Reproducibility of pulmonary magnetic resonance angiography in adults with muco-obstructive pulmonary disease.

BACKGROUND: Recent studies support magnetic resonance angiography (MRA) as a diagnostic tool for pulmonary arterial disease. PURPOSE: To determine MRA image quality and reproducibility, and the dependence of MRA image quality and reproducibility on disease severity in patients with chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). MATERIAL AND METHODS: Twenty patients with COPD (mean age 66.5 ± 8.9 years; FEV1% = 42.0 ± 13.3%) and 15 with CF (mean age 29.3 ± 9.3 years; FEV1% = 66.6 ± 15.8%) underwent morpho-functional chest magnetic resonance imaging (MRI) including time-resolved MRA twice one month apart (MRI1, MRI2), and COPD patients underwent non-contrast computed tomography (CT). Image quality was assessed visually using standardized subjective 5-point scales. Contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were measured by regions of interest. Disease severity was determined by spirometry, a well-evaluated chest MRI score, and by computational CT emphysema index (EI) for COPD. RESULTS: Subjective image quality was diagnostic for all MRA at MRI1 and MRI2 (mean score = 4.7 ± 0.6). CNR and SNR were 4 43.8 ± 8.7 and 50.5 ± 8.7, respectively. Neither image quality score nor CNR or SNR correlated with FEV1% or chest MRI score for COPD and CF (r = 0.239-0.248). CNR and SNR did not change from MRI1 to MRI2 (P = 0.434-0.995). Further, insignificant differences in CNR and SNR between MRA at MRI1 and MRI2 did not correlate with FEV1% nor chest MRI score in COPD and CF (r = -0.238-0.183), nor with EI in COPD (r = 0.100-0.111). CONCLUSION: MRA achieved diagnostic quality in COPD and CF patients and was highly reproducible irrespective of disease severity. This supports MRA as a robust alternative to CT in patients with underlying muco-obstructive lung disease.

First experience with real-time magnetic resonance imaging-based investigation of respiratory influence on cardiac function in pediatric congenital heart disease patients with chronic right ventricular volume overload.

BACKGROUND: Congenital heart disease (CHD) is often associated with chronic right ventricular (RV) volume overload. Real-time magnetic resonance imaging (MRI) enables the analysis of cardiac function during free breathing. OBJECTIVE: To evaluate the influence of respiration in pediatric patients with CHD and chronic RV volume overload. METHODS AND MATERIALS: RV volume overload patients (n=6) and controls (n=6) were recruited for cardiac real-time MRI at 1.5 tesla during free breathing. Breathing curves from regions of interest reflecting the position of the diaphragm served for binning images in four different tidal volume classes, each in inspiration and expiration. Tidal volumes were estimated from these curves by data previously obtained by magnetic resonance-compatible spirometry. Ventricular volumes indexed to body surface area and Frank-Starling relationships referenced to the typical tidal volume indexed to body height (TTVi) were compared. RESULTS: Indexed RV end-diastolic volume (RV-EDVi) and indexed RV stroke volume (RV-SVi) increased during inspiration (RV-EDVi/TTVi: RV load: + 16 ± 4%; controls: + 22 ± 13%; RV-SVi/TTVi: RV load: + 21 ± 6%; controls: + 35 ± 17%; non-significant for comparison). The increase in RV ejection fraction during inspiration was significantly lower in RV load patients (RV load: + 1.1 ± 2.2%; controls: + 6.1 ± 1.5%; P=0.01). The Frank-Starling relationship of the RV provided a significantly reduced slope estimate in RV load patients (inspiration: RV load: 0.75 ± 0.11; controls: 0.92 ± 0.02; P=0.02). CONCLUSION: In pediatric patients with CHD and chronic RV volume overload, cardiac real-time MRI during free breathing in combination with respiratory-based binning indicates an impaired Frank-Starling relationship of the RV.

Quantification of pulmonary perfusion abnormalities using DCE-MRI in COPD: comparison with quantitative CT and pulmonary function.

