Echo Time-Dependence of Observed Lung T1 in Patients With Cystic Fibrosis and Correlation With Clinical Metrics.

BACKGROUND: Noninvasive monitoring of early abnormalities and therapeutic intervention in cystic fibrosis (CF) lung disease using MRI is important. Lung T1 mapping has shown potential for local functional imaging without contrast material. Recently, it was discovered that observed lung T1 depends on the measurement echo time (TE). PURPOSE: To examine TE-dependence of observed T1 in patients with CF and its correlation with clinical metrics. STUDY TYPE: Prospective. POPULATION: In all, 75 pediatric patients with CF (8.6 ± 6.1 years, range 0.1-23 years), with 32 reexamined after 1 year. FIELD STRENGTH/SEQUENCE: Patients were examined at 1.5T using an established MRI protocol and a multiecho inversion recovery 2D ultrashort echo time (UTE) sequence for T1 (TE) mapping at five TEs including TE1 = 70 µs. ASSESSMENT: Morphological and perfusion MRI were assessed by a radiologist (M.W.) with 11 years of experience using an established CF-MRI scoring system. T1 (TE) was quantified automatically. Clinical data including spirometry (FEV1pred%) and lung clearance index (LCI) were collected. STATISTICAL TESTS: T1 (TE) was correlated with the CF-MRI score, clinical data, and LCI. RESULTS: T1 (TE) showed a different curvature in CF than in healthy adults: T1 at TE1 was shorter in CF (1157 ms ± 73 ms vs. 1047 ms ± 70 ms, P < 0.001), but longer at TE3 (1214 ms ± 72 ms vs. 1314 ms ± 68 ms, P < 0.001) and later TEs. The correlations of T1 (TE) with patient age (ρTE1-TE5 = -0.55, -0.44, -0.24, -0.30, -0.22), and LCI (ρTE1-TE5 = -0.43, -0.42, -0.33, 0.27, -0.22) were moderate at ultra-short to short TE (P < 0.001) but decreased for longer TE. Moderate but similar correlations at all TE were found with MRI perfusion score (ρTE1-TE5 = -0.43, -0.51, -0.47, -0.46, -0.44) and FEV1pred% (ρTE1-TE5 = +0.44, +0.44, +0.43, +0.40, +0.39) (P < 0.05). DATA CONCLUSION: TE should be considered when measuring lung T1 , since observed differences between CF and healthy subjects strongly depend on TE. The different variation of correlation coefficients with TE for structural vs. functional metrics implies that TE-dependence holds additional information which may help to discern effects of tissue structural abnormalities and abnormal perfusion. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1645-1654.

GOLD stage predicts thoracic aortic calcifications in patients with COPD.

Although some of the associations between chronic obstructive pulmonary disease (COPD) and atherosclerosis are based on shared risk factors such as smoking, recent epidemiological evidence suggests that COPD is a risk factor for vascular disease due to systemic inflammation. The present study assessed the hypothesis that disease severity (as expressed by the GOLD stage) independently predicts the extent of vascular calcifications. A total of 160 smokers diagnosed with COPD (GOLD I-IV, 40 subjects of each GOLD stage) and 40 smokers at risk (GOLD 0; median age of 60 years old; Q1:56;Q3:65; 135 males and 65 females) underwent non-contrast, non-electrocardiography synchronized chest computerised tomography. The volume of thoracic aortic calcifications was quantified semi-automatically within a region from T1 through T12. Multiparametric associations with GOLD stage, smoking history, sex, age, body mass index and emphysema index were evaluated using generalized linear regression analysis. Thoracic aortic calcifications were highly prevalent in this cohort (187/200 subjects, 709 (Q1:109;Q3:2163) mm3). Analysis of variance on ranks demonstrated a significant difference in calcium between different GOLD-stages as well as patients at risk of COPD (F=36.8, P<0.001). In the multivariable analysis, GOLD-stages were indicated to be predictive of thoracic aortic calcifications (P≤0.0033) besides age (P<0.0001), while age appeared to be the strongest predictor. Other variables were not statistically linked to thoracic aortic calcifications in the multivariable model. COPD severity, as expressed by the GOLD-stage, is a significant predictor of thoracic aortic calcifications, independent of covariates such as age or tobacco consumption.

