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In all ex-smokers, ADC values were significantly elevated in regions of PRM gas trapping, and VDP was quantitatively and spatially related to both PRM gas trapping and PRM emphysema. In patients with mild to moderate COPD, VDP was related to PRM gas trapping, whereas in patients with severe COPD, VDP correlated with both PRM gas trapping and PRM emphysema.

BackgroundAlthough radiotherapy is a key component of curative-intent treatment for locally advanced, unresectable non-small cell lung cancer (NSCLC), it can be associated with substantial pulmonary toxicity in some patients. Current radiotherapy planning techniques aim to minimize the radiation dose to the lungs, without accounting for regional variations in lung function. Many patients, particularly smokers, can have substantial regional differences in pulmonary ventilation patterns, and it has been hypothesized that preferential avoidance of functional lung during radiotherapy may reduce toxicity. Although several investigators have shown that functional lung can be identified using advanced imaging techniques and/or demonstrated the feasibility and theoretical advantages of avoiding functional lung during radiotherapy, to our knowledge this premise has never been tested via a prospective randomized clinical trial.Methods/DesignEligible patients will have Stage III NSCLC with intent to receive concurrent chemoradiotherapy (CRT). Every patient will undergo a pre-treatment functional lung imaging study using hyperpolarized 3He MRI in order to identify the spatial distribution of normally-ventilated lung. Before randomization, two clinically-approved radiotherapy plans will be devised for all patients on trial, termed standard and avoidance. The standard plan will be designed without reference to the functional state of the lung, while the avoidance plan will be optimized such that dose to functional lung is as low as reasonably achievable. Patients will then be randomized in a 1:1 ratio to receive either the standard or the avoidance plan, with both the physician and the patient blinded to the randomization results. This study aims to accrue a total of 64 patients within two years. The primary endpoint will be a pulmonary quality of life (QOL) assessment at 3 months post-treatment, measured using the functional assessment of cancer therapy–lung cancer subscale. Secondary endpoints include: pulmonary QOL at other time-points, provider-reported toxicity, overall survival, progression-free survival, and quality-adjusted survival.DiscussionThis randomized, double-blind trial will comprehensively assess the impact of functional lung avoidance on pulmonary toxicity and quality of life in patients receiving concurrent CRT for locally advanced NSCLC.Trial registrationClinicaltrials.gov identifier: NCT02002052.

Purpose To measure regional specific ventilation with free-breathing hydrogen 1 (H) magnetic resonance (MR) imaging without exogenous contrast material and to investigate correlations with hyperpolarized helium 3 (He) MR imaging and pulmonary function test measurements in healthy volunteers and patients with asthma. Materials and Methods Subjects underwent free-breathing H and static breath-hold hyperpolarizedHe MR imaging as well as spirometry and plethysmography; participants were consecutively recruited between January and June 2017. Free-breathing H MR imaging was performed with an optimized balanced steady-state free-precession sequence; images were retrospectively grouped into tidal inspiration or tidal expiration volumes with exponentially weighted phase interpolation. MR imaging volumes were coregistered by using optical flow deformable registration to generateH MR imaging-derived specific ventilation maps. Hyperpolarized He MR imaging- andH MR imaging-derived specific ventilation maps were coregistered to quantify regional specific ventilation within hyperpolarized He MR imaging ventilation masks. Differences between groups were determined with the Mann-Whitney test and relationships were determined with Spearman (ρ) correlation coefficients. Statistical analyses were performed with software. Results Thirty subjects (median age: 50 years; interquartile range [IQR]: 30 years), including 23 with asthma and seven healthy volunteers, were evaluated. BothH MR imaging-derived specific ventilation and hyperpolarized He MR imaging-derived ventilation percentage were significantly greater in healthy volunteers than in patients with asthma (specific ventilation: 0.14 [IQR: 0.05] vs 0.08 [IQR: 0.06], respectively, P< .0001; ventilation percentage: 99% [IQR: 1%] vs 94% [IQR: 5%], P < .0001). For all subjects, H MR imaging-derived specific ventilation correlated with plethysmography-derived specific ventilation (ρ = 0.54, P = .002) and hyperpolarizedHe MR imaging-derived ventilation percentage (ρ = 0.67, P < .0001) as well as with forced expiratory volume in 1 second (FEV) (ρ = 0.65, P = .0001), ratio of FEV to forced vital capacity (ρ = 0.75, P < .0001), ratio of residual volume to total lung capacity (ρ = -0.68, P< .0001), and airway resistance (ρ = -0.51, P = .004). H MR imaging-derived specific ventilation was significantly greater in the gravitational-dependent versus nondependent lung in healthy subjects (P = .02) but not in patients with asthma (P = .1). In patients with asthma, coregisteredH MR imaging specific ventilation and hyperpolarized He MR imaging maps showed that specific ventilation was diminished in correspondingHe MR imaging ventilation defects (0.05 ± 0.04) compared with well-ventilated regions (0.09 ± 0.05) (P < .0001). Conclusion H MR imaging-derived specific ventilation correlated with plethysmography-derived specific ventilation and ventilation defects seen by using hyperpolarizedHe MR imaging. RSNA, 2018 Online supplemental material is available for this article.