OBJECTIVES: Pulmonary perfusion abnormalities are prevalent in patients with chronic obstructive pulmonary disease (COPD), are potentially reversible, and may be associated with emphysema development. Therefore, we aimed to evaluate the clinical meaningfulness of perfusion defects in percent (QDP) using DCE-MRI. METHODS: We investigated a subset of baseline DCE-MRIs, paired inspiratory/expiratory CTs, and pulmonary function testing (PFT) of 83 subjects (age = 65.7 ± 9.0 years, patients-at-risk, and all GOLD groups) from one center of the "COSYCONET" COPD cohort. QDP was computed from DCE-MRI using an in-house developed quantification pipeline, including four different approaches: Otsu's method, k-means clustering, texture analysis, and 80th percentile threshold. QDP was compared with visual MRI perfusion scoring, CT parametric response mapping (PRM) indices of emphysema (PRMEmph) and functional small airway disease (PRMfSAD), and FEV1/FVC from PFT. RESULTS: All QDP approaches showed high correlations with the MRI perfusion score (r = 0.67 to 0.72, p < 0.001), with the highest association based on Otsu's method (r = 0.72, p < 0.001). QDP correlated significantly with all PRM indices (p < 0.001), with the strongest correlations with PRMEmph (r = 0.70 to 0.75, p < 0.001). QDP was distinctly higher than PRMEmph (mean difference = 35.85 to 40.40) and PRMfSAD (mean difference = 15.12 to 19.68), but in close agreement when combining both PRM indices (mean difference = 1.47 to 6.03) for all QDP approaches. QDP correlated moderately with FEV1/FVC (r = - 0.54 to - 0.41, p < 0.001). CONCLUSION: QDP is associated with established markers of disease severity and the extent corresponds to the CT-derived combined extent of PRMEmph and PRMfSAD. We propose to use QDP based on Otsu's method for future clinical studies in COPD. KEY POINTS: • QDP quantified from DCE-MRI is associated with visual MRI perfusion score, CT PRM indices, and PFT. • The extent of QDP from DCE-MRI corresponds to the combined extent of PRMEmph and PRMfSAD from CT. • Assessing pulmonary perfusion abnormalities using DCE-MRI with QDP improved the correlations with CT PRM indices and PFT compared to the quantification of pulmonary blood flow and volume.

Magnetic Resonance Imaging Detects Progression of Lung Disease and Impact of Newborn Screening in Preschool Children with Cystic Fibrosis.

Rationale: Previous cross-sectional studies have demonstrated that chest magnetic resonance imaging (MRI) is sensitive to detect early lung disease in infants and preschool children with cystic fibrosis (CF) without radiation exposure. However, the ability of MRI to detect the progression of lung disease and the impact of early diagnosis in preschool children with CF remains unknown. Objectives: To investigate the potential of MRI to detect progression of early lung disease and impact of early diagnosis by CF newborn screening (NBS) in preschool children with CF. Methods: An annual MRI was performed from diagnosis over 4 years in a cohort of 96 preschool children with CF (age, 0-4 yr) who received concurrent diagnoses on the basis of NBS (n = 28) or clinical symptoms (n = 68). MRI scans were evaluated using a dedicated morphofunctional score, and the relationship between longitudinal MRI score and respiratory symptoms, pulmonary exacerbations, upper airway microbiology, and mode of diagnosis was determined. Measurements and Main Results: The MRI global score increased in the total cohort of children with CF during preschool years (P < 0.001) and was associated with cough, pulmonary exacerbations (P < 0.0001), and the detection of Staphylococcus aureus and Haemophilus influenzae (P < 0.05). MRI-defined abnormalities in lung morphology-especially airway wall thickening/bronchiectasis-were lower in children with CF diagnosed by NBS than in children with clinically diagnosed CF throughout the observation period (P < 0.01). Conclusions: MRI detected progression of early lung disease and benefits of early diagnosis by NBS in preschool children with CF. These findings support MRI as a sensitive outcome measure for diagnostic monitoring and early intervention trials in preschool children with CF. Clinical trial registered with www.clinicaltrials.gov (NCT02270476).

Spirometry-based reconstruction of real-time cardiac MRI: Motion control and quantification of heart-lung interactions.

