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Therapy with Elexacaftor/Tezacaftor/Ivacaftor (ETI) was recently approved for adult cystic fibrosis (CF) patients with at least one F508del mutation. However, its effects on structural and functional lung abnormalities and chronic rhinosinusitis have not been studied by imaging.19 adults with CF (mean age 31±9y, range 19-55y) underwent standardized chest magnetic resonance imaging (MRI), and nine also same-session sinonasal MRI, before (MRI1) and after (MRI2) at least one month (mean duration 5 ± 3mon) on ETI. 24 control CF patients (30±7y, range 20-44y) without ETI underwent longitudinal chest MRI, and eleven also sinonasal MRI, twice (mean interval 40±15mon). MRI was assessed using the validated chest MRI score and chronic rhinosinusitis (CRS)-MRI score. Forced expiratory volume in 1 s percent predicted (FEV1%) was measured in all patients.In controls, the chest MRI global score and CRS-MRI sum score were stable from MRI1 to MRI2. In patients under ETI, the chest MRI global score improved (-11.4 ± 4.6, P0.001), mainly due to reduction of bronchiectasis/wall thickening and mucus plugging subscores (-3.3 ± 2.2 and -5.2 ± 1.5, P0.001, respectively). The improvement in chest MRI score correlated well with improved FEV1% (r=-0.703, P0.001). The CRS-MRI sum score also improved in patients under ETI (-6.9 ± 3.0, P0.001), mainly due to a reduction of mucopyoceles in the maxillary and ethmoid sinus (-50% and -39%, P0.05, respectively).MRI detects improvements of chest MRI and CRS-MRI scores in adult CF patients who first received ETI, demonstrating reversibility of structural lung and paranasal sinus abnormalities in patients with established disease.

Lung cancer screening may provide a favorable opportunity for a spirometry examination, to diagnose participants with undiagnosed lung function impairments, or to improve targeting of computed tomography (CT) screening intensity in view of expected net benefit.Spirometry was performed in the CT screening arm (n=2,029) of the German Lung Cancer Screening Intervention Study (LUSI)-a trial examining the effects of annual CT screening on lung cancer mortality, in 50-69-year-old long-term smokers. Participants were classified as having chronic obstructive pulmonary disease (COPD) [forced expiration in one second (FEVA total of 1,987 screening arm participants (98%) provided interpretable spirometry measurements; of these, 34.3% had spirometric patterns consistent with either COPD (18.6%) or PRISm (15.7%). Two thirds of participants with COPD or PRISm were asymptomatic, and only 23% reported a previous medical diagnosis concordant with COPD. Participants reporting a diagnosis tended to be more often current and heavier smokers, and more often had respiratory symptoms, cardiovascular comorbidities, or more severe lung function impairments. Independently of smoking history, moderate-to-severe (GOLD 2-4) COPD (OR =2.14; 95% CI: 1.54-2.98), and PRISm (OR =2.68; 95% CI: 1.61-4.40), were associated with increased lung cancer risk. Lung cancer patients with PRISm less frequently had adenocarcinomas, and more often squamous cell or small cell tumors, compared to those with normal spirometry (n=45), and both PRISm and COPD were associated with more advanced lung cancer tumor stage for screen-detected cancers. PRISm and COPD, depending on GOLD stage, were also associated with about 2- to 4-fold increases in risk of overall mortality, which to 87 percent had causes other than lung cancer.About one third of smokers eligible for lung cancer screening in Germany have COPD or PRISm. As these conditions were associated with detection of lung cancer, spirometry may help identify populations at high risk for death of lung cancer or other causes, and who might particularly benefit from CT screening.

