High-resolution transcriptomic and epigenetic profiling identifies novel regulators of COPD.

Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering its environmental cause, 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) across COPD stages. We show that the epigenetic landscape is changed early in COPD, with DNA methylation changes occurring predominantly in regulatory regions. RNA sequencing of matched fibroblasts demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization. Data integration identified 110 candidate regulators of disease phenotypes that were linked to fibroblast repair processes using phenotypic screens. Our study provides high-resolution multi-omic maps of HLFs across COPD stages. We reveal novel transcriptomic and epigenetic signatures associated with COPD onset and progression and identify new candidate regulators involved in the pathogenesis of chronic lung 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.

Phenotyping of COPD with MRI in comparison to same-day CT in a multi-centre trial.

OBJECTIVES: A prospective, multi-centre study to evaluate concordance of morphologic lung MRI and CT in chronic obstructive pulmonary disease (COPD) phenotyping for airway disease and emphysema. METHODS: A total of 601 participants with COPD from 15 sites underwent same-day morpho-functional chest MRI and paired inspiratory-expiratory CT. Two readers systematically scored bronchial wall thickening, bronchiectasis, centrilobular nodules, air trapping and lung parenchyma defects in each lung lobe and determined COPD phenotype. A third reader acted as adjudicator to establish consensus. Inter-modality and inter-reader agreement were assessed using Cohen's kappa (im-κ and ir-κ). RESULTS: The mean combined MRI score for bronchiectasis/bronchial wall thickening was 4.5/12 (CT scores, 2.2/12 for bronchiectasis and 6/12 for bronchial wall thickening; im-κ, 0.04-0.3). Expiratory right/left bronchial collapse was observed in 51 and 47/583 on MRI (62 and 57/599 on CT; im-κ, 0.49-0.52). Markers of small airways disease on MRI were 0.15/12 for centrilobular nodules (CT, 0.34/12), 0.94/12 for air trapping (CT, 0.9/12) and 7.6/12 for perfusion deficits (CT, 0.37/12 for mosaic attenuation; im-κ, 0.1-0.41). The mean lung defect score on MRI was 1.3/12 (CT emphysema score, 5.8/24; im-κ, 0.18-0.26). Airway-/emphysema/mixed COPD phenotypes were assigned in 370, 218 and 10 of 583 cases on MRI (347, 218 and 34 of 599 cases on CT; im-κ, 0.63). For all examined features, inter-reader agreement on MRI was lower than on CT. CONCLUSION: Concordance of MRI and CT for phenotyping of COPD in a multi-centre setting was substantial with variable inter-modality and inter-reader concordance for single diagnostic key features. CLINICAL RELEVANCE STATEMENT: MRI of lung morphology may well serve as a radiation-free imaging modality for COPD in scientific and clinical settings, given that its potential and limitations as shown here are carefully considered. KEY POINTS: • In a multi-centre setting, MRI and CT showed substantial concordance for phenotyping of COPD (airway-/emphysema-/mixed-type). • Individual features of COPD demonstrated variable inter-modality concordance with features of pulmonary hypertension showing the highest and bronchiectasis showing the lowest concordance. • For all single features of COPD, inter-reader agreement was lower on MRI than on CT.

Influence of CT dose reduction on AI-driven malignancy estimation of incidental pulmonary nodules.