PURPOSE: To test the feasibility of cardiac real-time MRI in combination with retrospective gating by MR-compatible spirometry, to improve motion control, and to allow quantification of respiratory-induced changes during free-breathing. METHODS: Cross-sectional real-time MRI (1.5T; 30 frames/s) using steady-state free precession contrast during free-breathing was combined with MR-compatible spirometry in healthy adult volunteers (n = 4). Retrospective binning assigned images to classes that were defined by electrocardiogram and spirometry. Left ventricular eccentricity index as an indicator of septal position and ventricular volumes in different respiratory phases were calculated to assess heart-lung interactions. RESULTS: Real-time MRI with MR-compatible spirometry is feasible and well tolerated. Spirometry-based binning improved motion control significantly. The end-diastolic epicardial eccentricity index increased significantly during inspiration (1.04 ± 0.04 to 1.19 ± 0.05; P < .05). During inspiration, right ventricular end-diastolic volume (79 ± 17 mL/m2 to 98 ± 18 mL/m2 ), stroke volume (41 ± 8 mL/m2 to 59 ± 11 mL/m2 ) and ejection fraction (53 ± 3% to 60 ± 1%) increased significantly, whereas the end-systolic volume remained almost unchanged. Left ventricular end-diastolic volume, left ventricular stroke volume, and left ventricular ejection fraction decreased during inspiration, whereas the left ventricular end-systolic volume increased. The relationship between stroke volume and end-diastolic volume (Frank-Starling relationship) based on changes induced by respiration allowed for a slope estimate of the Frank-Starling curve to be 0.9 to 1.1. CONCLUSION: Real-time MRI during free-breathing combined with MR-compatible spirometry and retrospective binning improves image stabilization, allows quantitative image analysis, and importantly, offers unique opportunities to judge heart-lung interactions.

Fully Automated Segmentation of Pulmonary Fibrosis Using Different Software Tools.

OBJECTIVE: Evaluation of software tools for segmentation, quantification, and characterization of fibrotic pulmonary parenchyma changes will strengthen the role of CT as biomarkers of disease extent, evolution, and response to therapy in idiopathic pulmonary fibrosis (IPF) patients. METHODS: 418 nonenhanced thin-section MDCTs of 127 IPF patients and 78 MDCTs of 78 healthy individuals were analyzed through 3 fully automated, completely different software tools: YACTA, LUFIT, and IMBIO. The agreement between YACTA and LUFIT on segmented lung volume and 80th (reflecting fibrosis) and 40th (reflecting ground-glass opacity) percentile of the lung density histogram was analyzed using Bland-Altman plots. The fibrosis and ground-glass opacity segmented by IMBIO (lung texture analysis software tool) were included in specific regression analyses. RESULTS: In the IPF-group, LUFIT outperformed YACTA by segmenting more lung volume (mean difference 242 mL, 95% limits of agreement -54 to 539 mL), as well as quantifying higher 80th (76 HU, -6 to 158 HU) and 40th percentiles (9 HU, -73 to 90 HU). No relevant differences were revealed in the control group. The 80th/40th percentile as quantified by LUFIT correlated positively with the percentage of fibrosis/ground-glass opacity calculated by IMBIO (r = 0.78/r = 0.92). CONCLUSIONS: In terms of segmentation of pulmonary fibrosis, LUFIT as a shape model-based segmentation software tool is superior to the threshold-based YACTA, tool, since the density of (severe) fibrosis is similar to that of the surrounding soft tissues. Therefore, shape modeling as used in LUFIT may serve as a valid tool in the quantification of IPF, since this mainly affects the subpleural space.

Immunohistological expression of oestrogen receptor, progesterone receptor, mammaglobin, human epidermal growth factor receptor 2 and GATA-binding protein 3 in non-small-cell lung cancer.

AIMS: Non-small-cell lung cancer (NSCLC) and breast cancer are common entities. Staining for oestrogen receptor (ER), progesterone receptor (PgR), mammaglobin (MAMG) and GATA-binding protein 3 (GATA3) is frequently performed to confirm a mammary origin in the appropriate diagnostic setting. However, comprehensive data on the immunohistological expression of these markers in NSCLC are limited. Therefore, the aim of this study was to analyse a large cohort of NSCLCs and correlate the staining results with clinicopathological variables. METHODS AND RESULTS: A tissue microarray was stained for ER, PgR, MAMG, human epidermal growth factor receptor 2 (HER2), and GATA3, and included 636 adenocarcinomas (ADCs), 536 squamous cell carcinomas (SqCCs), 65 large-cell-carcinomas, 34 pleomorphic carcinomas, and 20 large-cell neuroendocrine carcinomas. HER2 status was determined for immunohistochemically positive cases with chromogenic in-situ hybridisation. Markers with a proportion of ≥5% positive cases in ADC and SqCC were considered for survival analysis. Among ADCs, 62 (10%), 17 (3%), one (<1%), seven (1%), and 49 (8%) cases were positive for ER, PgR, MAMG, HER2, and GATA3, respectively. Among SqCCs, 10 (2%), 14 (3%), two (<1%) and 109 (20%) cases were positive for ER, PgR, HER2, and GATA3, but none of the samples showed positivity for MAMG. ER positivity was associated with ADC, female sex, smaller tumour size, and lower clinical stage. None of the markers had an impact on survival. CONCLUSION: We report on ER, PgR, MAMG, HER2 and GATA3 expression in a large cohort of NSCLCs. Interpretation of these markers in the differential diagnostic setting should be based on a multimarker panel.