RATIONALE Lumacaftor/ivacaftor (LUM/IVA) was shown to be safe and well tolerated in children 2 through 5 years of age with cystic fibrosis (CF) homozygous for F508del-CFTR in a phase 3 open-label study. Improvements in sweat chloride concentration, markers of pancreatic function, and lung clearance index2.5 (LCI2.5), along with increases in growth parameters, suggested the potential for early disease modification with LUM/IVA treatment. OBJECTIVE To further assess the effects of LUM/IVA on CF disease progression in children 2 through 5 years of age using chest magnetic resonance imaging (MRI). METHODS This phase 2 study had two parts: a 48-week, randomized, double-blind, placebo-controlled treatment period in which children 2 through 5 years of age with CF homozygous for F508del-CFTR received either LUM/IVA or placebo (Part 1) followed by an open-label period in which all children received LUM/IVA for an additional 48 weeks (Part 2). We report results from Part 1. The primary endpoint was absolute change from baseline in chest MRI global score at Week 48. Secondary endpoints included absolute change in LCI2.5 through Week 48 and absolute changes in weight-for-age, stature-for-age, and body mass index-for-age z-scores at Week 48. Additional endpoints included absolute changes in sweat chloride concentration, fecal elastase-1 levels, serum immunoreactive trypsinogen, and fecal calprotectin through Week 48. The primary endpoint was analyzed using Bayesian methods, where the actual Bayesian posterior probability of LUM/IVA being superior to placebo in the MRI global chest score at Week 48 was calculated using a vague normal prior distribution; secondary and additional endpoints were analyzed using descriptive summary statistics. RESULTS Fifty-one children were enrolled and received LUM/IVA (n=35) or placebo (n=16). For the change in MRI global chest score at Week 48, the Bayesian posterior probability of LUM/IVA being better than placebo (treatment difference

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.

Chronic rhinosinusitis (CRS) contributes to morbidity in patients with cystic fibrosis (CF). However, longitudinal data on CRS onset and progression is lacking.To longitudinally evaluate CRS in CF from infancy to school age with paranasal sinus magnetic resonance imaging (MRI).64 children with CF (mean age at baseline 1.1±1.6y, range 0-5y) underwent a mean of 5.8±2.2 (range 3-11) subsequent annual MRI examinations. Additional 24 children (9.2±4.4y, range 3-17y) homozygous for the F508del mutation underwent MRI before and at least two months after starting lumacaftor/ivacaftor. MRI was assessed using the previously evaluated CRS-MRI score.In infancy, 65-87% of paranasal sinuses were opacified, and mucosal swelling was the dominant abnormality (58-97%). At preschool age (1-5y), 79-94% of sinuses were opacified (P0.05 vs. infancy), and mucosal swelling was the most dominant abnormality (79-94%, P0.05). At school age (≥6y), almost all sinuses were opacified (71-99%, P0.001-0.357 vs. preschool age), and mucopyoceles were the dominant abnormality in maxillary and frontal sinuses (53-56%, P0.05-0.808). The CRS-MRI sum score increased from 22.4±9.6 in infancy to 34.2±9.6 in preschool age (P0.001) and was 34.0±5.7 in school age (P=0.052). In children under lumacaftor/ivacaftor therapy the CRS-MRI sum score (-0.5±3.3, P0.05) and maxillary sinus subscore (-0.5±1.5, P0.05) improved.Longitudinal paranasal sinus MRI detects an early onset and progression of severity of CRS from infancy to school age, and response to lumacaftor/ivacaftor therapy in children with CF. Our data support its role for comprehensive non-invasive monitoring of CRS in children with CF. Clinical trial registered with ClinicalTrials.gov (NCT02270476).

ZusammenfassungDie Mukoviszidose (zystische Fibrose, CF) gilt als häufigste, früh zum Tod führende angeborene Erkrankung in der weißen Bevölkerung. Die Beteiligung der Lunge ist wesentlich für die eingeschränkte Lebensqualität und das vorzeitige Versterben der Betroffenen verantwortlich. In der Bildgebung der letzten 10 Jahre wird – immer häufiger und wann immer möglich – die strahlenfreie MRT den Bildgebungsverfahren mit ionisierender Strahlung vorgezogen.

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 fib...

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 r = 0.72, p p Emph (r = 0.70 to 0.75, p Emph (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 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.

Die Schwere des Verlaufs und die Sterblichkeit der Mukoviszidose (zystische Fibrose, CF) ist wesentlich durch die pulmonale Manifestation gepragt. Eine fruhe Diagnose und rasch einsetzende Therapie sind entscheidend fur einen langfristigen Erhalt der Lungenfunktion. Rontgen-Thorax und Computertomographie (CT) stehen bei der Diagnostik im Vordergrund, um den Krankheitsverlauf und das Verteilungsmuster erkennen zu konnen. Zur Vermeidung von Folgeschaden aufgrund ionisierender Strahlung durch Rontgen und CT ist das Interesse an der Magnetresonanztomographie (MRT) in der vergangenen Dekade gewachsen. Wesentliche Befunde sind Bronchialwandveranderungen, Bronchiektasen und „mucus plugging“, welche bis zu 60 % bei Kindern im Vorschulalter gefunden werden. Pleuraveranderungen und Konsolidierungen treten gehauft bei pulmonalen Exazerbationen auf. An funktionellen Veranderungen zeigen junge CF-Patienten haufig ein Mosaikmuster, und bereits ab Geburt konnen Perfusionsstorungen unterschiedlicher und im Verlauf wechselnder Schwere in 50 % der Falle (Erwachsene: bis zu 90 %) mittels kontrastmittelverstarkter Bildgebung identifiziert werden. Dilatierte Bronchialarterien zeigen ein erhohtes Risiko fur Hamoptysen an. Die Protonen-MRT ist das einzige Verfahren, welches strukturelle und funktionelle Veranderungen in einem Untersuchungsgang zeigt. Bei der Erfassung des Schweregrads aller Veranderungen hilft die strukturierte Befundung anhand eines Scoringsystems. Die MRT der Lunge bei Mukoviszidose kann heute als etabliertes Standardverfahren an erfahrenen Zentren routinemasig durchgefuhrt werden. Seit Neuestem wird sie auch im Rahmen von klinischen Studien als Endpunkt verwendet.

