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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.

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.

Automated image analysis plays an increasing role in radiology in detecting and quantifying image features outside of the perception of human eyes. Common AI-based approaches address a single medical problem, although patients often present with multiple interacting, frequently subclinical medical conditions. A holistic imaging diagnostics tool based on artificial intelligence (AI) has the potential of providing an overview of multi-system comorbidities within a single workflow. An interdisciplinary, multicentric team of medical experts and computer scientists designed a pipeline, comprising AI-based tools for the automated detection, quantification and characterization of the most common pulmonary, metabolic, cardiovascular and musculoskeletal comorbidities in chest computed tomography (CT). To provide a comprehensive evaluation of each patient, a multidimensional workflow was established with algorithms operating synchronously on a decentralized Joined Imaging Platform (JIP). The results of each patient are transferred to a dedicated database and summarized as a structured report with reference to available reference values and annotated sample images of detected pathologies. Hence, this tool allows for the comprehensive, large-scale analysis of imaging-biomarkers of comorbidities in chest CT, first in science and then in clinical routine. Moreover, this tool accommodates the quantitative analysis and classification of each pathology, providing integral diagnostic and prognostic value, and subsequently leading to improved preventive patient care and further possibilities for future studies.

Background Bronchoscopic valve placement constitutes an effective endoscopic lung volume reduction (ELVR) therapy in patients with severe emphysema and low collateral ventilation. After the most destroyed lobe is occluded with valves, significant target lobe volume reduction leads to improvements in lung function, exercise capacity, and quality of life. The effects are not consistent in some patients, leading to long-term therapy failure. We hypothesized that surgical lung volume reduction (LVRS) would reestablish ELVR short-term clinical improvements after ELVR long-term failure. Methods This retrospective single-center analysis included all patients who underwent consolidating LVRS by lobectomy after long-term failure of valve therapy between 2010 and 2015. Changes in forced expiratory volume in 1 second, residual volume, 6-minute walking distance, and Modified Medical Research Council dyspnea score 90 days after ELVR and LVRS were analyzed, and the outcomes of both procedures were compared. Results LVRS was performed in 20 patients after ELVR failure. A lower lobectomy was performed in 90%. The 30-day mortality of the cohort was 0% and 90-day mortality was 5% (1 of 20). The remaining 19 patients showed a significant increase in forced expiratory volume in 1 second (+27.5% ± 19.4%) and a reduction in residual volume (−21.0% ± 17.4%) and total lung capacity (−11.1% ± 11.1%). This resulted in significant improvements in exercise tolerance (6-minute walking distance: +56 ± 60 m) and relief of dyspnea (ΔModified Medical Research Council: −1.8 ± 1.4 points.). Conclusions Consolidating LVRS by lobectomy after failure of a previously successful ELVR is feasible and results in significant symptom relief and improvement of lung function.

Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering the environmental cause of COPD (e.g., cigarette smoke) and disease phenotypes, including stem-cell senescence and impaired differentiation, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) isolated from distal parenchyma of ex-smoker controls and COPD patients, with both mild and severe disease. The epigenetic landscape is markedly changed in lung fibroblasts across COPD stages, with DNA methylation changes occurring predominantly in regulatory regions, including promoters and enhancers. RNA sequencing of matched fibroblasts demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization. Notably, we identified epigenetic and transcriptional dysregulation already in mild COPD patients, providing unique insights into early disease. Integration of profiling data identified 110 candidate regulators of disease phenotypes, including epigenetic factors. Using phenotypic screens, we verified the regulator capacity of multiple candidates and linked them to repair processes in the human lung.Our study provides first integrative high-resolution epigenetic and transcriptomic maps of human lung fibroblasts across stages of COPD. We reveal novel transcriptomic and epigenetic signatures associated with COPD onset and progression and identify new candidate regulators involved in the pathogenesis of chronic respiratory diseases. The presence of various epigenetic factors among the candidates demonstrates that epigenetic regulation in COPD is an exciting research field that holds promise for novel therapeutic avenues for patients.

There is a clinical need for imaging-derived biomarkers for the management of chronic obstructive pulmonary disease (COPD). Observed pulmonary TTo investigate the potential diagnostic value of TProspective non-randomized diagnostic study.Thirty COPD patients (67.7 ± 6.6 years). Data from a previous study (15 healthy volunteers [26.2 ± 3.9 years) were used as reference.Study participants were examined at 1.5 T using dynamic contrast-enhanced three-dimensional gradient echo keyhole perfusion sequence and a multi-echo inversion recovery two-dimensional UTE (ultra-short TE) sequence for TPerfusion images were scored by three radiologists. TSpearman rank correlation coefficients (ρ) were calculated between TMedian values were TIn COPD patients, the increase of T2 TECHNICAL EFFICACY: Stage 1.