Echo Time-Dependence of Observed Lung T1 in Patients With Cystic Fibrosis and Correlation With Clinical Metrics.

BACKGROUND: Noninvasive monitoring of early abnormalities and therapeutic intervention in cystic fibrosis (CF) lung disease using MRI is important. Lung T1 mapping has shown potential for local functional imaging without contrast material. Recently, it was discovered that observed lung T1 depends on the measurement echo time (TE). PURPOSE: To examine TE-dependence of observed T1 in patients with CF and its correlation with clinical metrics. STUDY TYPE: Prospective. POPULATION: In all, 75 pediatric patients with CF (8.6 ± 6.1 years, range 0.1-23 years), with 32 reexamined after 1 year. FIELD STRENGTH/SEQUENCE: Patients were examined at 1.5T using an established MRI protocol and a multiecho inversion recovery 2D ultrashort echo time (UTE) sequence for T1 (TE) mapping at five TEs including TE1 = 70 µs. ASSESSMENT: Morphological and perfusion MRI were assessed by a radiologist (M.W.) with 11 years of experience using an established CF-MRI scoring system. T1 (TE) was quantified automatically. Clinical data including spirometry (FEV1pred%) and lung clearance index (LCI) were collected. STATISTICAL TESTS: T1 (TE) was correlated with the CF-MRI score, clinical data, and LCI. RESULTS: T1 (TE) showed a different curvature in CF than in healthy adults: T1 at TE1 was shorter in CF (1157 ms ± 73 ms vs. 1047 ms ± 70 ms, P < 0.001), but longer at TE3 (1214 ms ± 72 ms vs. 1314 ms ± 68 ms, P < 0.001) and later TEs. The correlations of T1 (TE) with patient age (ρTE1-TE5 = -0.55, -0.44, -0.24, -0.30, -0.22), and LCI (ρTE1-TE5 = -0.43, -0.42, -0.33, 0.27, -0.22) were moderate at ultra-short to short TE (P < 0.001) but decreased for longer TE. Moderate but similar correlations at all TE were found with MRI perfusion score (ρTE1-TE5 = -0.43, -0.51, -0.47, -0.46, -0.44) and FEV1pred% (ρTE1-TE5 = +0.44, +0.44, +0.43, +0.40, +0.39) (P < 0.05). DATA CONCLUSION: TE should be considered when measuring lung T1 , since observed differences between CF and healthy subjects strongly depend on TE. The different variation of correlation coefficients with TE for structural vs. functional metrics implies that TE-dependence holds additional information which may help to discern effects of tissue structural abnormalities and abnormal perfusion. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1645-1654.

Quantitative CT detects progression in COPD patients with severe emphysema in a 3-month interval.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by variable contributions of emphysema and airway disease on computed tomography (CT), and still little is known on their temporal evolution. We hypothesized that quantitative CT (QCT) is able to detect short-time changes in a cohort of patients with very severe COPD. METHODS: Two paired in- and expiratory CT each from 70 patients with avg. GOLD stage of 3.6 (mean age = 66 ± 7.5, mean FEV1/FVC = 35.28 ± 7.75) were taken 3 months apart and analyzed by fully automatic software computing emphysema (emphysema index (EI), mean lung density (MLD)), air-trapping (ratio expiration to inspiration of mean lung attenuation (E/I MLA), relative volume change between - 856 HU and - 950 HU (RVC856-950)), and parametric response mapping (PRM) parameters for each lobe separately and the whole lung. Airway metrics measured were wall thickness (WT) and lumen area (LA) for each airway generation and the whole lung. RESULTS: The average of the emphysema parameters (EI, MLD) increased significantly by 1.5% (p < 0.001) for the whole lung, whereas air-trapping parameters (E/I MLA, RVC856-950) were stable. PRMEmph increased from 34.3 to 35.7% (p < 0.001), whereas PRMNormal decrased from 23.6% to 22.8% (p = 0.012). WT decreased significantly from 1.17 ± 0.18 to 1.14 ± 0.19 mm (p = 0.036) and LA increased significantly from 25.08 ± 4.49 to 25.84 ± 4.87 mm2 (p = 0.041) for the whole lung. The generation-based analysis showed heterogeneous results. CONCLUSION: QCT detects short-time progression of emphysema in severe COPD. The changes were partly different among lung lobes and airway generations, indicating that QCT is useful to address the heterogeneity of COPD progression. KEY POINTS: • QCT detects short-time progression of emphysema in severe COPD in a 3-month period. • QCT is able to quantify even slight parenchymal changes, which were not detected by spirometry. • QCT is able to address the heterogeneity of COPD, revealing inconsistent changes individual lung lobes and airway generations.