Die Computertomographie (CT) bietet durch ihre hohe Detailauflosung und die Moglichkeit der multidimensionalen Rekonstruktion eine zuverlassige Moglichkeit der Diagnostik und Verlaufskontrolle morphologischer Zeichen der Mukoviszidose (zystische Fibrose, CF) der Lunge. Standardisierte Leitlinien zur technischen Durchfuhrung bestehen aktuell noch nicht, werden aber fur verschiedene Altersgruppen diskutiert. Zentral bleibt die Applikation ionisierender Strahlung, die stets – jedoch auch besonders in Hinblick auf uberwiegend junge CF-Patienten – einer strengen rechtfertigenden Indikation bedarf. Der Einsatz von CT-Kontrastmitteln ist meist fur Notfallindikationen erforderlich. In der CT finden sich bereits fruhzeitig typische Lungenveranderungen der CF wie Bronchiektasien, Schleimretentionen („mucus plugging“) oder Zeichen der Uberblahung (Air Trapping). Mit der Zeit wurden verschiedene Bewertungsrichtlinien fur eine systematische Schweregradeinteilung etabliert. Diese dienen nicht nur zur individuellen Krankheitseinschatzung, sondern auch im Rahmen von Studien zur Verlaufsbeurteilung und Therapiekontrolle. Unter der technischen Entwicklung der CT kommen auch zunehmend computerbasierte Nachverarbeitungsprogramme zur halbautomatischen Auswertung und Quantifizierung zum Einsatz. Diese sollen nicht nur den klinischen Alltag erleichtern, sondern auch dazu beitragen, standardisierte und quantitative Protokolle und Auswertungen, z. B. im Rahmen von Studien, zu ermoglichen. Parallel wird nach Alternativen der Bildgebung gesucht. Zunehmende Bedeutung gewinnt die Magnetresonanztomographie (MRT), die durch verbesserte Bildqualitat sowie spezialisierte Protokolle an Bedeutung gewinnt und die CT fur Langzeitverlaufe an zahlreichen spezialisierten Zentren bereits haufig ablost.

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

Rationale: Chronic rhinosinusitis (CRS) contributes to disease burden of patients with cystic fibrosis (CF). However, its onset and progression in infants and preschool children with CF remain poor...

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. 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. 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. 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.

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.

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.

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 (

Background A recent single-centre study demonstrated that MRI is sensitive to detect early abnormalities in the lung and response to therapy in infants and preschool children with cystic fibrosis (CF) supporting MRI as an outcome measure of early CF lung disease. However, the feasibility of multicentre standardisation remains unknown. Objective To determine the feasibility of multicentre standardisation of chest MRI in infants and preschool children with CF. Methods A standardised chest 1.5 T MRI protocol was implemented across four specialised CF centres. Following training and initiation visits, 42 infants and preschool children (mean age 3.2 ± 1.5 years, range 0–6 years) with clinically stable CF underwent MRI and chest X-ray (CXR). Image quality and lung abnormalities were assessed using a standardised questionnaire and an established CF MRI and CXR score. Results MRI was successfully performed with diagnostic quality in all patients (100%). Incomplete lung coverage was observed in 6% and artefacts also in 6% of sequence acquisitions, but these were compensated by remaining sequences in all patients. The range of the MRI score in CF patients was similar across centres with a mean global MRI score of 13.3 ± 5.8. Cross-validation of the MRI against the CXR score revealed a moderate correlation (r = 0.43–0.50, p Conclusion Our results demonstrate that multicentre standardisation of chest MRI is feasible and support its use as radiation-free outcome measure of lung disease in infants and preschool children with CF.

