Magnetic Resonance Imaging Ventilation 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.

Comparison of Free-Breathing 3D Phase-Resolved Functional Lung (PREFUL) MRI With Dynamic 19 F Ventilation MRI in Patients With Obstructive Lung Disease and Healthy Volunteers.

Non-contrast-enhanced 1 H magnetic resonance imaging (MRI) with full lung coverage shows promise for assessment of regional lung ventilation but a comparison with direct ventilation measurement using 19 F MRI is lacking. To compare ventilation parameters calculated using 3D phase-resolved functional lung (PREFUL) MRI with 19 F MRI. Prospective. Fifteen patients with asthma, 14 patients with chronic obstructive lung disease, and 13 healthy volunteers. A 3D gradient-echo pulse sequence with golden-angle increment and stack-of-stars encoding at 1.5 T. All participants underwent 3D PREFUL MRI and 19 F MRI. For 3D PREFUL, static regional ventilation (RVent) and dynamic flow-volume cross-correlation metric (FVL-CM) were calculated. For both parameters, ventilation defect percentage (VDP) values and ventilation defect (VD) maps (including a combination of both parameters [VDPCombined ]) were determined. For 19 F MRI, images from eight consecutive breaths under volume-controlled inhalation of perfluoropropane were acquired. Time-to-fill (TTF) and wash-in (WI) parameters were extracted. For all 19 F parameters, a VD map was generated and the corresponding VDP values were calculated. For all parameters, the relationship between the two techniques was assessed using a Spearman correlation (r). Differences between VDP values were compared using Bland-Altman analysis. For regional comparison of VD maps, spatial overlap and Sørensen-Dice coefficients were computed. 3D PREFUL VDP values were significantly correlated to VDP measures by 19 F (r range: 0.59-0.70). For VDPRVent , no significant bias was observed with VDP of the third and fourth breath (bias range = -6.8:7.7%, P range = 0.25:0.30). For VDPFVL-CM , no significant bias was found with VDP values of fourth-eighth breaths (bias range = -2.0:12.5%, P range = 0.12:0.75). The overall spatial overlap of all VD maps increased with each breath, ranging from 61% to 81%, stabilizing at the fourth breath. 3D PREFUL MRI parameters showed moderate to strong correlation with 19 F MRI. Depending on the 3D PREFUL VD map, the best regional agreement was found to 19 F VD maps of third-fifth breath. 3 TECHNICAL EFFICACY: Stage 2.

Chest MRI and CT Predictors of 10-Year All-Cause Mortality in COPD

Pulmonary imaging measurements using magnetic resonance imaging (MRI) and computed tomography (CT) have the potential to deepen our understanding of chronic obstructive pulmonary disease (COPD) by measuring airway and parenchymal pathologic information that cannot be provided by spirometry. Currently, MRI and CT measurements are not included in mortality risk predictions, diagnosis, or COPD staging. We evaluated baseline pulmonary function, MRI and CT measurements alongside imaging texture-features to predict 10-year all-cause mortality in ex-smokers with (n = 93; 31 females; 70 ± 9years) and without (n = 69; 29 females, 69 ± 9years) COPD. CT airway and vessel measurements, helium-3 (3He) MRI ventilation defect percent (VDP) and apparent diffusion coefficients (ADC) were quantified. MRI and CT texture-features were extracted using PyRadiomics (version2.2.0). Associations between 10-year all-cause mortality and all clinical and imaging measurements were evaluated using multivariable regression model odds-ratios. Machine-learning predictive models for 10-year all-cause mortality were evaluated using area-under-receiver-operator-characteristic-curve (AUC), sensitivity and specificity analyses. DLCO (%pred) (HR = 0.955, 95%CI: 0.934-0.976, p < 0.001), MRI ADC (HR = 1.843, 95%CI: 1.260-2.871, p < 0.001), and CT informational-measure-of-correlation (HR = 3.546, 95% CI: 1.660-7.573, p = 0.001) were the strongest predictors of 10-year mortality. A machine-learning model trained on clinical, imaging, and imaging textures was the best predictive model (AUC = 0.82, sensitivity = 83%, specificity = 84%) and outperformed the solely clinical model (AUC = 0.76, sensitivity = 77%, specificity = 79%). In ex-smokers, regardless of COPD status, addition of CT and MR imaging texture measurements to clinical models provided unique prognostic information of mortality risk that can allow for better clinical management.Clinical Trial Registration: www.clinicaltrials.gov NCT02279329

Evaluation of image registration algorithms for 3D phase-resolved functional lung ventilation magnetic resonance imaging in healthy volunteers and chronic obstructive pulmonary disease patients.