Background: Fibrosing interstitial lung diseases other than IPF can develop a progressive phenotype (PF-ILD). While recent clinical trials have gained significant insights into management aspects for PF-ILD, different definitions were applied. We therefore aimed to compare patient cohorts according to these definitions and associated outcomes Methods: 587 fILDs with a follow up > 24 months were identified at our tertiary ILD referral Center. Patient characteristics and outcomes were assessed retrospectively and categorized as PF-ILD according to INBUILD (IN), RELIEF (RE) and Cottin (CO; ERR 2018). Results: Patients had HP (39%), iNSIP (13%), uILD (22%), CTD-ILD (24%), and others (1%). 53.4% were male, mean age 65±11.8 years, mean FVC% 72.8±2, mean DLCO% 47.3±1. The percentage of PF-ILD differed according to the 3 criteria (CO, RE, IN) (41%, 32%, 48%, fig). Acute exacerbations occurred more frequently in PF-ILD (25.6%, 23.9%, 24.9%) than in non PF-ILD (p 12 months while RELIEF identified a worse cohort. Conclusions: This study reveals that the categorization as PF-ILD differs between definitions which has important prognostic and therapeutic implications. Prospective studies are needed to confirm these results and international accepted criteria for PF-ILD have to be defined.

Computed tomography (CT) scans are the gold standard to measure treatment success of non-small cell lung cancer (NSCLC) therapies. Here, we investigated the very early tumor response of patients receiving chemotherapy or targeted therapies using a panel of already established and explorative liquid biomarkers. Blood samples from 50 patients were taken at baseline and at three early time points after therapy initiation. DNA mutations, a panel of 17 microRNAs, glycodelin, glutathione disulfide, glutathione, soluble caspase-cleaved cytokeratin 18 (M30 antigen), and soluble cytokeratin 18 (M65 antigen) were measured in serum and plasma samples. Baseline and first follow-up CT scans were evaluated and correlated with biomarker data. The detection rate of the individual biomarkers was between 56% and 100%. While only keratin 18 correlated with the tumor load at baseline, we found several individual markers correlating with the tumor response to treatment for each of the three time points of blood draws. A combination of the five best markers at each time point resulted in highly significant marker panels indicating therapeutic response (R2 = 0.78, R2 = 0.71, and R2 = 0.71). Our study demonstrates that an early measurement of biomarkers immediately after therapy start can assess tumor response to treatment and might support an adaptation of treatment to improve patients&rsquo, outcome.

Bronchial thermoplasty (BT) can be considered in the treatment of severe asthma to reduce airway smooth muscle mass and bronchoconstriction. We hypothesized that BT may thus have long-term effects on airway dimensions and air-trapping detectable by quantitative computed tomography (QCT).Paired in- and expiratory CT and inspiratory CT were acquired in 17 patients with severe asthma before and up to two years after bronchial thermoplasty and in 11 additional conservatively treated patients with serve asthma, respectively. A fully automatic software calculated the airways metrics for wall thickness (WT), wall percentage (WP), lumen area (LA) and total diameter (TD). Furthermore, lung air-trapping was quantified by determining the quotient of mean lung attenuation in expiration vs. inspiration (E/I MLA) and relative volume change in the Hounsfield interval -950 to -856 in expiration to inspiration (RVCBT reduced WT for the combined analysis of the 2nd-7th airway generation significantly by 0.06 mm (p = 0.026) and WP by 2.05% (p 0.001), whereas LA and TD did not change significantly (p = 0.147, p = 0.706). No significant changes were found in the control group. Furthermore, E/I MLA and RVCBT significantly reduced airway narrowing and air-trapping in patients with severe asthma. This can be interpreted as direct therapeutic effects caused by a reduction in airway-smooth muscle mass and changes in innervation. A reduction in air-trapping indicates an influence on more peripheral airways not directly treated by the BT procedure.

PURPOSE: To examine the performance of radiologists in differentiating COVID-19 from non-COVID-19 atypical pneumonia and to perform an analysis of CT patterns in a study cohort including viral, fungal and atypical bacterial pathogens. METHODS: Patients with positive RT-PCR tests for COVID-19 pneumonia (n = 90) and non-COVID-19 atypical pneumonia (n = 294) were retrospectively included. Five radiologists, blinded to the pathogen test results, assessed the CT scans and classified them as COVID-19 or non-COVID-19 pneumonia. For both groups specific CT features were recorded and a multivariate logistic regression model was used to calculate their ability to predict COVID-19 pneumonia. RESULTS: The radiologists differentiated between COVID-19 and non-COVID-19 pneumonia with an overall accuracy, sensitivity, and specificity of 88% ± 4 (SD), 79% ± 6 (SD), and 90% ± 6 (SD), respectively. The percentage of correct ratings was lower in the early and late stage of COVID-19 pneumonia compared to the progressive and peak stage (68 and 71% vs 85 and 89%). The variables associated with the most increased risk of COVID-19 pneumonia were band like subpleural opacities (OR 5.55, p

Lung cancer screening with low-dose CT can save lives. This European Union (EU) position statement presents the available evidence and the major issues that need to be addressed to ensure the successful implementation of low-dose CT lung cancer screening in Europe. This statement identified specific actions required by the European lung cancer screening community to adopt before the implementation of low-dose CT lung cancer screening. This position statement recommends the following actions: a risk stratification approach should be used for future lung cancer low-dose CT programmes; that individuals who enter screening programmes should be provided with information on the benefits and harms of screening, and smoking cessation should be offered to all current smokers; that management of detected solid nodules should use semi-automatically measured volume and volume-doubling time; that national quality assurance boards should be set up to oversee technical standards; that a lung nodule management pathway should be established and incorporated into clinical practice with a tailored screening approach; that non-calcified baseline lung nodules greater than 300 mm(3), and new lung nodules greater than 200 mm(3), should be managed in multidisciplinary teams according to this EU position statement recommendations to ensure that patients receive the most appropriate treatment; and planning for implementation of low-dose CT screening should start throughout Europe as soon as possible. European countries need to set a timeline for implementing lung cancer screening.