Outracing Lung Signal Decay - Potential of Ultrashort Echo Time MRI.

BACKGROUND: Magnetic resonance imaging (MRI) of the pulmonary parenchyma is generally hampered by multiple challenges related to patient respiratory- and circulation-related motion, low proton density and extremely fast signal decay due to the structure of the lungs evolved for gas exchange. METHODS: Systematic literature database research as well as annual participation in conferences dedicated to pulmonary MRI for more than the past 20 years by at least one member of the author team. RESULTS AND CONCLUSION: The problem of motion has been addressed in the past by developments such as triggering, gating and parallel imaging. The second problem has, in part, turned out to be an advantage in those diseases that lead to an increase in lung substance and thus an increase in signal relative to the background. To reduce signal decay, ultrashort echo time (UTE) methods were developed to minimize the time between excitation and readout. Having been postulated a while ago, improved hardware and software now open up the possibility of achieving echo times shorter than 200 µs, increasing lung signal significantly by forestalling signal decay and more effectively using the few protons available. Such UTE techniques may not only improve structural imaging of the lung but also enhance functional imaging, including ventilation and perfusion imaging as well as quantitative parameter mapping. Because of accelerating progress in this field of lung MRI, the review at hand seeks to introduce some technical properties as well as to summarize the growing data from applications in humans and disease, which promise that UTE MRI will play an important role in the morphological and functional assessment of the lung in the near future. KEY POINTS: · Ultrashort echo time MRI is technically feasible with state-of-the-art scanner hardware.. · UTE MRI allows for CT-like image quality for structural lung imaging.. · Preliminary studies show improvements over conventional morphological imaging in lung cancer and airways diseases.. · UTE may improve sensitivity for functional processes like perfusion and tissue characterization.. CITATION FORMAT: · Wielpütz MO, Triphan SM, Ohno Y et al. Outracing Lung Signal Decay - Potential of Ultrashort Echo Time MRI. Fortschr Röntgenstr 2019; 191: 415 - 423.

Longitudinal airway remodeling in active and past smokers in a lung cancer screening population.

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 mm2 vs. 13.51 mm2 (p < 0.001), respectively. RQ showed higher TD (6.15 mm vs. 5.93 mm, n.s.) and significantly higher LA (14.77 mm2 vs. 13.51 mm2, 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.

Multicentre standardisation of chest MRI as radiation-free outcome measure of lung disease in young children with cystic fibrosis.

BACKGROUND: A recent single-centre study demonstrated that MRI is sensitive to detect early abnormalities in the lung and response to therapy in infants and preschool children with cystic fibrosis (CF) supporting MRI as an outcome measure of early CF lung disease. However, the feasibility of multicentre standardisation remains unknown. OBJECTIVE: To determine the feasibility of multicentre standardisation of chest MRI in infants and preschool children with CF. METHODS: A standardised chest 1.5T MRI protocol was implemented across four specialised CF centres. Following training and initiation visits, 42 infants and preschool children (mean age 3.2±1.5years, range 0-6years) with clinically stable CF underwent MRI and chest X-ray (CXR). Image quality and lung abnormalities were assessed using a standardised questionnaire and an established CF MRI and CXR score. RESULTS: MRI was successfully performed with diagnostic quality in all patients (100%). Incomplete lung coverage was observed in 6% and artefacts also in 6% of sequence acquisitions, but these were compensated by remaining sequences in all patients. The range of the MRI score in CF patients was similar across centres with a mean global MRI score of 13.3±5.8. Cross-validation of the MRI against the CXR score revealed a moderate correlation (r=0.43-0.50, p<0.01). CONCLUSION: Our results demonstrate that multicentre standardisation of chest MRI is feasible and support its use as radiation-free outcome measure of lung disease in infants and preschool children with CF.