OBJECTIVES: The purpose of this study was to determine the influence of dose reduction on a commercially available lung cancer prediction convolutional neuronal network (LCP-CNN). METHODS: CT scans from a cohort provided by the local lung cancer center (n = 218) with confirmed pulmonary malignancies and their corresponding reduced dose simulations (25% and 5% dose) were subjected to the LCP-CNN. The resulting LCP scores (scale 1-10, increasing malignancy risk) and the proportion of correctly classified nodules were compared. The cohort was divided into a low-, medium-, and high-risk group based on the respective LCP scores; shifts between the groups were studied to evaluate the potential impact on nodule management. Two different malignancy risk score thresholds were analyzed: a higher threshold of ≥ 9 ("rule-in" approach) and a lower threshold of > 4 ("rule-out" approach). RESULTS: In total, 169 patients with 196 nodules could be included (mean age ± SD, 64.5 ± 9.2 year; 49% females). Mean LCP scores for original, 25% and 5% dose levels were 8.5 ± 1.7, 8.4 ± 1.7 (p > 0.05 vs. original dose) and 8.2 ± 1.9 (p < 0.05 vs. original dose), respectively. The proportion of correctly classified nodules with the "rule-in" approach decreased with simulated dose reduction from 58.2 to 56.1% (p = 0.34) and to 52.0% for the respective dose levels (p = 0.01). For the "rule-out" approach the respective values were 95.9%, 96.4%, and 94.4% (p = 0.12). When reducing the original dose to 25%/5%, eight/twenty-two nodules shifted to a lower, five/seven nodules to a higher malignancy risk group. CONCLUSION: CT dose reduction may affect the analyzed LCP-CNN regarding the classification of pulmonary malignancies and potentially alter pulmonary nodule management. CLINICAL RELEVANCE STATEMENT: Utilization of a "rule-out" approach with a lower malignancy risk threshold prevents underestimation of the nodule malignancy risk for the analyzed software, especially in high-risk cohorts. KEY POINTS: • LCP-CNN may be affected by CT image parameters such as noise resulting from low-dose CT acquisitions. • CT dose reduction can alter pulmonary nodule management recommendations by affecting the outcome of the LCP-CNN. • Utilization of a lower malignancy risk threshold prevents underestimation of pulmonary malignancies in high-risk cohorts.

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

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

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

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

Utility of Automated Cardiac Chamber Volumetry by Nongated CT Pulmonary Angiography for Detection of Pulmonary Hypertension Using the 2018 Updated Hemodynamic Definition.

BACKGROUND. Noninvasive tests for pulmonary hypertension (PH) are needed to help select patients for diagnostic right heart catheterization (RHC). CT pulmonary angiography (CTPA) is commonly performed for suspected PH. OBJECTIVE. The purpose of this study was to assess the utility of CTPA-based cardiac chamber volumetric measurements for the diagnosis of PH in comparison with echocardiographic and conventional CTPA parameters, with the 2018 updated hemodynamic definition used as reference. METHODS. This retrospective study included 109 patients (72 women and 37 men; median age, 68 years) who underwent nongated CTPA, transthoracic echocardiography, and RHC for the workup of suspected PH between August 2013 and February 2016. Two radiologists independently used automated 3D segmentation software to determine the volumes of the right ventricle (RV), right atrium (RA), left ventricle (LV), and left atrium (LA) and also measured the axial diameters of the cardiac chambers, main pulmonary artery, and ascending aorta. Interobserver agreement was assessed, and mean values were obtained; one observer repeated volumetric measurements to assess intraobserver agreement. ROC analysis was used to assess diagnostic performance for the detection of PH. A multivariable binary logistic regression model was established. RESULTS. A total of 60 of 109 patients had PH. Intra- and interobserver agreements were excellent for all volume measurements (intraclass correlation coefficients, 0.935-0.999). In patients with PH versus those without PH, RV volume was 172.6 versus 118.1 mL, and RA volume was 130.2 versus 77.0 mL (both p < .05). Cardiac chamber measurements with the highest AUC for PH were the RV/LV volume ratio and RA volume (both 0.791). Significant predictors of PH20 (as defined using the 2018 hemodynamic definition from the Sixth World Symposium on Pulmonary Hypertension) after adjustment for age, sex, and body surface area included RV volume per 10 mL (odds ratio [OR], 1.21), RA volume per 10 mL (OR, 1.27), RV/LV volume ratio (OR, 2.91), and RA/LA volume ratio (OR, 11.22). Regression analysis yielded a predictive model for PH that contained two independent predictors: echocardiographic pulmonary arterial systolic pressure and CTPA-based RA volume; the model had an AUC of 0.898, sensitivity of 83.3%, and specificity of 85.7%. CONCLUSION. Automated cardiac chamber volumetry using nongated CTPA, particularly of the RA, provides incremental utility relative to echocardiographic and conventional CTPA parameters for diagnosis of PH. CLINICAL IMPACT. Automated volumetry of cardiac chambers based on nongated CTPA may facilitate early noninvasive detection of PH, identifying patients who warrant further evaluation by RHC.