IntroductionQuantitative analysis of multi-detector computed tomography (MDCT) plays an increasingly important role in assessing airway disease. Depending on the algorithms used, airway dimensions may be over- or underestimated, primarily if contrast material was used. Therefore, we tested a modified integral-based method (IBM) to address this problem.MethodsTemporally resolved cine-MDCT was performed in seven ventilated pigs in breath-hold during iodinated contrast material (CM) infusion over 60s. Identical slices in non-enhanced (NE), pulmonary-arterial (PA), systemic-arterial (SA), and venous phase (VE) were subjected to an in-house software using a standard and a modified IBM. Total diameter (TD), lumen area (LA), wall area (WA), and wall thickness (WT) were measured for ten extra- and six intrapulmonary airways.ResultsThe modified IBM significantly reduced TD by 7.6%, LA by 12.7%, WA by 9.7%, and WT by 3.9% compared to standard IBM on non-enhanced CT (pConclusionsThe modified IBM can optimize airway wall segmentation and reduce the influence of CM on quantitative CT. This allows a more precise measurement as well as potentially the comparison of enhanced with non-enhanced scans in inflammatory airway disease.

In 2011, the U.S. National Lung Cancer Screening Trial (NLST) reported a 20% reduction of lung cancer mortality after regular screening by low-dose computed tomography (LDCT), as compared to X-ray screening. The introduction of lung cancer screening programs in Europe awaits confirmation of these first findings from European trials that started in parallel with the NLST. The German Lung cancer Screening Intervention (LUSI) is a randomized trial among 4,052 long-term smokers, 50-69 years of age, recruited from the general population, comparing five annual rounds of LDCT screening (screening arm; n = 2,029 participants) with a control arm (n = 2,023) followed by annual postal questionnaire inquiries. Data on lung cancer incidence and mortality and vital status were collected from hospitals or office-based physicians, cancer registries, population registers and health offices. Over an average observation time of 8.8 years after randomization, the hazard ratio for lung cancer mortality was 0.74 (95% CI: 0.46-1.19; p = 0.21) among men and women combined. Modeling by sex, however showed a statistically significant reduction in lung cancer mortality among women (HR = 0.31 [95% CI: 0.10-0.96], p = 0.04), but not among men (HR = 0.94 [95% CI: 0.54-1.61], p = 0.81) screened by LDCT (pheterogeneity = 0.09). Findings from LUSI are in line with those from other trials, including NLST, that suggest a stronger reduction of lung cancer mortality after LDCT screening among women as compared to men. This heterogeneity could be the result of different relative counts of lung tumor subtypes occurring in men and women.

BACKGROUND: Recent findings indicate that the currently approved predictive biomarker for immune checkpoint blockade (ICB), i.e. PD-L1 expression, is imperfect. Hence, additional biomarkers are warranted, and ICB-related gene expression profiling (GEP) was advocated as a promising approach enabling comprehensive interrogation of the ICB-effector compartment. Here, we assessed inter- and intra-tumor heterogeneity (ITH) of the immunological microenvironment using a comprehensive gene expression profiling approach (770 genes) to further elucidate the biological basis for new diagnostic applications. METHODS: All formalin-fixed paraffin-embedded tissue specimens used for this study were derived from surgically resected lung adenocarinomas at the Thoraxklinik at Heidelberg University Hospital and diagnosed (according to 2015 WHO Classification of lung tumors) at the Institute of Pathology at Heidelberg University Hospital. To evaluate the significance of ITH on gene expression profiling, multi-regional gene expression analysis (2-4 samples per tumor) was performed for 24 ADC using the NanoString IO 360 Panel. ANOVA was used to compare inter-tumor variance to intra-tumor variance of mRNA expression. The F statistics was calculated as ratio of these quantities. A list of genes with significantly higher inter-tumor variance was isolated using the F-test. Multiple testing was addressed using the Benjamini-Hochberg method to control the false discovery rate (FDR). RESULTS: In an unsupervised hierarchical clustering analysis of the entire set of 770 genes, the two to four segments of each of the tumors clustered together. For 752 of the 770 genes (97.7%) the inter-tumor variance was significantly higher than the intra-tumor variance (FDR CONCLUSION: In our preliminary analysis of ICB-GEP, variance of expression levels between tumors was substantial and exceeded ITH for the majority of analyzed genes. In-depth analyses are ongoing to further delineate the influence on gene signatures and ICB related pathways. Citation Format: Daniel Kazdal, Jan Budczies, Martina Kirchner, Klaus Kluck, Michael Allgäuer, Olaf Neumann, Regine Brandt, Eugen Rempel, Carolin Ploeger, Moritz von Winterfeld, Marc Schneider, Steffen Dietz, Hauke Winter, Thomas Muley, Holger Sülmann, Michael Meister, Felix Herth, Claus Heussel, Roland Penzel, Volker Endris, Peter Schirmacher, Michael Thomas, Petros Christopoulos, Albrecht Stenzinger. Inter- and intra- tumorheterogeneity of the microenvironment in pulmonary adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1571.

