before this modality can be considered for assessing clinical or investigational interventions, baseline repeatability needs to be established. We assessed repeatability of lung function measurement using HP helium-3 MRI (HP (3)He MRI) in a small cohort of patients with cystic fibrosis (CF). We examined repeatability of HP (3)He MR images of five patients with CF in four scanning sessions over a 4-week period. We acquired images on a Philips 3.0Tesla Achieva MRI scanner using a quadrature, flexible, wrap-around, (3)He radiofrequency coil with a fast gradient-echo pulse sequence. We determined ventilation volume and ventilation defect volume using an advanced semiautomatic segmentation algorithm and also quantified ventilation heterogeneity. There were no significant differences in total ventilation volume, ventilation defect volume, ventilation defect percentage, or mean ventilation heterogeneity (repeated-measures analysis of variance, P=.2116, P=.2825, P=.2871, and P=.7265, respectively) in the patients across the four scanning sessions. Our results indicate that total ventilation volume, ventilation defect volume, ventilation defect percentage, and mean ventilation heterogeneity as assessed by HP gas MRI in CF patients with stable health are reproducible over time. This repeatability and the technique's capability to provide noninvasive high-resolution data on regional lung function without ionizing radiation make (3)He MRI a potentially useful outcome measure for CF-related clinical trials.

In vivo lung morphometry with accelerated hyperpolarized (3) He diffusion MRI: a preliminary study.

Parallel imaging can be used to reduce imaging time and to increase the spatial coverage in hyperpolarized gas magnetic resonance imaging of the lung. In this proof-of-concept study, we investigate the effects of parallel imaging on the morphometric measurement of lung microstructure using diffusion magnetic resonance imaging with hyperpolarized (3) He. Fully sampled and under-sampled multi-b diffusion data were acquired from human subjects using an 8-channel (3) He receive coil. A parallel imaging reconstruction technique (generalized autocalibrating partially parallel acquisitions [GRAPPA]) was used to reconstruct under-sampled k-space data. The morphometric results of the generalized autocalibrating partially parallel acquisitions-reconstructed data were compared with the results of fully sampled data for three types of subjects: healthy volunteers, mild, and moderate chronic obstructive pulmonary disease patients. Morphometric measurements varied only slightly at mild acceleration factors. The results were largely well preserved compared to fully sampled data for different lung conditions. Parallel imaging, given sufficient signal-to-noise ratio, provides a reliable means to accelerate hyperpolarized-gas magnetic resonance imaging with no significant difference in the measurement of lung morphometry from the fully sampled images. GRAPPA is a promising technique to significantly reduce imaging time and/or to improve the spatial coverage for the morphometric measurement with hyperpolarized gases.

Pulmonary Functional Imaging Using Hyperpolarized Noble Gas MRI: Six Years of Start-up Experience at a Single Site

In this review, we summarize our experience evaluating pulmonary function in 330 different subjects using hyperpolarized noble gas magnetic resonance imaging (MRI) after enrollment and screening of >1100 subjects with and without respiratory disease during the period February 1, 2006, through November 1,2012. We discuss the feasibility of hyperpolarized gas MRI research in a small nonhospital research unit and provide an overview of our experience since we initiated patient-based studies. We also discuss the importance of infrastructure support, collaboration, research trainees, and a large and willing patient population that helped to advance the research and technological deliverables. A summary of patient safety and tolerability, key feasibility, and research milestones is provided, as well as a roadmap for future studies. Hyperpolarized (3)He and (129)Xe gas MRI is feasible at smaller centers without significant human resources for large and small longitudinal studies by virtue of its excellent patient safety and tolerability, the speed with which images can be acquired and quantitatively analyzed and the high spatial-temporal dynamics of the method that allows for acute and chronic therapy studies. The hyperpolarized noble gas MRI community's highly collaborative efforts and motivation to further the development and application of this tool has resulted in a moment-of-opportunity to translate the method clinically to provide an improved understanding of pulmonary disease. There are, as well, new and unprecedented opportunities for the evaluation of disease progression and to help develop the new treatments and interventions critically required for chronic pulmonary disease.

