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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 80 th percentile threshold. QDP was compared with visual MRI perfusion scoring, CT parametric response mapping (PRM) indices of emphysema (PRM Emph ) and functional small airway disease (PRM fSAD ), 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 PRM Emph  (r = 0.70 to 0.75, p < 0.001). QDP was distinctly higher than PRM Emph  (mean difference = 35.85 to 40.40) and PRM fSAD (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 PRM Emph  and PRM fSAD . 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 PRM Emph  and PRM fSAD 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., (© 2021. The Author(s).)

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 (RVC 856-950 )), 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, RVC 856-950 ) were stable. PRM Emph increased from 34.3 to 35.7% (p < 0.001), whereas PRM Normal 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 mm 2 (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.

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

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

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

Three-dimensional (3D) dynamic contrast-enhanced magnetic resonance imaging (3D DCE-MRI) has been proposed for the assessment of regional perfusion. The aim of this work was the implementation of an algorithm for a 3D parametric visualization of lung perfusion using different cutting planes and volume rendering. Our implementation was based on 3D DCE-MRI data of the lungs of five patients and five healthy volunteers. Using the indicator dilution theory, the regional perfusion parameters, tissue blood flow, blood volume and mean transit time were calculated. Due to the required temporal resolution, the volume elements of dynamic MR data sets show a reduced spatial resolution in the z-direction. Therefore, perfusion parameter volumes were interpolated. Linear interpolation and a combination of linear and nearest-neighbor interpolation were evaluated. Additionally, ray tracing was applied for 3D visualization. The linear interpolation algorithm caused interpolation errors at the lung borders. Using the combined interpolation, visualization of perfusion information in arbitrary cutting planes and in 3D using volume rendering was possible. This facilitated the localization of perfusion deficits compared with the coronal orientated source data. The 3D visualization of perfusion parameters using a combined interpolation algorithm is feasible. Further studies are required to evaluate the additional benefit from the 3D visualization.

Goals of our study were to compare the pulmonary hemodynamics between healthy volunteers and patients with pulmonary arterial hypertension (PAH) and correlate MR flow measurements with echocardiography. Twenty-five patients with PAH and 25 volunteers were examined at 1.5 T. Phase-contrast flow measurements were performed in the ascending aorta and pulmonary trunk, resulting in the following parameters: peak velocity (cm/s), average blood flow (l/min), time to peak velocity (ms), velocity rise gradient and pulmonary distensibility (cm(2)). The bronchosystemic shunt was calculated. In PAH patients transthoracic echocardiography and right-heart catheterization (RHC) served as the gold standard. In comparison to volunteers, the PAH patients showed significantly reduced pulmonary velocities (P = 0.002), blood flow (P = 0.002) and pulmonary distensibility (P = 0.008). In patients, the time to peak velocity was shorter (P<0.001), and the velocity rise gradient was steeper (P = 0.002) than in volunteers. While in volunteers the peak velocity in the aorta was reached earlier, it was the reverse in patients. Patients showed a significant bronchosystemic shunt (P = 0.01). No meaningful correlation was found between MRI measurements and echocardiography or RHC. MRI is a feasible technique for the differentiation between PAH and volunteers. Further studies have to be conducted for the absolute calculation of pressure estimates.

Cystic fibrosis (CF) is the most frequent inherited disorder leading to premature death in the Caucasian population. As life expectancy is limited by pulmonary complications, repeated imaging [chest X-ray, multislice high-resolution computed tomography (MS-HRCT)] is required in the follow-up. Magnetic resonance imaging (MRI) of the lung parenchyma is a promising new diagnostic tool. Its value for imaging lung changes caused by CF compared with CT is demonstrated. MRI performs well when compared with CT, which serves as the gold standard. Its lack in spatial resolution is obvious, but advantages in contrast and functional assessment compensate for this limitation. Thus, MRI is a reasonable alternative for imaging the CF lung and should be introduced as a radiation-free modality for follow-up studies in CF patients. For further evaluation of the impact of MRI, systematic studies comparing MRI and conventional imaging modalities are necessary. Furthermore, the value of the additional functional MRI (fMRI) information has to be studied, and a scoring system for the morphological and functional aspect of MRI has to be established.

This paper is a feasibility study of magnetic resonance imaging (MRI) of lung perfusion in children with cystic fibrosis (CF) using contrast-enhanced 3D MRI. Correlation assessment of perfusion changes with structural abnormalities. Eleven CF patients (9 f, 2 m; median age 16 years) were examined at 1.5 T. Morphology: HASTE coronal, transversal (TR/TE/alpha/ST: 600 ms/28 ms/180 degrees /6 mm), breath-hold 18 s. Perfusion: Time-resolved 3D GRE pulse sequence (FLASH, TE/TR/alpha: 0.8/1.9 ms/40 degrees ), parallel imaging (GRAPPA, PAT 2). Twenty-five data sets were acquired after intravenous injection of 0.1 mmol/kg body weight of gadodiamide, 3-5 ml/s. A total of 198 lung segments were analyzed by two radiologists in consensus and scored for morphological and perfusion changes. Statistical analysis was performed by Mantel-Haenszel chi-square test. Results showed that perfusion defects were observed in all patients and present in 80% of upper, and 39% of lower lobes. Normal lung parenchyma showed homogeneous perfusion (86%, P<0.0001). Severe morphological changes led to perfusion defects (97%, P<0.0001). Segments with moderate morphological changes showed normal (53%) or impaired perfusion (47%). In conclusion, pulmonary perfusion is easy to judge in segments with normal parenchyma or severe changes. In moderately damaged segments, MRI of lung perfusion may help to better assess actual functional impairment. Contrast-enhanced 3D MRI of lung perfusion has the potential for early vascular functional assessment and therapy control in CF patients.