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Airflow limitation in chronic obstructive pulmonary disease (COPD) is associated with influx of various inflammatory cells (e.g. eosinophils, neutrophils, lymphocytes, macrophages) into the airways. Approximately one-third of stable COPD patients and one in five COPD exacerbations are associated with eosinophilic bronchitis that usually responds to inhaled or ingested corticosteroids [1]. Specific anti-eosinophil agents like mepolizumab, a humanised monoclonal antibody against interleukin 5 (IL-5), reduce severe asthma exacerbations and improve lung function [2][3][4]. The improvement in forced expiratory volume in 1 s (FEV1) is also associated with a decrease in biomarkers of airway remodelling, such as sputum hyaluronan and versican, over a 6-month treatment period [5]. It is not known if the same benefits are observed in patients with COPD and eosinophilia in whom the airflow obstruction is due to cigarette smoke-related bronchitis and emphysema.The primary objective of this "proof of principle", single centre, randomised, placebo-controlled, parallelgroup, double-blinded, 6-month trial (with 4-month follow up) was to determine if mepolizumab could decrease sputum eosinophil percentage in those patients with cigarette smoke-related COPD who have persistent sputum eosinophilia. The other objectives were to assess the effects of mepolizumab on blood eosinophil count, lung function, exacerbation rate, symptoms and quality of life, and sputum hyaluronan and versican as markers of airway remodelling. The study enrolled adults aged 40-80 years, with moderate to severe COPD (post-bronchodilator FEV1 to forced vital capacity ratio <70% and FEV1 <60% predicted, on high doses of inhaled corticosteroids and long-acting bronchodilator β-agonists, muscarinic agonist or both) and at least one major exacerbation requiring prednisone in the preceding year and who had demonstrated, within the past 24 months, at least 100 mL improvement in FEV1 with a 5-day course of 30 mg prednisone daily. Participants were current or past smokers with a tobacco smoking history of ⩾10 pack-years with sputum eosinophils >3%, or many (3+

Background: Fixed airflow limitation and ventilation heterogeneity are common in chronic obstructive pulmonary disease (COPD). Conventional noncontrast CT provides airway and parenchymal measurements but cannot be used to directly determine lung function. Purpose: To develop, train, and test a CT texture analysis and machine-learning algorithm to predict lung ventilation heterogeneity in participants with COPD. Materials and Methods: In this prospective study (ClinicalTrials.gov: NCT02723474; conducted from January 2010 to February 2017), participants were randomized to optimization (n = 1), training (n = 67), and testing (n = 27) data sets. Hyperpolarized (HP) helium 3 (3 He) MRI ventilation maps were co-registered with thoracic CT to provide ground truth labels, and 87 quantitative imaging features were extracted and normalized to lung averages to generate 174 features. The volume-of-interest dimension and the training data sampling method were optimized to maximize the area under the receiver operating characteristic curve (AUC). Forward feature selection was performed to reduce the number of features; logistic regression, linear support vector machine, and quadratic support vector machine classifiers were trained through fivefold cross validation. The highest-performing classification model was applied to the test data set. Pearson coefficients were used to determine the relationships between the model, MRI, and pulmonary function measurements. Results: The quadratic support vector machine performed best in training and was applied to the test data set. Model-predicted ventilation maps had an accuracy of 88% (95% confidence interval [CI]: 88%, 88%) and an AUC of 0.82 (95% CI: 0.82, 0.83) when the HP 3 He MRI ventilation maps were used as the reference standard. Model-predicted ventilation defect percentage (VDP) was correlated with VDP at HP 3 He MRI (r = 0.90, P , .001). Both model-predicted and HP 3 He MRI VDP were correlated with forced expiratory volume in 1 second (FEV 1