Longitudinal airway remodeling in active and past smokers in a lung cancer screening population.

OBJECTIVES: To longitudinally investigate smoking cessation-related changes of quantitative computed tomography (QCT)-based airway metrics in a group of heavy smokers. METHODS: CT scans were acquired in a lung cancer screening population over 4 years at 12-month intervals in 284 long-term ex-smokers (ES), 405 continuously active smokers (CS), and 31 subjects who quitted smoking within 2 years after baseline CT (recent quitters, RQ). Total diameter (TD), lumen area (LA), and wall percentage (WP) of 1st-8th generation airways were computed using airway analysis software. Inter-group comparison was performed using Mann-Whitney U test or Student's t test (two groups), and ANOVA or ANOVA on ranks with Dunn's multiple comparison test (more than two groups), while Fisher's exact test or chi-squared test was used for categorical data. Multiple linear regression was used for multivariable analysis. RESULTS: At any time, TD and LA were significantly higher in ES than CS, for example, in 5th-8th generation airways at baseline with 6.24 mm vs. 5.93 mm (p < 0.001) and 15.23 mm2 vs. 13.51 mm2 (p < 0.001), respectively. RQ showed higher TD (6.15 mm vs. 5.93 mm, n.s.) and significantly higher LA (14.77 mm2 vs. 13.51 mm2, p < 0.001) than CS after 3 years, and after 4 years. In multivariate analyses, smoking status independently predicted TD, LA, and WP at baseline, at 3 years and 4 years (p < 0.01-0.001), with stronger impact than pack years. CONCLUSIONS: Bronchial dimensions depend on the smoking status. Smoking-induced airway remodeling can be partially reversible after smoking cessation even in long-term heavy smokers. Therefore, QCT-based airway metrics in clinical trials should consider the current smoking status besides pack years. KEY POINTS: • Airway lumen and diameter are decreased in active smokers compared to ex-smokers, and there is a trend towards increased airway wall thickness in active smokers. • Smoking-related airway changes improve within 2 years after smoking cessation. • Smoking status is an independent predictor of airway dimensions.

Transbronchial Cryobiopsies for Diagnosing Interstitial Lung Disease: Real-Life Experience from a Tertiary Referral Center for Interstitial Lung Disease.

BACKGROUND: Transbronchial cryobiopsy (cTBB) may offer an alternative to surgical lung biopsy (SLB) for histopathological diagnosis of interstitial lung diseases (ILDs). However, real-life experience is limited, although case series are increasingly reported. OBJECTIVES: We aimed to evaluate the value of cTBB performed under real-life conditions in a tertiary care center for ILDs. METHODS: Data on all patients undergoing a cTBB for evaluation of suspected ILD between October 2015 and January 2017 were included in this retrospective case series. Procedure details, complication rates, histopathological results, and diagnostic consensus reached by a multidisciplinary team (MDT) discussion were collated and evaluated. RESULTS: A total of 109 patients (mean age 64 years, range 19-85; 66% male, 38% never smokers) referred to our center with features suggestive of ILD underwent cTBB. The mean FVC% predicted was 77% (range 41-131), with a mean DLCO of 51% (range 20-86), and a 6-min walking test (6MWT) of 402 m (range 100-642). On average, 4 samples were taken from each patient (range 1-8), with a mean biopsy diameter of 5 mm (range 2-12). Complications included pneumothorax (11.9%), all treated with chest drain. Moderate bleeding occurred in 28.4% (all resolved without active measures). No acute disease exacerbations and no deaths occurred. A histopathological pattern diagnosis was possible in 80 cases (73.4%), and 26.6% of cases were considered nonspecific. An MDT consensus diagnosis was reached in 83.5% of cases. Subsequent SLB was proposed in 13 cases and performed in 8 cases. CONCLUSIONS: In the real-world setting, cTBB has a meaningful diagnostic value in the context of a MDT approach and may enable histopathological assessment even in patients with more advanced disease unsuitable for SLB.