Effect of smoking cessation on quantitative computed tomography in smokers at risk in a lung cancer screening population.

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.

Morpho-Functional 1H-MRI of the Lung in COPD: Short-Term Test-Retest Reliability.

PURPOSE: Non-invasive end-points for interventional trials and tailored treatment regimes in chronic obstructive pulmonary disease (COPD) for monitoring regionally different manifestations of lung disease instead of global assessment of lung function with spirometry would be valuable. Proton nuclear magnetic resonance imaging (1H-MRI) allows for a radiation-free assessment of regional structure and function. The aim of this study was to evaluate the short-term reproducibility of a comprehensive morpho-functional lung MRI protocol in COPD. MATERIALS AND METHODS: 20 prospectively enrolled COPD patients (GOLD I-IV) underwent 1H-MRI of the lung at 1.5T on two consecutive days, including sequences for morphology, 4D contrast-enhanced perfusion, and respiratory mechanics. Image quality and COPD-related morphological and functional changes were evaluated in consensus by three chest radiologists using a dedicated MRI-based visual scoring system. Test-retest reliability was calculated per each individual lung lobe for the extent of large airway (bronchiectasis, wall thickening, mucus plugging) and small airway abnormalities (tree in bud, peripheral bronchiectasis, mucus plugging), consolidations, nodules, parenchymal defects and perfusion defects. The presence of tracheal narrowing, dystelectasis, pleural effusion, pulmonary trunk ectasia, right ventricular enlargement and, finally, motion patterns of diaphragma and chest wall were addressed. RESULTS: Median global scores [10(Q1:8.00;Q3:16.00) vs.11(Q1:6.00;Q3:15.00)] as well as category subscores were similar between both timepoints, and kappa statistics indicated "almost perfect" global agreement (ĸ = 0.86, 95%CI = 0.81-0.91). Most subscores showed at least "substantial" agreement of MRI1 and MRI2 (ĸ = 0.64-1.00), whereas the agreement for the diagnosis of dystelectasis/effusion (ĸ = 0.42, 95%CI = 0.00-0.93) was "moderate" and of tracheal abnormalities (ĸ = 0.21, 95%CI = 0.00-0.75) "fair". Most MRI acquisitions showed at least diagnostic quality at MRI1 (276 of 278) and MRI2 (259 of 264). CONCLUSION: Morpho-functional 1H-MRI can be obtained with reproducible image quality and high short-term test-retest reliability for COPD-related morphological and functional changes of the lung. This underlines its potential value for the monitoring of regional lung characteristics in COPD trials.

Computer-aided detection of artificial pulmonary nodules using an ex vivo lung phantom: influence of exposure parameters and iterative reconstruction.

OBJECTIVES: To evaluate the influence of exposure parameters and raw-data based iterative reconstruction (IR) on the performance of computer-aided detection (CAD) of pulmonary nodules on chest multidetector computed tomography (MDCT). MATERIAL AND METHODS: Seven porcine lung explants were inflated in a dedicated ex vivo phantom shell and prepared with n=162 artificial nodules of a clinically relevant volume and maximum diameter (46-1063 µl, and 6.2-21.5 mm). n=118 nodules were solid and n=44 part-solid. MDCT was performed with different combinations of 120 and 80 kV with 120, 60, 30 and 12 mA*s, and reconstructed with both filtered back projection (FBP) and IR. Subsequently, 16 datasets per lung were subjected to dedicated CAD software. The rate of true positive, false negative and false positive CAD marks was measured for each reconstruction. RESULTS: The rate of true positive findings ranged between 88.9-91.4% for FBP and 88.3-90.1% for IR (n.s.) with most exposure settings, but was significantly lower with the combination of 80 kV and 12 mA*s (80.9% and 81.5%, respectively, p<0.05). False positive findings ranged between 2.3-8.1 annotations per lung. For nodule volumes <200 µl the rate of true positives was significantly lower than for >300 µl (p<0.05). Similarly, it was significantly lower for diameters <12 mm compared to ≥12 mm (p<0.05). The rate of true positives for solid and part-solid nodules was similar. CONCLUSIONS: Nodule CAD on chest MDCT is robust over a wide range of exposure settings. Noise reduction by IR is not detrimental for CAD, and may be used to improve image quality in the setting of low-dose MDCT for lung cancer screening.