To assess the stability and reproducibility of different breath-hold levels in healthy volunteers and patients using dynamic MRI (dMRI). In ten healthy volunteers and ten patients with pulmonary hypertension (PH) and normal lung function craniocaudal intrathoracic distances (CCD) were measured during inspiratory and expiratory breath-hold (15 s) (in healthy volunteers additionally at a self-chosen mid-inspiratory breath-hold) using dMRI (trueFISP, three images/s). To evaluate stability and intraobserver reproducibility of the different breath-hold levels, CCDs, time-distance curves, confidence intervals (CIs), Mann-Witney U test and regression equations were calculated. In healthy volunteers there was a substantial decrease of the CCD during the inspiratory breath-hold in contrast to the expiratory breath-hold. The CI at inspiration was 2.84+/-1.28 in the right and 2.1+/-0.68 in the left hemithorax. At expiration the CI was 2.54+/-1.18 and 2.8+/-1.48. Patients were significantly less able to hold their breath at inspiration than controls (P<0.05). In patients CI was 4.53+/-4.06 and 3.46+/-2.21 at inspiration and 4.45+/-4.23 and 4.76+/-3.73 at expiration. Intraobserver variability showed no significant differences either in patients or in healthy subjects. Reproducibility was significantly lower at a self-chosen breath-hold level of the healthy volunteers. DMRI is able to differentiate stability and reproducibility of different breath-hold levels. Expiratory breath-hold proved to be more stable than inspiratory breath-hold in healthy volunteers and patients.

Differentiation between different forms of pulmonary hypertension (PH) is essential for correct disease management. The goal of this study was to elucidate the clinical impact of high spatial resolution MR angiography (SR-MRA) and time-resolved MRA (TR-MRA) to differentiate between patients with chronic thromboembolic PH (CTEPH) and idiopathic pulmonary arterial hypertension (IPAH). Ten PH patients and five volunteers were examined. Twenty TR-MRA data sets (TA 1.5 s) and SR-MRA (TA 23 s) were acquired. TR-MRA data sets were subtracted as angiography and perfusion images. Evaluation comprised analysis of vascular pathologies on a segmental basis, detection of perfusion defects, and bronchial arteries by two readers in consensus. Technical evaluation comprised evaluation of image quality, signal-to-noise ratio (SNR) measurements, and contrast-media passage time. Visualization of the pulmonary arteries was possible down to a subsegmental (SR-MRA) and to a segmental (TR-MRA) level. SR-MRA outperformed TR-MRA in direct visualization of intravascular changes. Patients with IPAH predominantly showed tortuous pulmonary arteries while in CTEPH wall irregularities and abnormal proximal-to-distal tapering was found. Perfusion images showed a diffuse pattern in IPAH and focal defects in CTEPH. TR-MRA and SR-MRA resulted in the same final diagnosis. Both MRA techniques allowed for differentiation between IPAH and CTEPH. Therefore, TR-MRA can be used in the clinical setting, especially in dyspneic patients.

Cystic fibrosis (CF) leads to disabling lung disease and pulmonary hypertension (PH). The goal of this study was to assess the hemodynamics in the systemic and pulmonary arterial circulation of patients with CF using MRI. Ten patients with CF and 15 healthy volunteers were examined (1.5-T MRI). Phase-contrast flow measurements were assessed in the ascending aorta, pulmonary trunc, and the left and right pulmonary arteries (PA), resulting in the following parameters: peak velocity (PV) (centimeters per second) velocity rise gradient (VRG), time to PV (milliseconds), and the average area (centimeters squared). The blood flow ratio between the right and left lungs and the bronchosystemic shunt were calculated. For the ascending aorta and pulmonary trunc no parameter was significantly different between both populations. In the right PA a significantly lower PV (p=0.001) and VRG (p=0.02) was found. In the left PA there was a significantly (p=0.007) lower PV but no significant (p=0.07) difference between the VRG. The areas of the right (p=0.08) and left (p=0.5) PA were not significantly enlarged. For the volunteers a linear increase of PV in both PA was found with age, while it decreased in patients with CF. The blood flow distribution (right/left lung) showed no significant (p=0.7) difference between the groups. There was a significantly (p<0.001) higher bronchosystemic shunt volume in patients with CF (1.3 l/min) than in volunteers (0.1 l/min). Magnetic resonance based flow measurements in the right and left PA showed first indications for early development of PH. The significant increase in bronchosystemic shunt volume might be indicative fo the extent of parenchymal changes.

The purpose of this study was to assess diaphragmatic length and shortening during the breathing cycle in healthy volunteers and patients with a lung tumor using dynamic MRI (dMRI). In 15 healthy volunteers and 28 patients with a solitary lung tumor, diaphragmatic motion and length were measured during the breathing cycle using a trueFISP sequence (three images per second in the coronal and sagittal plane). Time-distance curves and maximal length reduction (= shortening) of the diaphragm were calculated. The influence of tumor localization on diaphragmatic shortening was examined. In healthy volunteers maximal diaphragmatic shortening was 30% in the coronal and 34% in the sagittal orientation, with no difference between both hemithoraces. Tumors of the upper and middle lung region did not affect diaphragmatic shortening. In contrast, tumors of the lower lung region changed shortening significantly ( P<0.05). In hemithoraces with a tumor in the lower region, shortening was 18% in the coronal and 19% in the sagittal plane. The ratio of diaphragmatic length change from inspiration to expiration changed significantly from healthy subjects (inspiration length >> expiratory length, P<0.05) to patients with a tumor in the lower lung region (inspiratory length = expiratory length). dMRI is a simple, non-invasive method to evaluate diaphragmatic motion and shortening in volunteers and patients during the breathing cycle. Tumors of the lower lung region have a significant influence on shortening of the diaphragm.