Echo Time-Dependent Observed Lung T1 in Patients With Chronic Obstructive Pulmonary Disease in Correlation With Quantitative Imaging and Clinical Indices.

BACKGROUND: There is a clinical need for imaging-derived biomarkers for the management of chronic obstructive pulmonary disease (COPD). Observed pulmonary T1 (T1 (TE)) depends on the echo-time (TE) and reflects regional pulmonary function. PURPOSE: To investigate the potential diagnostic value of T1 (TE) for the assessment of lung disease in COPD patients by determining correlations with clinical parameters and quantitative CT. STUDY TYPE: Prospective non-randomized diagnostic study. POPULATION: 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. FIELD STRENGTH/SEQUENCE: 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 T1 (TE) mapping at TE1-5  = 70 µsec, 500 µsec, 1200 µsec, 1650 µsec, and 2300 µsec. ASSESSMENT: Perfusion images were scored by three radiologists. T1 (TE) was automatically quantified. Computed tomography (CT) images were quantified in software (qCT). Clinical parameters including pulmonary function testing were also acquired. STATISTICAL TESTS: Spearman rank correlation coefficients (ρ) were calculated between T1 (TE) and perfusion scores, clinical parameters and qCT. A P-value <0.05 was considered statistically significant. RESULTS: Median values were T1 (TE1-5 ) = 644 ± 78 msec, 835 ± 92 msec, 835 ± 87 msec, 831 ± 131 msec, 893 ± 220 msec, all significantly shorter than previously reported in healthy subjects. A significant increase of T1 was observed from TE1 to TE2 , with no changes from TE2 to TE3 (P = 0.48), TE3 to TE4 (P = 0.94) or TE4 to TE5 (P = 0.02) which demonstrates an increase at shorter TEs than in healthy subjects. Moderate to strong Spearman's correlations between T1 and parameters including the predicted diffusing capacity for carbon monoxide (DLCO, ρ < 0.70), mean lung density (MLD, ρ < 0.72) and the perfusion score (ρ > -0.69) were found. Overall, correlations were strongest at TE2 , weaker at TE1 and rarely significant at TE4 -TE5 . DATA CONCLUSION: In COPD patients, the increase of T1 (TE) with TE occurred at shorter TEs than previously found in healthy subjects. Together with the lack of correlation between T1 and clinical parameters of disease at longer TEs, this suggests that T1 (TE) quantification in COPD patients requires shorter TEs. The TE-dependence of correlations implies that T1 (TE) mapping might be developed further to provide diagnostic information beyond T1 at a single TE. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Lung cancer mortality reduction by LDCT screening-Results from the randomized German LUSI trial.

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.

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

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

EML4-ALK fusion variant V3 is a high-risk feature conferring accelerated metastatic spread, early treatment failure and worse overall survival in ALK+ non-small cell lung cancer.