Chronic rhinosinusitis (CRS) is a characteristic feature of cystic fibrosis (CF) multiorgan disease and develops early in the life of patients with CF. The study aimed to correlate the inflammatory markers and the presence of structural abnormalities detected by MRI in the paranasal sinuses of patients with CF. Methods: Nasal lavage and MRI of the paranasal sinuses was performed in a cohort of 30 CF patients (median age 14 y, range 7–20 y). Morphological abnormalities characteristic of CF were evaluated with a dedicated CRS MRI scoring system and correlated with different inflammation parameters measured in nasal lavage. Inflammation of the paranasal sinuses was positively associated with structural abnormalities in MRI. The concentration of the pro-inflammatory markers neutrophil elastase (NE) and the neutrophil elastase/alpha1-antitrypsin (NE/A1AT) complex correlated significantly with CRS-MRI sum score (p &lt, 0.05, r = 0.416 and p &lt, 0.05, r = 0.366, respectively). S. aureus infection was associated with the increased pro-inflammatory cytokine activity of IL-6 and IL-8, and increased levels of NE/A1AT complex in our patients (p &lt, 0.05, respectively). CRS-MRI sum score and individual sinus MRI scores were positively associated with inflammatory activity as a sign of CRS pathology present in CF.

Introduction: Common variable immunodeficiency (CVID) patients are susceptible to respiratory diseases including bronchiectasis and granulomatous lymphocytic interstitial lung disease (GLILD). As data on evaluating CVID with and without GLILD are sparse, we aimed to compare these groups. Methods: 21 CVID patients were analyzed retrospectively for characteristics and outcomes and grouped into CVID with (ILD,n=9) and without GLILD (noILD,n=12). CT scoring (CTS) assessed 11 patterns (ground glass opacities, reticulations, traction bronchiectasis, honeycombing, consolidations, air-trapping, nodules, bronchial wall thickening, bronchiectasis, mucus plugging, effusion). Histology scoring (HS) evaluated changes of the bronchial wall and of the interstitium (fibrosis, inflammation, anthracosis, granuloma, tumor, infection, metaplasia, mucoid impactation, microhoneycombing, eosinophilia). Results: Baseline characteristics were similar between groups. Most CVID patients received immunoglobulins (Ig) and all ILD patients were treated immunosuppressive (IS). Under Ig and IS lung function remained stable in ILD. CTS were worse for ILD than noILD (ILD:16.5±8.7 vs. noILD:9.4±4.9, p=0.02) while HS (ILD:5.8±2.7, noILD 6.0±2.6) were similar. CTS deteriorated in ILD but not in noILD with pattern changes in ILD, from initial mainly GGO to fibrosis (p Conclusion: CVID with and without GLILD has similar clinical characteristics but differs mainly in CT scoring. Future work has to assess clinical predictors of GLILD.

Initial reports of SARS-CoV-2 infection indicate only mild disease in 81% of symptomatic cases [1]. Nearly half of the infected individuals do not seem to develop clinical symptoms at all depending on the cohort investigated [2]. Comorbidities and older age were identified early during the pandemic as predictors for severe or critical disease [3] which is found in about 19% [1]. Independently from disease severity, little is known about longer-term outcomes as well as resolution of symptoms. We therefore set out to systematically evaluate residual symptoms and lung function impairment in patients after SARS-CoV-2 infection., About half of the patients recovering from SARS-CoV-2 have persistent symptoms and reduced lung function as long as 2 months after infection. This is common even in younger SARS-CoV-2 convalescents with few comorbidities.

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.

To longitudinally investigate smoking cessation-related changes of quantitative computed tomography (QCT)–based airway metrics in a group of heavy smokers. 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. 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

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.

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). 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. 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