Endothelial cell seeding fails to prevent intimal hyperplasia following arterial injury in the rat carotid model.

PURPOSE: Aim of the study was to evaluate the therapeutic potential of endothelial cell seeding to inhibit the neointimal response after balloon injury of the rat carotid artery. METHODS AND RESULTS: Endothelial cells were isolated from peripheral blood after cytokine-stimulation (PB-EC), the bone marrow compartment (BM-EC), and the thoracic aorta (AO-EC) of male rats. The EC-populations were characterized by microscopy, cytofluorometry, and PCR-analysis, and displayed distinct patterns of RNA-expression of the EC-markers VEGF-receptor 1 and 2, and TIE2. 5 x 10(5) ECs were incubated in the freshly balloon-denuded arterial bed for 30 min achieving about 70% coverage with all 3 EC-populations. However, the neointimal response 2 weeks after the procedure was significantly aggravated in the EC-seeded carotids (I/M-ratio: non-seeded Control 1.00 +/- 0.10, PB-EC 1.53 +/- 0.07, BM-EC 1.64 +/- 0.12, and AO-EC 1.55 +/- 0.14; P < 0.05 vs. Control for all). We found evidence for an accelerated cell-turnover (TUNEL-assay, total cell-density, infiltration with CD45(pos) haematopoietic cells) especially in the adventitia of the treated vessels. CONCLUSION: Endothelial cell seeding fails to prevent intimal hyperplasia following arterial injury in the rat carotid model.

A systemic combination therapy with granulocyte-colony stimulating factor plus erythropoietin aggravates the healing process of balloon-injured rat carotid arteries.

OBJECTIVE: Percutaneous vascular interventions lead inevitably to a destruction of the endothelial lining at the site of injury. There are conflicting data on the therapeutic benefit of hematopoietic growth factors aiming at mobilisation of circulating endothelial cells to accelerate the reendothelialisation process. Aim of our study was to evaluate the impact of a maximised 7 day-combination therapy with G-CSF plus EPO on the healing process following balloon injury of the rat carotid artery. METHODS AND RESULTS: Osmotic pumps to systemically deliver G-CSF and EPO at saturating doses during the first seven days post injury were implanted into the peritoneal cavity of splenectomised male Sprague-Dawley rats. Cytokine treatment resulted in significantly elevated numbers of white blood cells, hematocrit levels, circulating hematopoietic stem cells, and-temporarily-circulating endothelial precursors. Functional reendothelialisation as assessed by Evan's blue staining on day 14 post injury was not affected by the cytokine treatment. The neointimal response was analysed on day 7 and 28 post injury, and was significantly higher at the day 7 timepoint (Cytokines: I/M-ratio 1.10+/-0.09 vs. Saline: 0.36+/-0.06). Cytokine treated rats also displayed higher rates of thrombotic occlusion (Cytokines: 25-33% vs. Saline: 0%). Serum levels of PAI-1, TGFbeta1, and PDGF-BB were not elevated in the cytokine treated rats. The proliferative rates both in the injured vessel wall and the surrounding adventitia as assessed by BrdU incorporation were significantly higher in the cytokine treated animals. The number of CD45(pos) hematopoietic cells was significantly higher in the adventitia of the cytokine treated rats. Vasa vasorum were not found to be significantly different. The increased neointimal response was not due to expression of G-CSF- or EPO-receptors on VSMCs within the vessel wall or myofibroblasts in the adventitia. CONCLUSION: The systemic administration of G-CSF plus EPO during the first week after balloon-injury impairs the vascular healing process by increasing the neointimal response and the risk for thrombotic occlusion.