The purpose of the current study was to assess the influence of the registration algorithms on the repeatability of three-dimensional (3D) phase-resolved functional lung (PREFUL) ventilation magnetic resonance imaging (MRI). Twenty-three healthy volunteers and 10 patients with chronic obstructive pulmonary disease (COPD) underwent 3D PREFUL MRI during tidal breathing. The registration of dynamically acquired data to a fixed image was executed using single-step, stepwise, and group-oriented registration (GOREG) approaches. Advanced Normalization Tools (ANTs) and the Forsberg image-registration package were used for the registration. Image registration algorithms were tested for differences and evaluated by the repeatability analysis of ventilation parameters using coefficient of variation (CoV), intraclass-correlation coefficient, Bland-Altman plots, and correlation to spirometry. Also, the registration time and image quality were computed for all registration approaches. Very strong to strong correlations (r range: 0.917-0.999) were observed between ventilation parameters derived using various registration approaches. Median CoV values of the cross-correlation (CC) parameter were significantly lower (all p ≤ 0.0054) for ANTs GOREG compared with single-step and stepwise ANTs registration. The majority of comparisons between COPD patients and age-matched healthy volunteers showed agreement among the registration approaches. The repeatability of regional ventilation (RVent)-based ventilation defect percentage (VDPRVent ) and VDPCC was significantly higher (both p ≤ 0.0054) for Forsberg GOREG compared with ANTs GOREG. All 3D PREFUL-derived ventilation parameters correlated with forced expiratory volume in 1 s (FEV1 ) and the FEV1 / forced vital capacity (FVC) ratio (all |r| > 0.40, all p< 0.03). The image sharpness of RVent maps was statistically elevated (all p< 0.001) using GOREG compared with single-step and stepwise registration approaches using ANTs. The best computational performance was achieved with Forsberg GOREG. The GOREG scheme improves the repeatability and image quality of dynamic 3D PREFUL ventilation parameters. Registration time can be ~10-fold reduced to 9min using the Forsberg method with equal or even improved repeatability and comparable PREFUL ventilation results compared with the ANTs method.

165 Hyperpolarized xenon gas ventilation magnetic resonance imaging detects lung ventilation improvement in children with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor in a multisite study

165 Hyperpolarized xenon gas ventilation magnetic resonance imaging detects lung ventilation improvement in children with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor in a multisite study

Image Phenotyping of Preterm-Born Children Using Hyperpolarized 129Xe Lung Magnetic Resonance Imaging and Multiple-Breath Washout.

Rationale: Preterm birth is associated with low lung function in childhood, but little is known about the lung microstructure in childhood. Objectives: We assessed the differential associations between the historical diagnosis of bronchopulmonary dysplasia (BPD) and current lung function phenotypes on lung ventilation and microstructure in preterm-born children using hyperpolarized 129Xe ventilation and diffusion-weighted magnetic resonance imaging (MRI) and multiple-breath washout (MBW). Methods: Data were available from 63 children (aged 9-13 yr), including 44 born preterm (⩽34 weeks' gestation) and 19 term-born control subjects (⩾37 weeks' gestation). Preterm-born children were classified, using spirometry, as prematurity-associated obstructive lung disease (POLD; FEV1 < lower limit of normal [LLN] and FEV1/FVC < LLN), prematurity-associated preserved ratio of impaired spirometry (FEV1 < LLN and FEV1/FVC ⩾ LLN), preterm-(FEV1 ⩾ LLN) and term-born control subjects, and those with and without BPD. Ventilation heterogeneity metrics were derived from 129Xe ventilation MRI and SF6 MBW. Alveolar microstructural dimensions were derived from 129Xe diffusion-weighted MRI. Measurements and Main Results: 129Xe ventilation defect percentage and ventilation heterogeneity index were significantly increased in preterm-born children with POLD. In contrast, mean 129Xe apparent diffusion coefficient, 129Xe apparent diffusion coefficient interquartile range, and 129Xe mean alveolar dimension interquartile range were significantly increased in preterm-born children with BPD, suggesting changes of alveolar dimensions. MBW metrics were all significantly increased in the POLD group compared with preterm- and term-born control subjects. Linear regression confirmed the differential effects of obstructive disease on ventilation defects and BPD on lung microstructure. Conclusion: We show that ventilation abnormalities are associated with POLD, and BPD in infancy is associated with abnormal lung microstructure.