A rise in radiology consult, in parallel with an ever-growing offer of value-based services, is currently increasing patient awareness of the radiologist’s role in clinical care. A German and a North American example of radiology consult are shown in this chapter. The German example, taken from the Radiology Department of the Thoraxklinik University Heidelberg, chaired by Prof. Dr. Claus Peter Heussel, will show different aspects like the workflow regarding severely immunocompromised patients being submitted to thoracic CT, the image-guided biopsy and re-biopsy of nodules or masses, regular tumor boards, and the Interstitial Lung Disease multidisciplinary conference (with pneumologist, radiologist, and pathologist). The University of Pennsylvania at Philadelphia embedded thoracic radiology reading room within an integrated Lung Center Clinic, is the North American example. A survey taken in this large tertiary academic medical center by Dr. Mortani Barbosa Jr. found an overwhelming positive response from the referring healthcare providers, and major positive impact on patient care and management. The most common reasons for consultation were to clarify interpretation of imaging studies and diagnoses, to assess for temporal changes, and in up to 25% of the cases to discuss management options. The radiology consult models we proposed can be implemented in most mid- to large-size hospitals. The radiologist as a consultant should be seen as the future but also a return to a past in which the interaction of radiologists and referring practitioners was the foundation of diagnosis and medical decision-making.

Novel therapeutic options in chronic obstructive pulmonary disease (COPD) require delicate patient selection and thus demand for expert radiologists visually and quantitatively evaluating high-resolution computed tomography (CT) with additional functional acquisitions such as paired inspiratory-expiratory scans or dynamic airway CT. The differentiation between emphysema-dominant and airway-dominant COPD phenotypes by imaging has immediate clinical value for patient management. Assessment of emphysema severity, distribution patterns, and fissure integrity are essential for stratifying patients for different surgical and endoscopic lung volume reduction procedures. This is supported by quantitative software-based postprocessing of CT data sets, which delivers objective emphysema and airway remodelling metrics. However, the significant impact of scanning and reconstruction parameters, as well as intersoftware variability still hamper comparability between sites and studies. In earlier stage COPD imaging, it is less clear as to what extent quantitative CT might impact decision making and therapy follow-up, as emphysema progression is too slow to realistically be useful as a mid-term outcome measure in an individual, and longitudinal data on airway remodelling are still very limited.

Introduction The German Lung Cancer Screening Intervention Trial (LUSI) is one of the European randomized trials investigating the efficacy of low-dose multislice computed tomography (MSCT) as a screening tool for lung cancer. In the evaluation of the first (prevalence) screening round, we observed exceptionally high early recall rates, which made the routine application of MSCT screening questionable. Because screening may behave differently in subsequent (incidence) screening rounds, we analyzed (a) basic characteristics for the annual rounds 2 to 4, which have now also been completed, and (b) the first 3 years with complete follow-up since time of randomization. Methods Data material was the data record of LUSI after the fourth screening round and the 3-year follow-up had been completed. Basic characteristics of screening, e.g., early recall rate, detection rate, and interval cancers as well of proportion of advanced cancers, were descriptively evaluated and, if informative, group differences were tested for statistical significance. Results Early recall rates were significantly lower in the subsequent screening rounds than in the first one if the MSCT information from the previous screening rounds was available. Detection and biopsy rates were approximately 1% or lower, ratio of benign:malignant biopsies: 1:1.6 to 1:3. Conclusion Our recent data may not only settle one concern regarding high recall rates in routine MSCT screening but also indicate that screening must be strictly organized to be effective. Performance indicators are similar to those in mammography screening. Nevertheless, possible consequences for the participants (diagnostic workup of suspicious findings, biopsies) are more invasive than in mammography screening.

INTRODUCTION:As there is an increasing number of multicentre lung imaging studies with MRI in patients, dedicated reference phantoms are required to allow for the assessment and comparison of image quality in multi-vendor and multi-centre environments. However, appropriate phantoms for this purpose are so far not available commercially. It was therefore the purpose of this project to design and apply a cost-effective and simple to use reference phantom which addresses the specific requirements for imaging the lungs with MRI. METHODS:The phantom was designed to simulate 4 compartments (lung, blood, muscle and fat) which reflect the specific conditions in proton-MRI of the chest. Multiple phantom instances were produced and measured at 15 sites using a contemporary proton-MRI protocol designed for an in vivo COPD study at intervals over the course of the study. Measures of signal- and contrast-to-noise ratio, as well as structure and edge depiction were extracted from conventionally acquired images using software written for this purpose. RESULTS:For the signal to noise ratio, low intra-scanner variability was found with 4.5% in the lung compartment, 4.0% for blood, 3.3% for muscle and 3.7% for fat. The inter-scanner variability was substantially higher, with 41%, 32%, 27% and 32% for the same order of compartments. In addition, measures of structure and edge depiction were found to both vary significantly among several scanner types and among scanners of the same model which were equipped with different gradient systems. CONCLUSION:The described reference phantom reproducibly quantified image quality aspects and detected substantial inter-scanner variability in a typical pulmonary multicentre proton MRI study, while variability was greater in lung tissue compared to other tissue types. Accordingly, appropriate reference phantoms can help to detect bias in multicentre in vivo study results and could also be used to harmonize equipment or data.

