Hyperpolarized Gas Magnetic Resonance Imaging Research Articles

Three-Dimensional Phase Resolved Functional Lung Magnetic Resonance Imaging.

Pulmonary magnetic resonance imaging (MRI) offers a variety of radiation-free techniques tailored to assess regional lung ventilation or its surrogates. These techniques encompass direct measurements, exemplified by hyperpolarized gas MRI and fluorinated gas MRI, as well as indirect measurements facilitated by oxygen-enhanced MRI and proton-based Fourier decomposition (FD) MRI. In recent times, there has been substantial progress in the field of FD MRI, which involved improving spatial/temporal resolution, refining sequence design and postprocessing, and developing a comprehensive whole-lung approach. The two-dimensional (2D) phase-resolved functional lung (PREFUL) MRI stands out as an FD-based approach developed for the comprehensive assessment of regional ventilation and perfusion dynamics, all within a single MR acquisition. Recently, a new advancement has been made with the development of 3D PREFUL to assess dynamic ventilation of the entire lung using 8 min exam with a self-gated sequence. The 3D PREFUL acquisition involves employing a stack-of-stars spoiled-gradient-echo sequence with a golden angle increment. Following the compressed sensing image reconstruction of approximately 40 breathing phases, all the reconstructed respiratory-resolved images undergo registration onto a fixed breathing phase. Subsequently, the ventilation parameters are extracted from the registered images. In a study cohort comprising healthy volunteers and patients with chronic obstructive pulmonary disease, the 3D PREFUL ventilation parameters demonstrated strong correlations with measurements obtained from pulmonary function tests. Additionally, the interscan repeatability of the 3D PREFUL technique was deemed to be acceptable, indicating its reliability for repeated assessments of the same individuals. In summary, 3D PREFUL ventilation MRI provides a whole lung coverage and captures ventilation dynamics with enhanced spatial resolution compared to 2D PREFUL. 3D PREFUL technique offers a cost-effective alternative to hyperpolarized 129Xe MRI, making it an attractive option for patient-friendly evaluation of pulmonary ventilation.

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.

Functional lung imaging using novel and emerging MRI techniques.

Respiratory diseases are leading causes of death and disability in the world. While early diagnosis is key, this has proven difficult due to the lack of sensitive and non-invasive tools. Computed tomography is regarded as the gold standard for structural lung imaging but lacks functional information and involves significant radiation exposure. Lung magnetic resonance imaging (MRI) has historically been challenging due to its short T2 and low proton density. Hyperpolarised gas MRI is an emerging technique that is able to overcome these difficulties, permitting the functional and microstructural evaluation of the lung. Other novel imaging techniques such as fluorinated gas MRI, oxygen-enhanced MRI, Fourier decomposition MRI and phase-resolved functional lung imaging can also be used to interrogate lung function though they are currently at varying stages of development. This article provides a clinically focused review of these contrast and non-contrast MR imaging techniques and their current applications in lung disease.

Hyperpolarized 129Xe MRI at low field: Current status and future directions

Magnetic Resonance Imaging (MRI) is dictated by the magnetization of the sample, and is thus a low-sensitivity imaging method. Inhalation of hyperpolarized (HP) noble gases, such as helium–3 and xenon-129, is a non-invasive, radiation-risk free imaging technique permitting high resolution imaging of the lungs and pulmonary functions, such as the lung microstructure, diffusion, perfusion, gas exchange, and dynamic ventilation. Instead of increasing the magnetic field strength, the higher spin polarization achievable from this method results in significantly higher net MR signal independent of tissue/water concentration. Moreover, the significantly longer apparent transverse relaxation time T2* of these HP gases at low magnetic field strengths results in fewer necessary radiofrequency (RF) pulses, permitting larger flip angles; this allows for high-sensitivity imaging of in vivo animal and human lungs at conventionally low (<0.5 T) field strengths and suggests that the low field regime is optimal for pulmonary MRI using hyperpolarized gases.In this review, theory on the common spin-exchange optical-pumping method of hyperpolarization and the field dependence of the MR signal of HP gases are presented, in the context of human lung imaging. The current state-of-the-art is explored, with emphasis on both MRI hardware (low field scanners, RF coils, and polarizers) and image acquisition techniques (pulse sequences) advancements. Common challenges surrounding imaging of HP gases and possible solutions are discussed, and the future of low field hyperpolarized gas MRI is posed as being a clinically-accessible and versatile imaging method, circumventing the siting restrictions of conventional high field scanners and bringing point-of-care pulmonary imaging to global facilities.

Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial

RationaleThe long-acting β2-agonist/long-acting muscarinic antagonist combination indacaterol/glycopyrronium (IND/GLY) elicits bronchodilation, improves symptoms, and reduces exacerbations in COPD. Magnetic resonance imaging (MRI) of the lung with hyperpolarized gas and gadolinium contrast enhancement enables assessment of whole lung functional responses to IND/GLY.ObjectivesThe primary objective was assessment of effect of IND/GLY on global ventilated lung volume (%VV) versus placebo in COPD. Lung function, regional ventilation and perfusion in response to IND/GLY were also measured.MethodsThis double-blind, randomized, placebo-controlled, crossover study assessed %VV and pulmonary perfusion in patients with moderate-to-severe COPD after 8 days of once-daily IND/GLY treatment (110/50 µg) followed by 8 days of placebo, or vice versa, using inhaled hyperpolarized 3He gas and gadolinium contrast-enhanced MRI, respectively. Lung function measures including spirometry were performed for each treatment after 8 days.Measurements and main resultsOf 31 patients randomized, 29 completed both treatment periods. IND/GLY increased global %VV versus placebo (61.73% vs. 56.73%, respectively, least squares means treatment difference: 5.00% [90% CI 1.40 to 8.60]; P = 0.025). IND/GLY improved whole lung index of ventilation volume to perfusion volume (V/Q) ratio versus placebo; 94% (90% CI 83 to 105) versus 86% (90% CI 75 to 97; P = 0.047), respectively. IND/GLY showed a trend to improve diffusing capacity for carbon monoxide (DLCO) (+ 0.66 mL/min/mmHg; P = 0.082). By Day 8, forced expiratory volume in 1 s (FEV1) was increased by 0.32 L versus placebo (90% CI 0.26 to 0.38; P < 0.0001), substantiating earlier findings and providing evidence of assay sensitivity for this trial.ConclusionsIND/GLY improved lung ventilation assessed by 3He MRI after 1 week of treatment. This observation may provide mechanistic support for the symptomatic clinical benefit shown with IND/GLY in COPD.Clinical trial registered with www.clinicaltrials.gov (NCT02634983).

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.

Novel Thoracic MRI Approaches for the Assessment of Pulmonary Physiology and Inflammation.

Excessive pulmonary inflammation can lead to damage of lung tissue, airway remodelling and established structural lung disease. Novel therapeutics that specifically target inflammatory pathways are becoming increasingly common in clinical practice, but there is yet to be a similar stepwise change in pulmonary diagnostic tools. A variety of thoracic magnetic resonance imaging (MRI) tools are currently in development, which may soon fulfil this emerging clinical need for highly sensitive assessments of lung structure and function. Given conventional MRI techniques are poorly suited to lung imaging, alternate strategies have been developed, including the use of inhaled contrast agents, intravenous contrast and specialized lung MR sequences. In this chapter, we discuss technical challenges of performing MRI of the lungs and how they may be overcome. Key thoracic MRI modalities are reviewed, namely, hyperpolarized noble gas MRI, oxygen-enhanced MRI (OE-MRI), ultrashort echo time (UTE) MRI and dynamic contrast-enhanced (DCE) MRI. Finally, we consider potential clinical applications of these techniques including phenotyping of lung disease, evaluation of novel pulmonary therapeutic efficacy and longitudinal assessment of specific patient groups.

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.