A pilot study of function-based radiation therapy planning for lung cancer using hyperpolarized xenon-129 ventilation MRI.

PurposeRadiation‐induced lung injury (RILI) is a common side effect in patients with non‐small cell lung cancer (NSCLC) treated with radiotherapy. Minimizing irradiation into highly functional areas of the lung may reduce the occurrence of RILI. The aim of this study is to evaluate the feasibility and utility of hyperpolarized xenon‐129 magnetic resonance imaging (MRI), an imaging tool for evaluation of the pulmonary function, to guide radiotherapy planning.MethodsTen locally advanced NSCLC patients were recruited. Each patient underwent a simulation computed tomography (CT) scan and hyperpolarized xenon‐129 MRI, then received 64 Gyin 32 fractions for radiotherapy. Clinical contours were drawn on CT. Lung regions with good ventilation were contoured based on the MRI. Two intensity‐modulated radiation therapy plans were made for each patient: an anatomic plan (Plan‐A) based on CT alone and a function‐based plan (Plan‐F) based on CT and MRI results. Compared to Plan‐A, Plan‐F was generated with two additional steps: (1) beam angles were carefully chosen to minimize direct radiation entering well‐ventilated areas, and (2) additional optimization criteria were applied to well‐ventilated areas to minimize dose exposure. V20Gy, V10Gy, V5Gy, and the mean dose in the lung were compared between the two plans.ResultsPlan‐A and Plan‐F were both clinically acceptable and met similar target coverage and organ‐at‐risk constraints (p > 0.05) except for the ventilated lungs. Compared with Plan‐A, V5Gy (Plan‐A: 30.7 ± 11.0%, Plan‐F: 27.2 ± 9.3%), V10Gy (Plan‐A: 22.0 ± 8.6%, Plan‐F: 19.3 ± 7.0%), and V20Gy (Plan‐A: 12.5 ± 5.6%, Plan‐F: 11.0 ± 4.1%) for well‐ventilated lung areas were significantly reduced in Plan‐F (p < 0.05).ConclusionIn this pilot study, function‐based radiotherapy planning using hyperpolarized xenon‐129 MRI is demonstrated to be feasible in 10 patients with NSCLC with the potential to reduce radiation exposure in well‐ventilated areas of the lung defined by hyperpolarized xenon‐129 MRI.

Xenon ventilation MRI in difficult asthma: initial experience in a clinical setting.

BackgroundHyperpolarised gas magnetic resonance imaging (MRI) can be used to assess ventilation patterns. Previous studies have shown the image-derived metric of ventilation defect per cent (VDP) to correlate with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and FEV1 in asthma.ObjectivesThe aim of this study was to explore the utility of hyperpolarised xenon-129 (129Xe) ventilation MRI in clinical care and examine its relationship with spirometry and other clinical metrics in people seen in a severe asthma service.Methods26 people referred from a severe asthma clinic for MRI scanning were assessed by contemporaneous 129Xe MRI and spirometry. A subgroup of 18 patients also underwent reversibility testing with spirometry and MRI. Quantitative MRI measures of ventilation were calculated, VDP and the ventilation heterogeneity index (VHI), and compared to spirometry, Asthma Control Questionnaire 7 (ACQ7) and blood eosinophil count. Images were reviewed by a multidisciplinary team.ResultsVDP and VHI correlated with FEV1, FEV1/FVC and forced expiratory flow between 25% and 75% of FVC but not with ACQ7 or blood eosinophil count. Discordance of MRI imaging and symptoms and/or pulmonary function tests also occurred, prompting diagnostic re-evaluation in some cases.ConclusionHyperpolarised gas MRI provides a complementary method of assessment in people with difficult to manage asthma in a clinical setting. When used as a tool supporting clinical care in a severe asthma service, occurrences of discordance between symptoms, spirometry and MRI scanning indicate how MRI scanning may add to a management pathway.