In order to identify anaplastic lymphoma kinase-driven non-small cell lung cancer (ALK+ NSCLC) patients with a worse outcome, who might require alternative therapeutic approaches, we retrospectively analyzed all stage IV cases treated at our institutions with one of the main echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion variants V1, V2 and V3 as detected by next-generation sequencing or reverse transcription-polymerase chain reaction (n = 67). Progression under tyrosine kinase inhibitor (TKI) treatment was evaluated both according to Response Evaluation Criteria in Solid Tumors (RECIST) and by the need to change systemic therapy. EML4-ALK fusion variants V1, V2 and V3 were found in 39%, 10% and 51% of cases, respectively. Patients with V3-driven tumors had more metastatic sites at diagnosis than cases with the V1 and V2 variants (mean 3.3 vs. 1.9 and 1.6, p = 0.005), which suggests increased disease aggressiveness. Furthermore, V3-positive status was associated with earlier failure after treatment with first and second-generation ALK TKI (median progression-free survival [PFS] by RECIST in the first line 7.3 vs. 39.3 months, p = 0.01), platinum-based combination chemotherapy (median PFS 5.4 vs. 15.2 months for the first line, p = 0.008) and cerebral radiotherapy (median brain PFS 6.1 months vs. not reached for cerebral radiotherapy during first-line treatment, p = 0.028), and with inferior overall survival (39.8 vs. 59.6 months in median, p = 0.017). Thus, EML4-ALK fusion variant V3 is a high-risk feature for ALK+ NSCLC. Determination of V3 status should be considered as part of the initial workup for this entity in order to select patients for more aggressive surveillance and treatment strategies.

European position statement on lung cancer screening.

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 mm3, and new lung nodules greater than 200 mm3, 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.

Rapid 3D in vivo 1H human lung respiratory imaging at 1.5 T using ultra-fast balanced steady-state free precession.

PURPOSE: To introduce a reproducible, nonenhanced 1H MRI method for rapid in vivo functional assessment of the whole lung at 1.5 Tesla (T). METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Retrospective study in 23 patients of the self-expanding sinus-XL stent for treatment of malignant superior vena cava obstruction caused by non-small cell lung cancer.

PURPOSE: To evaluate retrospectively the self-expanding nitinol Sinus-XL stent (OptiMed, Ettlingen, Germany) for the treatment of superior vena cava (SVC) obstruction caused by non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between October 2009 and December 2012, 23 patients (7 women and 16 men; age, 62.5 y ± 8.5) with stage IIIA (1 patient), IIIB (4 patients) or IV (18 patients) NSCLC and acute SVC obstruction were scheduled for urgent stent implantation. The primary study endpoints were technical success (defined as accurate stent placement with complete coverage of the obstructed SVC), residual stenosis < 30%, and clinical efficacy. Complications were assessed as a secondary study endpoint. RESULTS: There were 26 stents implanted in 23 patients. The technical success was 100%. Stent dilation was performed after deployment in 18 cases (78%). Stent migration into the right atrium occurred immediately after deployment in one patient; however, this stent was successfully repositioned and stabilized by a second stent. The clinical symptoms improved at least one category according to the International Consensus Committee on Chronic Venous Disease after stent implantation in all but one patient. The mean clinical follow-up was 66 days ± 83 (range, 1-305 d). Three minor complications (13%) and one major complication (4%) occurred. CONCLUSIONS: Implantation of the self-expanding Sinus-XL stent for treatment of SVC obstruction caused by NSCLC is a safe and effective urgent treatment in this palliative setting.

Simultaneous assessment of airway instability and respiratory dynamics with low-dose 4D-CT in chronic obstructive pulmonary disease: a technical note.

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.

Simultaneous assessment of heart and lungs with gated high-pitch ultra-low dose chest CT using artificial intelligence-based calcium scoring.