In order to identify anaplastic lymphoma kinase-driven non-small cell lung cancer (ALK

Introduction and Background: Bronchial thermoplasty can be considered in the treatment of severe uncontrolled asthma, reducing smooth muscle mass and thus reducing bronchoconstriction, leading to a reduction in symptoms and better asthma control. We hypothesized that quantitative computed tomography (QCT) may show changes in airway dimensions and lung parenchyma after thermoplasty. Methods: 26 CT scans from 13 asthma patients (mean age 55y, range 35-79y) before and after thermoplasty were assessed retrospectively. CT scans were analysed by a fully automatic in-house software (YACTA). Wall thickness (WT), total diameter (TD) and percent wall thickness (WT%) were calculated per airway generation (G1-G10), and volume, mean lung density (MLD), emphysema index (EI), and air-trapping indices (RVC856-950, A1) were calculated per lobe and whole-lung. Results: Averaged parameters for generations G2-G4 showed a slight decrease in WT of 0.033mm (p=0.331) and an increase in TD of 0.42mm (p=0.192) resulting in a significantly lower WT% (p=0.031) after treatment. Mean lung volume decreased by 94 ml, showing most changes in both upper lobes [58 ml right (p=0.984), 120 ml left (p=0.893]. Air-trapping showed a tendency to decrease [RVC856-950 -0.059 (p=0.508), A1=-2.509 (p=0.127)]. Conclusion: QCT was able to show changes induced by thermoplasty in patients with severe asthma. A significant reduction in WT% is probably related to a reduction of smooth muscle cells as well as neuronal changes. QCT parameters could also show reduced hyperinflation resulting in lower lung volume and reduced air-trapping. More research is necessary to show the significance in a larger cohort.

Introduction As there is an increasing number of multicentre lung imaging studies with MRI in patients, dedicated reference phantoms are required to allow for the assessment and comparison of image quality in multi-vendor and multi-centre environments. However, appropriate phantoms for this purpose are so far not available commercially. It was therefore the purpose of this project to design and apply a cost-effective and simple to use reference phantom which addresses the specific requirements for imaging the lungs with MRI. Methods The phantom was designed to simulate 4 compartments (lung, blood, muscle and fat) which reflect the specific conditions in proton-MRI of the chest. Multiple phantom instances were produced and measured at 15 sites using a contemporary proton-MRI protocol designed for an in vivo COPD study at intervals over the course of the study. Measures of signal- and contrast-to-noise ratio, as well as structure and edge depiction were extracted from conventionally acquired images using software written for this purpose. Results For the signal to noise ratio, low intra-scanner variability was found with 4.5% in the lung compartment, 4.0% for blood, 3.3% for muscle and 3.7% for fat. The inter-scanner variability was substantially higher, with 41%, 32%, 27% and 32% for the same order of compartments. In addition, measures of structure and edge depiction were found to both vary significantly among several scanner types and among scanners of the same model which were equipped with different gradient systems. Conclusion The described reference phantom reproducibly quantified image quality aspects and detected substantial inter-scanner variability in a typical pulmonary multicentre proton MRI study, while variability was greater in lung tissue compared to other tissue types. Accordingly, appropriate reference phantoms can help to detect bias in multicentre in vivo study results and could also be used to harmonize equipment or data.

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.

Background: Advanced-stage chronic obstructive pulmonary disease (COPD) is associated with severely altered respiratory dynamics. Dynamic airway instability is usually diagnosed by invasive bronchoscopy. Cine-computed tomography (CT) may be used alternatively, but is limited to predefined anatomical positions. Also, a paradoxical diaphragmatic motion has been described in patients with emphysema. Objectives: As the airways and chest wall show inherently high contrast to airway lumen and lung tissue, low-dose CT acquisitions potentially suffice for depicting tracheobronchial and chest wall motion. Therefore, we propose low-dose dynamic respiratory-gated multidetector CT (4D-CT) of the whole chest as a new method to assess respiratory dynamics. Methods: 4D-CT was performed in 3 patients (52, 62 and 76 years old) with suspected tracheal instability due to COPD or tracheal stenosis at minimal pitch (0.09) and radiation exposure (1.4-1.9 mSv) during regular tidal breathing registered by a belt system. Image reconstruction involved a raw data-based iterative algorithm (1.5-mm slice thickness, 1.0-mm z-axis increment, 5% respiratory increment), resulting in a stack of 6,700 images, which were evaluated with a 4D-viewing tool. Results: An excessive dynamic collapse of the trachea in combination with tracheobronchomalacia (TBM) of the main-stem and segmental bronchi, and a paradoxical diaphragmatic motion were demonstrated in 1 case. Moreover, we detected a saber-sheath trachea and main-stem TBM in another case. The third case showed a fixed tracheal stenosis. Conclusions: 4D-CT provides unprecedented z-axis coverage and time-resolved volumetric datasets of the whole chest. Airway instability, stenosis and paradoxical diaphragmatic motion may be assessed simultaneously, preceding interventions such as airway stabilization or lung volume reduction.