Possible value of antifibrotic drugs in patients with progressive fibrosing non-IPF interstitial lung diseases.

BACKGROUND: Fibrosing, non-idiopathic pulmonary fibrosis (non-IPF) interstitial lung diseases (fILDs) are a heterogeneous group of diseases characterized by a different amount of inflammation and fibrosis. Therapy is currently based on corticosteroids and/or immunomodulators. However, response to these therapies is highly variable, sometimes without meaningful improvement, especially in more fibrosing forms. Pirfenidone and nintedanib have recently demonstrated to reduce functional decline in patients with IPF. However, their antifibrotic mechanism makes these two drugs an interesting approach for treatment of fibrosing ILDs other than IPF. OBJECTIVES: We here report our experience with antifibrotic drugs in fibrosing non-IPF ILDs patients having a progressive phenotype during immunosuppressive therapy. METHODS: Patients with a multidisciplinary team diagnosis of fibrosing non-IPF ILDs experiencing a progressive phenotype during treatment with corticosteroids and/or immunomodulators between October-2014 and January-2018 at our tertiary referral Center for ILDs were retrospectively analyzed. Antifibrotic therapy was administered after application with the respective health insurance company and after consent by the patient. Pulmonary-function-tests and follow-up visits were performed every 6 ± 1 months. RESULTS: Eleven patients were treated with antifibrotic drugs (8 males, mean age 62 ± 12.8 years, mean FVC% 62.8 ± 22.3, mean DLCO% 35.5 ± 10.7, median follow-up under antifibrotic treatment 11.1 months). Patients had a diagnosis of unclassifiable ILD in 6 cases, pleuroparenchymal fibroelastosis in 2 cases, idiopathic-NSIP in 1 case, asbestos-related ILD in 1 case and Hermansky-Pudlak syndrome in 1 case. Treatment before antifibrotics consisted of corticosteroids in all patients: 5 combined with Azathioprin, 1 with either methotrexate or cyclophosphamide (i.v.). Ten patients were treated with pirfenidone (2403 mg/die) and 1 with nintedanib (300 mg/die). Median FVC was 56, 56, 50%, at time points - 24, - 12, - 6 before initiation, 44% at time of initiation and 46.5% at 6 months after initiation of antifibrotic treatment. Antifibrotic treatment was generally well tolerated with a need of dose reduction in 2 cases (rash and nausea) and early termination in 3 cases. CONCLUSIONS: Antifibrotic treatment may be a valuable treatment option in patients with progressive fibrosing non-IPF ILD if currently no other treatment options exist. However, prospective, randomized clinical trials are urgently needed to assess the real impact of antifibrotic therapy in these patients.

Ten years of chest MRI for patients with cystic fibrosis : Translation from the bench to clinical routine.

BACKGROUND: Despite recent advances in our knowledge about the pathophysiology and treatment of cystic fibrosis (CF), pulmonary involvement remains the most important determinant of morbidity and mortality in patients with CF. Since lung function testing may not be sensitive enough for subclinical disease progression, and because young children may have normal spirometry results over a longer period of time, imaging today plays an increasingly important role in clinical routine and research for the monitoring of CF lung disease. In this regard, chest magnetic resonance imaging (MRI) could serve as a radiation-free modality for structural and functional lung imaging. METHODS: Our research agenda encompassed the entire process of development, implementation, and validation of appropriate chest MRI protocols for use with infant and adult CF patients alike. RESULTS: After establishing a general MRI protocol for state-of-the-art clinical 1.5-T scanners based on the available sequence technology, a semiquantitative scoring system was developed followed by cross-validation of the method against the established modalities of computed tomography, radiography, and lung function testing. Cross-sectional studies were then set up to determine the sensitivity of the method for the interindividual variation of the disease and for changes in disease severity after treatment. Finally, the MRI protocol was implemented at multiple sites to be validated in a multicenter setting. CONCLUSION: After more than a decade, lung MRI has become a valuable tool for monitoring CF in clinical routine application and as an endpoint for clinical studies.