Measuring and imaging small airways dysfunction in asthma

Asthma is a chronic inflammatory disorder of the airways causing typical symptoms, and the diagnosis is supported by evidence of airflow obstruction which is variable, reversible or inducible. However, standard assessment of lung function with spirometry does not measure dysfunction in small airways which are < 2 mm in diameter towards the periphery of the lung. These airways make only a small contribution to airway resistance under normal circumstances. Nevertheless, there is mounting evidence that pathology and dysfunction in these small airways are implicated in the pathogenesis and natural history of asthma. Using forced oscillation and the multibreath nitrogen washout techniques, uneven ventilation (ventilation heterogeneity) due to small airways dysfunction has been shown to be an important marker of asthma disease activity, even in the absence of abnormalities in standard spirometric measurements. Recent advances in imaging research, particularly with hyperpolarised gas magnetic resonance imaging, have also given insights into the significance and dynamic nature of ventilation heterogeneity in asthma. The challenge is to integrate these new physiological and imaging insights to further our understanding of asthma and facilitate potential new treatments.

Imaging the interaction of atelectasis and overdistension in surfactant-depleted lungs.

Atelectasis and surfactant depletion may contribute to greater distension-and thereby injury-of aerated lung regions; recruitment of atelectatic lung may protect these regions by attenuating such overdistension. However, the effects of atelectasis (and recruitment) on aerated airspaces remain elusive. We tested the hypothesis that during mechanical ventilation, surfactant depletion increases the dimensions of aerated airspaces and that lung recruitment reverses these changes. Prospective imaging study in an animal model. Research imaging facility. Twenty-seven healthy Sprague Dawley rats. Surfactant depletion was obtained by saline lavage in anesthetized, ventilated rats. Alveolar recruitment was accomplished using positive end-expiratory pressure and exogenous surfactant administration. Airspace dimensions were estimated by measuring the apparent diffusion coefficient of He, using diffusion-weighted hyperpolarized gas magnetic resonance imaging. Atelectasis was demonstrated using computerized tomography and by measuring oxygenation. Saline lavage increased atelectasis (increase in nonaerated tissue from 1.2% to 13.8% of imaged area, p < 0.001), and produced a concomitant increase in mean apparent diffusion coefficient (~33%, p < 0.001) vs. baseline; the heterogeneity of the computerized tomography signal and the variance of apparent diffusion coefficient were also increased. Application of positive end-expiratory pressure and surfactant reduced the mean apparent diffusion coefficient (~23%, p < 0.001), and its variance, in parallel to alveolar recruitment (i.e., less computerized tomography densities and heterogeneity, increased oxygenation). Overdistension of aerated lung occurs during atelectasis is detectable using clinically relevant magnetic resonance imaging technology, and could be a key factor in the generation of lung injury during mechanical ventilation. Lung recruitment by higher positive end-expiratory pressure and surfactant administration reduces airspace distension.

Hyperpolarized 129Xe Magnetic Resonance Imaging: Tolerability in Healthy Volunteers and Subjects with Pulmonary Disease

The objective of this study was to evaluate the tolerability of hyperpolarized (129)Xe gas inhaled from functional residual capacity and magnetic resonance imaging in healthy subjects and those with pulmonary disease. Twelve healthy volunteers (mean age, 59 ± 17 years), seven subjects with asthma (mean age, 47 ± 7 years), 10 subjects with chronic obstructive pulmonary disease (mean age, 74 ± 4 years), three subjects with cystic fibrosis (mean age, 27 ± 10 years), and a single subject with radiation-induced lung injury (age, 66 years) were enrolled and evaluated over 43 visits with 136 anoxic inhalations of 500 mL (129)Xe gas mixed with 500 mL (4)He gas. Oxygen saturation and heart rate were monitored during the breath-hold and imaging; subjects were queried for adverse events (AEs) before and immediately following gas inhalation and for 24 hours after the last dose. No subjects withdrew from the study or reported serious, hypoxic, or severe AEs. Over the course of 136 dose administrations, two mild AEs (1%) were reported in two different subjects (two of 33 [6%]). One of these AEs (light-headedness) was temporally related and judged as possibly related to (129)Xe administration and resolved without treatment within 2 minutes. Statistically significant but clinically insignificant changes in oxygen saturation and heart rate were observed after inhalation (P < .001), and both resolved 1 minute later, with no difference between subject groups. Inhalation of hyperpolarized (129)Xe gas and subsequent magnetic resonance imaging were well tolerated in healthy subjects and ambulatory subjects with obstructive and restrictive pulmonary disease.