Purpose: The combined testing for coronary artery and pulmonary diseases is of clinical interest as risk factors are shared. In this study, a novel ECG-gated tin-filtered ultra-low dose chest CT protocol (GCCT) for integrated heart and lung acquisition and the applicability of artificial intelligence (AI)-based coronary artery calcium scoring were assessed. Methods: In a clinical registry of 10481 patients undergoing heart and lung CT, GCCT was applied in 44 patients on a dual-source CT. Coronary calcium scans (CCS) with 120 kVp, 100 kVp, and tin-filtered 100 kVp (Sn100) of controls, matched with regard to age, sex, and body-mass index, were retrieved from the registry (ntotal=176, 66.5 (59.4-74.0) years, 52 men). Automatic tube current modulation was used in all scans. In 20 patients undergoing GCCT and Sn100 CCS, Agatston scores were measured both semi-automatically by experts and by AI, and classified into six groups (0, <10, <100, <400, <1000, ≥1000). Results: Effective dose decreased significantly from 120 kVp CCS (0.50 (0.41-0.61) mSv) to 100 kVp CCS (0.34 (0.26-0.37) mSv) to Sn100 CCS (0.14 (0.11-0.17) mSv). GCCT showed higher values (0.28 (0.21-0.32) mSv) than Sn100 CCS but lower than 120 kVp and 100 kVp CCS (all p < 0.05) despite greater scan length. Agatston scores correlated strongly between GCCT and Sn100 CCS in semi-automatic and AI-based measurements (both ρ = 0.98, p < 0.001) resulting in high agreement in Agatston score classification (κ = 0.97, 95% CI 0.92-1.00; κ = 0.89, 95% CI 0.79-0.99). Regarding chest findings, further diagnostic steps were recommended in 28 patients. Conclusions: GCCT allows for reliable coronary artery disease and lung cancer screening with ultra-low radiation exposure. GCCT-derived Agatston score shows excellent agreement with standard CCS, resulting in equivalent risk stratification.

Elexacaftor/Tezacaftor/Ivacaftor Improves Bronchial Artery Dilatation Detected by Magnetic Resonance Imaging in Patients with Cystic Fibrosis.

Rationale: Magnetic resonance imaging (MRI) detects improvements in mucus plugging and bronchial wall thickening, but not in lung perfusion in patients with cystic fibrosis (CF) treated with elexacaftor/tezacaftor/ivacaftor (ETI). Objectives: To determine whether bronchial artery dilatation (BAD), a key feature of advanced lung disease, indicates irreversibility of perfusion abnormalities and whether BAD could be reversed in CF patients treated with ETI. Methods: A total of 59 adults with CF underwent longitudinal chest MRI, including magnetic resonance angiography twice, comprising 35 patients with CF (mean age, 31 ± 7 yr) before (MRI1) and after (MRI2) at least 1 month (mean duration, 8 ± 4 mo) on ETI therapy and 24 control patients with CF (mean age, 31 ± 7 yr) without ETI. MRI was assessed using the validated chest MRI score, and the presence and total lumen area of BAD were assessed with commercial software. Results: The MRI global score was stable in the control group from MRI1 to MRI2 (mean difference, 1.1 [-0.3, 2.4]; P = 0.054), but it was reduced in the ETI group (-10.1 [-0.3, 2.4]; P < 0.001). In the control and ETI groups, BAD was present in almost all patients at baseline (95% and 94%, respectively), which did not change at MRI2. The BAD total lumen area did not change in the control group from MRI1 to MRI2 (1.0 mm2 [-0.2, 2.2]; P = 0.099) but decreased in the ETI group (-7.0 mm2 [-8.9, -5.0]; P < 0.001). This decrease correlated with improvements in the MRI global score (r = 0.540; P < 0.001). Conclusions: Our data show that BAD may be partially reversible under ETI therapy in adult patients with CF who have established disease.

MRI Compared with Low-Dose CT for Incidental Lung Nodule Detection in COPD: A Multicenter Trial.