Sensitive structural and functional measurements and 1-year pulmonary outcomes in pediatric cystic fibrosis

BackgroundTwo functional measurements (multiple breath washout [MBW] and hyperpolarized 129Xe ventilation magnetic resonance imaging [129Xe MRI]) have been shown to be more sensitive to cystic fibrosis (CF) lung obstruction than traditional spirometry. However, functional techniques may be sensitive to different underlying structural abnormalities. The purpose of this study was to determine relationships between these functional markers, their pathophysiology, and 1-year clinical outcomes. MethodsSpirometry, MBW, 129Xe MRI, and ultrashort echo-time (UTE) MRI were obtained in a same-day assessment of 27 pediatric CF patients (ages 11.5±5.0) who had not begun CFTR modulator therapies. UTE MRI was scored for structural abnormalities and functional metrics obtained via spirometry, MBW and 129Xe MRI. 1-year outcomes (ΔFEV1 and pulmonary exacerbations), during which ≈50% initiated modulator therapy, were obtained from the electronic medical record. ResultsMBW, 129Xe MRI, and UTE MRI detected clinically significant disease in more subjects (>78%) compared to spirometry (<30%). UTE MRI suggests increased odds of bronchial changes when mucus plugging is present in the same lobe. MBW and 129Xe MRI correlated best with mucus plugging, while spirometry correlated best with consolidations. Bronchial abnormalities were associated with future pulmonary exacerbations. ConclusionsMBW, 129Xe MRI, and UTE MRI are more sensitive for detection of pediatric CF lung disease when compared to spirometry. MBW and 129Xe MRI correlated with structural abnormalities which occur in early CF disease, suggesting MBW and 129Xe MRI are valuable tools in mild CF lung disease that can guide clinical decision making.

Quantitative Multivolume Proton-Magnetic Resonance Imaging in Lung Transplant Recipients: Comparison With Computed Tomography and Spirometry

Acute and chronic graft rejection remains the major problem in clinical surveillance of lung-transplanted patients and early detection of complications is of capital importance to allow the optimal therapeutic option. The aim of this study was to investigate the role of quantitative non contrast-enhanced magnetic resonance imaging (MRI) as a non-ionizing imaging modality to assess ventilation impairment in patients who have undergone lung transplantation, in comparison with quantitative computed tomography (CT) and spirometry. Ten lung-transplanted patients (39 ±12 years, forced-expiratory volume in 1 second (FEV1) = 81 ± 27%, forced vital capacity (FVC) = 87 ± 27%) were acquired in breath-hold at full-expiration and full-inspiration with 1.5T MRI and CT. Maps of expiratory-inspiratory difference in MR signal-intensity and CT-density were computed to estimate regional ventilation. Based on expiratory, inspiratory, and expiratory-inspiratory difference values, each pixel was classified as healthy (H), low ventilation (LV), air trapping (AT), and consolidation (C) and the percent extent of each class was quantified. Overall, expiratory-inspiratory difference in MR signal-intensity correlated to CT-density (r = 0.64, p < 0.0001) and to FEV1 (ρ = 0.71, p = 0.02). The linear correlation between MRI and CT functional maps considering all the four classes is r = 0.93 (p < 0.0001). MRI percent volumes of H, AT, and C correlated to FEV1 %pred, with the highest correlation reported for AT (ρ = -0.82). Results demonstrated a good agreement between MRI and CT ventilation imaging and between the corresponding percent volumes of lung damage. Quantitative MRI may represent an accurate non-ionizing imaging technique for longitudinal monitoring of lung transplant recipients.

The assessment of short and long term changes in lung function in CF using 129Xe MRI.

129Xe ventilation MRI is sensitive to detect early CF lung disease and response to treatment. 129Xe-MRI could play a significant role in clinical trials and patient management. Here we present data on the repeatability of imaging measurements and their sensitivity to longitudinal change. 29 children and adults with CF and a range of disease severity were assessed twice, a median [IQR] of 16.0 [14.4,19.5] months apart. Patients performed 129Xe-MRI, lung clearance index (LCI), body plethysmography and spirometry at both visits. Eleven patients repeated 129Xe-MRI in the same session to assess the within-visit repeatability. The ventilation defect percentage (VDP) was the primary metric calculated from 129Xe-MRI. At baseline, mean (sd) age=23.0 (11.1) years and FEV1 z-score=-2.2 (2.0). Median [IQR] VDP=9.5 [3.4,31.6]%, LCI=9.0 [7.7,13.7]. Within-visit and inter-visit repeatability of VDP was high. At 16 months there was no single trend of 129Xe-MRI disease progression. Visible 129Xe-MRI ventilation changes were common, which reflected changes in VDP. Based on the within-visit repeatability, a significant short-term change in VDP is >±1.6%. For longer-term follow up, changes in VDP of up to ±7.7% can be expected, or ±4.1% for patients with normal FEV1. No patient had a significant change in FEV1, however 59% had change in VDP >±1.6%. In patients with normal FEV1, there were significant changes in ventilation and in VDP. 129Xe-MRI is a highly effective method for assessing longitudinal lung disease in patients with CF. VDP has great potential as a sensitive clinical outcome measure of lung function and endpoint for clinical trials.