To introduce a reproducible, nonenhanced 1H MRI method for rapid in vivo functional assessment of the whole lung at 1.5 Tesla (T).At different respiratory volumes, the pulmonary signal of ultra-fast steady-state free precession (ufSSFP) follows an adapted sponge model, characterized by a respiratory index α. From the model, α reflects local ventilation-related information, is virtually independent from the lung density and thus from the inspiratory phase and breathing amplitude. Respiratory α-mapping is evaluated for healthy volunteers and patients with obstructive lung disease from a set of five consecutive 3D ultra-fast steady-state free precession (ufSSFP) scans performed in breath-hold and at different inspiratory volumes. For the patients, α-maps were compared with CT, dynamic contrast-enhanced MRI (DCE-MRI), and Fourier decomposition (FD).In healthy volunteers, respiratory α-maps showed good reproducibility and were homogeneous on iso-gravitational planes, but showed a gravity-dependent respiratory gradient. In patients with obstructive pulmonary disease, the functional impairment observed in respiratory α-maps was associated with emphysematous regions present on CT images, perfusion defects observable on DCE-MRI, and impairments visualized on FD ventilation and perfusion maps.Respiratory α-mapping derived from multivolumetric ufSSFP provides insights into functional lung impairment and may serve as a reproducible and normative measure for clinical studies. Magn Reson Med 78:1059-1069, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Background Intrabronchial valve placement for endoscopic lung volume reduction is used for patients with severe lung emphysema. Different treatment approaches are unilateral valve placement with the goal of complete occlusion and subsequent atelectasis leading to true volume reduction vs bilateral partial closure aiming for redistribution of ventilation but avoiding atelectasis. In this prospective pilot trial, we compared the efficacy of these treatment approaches. Methods Patients with severe bilateral heterogeneous emphysema were randomized to two groups. In the first group, patients received unilateral valves aiming for total occlusion of one lobe. In the other group, valves were placed in two contralateral lobes with incomplete closure. In all cases, one-way valves were placed via a flexible bronchoscope. Patients were followed at 30 and 90 days, end points being change in pulmonary function tests (PFTs), 6-min walk distance (6MWD), and dyspnea score as measured by the modified Medical Research Council (mMRC) dyspnea score, as well as quality of life as measured by the St. George Respiratory Questionnaire (SGRQ). Results Twenty-two patients were treated in this study, 11 patients in each arm. At 30 days and 90 days, significant differences were seen in PFT and 6MWD, as well as in mMRC and SGRQ scores, in favor of unilateral treatment. At 90 days, FEV 1 was improved by 21.4% ± 10.7% in this group, but not in the bilateral group (−0.03% ± 13.9%, P = .002). One patient in the unilateral group experienced a pneumothorax, and two patients in the bilateral group were treated for transient respiratory failure. Conclusions Unilateral intrabronchial valve placement with complete occlusion appears superior to bilateral partial occlusion. Trial registry ClinicalTrials.gov ; No.: NCT00995852; URL: www.clinicaltrials.gov

Low-dose multislice-CT (MSCT) detects many early-stage lung cancers with good prognosis, but whether it decreases lung cancer mortality and at which costs is yet insufficiently explored. Scope of the present study is to examine within a common European effort whether MSCT screening is capable to reduce the lung cancer mortality by at least 20 % and at which amount of undesired side effects this could be achieved. Overall 4,052 heavy smoking men and women were recruited by a population-based approach and randomized into a screening arm with five annual MSCT screens and an initial quit-smoking counseling, and a control arm with initial quit-smoking counseling and five annual questionnaire inquiries. In the first screening round, 2,029 participants received a MSCT providing 1,488 negative and 540 suspicious screens with early recalls (early recall rate 26.6 %) leading to 31 biopsies (biopsy rate 1.5 %) and 22 confirmed lung cancers (detection rate 1.1 %). Among the lung cancers, 15 were adenocarcinomas, 3 squamous cell carcinomas, one small-cell lung cancer, and 3 others, whereby 18 were in clinical stage I, one in stage II, and 3 in stage III. One interval cancer occurred. The indicated performance indicators fit into the range observed in comparable trials. The study continues finalizing the second screening round and for the first participants even the last screening round. The unresolved issue of the precise amount of side effects and the high early recall rate precludes currently the recommendation of MSCT as screening tool for lung cancer.