To evaluate the influence of exposure parameters and raw-data based iterative reconstruction (IR) on the performance of computer-aided detection (CAD) of pulmonary nodules on chest multidetector computed tomography (MDCT).Seven porcine lung explants were inflated in a dedicated ex vivo phantom shell and prepared with n=162 artificial nodules of a clinically relevant volume and maximum diameter (46-1063 μl, and 6.2-21.5 mm). n=118 nodules were solid and n=44 part-solid. MDCT was performed with different combinations of 120 and 80 kV with 120, 60, 30 and 12 mA*s, and reconstructed with both filtered back projection (FBP) and IR. Subsequently, 16 datasets per lung were subjected to dedicated CAD software. The rate of true positive, false negative and false positive CAD marks was measured for each reconstruction.The rate of true positive findings ranged between 88.9-91.4% for FBP and 88.3-90.1% for IR (n.s.) with most exposure settings, but was significantly lower with the combination of 80 kV and 12 mA*s (80.9% and 81.5%, respectively, p0.05). False positive findings ranged between 2.3-8.1 annotations per lung. For nodule volumes200 μl the rate of true positives was significantly lower than for300 μl (p0.05). Similarly, it was significantly lower for diameters12 mm compared to ≥12 mm (p0.05). The rate of true positives for solid and part-solid nodules was similar.Nodule CAD on chest MDCT is robust over a wide range of exposure settings. Noise reduction by IR is not detrimental for CAD, and may be used to improve image quality in the setting of low-dose MDCT for lung cancer screening.

To determine if morphological non-contrast enhanced magnetic resonance imaging (MRI) of the lung is sensitive to detect mosaic signal intensity in infants and preschool children with cystic fibrosis (CF).50 infant and preschool CF patients (mean age 3.5 ± 1.4y, range 0-6y) routinely underwent morphological (T2-weighted turbo-spin echo sequence with half-Fourier acquisition, HASTE) and contrast-enhanced 4D perfusion MRI (gradient echo sequence with parallel imaging and echo sharing, TWIST). MRI studies were independently scored by two readers blinded for patient age and clinical data (experienced Reader 1 = R1, inexperienced Reader 2 = R2). The extent of lung parenchyma signal abnormalities on HASTE was rated for each lobe from 0 (normal), 1 (50% of lobe affected) to 2 (≥50% of lobe affected). Perfusion MRI was rated according to the previously established MRI score, and served as the standard of reference.Inter-method agreement between MRI mosaic score and perfusion score was moderate with κ = 0.58 (confidence interval 0.45-0.71) for R1, and with κ = 0.59 (0.46-0.72) for R2. Bland-Altman analysis revealed a slight tendency of the mosaic score to underestimate perfusion abnormalities with a score bias of 0.48 for R1 and 0.46 for R2. Inter-reader agreement for mosaic score was substantial with κ = 0.71 (0.62-0.79), and a low bias of 0.02.This study demonstrates that non-contrast enhanced MRI reliably detects mosaic signal intensity in infants and preschool children with CF, reflecting pulmonary blood volume distribution. It may thus be used as a surrogate for perfusion MRI if contrast material is contra-indicated or alternative techniques are not available.

Fissure integrity (FI) plays a key role in selecting patients for interventional emphysema therapy. We investigated its interference with automated lobar segmentation in quantitative computed tomography (CT) and emphysema distribution.CT was available for 50 patients with chronic obstructive pulmonary disease (COPD). Lobe segmentation was performed fully automated by software and corrected manually. FI was evaluated visually using a %-scale. The influence of FI on emphysema ratio (ER=percentage of lung volume with density values-950 HU), mean lung density (MLD), emphysema and total volume of adjacent lobes was analyzed. Lobe-based results were compared with respect to FI.Differences in ER in adjacent lobes for complete vs. incomplete fissures were 12.4% for the right horizontal, 0.2% and 3% for the right oblique and 4.4% for the left oblique fissure (all p0.05). Results for emphysema comparing automated vs. manually corrected segmentation exceeded clinically acceptable values, but were not significantly affected by FI (p0.05). The widest limits of agreement for ER and MLD were noted in the right middle lobe ([-14, 17.4%], [-22.4, 32.4 Hounsfield Units]).Automated lobe segmentation and emphysema distribution are not significantly affected by FI. Manual correction of automated lobar segmentation is still recommended in severe emphysema.

Proton MRI is able to depict the major changes in CF lung disease in a similar way to CT, albeit there will be shortcomings in the detection of more subtle or smaller abnormalities. Further studies are warranted to determine whether the additional structural detail provided by CT is necessary for the evaluation of the severity and progression of CF lung disease. At the same time, proton and hyperpolarized gas MRI provide a broad spectrum of additional functional information in CF lung diseases that is otherwise not available to patients and clinicians. The MRI techniques to be applied in CF lung disease are novel and further development and studies are required to fully implement and assess their potential impact in CF. It is currently unknown whether the combination of functional and structural information from MRI will be more useful than the mere structural information provided by CT in the clinical assessment of CF. It is conceivable that MRI and CT will be complementary as they have different advantages and disadvantages in elucidating the complex interrelation of lung structure and function.