Is Computed Tomography Airway Count Related to Asthma Severity and Airway Structure and Function?

Rationale: In patients with asthma, X-ray computed tomography (CT) has provided evidence of thickened airway walls and airway occlusions, but the total number of CT-visible airways and its relationship with disease severity is unknown.Objectives: To measure CT total airway count (TAC) in asthma and evaluate relationships with asthma severity, airway morphology, pulmonary function, and magnetic resonance imaging (MRI) ventilation.Methods: Participants underwent post-bronchodilator inspiratory CT, and prebronchodilator and post-bronchodilator spirometry and hyperpolarized 3He MRI. CT TAC was quantified as the sum of airways in the segmented airway tree, and airway wall area percent (WA%) and lumen area were measured. MRI ventilation abnormalities were quantified as the ventilation defect percent.Measurements and Main Results: We evaluated 70 participants, including 15 Global Initiative for Asthma (GINA) steps 1 to 3, 19 GINA 4, and 36 GINA 5 participants with asthma. As compared with GINA 1 to 3, TAC was significantly diminished in GINA 4 (P = 0.03) and GINA 5 (P = 0.045). Terminal airway intraluminal occlusion was present in 5 (2 GINA 4 and 3 GINA 5) of 70 participants. Sub-subsegmental airways were CT-invisible or missing in 69 out of 70 participants; the most common number of missing sub-subsegments was 10. Participants with ≥10 missing subsegments had worse WA% (P < 0.0001), lumen area (P < 0.0001), and ventilation defect percent (P = 0.03) than those with <10 missing subsegments. In a multivariable model, TAC (standardized regression coefficient = 0.50; P = 0.001) independently predicted FEV1 (R2 = 0.27; P = 0.003) and, in a separate model, TAC (standardized regression coefficient = -0.53; P < 0.0001) independently predicted airway WA% (R2 = 0.32; P = 0.0001).Conclusions: TAC was significantly diminished in participants with greater asthma severity and was related to airway wall thickness and ventilation defects. Fewer airways in severe than in mild asthma challenges our understanding of airway disease in asthma.Clinical trial registered with www.clinicaltrials.gov (NCT02351141).

Delayed ventilation assessment using fast dynamic hyperpolarised Xenon-129 magnetic resonance imaging

ObjectivesTo investigate the use of a fast dynamic hyperpolarised 129Xe ventilation magnetic resonance imaging (DXeV-MRI) method for detecting and quantifying delayed ventilation in patients with chronic obstructive pulmonary disease (COPD).MethodsThree male participants (age range 31–43) with healthy lungs and 15 patients (M/F = 12:3, age range = 48–73) with COPD (stages II–IV) underwent spirometry tests, quantitative chest computed tomography (QCT), and DXeV-MRI at 1.5-Tesla. Regional delayed ventilation was captured by measuring the temporal signal change in each lung region of interest (ROI) in comparison to that in the trachea. In addition to its qualitative assessment through visual inspection by a clinical radiologist, delayed ventilation was quantitatively captured by calculating a covariance measurement of the lung ROI and trachea signals, and quantified using both the time delay, and the difference between the integrated areas covered by the signal-time curves of the two signals.ResultsRegional temporal ventilation, consistent with the expected physiological changes across a free breathing cycle, was demonstrated with DXeV-MRI in all patients. Delayed ventilation was observed in 13 of the 15 COPD patients and involved variable lung ROIs. This was in contrast to the control group, where no delayed ventilation was demonstrated (p = 0.0173).ConclusionsDXeV-MRI offers a non-invasive way of detecting and quantifying delayed ventilation in patients with COPD, and provides physiological information on regional pulmonary function during a full breathing cycle.Key Points• Dynamic xenon MRI allows for the non-invasive detection and measurement of delayed ventilation in COPD patients.• Dynamic xenon MRI during a free breathing cycle can provide unique information about pulmonary physiology and pulmonary disease pathophysiology.• With further validation, dynamic xenon MRI could offer a non-invasive way of measuring collateral ventilation which can then be used to guide lung volume reduction therapy (LVRT) for certain COPD patients.