Structural and Functional Pulmonary Magnetic Resonance Imaging in Pediatrics—From the Neonate to the Young Adult

The clinical imaging modalities available to investigate pediatric pulmonary conditions such as bronchopulmonary dysplasia, cystic fibrosis, and asthma are limited primarily to chest x-ray radiograph and computed tomography. As the challenges that historically limited the application of magnetic resonance imaging (MRI) to the lung have been overcome, its clinical potential has greatly expanded. In this review article, recent advances in pulmonary MRI including ultrashort echo time and hyperpolarized-gas MRI techniques are discussed with an emphasis on pediatric research and translational applications.

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.

Sputum Eosinophilia and Magnetic Resonance Imaging Ventilation Heterogeneity in Severe Asthma.

Inflammation and smooth muscle dysfunction are integral components of severe asthma that contribute to luminal obstruction causing airflow limitation, ventilation heterogeneity, and symptoms. This is important for guiding treatment decisions directed at the inflammatory (e.g., anti-T-helper cell type 2 monoclonal antibodies) and noninflammatory, smooth muscle-mediated (e.g., bronchial thermoplasty) components of severe asthma. To investigate the contribution of eosinophilic bronchitis and smooth muscle dysfunction to magnetic resonance imaging (MRI) ventilation heterogeneity in patients with severe asthma. We measured the inhaled hyperpolarized gas MRI response to salbutamol as a marker of smooth muscle dysfunction, and sputum eosinophils as a marker of airway inflammation, and their contributions to ventilation heterogeneity (quantified as the ventilation defect percent [VDP]) in 27 patients with severe asthma. Spirometry and forced oscillation airway resistance measurements were also acquired pre- and postsalbutamol. Patients were dichotomized on the basis of sputum eosinophilia, and pre- and postsalbutamol VDP and physiological measurements were evaluated. MRI VDP improved with salbutamol inhalation in patients in whom sputum eosinophilia was uncontrolled (≥3%, n = 16) (P = 0.002) and in those in whom it was controlled (<3%, n = 11) (P = 0.02), independent of improvements in FEV1, indicating smooth muscle response. In those patients in whom sputum eosinophilia was uncontrolled, greater VDP persisted postsalbutamol (P = 0.004). Postsalbutamol VDP correlated with sputum eosinophils (r = 0.63; P = 0.005). In patients with severe asthma, MRI regionally identifies the inflammatory and noninflammatory components of airway disease. Ventilation heterogeneity persists postsalbutamol in patients with uncontrolled eosinophilic bronchitis, which may be the functional consequence of airway inflammation.

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.

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.

Advances in Imaging Cystic Fibrosis Lung Disease.

Cystic fibrosis (CF) is a life shortening, multiorgan disease, in which morbidity and mortality are dominated by pulmonary pathologies, including mucous obstruction, chronic lung infections, progressive bronchiectasis, and declining lung function. Promising new therapies, including those that target the cystic fibrosis transmembrane conductance regulator (CFTR) protein, have shown impressive efficacy in treating CF patients with specific genotypes. While spirometry is the clinical gold standard for evaluating CF lung disease, it has known insensitivities to mild lung disease and statistical weaknesses in small cohorts. Imaging has begun to play an important role in evaluating the structural abnormalities associated with CF lung disease progression. X-ray computed tomography (CT) has been established as a modality with validated metrics to evaluate disease severity, even in young patients with mild disease. Magnetic resonance imaging (MRI), as a nonionizing alternative, has very strong potential for similar metrics and longitudinal use through the lifespan. In this brief review, recent advancements in imaging CF lung disease in pediatrics are discussed, specifically in the contexts of X-ray CT, ultra-short echo time MRI, and hyperpolarized-gas MRI, with an emphasis on how emerging techniques will likely impact the management of CF lung disease in the era of CFTR-modulator therapies, targeted at smaller subpopulations of CF with specific genotypes. In the future, techniques that provide sensitive, quantitative measurements of regional lung structure and function longitudinally will become increasingly important as outcome measures for clinical trials and for monitoring individual CF patients.

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.