Insights into the global and local pathophysiology of respiratory motion, e.g., in patients with chronic obstructive lung disease (COPD), are increasingly appreciated in clinical imaging and research. Dynamic MRI accelerated by parallel imaging and echo sharing reaches temporal resolutions of up to ten images per second in single plane acquisitions or one volume per second in time-resolved 3D imaging. Recently developed, externally, navigator- or self-navigated sequences allow for oversampling of image data during free breathing and retrospective reconstruction of high resolution data sets for different phases of the respiratory cycle. Dynamic MRI allows for repeated and prolonged measurements without radiation exposure to analyze respiratory motion of the lung, the diaphragm, and the chest wall in healthy subjects as well as patients. The analysis of respiratory motion has direct clinical impact for adaptive radiotherapy of moving organs like the lung or the liver. This has motivated the development of dynamic volume lung imaging with computed tomography (4D-CT) or MRI (4D-MRI). Both, 4D-CT and 4D-MRI, are principally capable of capturing respiratory motion. Additional morpho-functional imaging capacities of MRI and the radiation exposure involved with 4D-CT give good reasons to prefer dynamic MRI for this purpose. Near-isotropic imaging can be used to assess general and local respiratory mechanics of the lung as well as tumor displacement for adaptive radiotherapy. Dedicated systems with integrated MRI into the radiotherapy equipment are under development or already being installed. Beyond applications for radiation therapy, recent work has shown that 4D-MRI can be used to analyze regional lung ventilation without hyperpolarized gases or oxygen enhancement. This could be a valuable adjunct to classical spirometry giving deeper insights into local lung ventilation in healthy subjects and in patients opening the perspective for a broad spectrum of clinical applications.

Therapy monitoring in oncologic patient requires precise measurement methods. In order to improve the precision of measurements, we used a semi-automated generic segmentation algorithm to measure the size of large lung cancer tumors. The reproducibility of computer-assisted measurements were assessed and compared with manual measurements.CT scans of 24 consecutive lung cancer patients who were referred to our hospital over a period of 6 months were analyzed. The tumor sizes were measured manually by 3 independent radiologists, according to World Health Organization (WHO) and the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. At least 10 months later, measurements were repeated semi-automatically on the same scans by the same radiologists. The inter-observer reproducibility of all measurements was assessed and compared between manual and semi-automated measurements.Manual measurements of the tumor longest diameter were significantly (p0.05) smaller compared with the semi-automated measurements. The intra-rater correlations coefficients were significantly higher for measurements of longest diameter (intra-class correlation coefficients: 0.998 vs. 0.986; p0.001) and area (0.995 vs. 0.988; p = 0.032) using semi-automated compared with manual method. The variation coefficient for manual measurement of the tumor area (WHO guideline, 15.7% vs. 7.3%) and the longest diameter (RECIST guideline, 7.7% vs. 2.7%) was 2-3 times that of semi-automated measurement.By using computer-assisted size assessment in primary lung tumor, interobserver-variability can be reduced to about half to one-third compared to standard manual measurements. This indicates a high potential value for therapy monitoring in lung cancer patients.

To evaluate the fully automatic quantification of airway dimensions on chest multidetector computed tomography (MDCT) performed in cystic fibrosis (CF) patients. Airflow indices including predicted forced expiratory volume in 1 second (FEV1%) were used to study the impact on regional lung function.MDCT data of patients with CF (14 children and 23 adults) and of control patients (11 children and 22 adults) were used to compute total diameter (TD), lumen area (LA), and wall thickness (WT) using dedicated software. Pulmonary function testing including FEV1% was performed in parallel and correlated with MDCT parameters in a generation-based analysis.TD was largely increased in CF patients (third-generation to fourth-generation airways in children, first to ninth in adults; P0.05). LA remained unchanged, but WT was also larger in CF compared with controls (third generation to sixth generation in children, first to eleventh in adults; P0.05). In adult CF patients significant negative correlations for TD, LA, and WT with FEV1% were found for intermediate airways (fifth to seventh generation; r=-0.7 to -0.9) but not in pediatric CF patients and controls.Automatic airway analysis succeeded in quantifying specific pathologies such as airway dilatation and wall thickening in CF patients at different ages. Moreover, our results indicate a shift in main airflow resistance to intermediate airways in cases of chronic CF. The objective computational parameters TD, LA, and WT should be considered for assessment and follow-up of CF airway disease.

To longitudinally evaluate effects of smoking cessation on quantitative CT in a lung cancer screening cohort of heavy smokers over 4 years. 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). 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