Patterns of regional lung physiology in cystic fibrosis using ventilation magnetic resonance imaging and multiple-breath washout.

Hyperpolarised helium-3 (3He) ventilation magnetic resonance imaging (MRI) and multiple-breath washout (MBW) are sensitive methods for detecting lung disease in cystic fibrosis (CF). We aimed to explore their relationship across a broad range of CF disease severity and patient age, as well as assess the effect of inhaled lung volume on ventilation distribution.32 children and adults with CF underwent MBW and 3He-MRI at a lung volume of end-inspiratory tidal volume (EIV T). In addition, 28 patients performed 3He-MRI at total lung capacity. 3He-MRI scans were quantitatively analysed for ventilation defect percentage (VDP), ventilation heterogeneity index (VHI) and the number and size of individual contiguous ventilation defects. From MBW, the lung clearance index, convection-dependent ventilation heterogeneity (Scond) and convection-diffusion-dependent ventilation heterogeneity (Sacin) were calculated.VDP and VHI at EIV T strongly correlated with lung clearance index (r=0.89 and r=0.88, respectively), Sacin (r=0.84 and r=0.82, respectively) and forced expiratory volume in 1 s (FEV1) (r=-0.79 and r=-0.78, respectively). Two distinct 3He-MRI patterns were highlighted: patients with abnormal FEV1 had significantly (p<0.001) larger, but fewer, contiguous defects than those with normal FEV1, who tended to have numerous small volume defects. These two MRI patterns were delineated by a VDP of ∼10%. At total lung capacity, when compared to EIV T, VDP and VHI reduced in all subjects (p<0.001), demonstrating improved ventilation distribution and regions of volume-reversible and nonreversible ventilation abnormalities.

Development of a pulmonary imaging biomarker pipeline for phenotyping of chronic lung disease.

We designed and generated pulmonary imaging biomarker pipelines to facilitate high-throughput research and point-of-care use in patients with chronic lung disease. Image processing modules and algorithm pipelines were embedded within a graphical user interface (based on the .NET framework) for pulmonary magnetic resonance imaging (MRI) and x-ray computed-tomography (CT) datasets. The software pipelines were generated using C++ and included: (1)inhaled ventilation and apparent diffusion coefficients, (2)CT-MRI coregistration for lobar and segmental ventilation and perfusion measurements, (3)ultrashort echo-time proton density measurements, (4)free-breathing Fourier-decomposition ventilation/perfusion and free-breathing specific ventilation, (5)multivolume CT and MRI parametric response maps, and (6)MRI and CT texture analysis and radiomics. The image analysis framework was implemented on a desktop workstation/tablet to generate biomarkers of regional lung structure and function related to ventilation, perfusion, lung tissue texture, and integrity as well as multiparametric measures of gas trapping and airspace enlargement. All biomarkers were generated within 10min with measurement reproducibility consistent with clinical and research requirements. The resultant pulmonary imaging biomarker pipeline provides real-time and automated lung imaging measurements for point-of-care and high-throughput research.

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.

Human Pulmonary Hyperpolarized 129Xe MRI: a Preliminary Study**Supported by the National Natural Science Foundation of China under Grant Nos 81227902 and 81625011, the National Key Research and Development Program of China under Grant No 2016YFC1304702, and the Key Research Program of Frontier Sciences of CAS (QYZDY-SSW-SLH018).

We study the feasibility and safety of human lung hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI). There is no significant change in physiological parameters before and after the examinations of all subjects. Compared with computed tomography, HP 129Xe MRI is sensitive to earlier and smaller ventilation defects. The distribution of the HP 129Xe MRI signal reflects the pulmonary compliance with the gravity gradient. This is the first application of HP 129Xe MRI ventilation imaging in China, and this technology is expected to provide more useful information for clinical practice.