Summary Invasive fungal diseases are a significant cause of morbidity and mortality in the growing population of immunosuppressed patients. Appropriate early therapy is associated with a reduction in mortality, but relies on rapid diagnosis. Microbiological investigations are often a problem as it can take several days for a culture to mature. As a result, diagnostic imaging techniques play a larger role in the early recognition and characterisation of opportunistic fungal diseases. In April 2009, a 1-day interactive workshop titled ‘The role of diagnostic imaging in the management of invasive fungal diseases’ was held for specialists in haemato-oncology, pneumology and radiology. The aim of the workshop was to show the significance as well as the limitations of diagnostic imaging in the assessment of opportunistic fungal diseases and to provide education as to the radiological findings that aid disease evaluation.

BACKGROUND: Functional magnetic resonance imaging (fMRI) of fluorine-19 allows for the mapping of oxygen partial pressure within perfluorocarbons in the alveolar space (Pao(2)). Theoretically, fMRI-detected Pao(2) can be combined with the Fick principle approach, i.e., a mass balance of oxygen uptake by ventilation and delivery by perfusion, to quantify the ventilation-perfusion ratio (Va/Q) of a lung region: The mixed venous blood and the inspiratory oxygen fraction, which are equal for all lung regions, are measured. In addition, the local expiratory oxygen fraction and the end capillary oxygen content, both of which may differ between the lung regions, are calculated using the fMRI-detected Pao(2). We investigated this approach by numerical simulations and applied it to quantify local Va/Q in the perfluorocarbons during partial liquid ventilation. METHODS: Numerical simulations were performed to analyze the sensitivity of the Va/Q calculation and to compare this approach with another one proposed by Rizi et al. in 2004 (Magn Reson Med 2004;52:65-72). Experimentally, the method was used during partial liquid ventilation in 7 anesthetized pigs. The Pao(2) distribution in intraalveolar perflubron was measured by fluorine-19 MRI. Respiratory gas fractions together with arterial and mixed venous blood samples were taken to quantify oxygen partial pressure and content. Using the Fick principle, the local Va/Q was estimated. The impact of gravity (nondependent versus dependent) of perflubron dose (10 vs 20 mL/kg body weight) and of inspired oxygen fraction (Fio(2)) (0.4-1.0) on Va/Q was examined. RESULTS: In numerical simulations, the Fick principle proved to be appropriate over the Va/Q range from 0.02 to 2.5. Va/Q values were in acceptable agreement with the method published by Rizi et al. In the experimental setting, low mean Va/Q values were found in perflubron (confidence interval [CI] 0.08-0.29 with 20 mL/kg perflubron). At this dose, Va/Q in the nondependent lung was higher (CI 0.18-0.39) than in the dependent lung regions (CI 0.06-0.16; P = 0.006; Student t test). Differences depending on Fio(2) or perflubron dose were, however, small. CONCLUSION: The results show that derivation of Va/Q from local Po(2) measurements using fMRI in perflubron is feasible. The low detected Va/Q suggests that oxygen transport into the perflubron-filled alveolar space is significantly restrained.

Magnetic resonance imaging of inhaled fluorinated inert gases ((19)F-MRI) such as sulfur hexafluoride (SF(6)) allows for analysis of ventilated air spaces. In this study, the possibility of using this technique to image lung function was assessed. For this, (19)F-MRI of inhaled SF(6) was compared with respiratory gas analysis, which is a global but reliable measure of alveolar gas fraction. Five anesthetized pigs underwent multiple-breath wash-in procedures with a gas mixture of 70% SF(6) and 30% oxygen. Two-dimensional (19)F-MRI and end-expiratory gas fraction analysis were performed after 4 to 24 inhaled breaths. Signal intensity of (19)F-MRI and end-expiratory SF(6) fraction were evaluated with respect to linear correlation and reproducibility. Time constants were estimated by both MRI and respiratory gas analysis data and compared for agreement. A good linear correlation between signal intensity and end-expiratory gas fraction was found (correlation coefficient 0.99+/-0.01). The data were reproducible (standard error of signal intensity 8% vs. that of gas fraction 5%) and the comparison of time constants yielded a sufficient agreement. According to the good linear correlation and the acceptable reproducibility, we suggest the (19)F-MRI to be a valuable tool for quantification of intrapulmonary SF(6) and hence lung function.

The technology of multislice X-ray computed tomography (MSCT) provides volume data sets with approximately isotropic resolution, which permits a noninvasive 3-D measurement and quantification of airway geometry. In different diseases, like emphysema, chronic obstructive pulmonary disease (COPD), or cystic fribrosis, changes in lung parenchyma are associated with an increase in airway wall thickness. In this paper, we describe an objective measuring method of the airway geometry in the 3-D space. The limited spatial resolution of clinical CT scanners in comparison to thin structures like airway walls causes difficulties in the measurement of the density and the thickness of these structures. Initially, these difficulties will be addressed and then a new method is introduced to circumvent the problems. Therefore the wall thickness is approximated by an integral based closed-form solution, based on the volume conservation property of convolution. We evaluated the method with a phantom containing 10 silicone tubes and proved the repeatability in datasets of eight pigs scanned twice. Furthermore, a comparison of CT datasets of 16 smokers and 15 nonsmokers was done. Further medical studies are ongoing.

