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.

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.

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.

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.

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.

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.

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.

Unsupervised clustering algorithms improve the reproducibility of dynamic contrast-enhanced magnetic resonance imaging pulmonary perfusion quantification in muco-obstructive lung diseases.

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows the assessment of pulmonary perfusion, which may play a key role in the development of muco-obstructive lung disease. One problem with quantifying pulmonary perfusion is the high variability of metrics. Quantifying the extent of abnormalities using unsupervised clustering algorithms in residue function maps leads to intrinsic normalization and could reduce variability. Purpose: We investigated the reproducibility of perfusion defects in percent (QDP) in clinically stable patients with cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Methods: 15 CF (29.3 ± 9.3y, FEV1%predicted = 66.6 ± 15.8%) and 20 COPD (66.5 ± 8.9y, FEV1%predicted = 42.0 ± 13.3%) patients underwent DCE-MRI twice 1 month apart. QDP, pulmonary blood flow (PBF), and pulmonary blood volume (PBV) were computed from residue function maps using an in-house quantification pipeline. A previously validated MRI perfusion score was visually assessed by an expert reader. Results: Overall, mean QDP, PBF, and PBV did not change within 1 month, except for QDP in COPD (p < 0.05). We observed smaller limits of agreement (± 1.96 SD) related to the median for QDP (CF: ± 38%, COPD: ± 37%) compared to PBF (CF: ± 89%, COPD: ± 55%) and PBV (CF: ± 55%, COPD: ± 51%). QDP correlated moderately with the MRI perfusion score in CF (r = 0.46, p < 0.05) and COPD (r = 0.66, p < 0.001). PBF and PBV correlated poorly with the MRI perfusion score in CF (r =-0.29, p = 0.132 and r =-0.35, p = 0.067, respectively) and moderately in COPD (r =-0.57 and r =-0.57, p < 0.001, respectively). Conclusion: In patients with muco-obstructive lung diseases, QDP was more robust and showed a higher correlation with the MRI perfusion score compared to the traditionally used perfusion metrics PBF and PBV.

AI-Supported Comprehensive Detection and Quantification of Biomarkers of Subclinical Widespread Diseases at Chest CT for Preventive Medicine.

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.

Magnetic resonance imaging detects improvements of pulmonary and paranasal sinus abnormalities in response to elexacaftor/tezacaftor/ivacaftor therapy in adults with cystic fibrosis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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, P<0.001), mainly due to reduction of bronchiectasis/wall thickening and mucus plugging subscores (-3.3 ± 2.2 and -5.2 ± 1.5, P<0.001, respectively). The improvement in chest MRI score correlated well with improved FEV1% (r=-0.703, P<0.001). The CRS-MRI sum score also improved in patients under ETI (-6.9 ± 3.0, P<0.001), mainly due to a reduction of mucopyoceles in the maxillary and ethmoid sinus (-50% and -39%, P<0.05, respectively). CONCLUSIONS: 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.

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.

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.

Sarcopenia on preoperative chest computed tomography predicts cancer-specific and all-cause mortality following pneumonectomy for lung cancer: A multicenter analysis.

BACKGROUND: Mortality risk prediction in patients undergoing pneumonectomy for non-small cell lung cancer (NSCLC) remains imperfect. Here, we aimed to assess whether sarcopenia on routine chest computed tomography (CT) independently predicts worse cancer-specific (CSS) and overall survival (OS) following pneumonectomy for NSCLC. METHODS: We included consecutive adults undergoing standard or carinal pneumonectomy for NSCLC at Massachusetts General Hospital and Heidelberg University from 2010 to 2018. We measured muscle cross-sectional area (CSA) on CT at thoracic vertebral levels T8, T10, and T12 within 90 days prior to surgery. Sarcopenia was defined as T10 muscle CSA less than two standard deviations below the mean in healthy controls. We adjusted time-to-event analyses for age, body mass index, Charlson Comorbidity Index, forced expiratory volume in 1 second in % predicted, induction therapy, sex, smoking status, tumor stage, side of pneumonectomy, and institution. RESULTS: Three hundred and sixty-seven patients (67.4% male, median age 62 years, 16.9% early-stage) underwent predominantly standard pneumonectomy (89.6%) for stage IIIA NSCLC (45.5%) and squamous cell histology (58%). Sarcopenia was present in 104 of 367 patients (28.3%). Ninety-day all-cause mortality was 7.1% (26/367). After a median follow-up of 20.5 months (IQR, 9.2-46.9), 183 of 367 patients (49.9%) had died. One hundred and thirty-three (72.7%) of these deaths were due to lung cancer. Sarcopenia was associated with shorter CSS (HR 1.7, p = 0.008) and OS (HR 1.7, p = 0.003). CONCLUSIONS: This transatlantic multicenter study confirms that sarcopenia on preoperative chest CT is an independent risk factor for CSS and OS following pneumonectomy for NSCLC.

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.

Consolidating Lung Volume Reduction Surgery After Endoscopic Lung Volume Reduction Failure.

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.

Optimizing airway wall segmentation and quantification by reducing the influence of adjacent vessels and intravascular contrast material with a modified integral-based algorithm in quantitative computed tomography.

INTRODUCTION: Quantitative 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. METHODS: Temporally 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. RESULTS: The 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 (p<0.05). Using standard IBM, CM led to a decrease of all airway parameters compared to NE. For example, LA decreased from 80.85±49.26mm2 at NE, to 75.14±47.96mm2 (-7.1%) at PA (p<0.001), 74.96±48.55mm2 (-7.3%) at SA (p<0.001), and to 78.95±48.94mm2 (-2.4%) at VE (p = 0.200). Using modified IBM, the differences were reduced to -3.1% at PA, -2.9% at SA and -0.7% at VE (p<0.001; p<0.001; p = 1.000). CONCLUSIONS: The 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.

Novel Liquid Biomarker Panels for A Very Early Response Capturing of NSCLC Therapies in Advanced Stages.

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' outcome.

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.

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.