Effect of smoking cessation on quantitative computed tomography in smokers at risk in a lung cancer screening population.

OBJECTIVE: To longitudinally evaluate effects of smoking cessation on quantitative CT in a lung cancer screening cohort of heavy smokers over 4 years. METHODS: After 4 years, low-dose chest CT was available for 314 long-term ex-smokers (ES), 404 continuous smokers (CS) and 39 recent quitters (RQ) who quitted smoking within 2 years after baseline CT. CT acquired at baseline and after 3 and 4 years was subjected to well-evaluated densitometry software, computing mean lung density (MLD) and 15th percentile of the lung density histogram (15TH). RESULTS: At baseline, active smokers showed significantly higher MLD and 15TH (-822±35 and -936±25 HU, respectively) compared to ES (-831±31 and -947±22 HU, p<0.01-0.001). After 3 years, CS again had significantly higher MLD and 15TH (-801±29 and -896±23 HU) than ES (-808±27 and -906±20 HU, p<0.01-0.001) but also RQ (-813±20 and -909±15 HU, p<0.05-0.001). Quantitative CT parameters did not change significantly after 4 years. Importantly, smoking status independently predicted MLD at baseline and year 3 (p<0.001) in multivariate analysis. CONCLUSION: On quantitative CT, lung density is higher in active smokers than ex-smokers, and sustainably decreases after smoking cessation, reflecting smoking-induced inflammation. Interpretations of quantitative CT data within clinical trials should consider smoking status. KEY POINTS: • Lung density is higher in active smokers than ex-smokers. • Lung density sustainably decreases after smoking cessation. • Impact of smoking cessation on lung density is independent of potentially confounding factors. • Smoke-induced pulmonary inflammation and particle deposition influence lung density on CT.

Comparison of Lung Clearance Index and Magnetic Resonance Imaging for Assessment of Lung Disease in Children with Cystic Fibrosis.

RATIONALE: Early onset and progression of lung disease in children with cystic fibrosis (CF) indicates that sensitive noninvasive outcome measures are needed for diagnostic monitoring and early intervention clinical trials. The lung clearance index (LCI) and chest magnetic resonance imaging (MRI) were shown to detect early lung disease in CF; however, the relationship between the two measures remains unknown. OBJECTIVES: To correlate the LCI with abnormalities detected by MRI and compare the sensitivity of the two techniques to detect responses to therapy for pulmonary exacerbations in children with CF. METHODS: LCI determined by age-adapted multiple breath washout techniques and MRI studies were performed in 97 clinically stable children with CF across the pediatric age range (0.2-21.1 yr). Furthermore, LCI (n = 26) or MRI (n = 10) were performed at the time of pulmonary exacerbation and after antibiotic therapy. MRI was evaluated using a dedicated morphofunctional score. MEASUREMENTS AND MAIN RESULTS: The LCI correlated with the global MRI score as well as MRI-defined airway wall abnormalities, mucus plugging, and abnormal lung perfusion in infants and toddlers (P < 0.05 to P < 0.001) and in older children (P < 0.001) with CF. LCI and MRI were sensitive to detect response to antibiotic therapy for pulmonary exacerbations. CONCLUSIONS: Our results indicate that LCI and MRI may be useful complementary tools for noninvasive monitoring and as quantitative endpoints in early intervention trials in children with CF. In this context, MRI enables detection of disease heterogeneity, including regional mucus plugging associated with abnormal lung perfusion in early CF lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 02270476).

Pleuroparenchymal fibroelastosis in association with carcinomas.

PPFE is a rare disease characterized by upper lobe pleural fibrosis and parenchymal fibroelastosis. Its aetiology is considered idiopathic, although possible causative factors have been described. An association of PPFE with solid tumours is unknown and has not been considered previously. We identified six patients with PPFE, four of them with a coexisting malignancy. The case series suggests that PPFE might be an implication of varying factors rather than being an exclusively idiopathic condition.