Methods: Retrospective analysis of 68 patients ([male]/[female]:32/36, age: 64±7 years). A total of 10 coils were implanted in a single lobe. 16 patients received additional treatment contralaterally. At 90 days follow-up changes in pulmonary function tests (PFT), 6-Minute-Walk-Test (6MWT) and modified Medical Research Council (mMRC) dyspnea scale, as well as possible complications were recorded. Results: Forced expiratory volume in the 1st second (0.70±0.20L vs 0.76±0.22L, p:0.004), vital capacity (2.1±0.70L vs 2.30±0.79L, p

Summary In recent years, percutaneous radiofrequency ablation (RFA) has been developed as a new tool in the treatment of non-small-cell lung cancer (NSCLC) in non-surgical patients. There is growing evidence that RFA-mediated necrosis can modulate host immune responses. Here we analysed serum inflammatory factors as well as immunosuppressive cells in the peripheral blood to discover possible prognostic indicators. Peripheral blood and serum samples were collected before RFA and within 3 months after the treatment in a total of 12 patients. Inflammatory cytokines and growth factors were measured in serum by the Bio-Plex assay. Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) were evaluated in the peripheral blood via flow cytometry. In patients developing local or lymphogenic tumour relapse (n = 4), we found an early significant increase in the concentration of tumour necrosis factor (TNF)-α as well as chemokine (C-C motif) ligand (CCL)-2 and CCL-4 compared to patients without relapse (n = 4) and healthy donors (n = 5). These changes were associated with an elevated activity of circulating MDSC indicated by an increased nitric oxide (NO) production in these cells. Elevated serum levels of TNF-α, CCL-2 and CCL-4 associated with an increased NO production in circulating MDSCs might be an early indicator of the incomplete RFA and subsequently a potential tumour relapse in NSCLC.

Cystic fibrosis (CF) is a multi-systemic disease with major impact on the lungs. Pulmonary manifestation is crucial for the prognosis and life expectancy of patients. Imaging modalities and lung function tests reflect the pulmonary status in these patients. The standard imaging modality for diagnosis and follow-up of pulmonary changes is chest x-ray. The gold standard for the detection of parenchymal lung changes remains high resolution computed tomography (HRCT), but this is not used routinely for CF-patients due to radiation exposure. Magnetic resonance imaging (MRI) used to be of no importance in monitoring cystic fibrosis lung disease, as shown in studies from the 1980s and early 1990 s. The continuing improvement of MRI techniques, however, has allowed for an adequate application of this non-radiation method in diagnosing the major pulmonary findings in CF, in addition to the assessment of lung function.

Minimal scan times in rapid fluorine-19 MRI using sulfur hexafluoride (SF6) have been on the order of 10 s. Because of the very short T1 relaxation time of SF6 (T1 = 1.65 ms), high receiver bandwidths are necessary to allow for a high number of excitations. Since high bandwidths cause high levels of electronic noise, SNR per acquisition has been too low to further reduce scan time. The purpose of this study was to investigate whether scan times could be reduced using hexafluoroethane (C2F6), a gas with a longer T1 (T1 = 7.9 ms) at a relatively low bandwidth of 488 Hz/pixel. Gradient-echo images were acquired during and after completion of the wash-in of a 70% C2F6- 30% O2 mixture. Peak SNR values of 16 and 7.9 were observed for coronal projection images acquired within 2 s and 260 ms, respectively. These results demonstrate that subsecond imaging is feasible using C2F6.

Magnetic resonance imaging of the apparent diffusion coefficient (ADC) of hyperpolarized Helium-3 is a new technique for probing pulmonary microstructure in vivo. The aim of this study was the assessment of potential sources of systematic errors of the ADC measurement. The influence of macroscopic motion was determined by measurements at two different delays after initiating the breath-hold, and before and after cardiac arrest. An intercentre comparison was performed in two age- and lung function-matched groups of lung-healthy volunteers at two research sites. Moreover, measurements of diffusion anisotropy were performed. We found no dependency of the ADC as a function of the delay after stop of inspiration. The influence of cardiac motion was less than 10%. In the intercentre comparison study, an excellent agreement between the two sites was found. First measurements of the diffusion tensor of intrapulmonary Helium-3 are shown.

Die radiologische Untersuchung der Lunge basiert traditionell auf Rontgenechniken. Die klinisch ubliche Wasserstoff-MRT ist durch die geringe Protonendichte des Lungenparenchyms und statische Feldinhomogenitaten innerhalb der Lunge stark limitiert. Die Einfuhrung hyperpolarisierter Edelgase hat zu einer rapiden Entwicklung der Magnetresonanztomographie des Thorax gefuhrt und eine Reihe neuer funktioneller Messverfahren ermoglicht, die bisher in dieser Art nicht erreicht wurden. Der vorliegende Artikel umreist den physikalischen Hintergrund und mogliche klinische Anwendungen dieser Technik. Eingehend werden die Erfassung der statischen und der dynamischen Verteilung der Ventilation, die Messung der Mikrostruktur der Lunge und die Sauerstoffpartialdruckmessung beschrieben.