Purpose: To investigate morphofunctional chest MRI for the detection and management of incidental pulmonary nodules in participants with chronic obstructive pulmonary disease (COPD). Materials and Methods: In this prospective study, 567 participants (mean age, 66 years ± 9 [SD]; 340 men) underwent same-day contrast-enhanced MRI and nonenhanced low-dose CT (LDCT) in a nationwide multicenter trial (clinicaltrials.gov: NCT01245933). Nodule dimensions, morphologic features, and Lung Imaging Reporting and Data System (Lung-RADS) category were assessed at MRI by two blinded radiologists, and consensual LDCT results served as the reference standard. Comparisons were performed using the Student t test, and agreements were assessed using the Cohen weighted κ. Results: A total of 525 nodules larger than 3 mm in diameter were detected at LDCT in 178 participants, with a mean diameter of 7.2 mm ± 6.1 (range, 3.1-63.1 mm). Nodules were not detected in the remaining 389 participants. Sensitivity and positive predictive values with MRI for readers 1 and 2, respectively, were 63.0% and 84.8% and 60.2% and 83.9% for solid nodules (n = 495), 17.6% and 75.0% and 17.6% and 60.0% for part-solid nodules (n = 17), and 7.7% and 100% and 7.7% and 50.0% for ground-glass nodules (n = 13). For nodules 6 mm or greater in diameter, sensitivity and positive predictive values were 73.3% and 92.2% for reader 1 and 71.4% and 93.2% for reader 2, respectively. Readers underestimated the long-axis diameter at MRI by 0.5 mm ± 1.7 (reader 1) and 0.5 mm ± 1.5 (reader 2) compared with LDCT (P < .001). For Lung-RADS categorization per nodule using MRI, there was substantial to perfect interreader agreement (κ = 0.75-1.00) and intermethod agreement compared with LDCT (κ = 0.70-1.00 and 0.69-1.00). Conclusion: In a multicenter setting, morphofunctional MRI showed moderate sensitivity for detection of incidental pulmonary nodules in participants with COPD but high agreement with LDCT for Lung-RADS classification of nodules.Clinical trial registration no. NCT01245933 and NCT02629432Keywords: MRI, CT, Thorax, Lung, Chronic Obstructive Pulmonary Disease, Screening© RSNA, 2023 Supplemental material is available for this article.

Echo time-dependent observed T1 and quantitative perfusion in chronic obstructive pulmonary disease using magnetic resonance imaging.

Introduction: Due to hypoxic vasoconstriction, perfusion is interesting in the lungs. Magnetic Resonance Imaging (MRI) perfusion imaging based on Dynamic Contrast Enhancement (DCE) has been demonstrated in patients with Chronic Obstructive Pulmonary Diseases (COPD) using visual scores, and quantification methods were recently developed further. Inter-patient correlations of echo time-dependent observed T1 [T1(TE)] have been shown with perfusion scores, pulmonary function testing, and quantitative computed tomography. Here, we examined T1(TE) quantification and quantitative perfusion MRI together and investigated both inter-patient and local correlations between T1(TE) and quantitative perfusion. Methods: 22 patients (age 68.0 ± 6.2) with COPD were examined using morphological MRI, inversion recovery multi-echo 2D ultra-short TE (UTE) in 1-2 slices for T1(TE) mapping, and 4D Time-resolved angiography With Stochastic Trajectories (TWIST) for DCE. T1(TE) maps were calculated from 2D UTE at five TEs from 70 to 2,300 µs. Pulmonary Blood Flow (PBF) and perfusion defect (QDP) maps were produced from DCE measurements. Lungs were automatically segmented on UTE images and morphological MRI and these segmentations registered to DCE images. DCE images were separately registered to UTE in corresponding slices and divided into corresponding subdivisions. Spearman's correlation coefficients were calculated for inter-patient correlations using the entire segmented slices and for local correlations separately using registered images and subdivisions for each TE. Median T1(TE) in normal and defect areas according to QDP maps were compared. Results: Inter-patient correlations were strongest on average at TE2 = 500 µs, reaching up to |ρ| = 0.64 for T1 with PBF and |ρ| = 0.76 with QDP. Generally, local correlations of T1 with PBF were weaker at TE2 than at TE1 or TE3 and with maximum values of |ρ| = 0.66 (from registration) and |ρ| = 0.69 (from subdivision). In 18 patients, T1 was shorter in defect areas than in normal areas, with the relative difference smallest at TE2. Discussion: The inter-patient correlations of T1 with PBF and QDP found show similar strength and TE-dependence as those previously reported for visual perfusion scores and quantitative computed tomography. The local correlations and median T1 suggest that not only base T1 but also the TE-dependence of observed T1 in normal areas is closer to that found previously in healthy volunteers than in defect areas.