Spontaneous Pneumomediastinum as a Potential Predictor of Mortality in Patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Spontaneous pneumomediastinum (PM) is a rare event in patients with idiopathic pulmonary fibrosis (IPF) with unknown prognostic implications. OBJECTIVES: To analyze the incidence and prognostic impact of PM in a cohort of patients with IPF. METHODS: PM diagnosed by computed tomography was identified retrospectively in the clinical and radiological records of 182 patients with IPF who were admitted to our center between August 2006 and July 2013. PM patients were compared to matched IPF patients not affected by PM and analyzed for survival. RESULTS: PM occurred in 9/182 IPF patients [5%; 6 males; median age: 63 years; median percent predicted of vital capacity (VC%) at baseline: 53%]. The median time between IPF diagnosis and PM occurrence was 3 months (interquartile range: 0-33). The control group included 36 IPF patients (28 males; median age: 69 years; VC% at baseline: 57%). In a multivariate Cox regression analysis, PM was a significant predictor of mortality [hazard ratio (HR): 3.0; p = 0.032]. Considering only patients experiencing PM at the time of IPF diagnosis (n = 4), PM was a strongly significant predictor of mortality in multivariate analysis (HR: 6.4; p = 0.007). CONCLUSIONS: Spontaneous PM is a rare but serious complication in patients with IPF and may be considered as a potential predictor of mortality.

Screening for Helicobacter pylori in Idiopathic Pulmonary Fibrosis Lung Biopsies.

BACKGROUND: Increasing evidence suggests a role of gastro-oesophageal reflux (GER) in idiopathic pulmonary fibrosis (IPF) pathogenesis. Recently, an association between serum Helicobacter pylori (HP) antibody positivity and more severe disease was described, but HP has not been directly analysed in lung tissue so far. OBJECTIVE: To investigate the presence of HP in the lung tissue of IPF patients. METHODS: Two tertiary interstitial lung disease care centre databases were screened for available lung biopsy material from IPF patients. Clinical and radiological data, including presence of GER and antiacid medication, were evaluated. HP-specific PCR was carried out on the IPF lung biopsy specimens. RESULTS: A total of 39 IPF patients were included, of whom 85% were male. The patients' median age was 66 years, their vital capacity was 79% predicted, and their diffusing capacity for carbon monoxide was 53% predicted. In all, 82% of the lung biopsies were surgical and 18% transbronchial. Comorbidities were GER disease in 23% (n = 9), sleep apnoea in 13% (n = 5) and hiatal hernia in 38% of the cases (n = 15). Proton pump inhibitors were prescribed at the time of biopsy in 21% of the cases (n = 9). After a median follow-up of 25 months (range 6-69), there were 1 death, 1 lung transplantation and 8 acute exacerbations without relevant differences between the GER and non-GER subgroups. HP DNA was not detected in any of the lung tissue samples. CONCLUSION: The fact that no HP DNA was detected in the lung tissues calls into question the proposed relevance of HP to the direct pathogenesis of IPF.

T2 mapping of CT remodelling patterns in interstitial lung disease.

OBJECTIVES: To evaluate lung T2 mapping for quantitative characterization and differentiation of ground-glass opacity (GGO), reticulation (RE) and honeycombing (HC) in usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). METHODS: Twelve patients with stable UIP or NSIP underwent thin-section multislice CT and 1.5-T MRI of the lung. A total of 188 regions were classified at CT into normal (n = 29) and pathological areas, including GGO (n = 48), RE (n = 60) and HC (n = 51) predominant lesions. Entire lung T2 maps based on multi-echo single shot TSE sequence (TE: 20, 40, 79, 140, 179 ms) were generated from each subject with breath-holds at end-expiration and ECG-triggering. RESULTS: The median T2 relaxation of GGO was 67 ms (range 60-72 ms). RE predominant lesions had a median relaxation of 74 ms (range 69-79 ms), while for HC pattern this was 79 ms (range 74-89 ms). The median T2 relaxation for normal lung areas was 41 ms (ranged 38-49 ms), and showed significant difference to pathological areas (p < 0.001). A statistical difference was found between the T2 relaxation of GGO, RE and HC (p < 0.05). CONCLUSIONS: The proposed method provides quantitative information for pattern differentiation, potentially allowing for monitoring of progression and response to treatment, in interstitial lung disease. KEY POINTS: • Multi-echo single shot TSE sequence allows for entire lung T2 mapping. • Lung remodelling patterns in ILD show different T2 relaxation. • Quantitative T2 mapping may provide information for monitoring of ILD.