Oscillometry and pulmonary MRI measurements of ventilation heterogeneity in obstructive lung disease: relationship to quality of life and disease control.

Ventilation heterogeneity is a hallmark finding in obstructive lung disease and may be evaluated using a variety of methods, including multiple-breath gas washout and pulmonary imaging. Such methods provide an opportunity to better understand the relationships between structural and functional abnormalities in the lungs, and their relationships with important clinical outcomes. We measured ventilation heterogeneity and respiratory impedance in 100 subjects [50 patients with asthma, 22 ex-smokers, and 28 patients with chronic obstructive pulmonary disease (COPD)] using oscillometry and hyperpolarized 3He magnetic resonance imaging (MRI) and determined their relationships with quality of life scores and disease control/exacerbations. We also coregistered MRI ventilation maps to a computational airway tree model to generate patient-specific respiratory impedance predictions for comparison with experimental measurements. In COPD and asthma patients, respectively, forced oscillation technique (FOT)-derived peripheral resistance (5-19 Hz) and MRI ventilation defect percentage (VDP) were significantly related to quality of life (FOT: COPD ρ = 0.4, P = 0.004; asthma ρ = -0.3, P = 0.04; VDP: COPD ρ = 0.6, P = 0.003; asthma ρ = -0.3, P = 0.04). Patients with poorly controlled asthma (Asthmatic Control Questionnaire >2) had significantly increased resistance (5 Hz: P = 0.01; 5-19 Hz: P = 0.006) and reactance (5 Hz: P = 0.03). FOT-derived peripheral resistance (5-19 Hz) was significantly related to VDP in patients with asthma and COPD patients (asthma: ρ = 0.5, P < 0.001; COPD: ρ = 0.5, P = 0.01), whereas total respiratory impedance was related to VDP only in patients with asthma (resistance 5 Hz: ρ = 0.3, P = 0.02; reactance 5 Hz: ρ = -0.5, P < 0.001). Model-predicted and FOT-measured reactance (5 Hz) were correlated in patients with asthma (ρ = 0.5, P = 0.001), whereas in COPD patients, model-predicted and FOT-measured resistance (5-19 Hz) were correlated (ρ = 0.5, P = 0.004). In summary, in patients with asthma and COPD patients, we observed significant, independent relationships for FOT-measured impedance and MRI ventilation heterogeneity measurements with one another and with quality of life scores. NEW & NOTEWORTHY In 100 patients, including patients with asthma and ex-smokers, 3He MRI ventilation heterogeneity and respiratory system impedance were correlated and both were independently related to quality of life scores and asthma control. These findings demonstrated the critical relationships between respiratory system impedance and ventilation heterogeneity and their role in determining quality of life and disease control. These observations underscore the dominant role that abnormalities in the lung periphery play in ventilation heterogeneity that results in patients' symptoms.

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.

This is what asthma looks like: Review of new and emerging functional imaging methods and results

ABSTRACTIn asthma, diffuse and homogeneously distributed airway abnormalities have been thought responsible for symptoms and disease worsening, despite evidence over six-decades ago of ventilation heterogeneity using multiple-breath gas-washout studies. Such ventilation heterogeneity could stem from heterogeneously distributed airway abnormalities and, recently, pulmonary imaging including nuclear medicine methods, x-ray computed tomography (CT) and magnetic resonance imaging (MRI), has revealed focal ventilation defects and abnormal, heterogeneous ventilation patterns in asthmatics. In this review, we summarize pulmonary functional MRI findings that provide supportive evidence that in asthmatics, some ventilation abnormalities are temporally and spatially persistent while others come and go intermittently, but in the same, predictable spatial locations. Importantly, MRI ventilation defects also worsen in response to methacholine and exercise in the same spatial locations, despite differing underlying asthma response mechanisms, and in most patients, ventilation defects improve post-bronchodilator. In asthmatics, focal ventilation defects have been shown to be quantitatively and spatially related to airways with abnormal wall and lumen morphology, possibly stemming from remodelling, smooth muscle dysfunction and/or inflammation that may occur concurrently or independently. Finally, because MRI ventilation defects were also shown to be related to eosinophilic airway inflammation, asthma symptoms and disease control, we think MRI may be considered clinically to guide asthma therapy decisions in patients, to develop novel therapies and better understand mechanisms of asthma progression and therapy response in individual patients.