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.

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.

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.

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.

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.

Computed Tomography Imaging for Novel Therapies of Chronic Obstructive Pulmonary Disease.

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

Towards quantitative perfusion MRI of the lung in COPD: The problem of short-term repeatability.

PURPOSE: 4D perfusion magnetic resonance imaging (MRI) with intravenous injection of contrast agent allows for a radiation-free assessment of regional lung function. It is therefore a valuable method to monitor response to treatment in patients with chronic obstructive pulmonary disease (COPD). This study was designed to evaluate its potential for monitoring short-term response to hyperoxia in COPD patients. MATERIALS AND METHODS: 19 prospectively enrolled COPD patients (median age 66y) underwent paired dynamic contrast-enhanced 4D perfusion MRI within 35min, first breathing 100% oxygen (injection 1, O2) and then room air (injection 2, RA), which was repeated on two consecutive days (day 1 and 2). Post-processing software was employed to calculate mean transit time (MTT), pulmonary blood volume (PBV) and pulmonary blood flow (PBF), based on the indicator dilution theory, for the automatically segmented whole lung and 12 regions of equal volume. RESULTS: Comparing O2 with RA conditions, PBF and PBV were found to be significantly lower at O2, consistently on both days (p<10-8). Comparing day 2 to day 1, MTT was shorter by 0.59±0.63 s (p<10-8), PBF was higher by 22±80 ml/min/100ml (p<3·10-4), and PBV tended to be lower by 0.2±7.2 ml/100ml (p = 0.159) at both, RA and O2, conditions. CONCLUSION: The second injection (RA) yielded higher PBF and PBV, which apparently contradicts the established hypothesis that hyperoxia increases lung perfusion. Quantification of 4D perfusion MRI by current software approaches may thus be limited by residual circulating contrast agent in the short-term and even the next day.

Design and application of an MR reference phantom for multicentre lung imaging trials.

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

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.

Influence of fissure integrity on quantitative CT and emphysema distribution in emphysema-type COPD using a dedicated COPD software.

OBJECTIVES: Fissure integrity (FI) plays a key role in selecting patients for interventional emphysema therapy. We investigated its interference with automated lobar segmentation in quantitative computed tomography (CT) and emphysema distribution. METHODS: CT was available for 50 patients with chronic obstructive pulmonary disease (COPD). Lobe segmentation was performed fully automated by software and corrected manually. FI was evaluated visually using a %-scale. The influence of FI on emphysema ratio (ER=percentage of lung volume with density values<-950 HU), mean lung density (MLD), emphysema and total volume of adjacent lobes was analyzed. Lobe-based results were compared with respect to FI. RESULTS: Differences in ER in adjacent lobes for complete vs. incomplete fissures were 12.4% for the right horizontal, 0.2% and 3% for the right oblique and 4.4% for the left oblique fissure (all p>0.05). Results for emphysema comparing automated vs. manually corrected segmentation exceeded clinically acceptable values, but were not significantly affected by FI (p>0.05). The widest limits of agreement for ER and MLD were noted in the right middle lobe ([-14, 17.4%], [-22.4, 32.4 Hounsfield Units]). CONCLUSIONS: Automated lobe segmentation and emphysema distribution are not significantly affected by FI. Manual correction of automated lobar segmentation is still recommended in severe emphysema.

Influence of exposure parameters and iterative reconstruction on automatic airway segmentation and analysis on MDCT-An ex vivo phantom study.

OBJECTIVES: To evaluate the influence of exposure parameters and raw-data-based iterative reconstruction (IR) on computer-aided segmentation and quantitative analysis of the tracheobronchial tree on multidetector computed tomography (MDCT). MATERIAL AND METHODS: 10 porcine heart-lung-explants were mounted inside a dedicated chest phantom. MDCT was performed at 120kV and 80kV with 120, 60, 30 and 12 mAs each. All scans were reconstructed with filtered back projection (FBP) or IR, resulting in a total of 160 datasets. The maximum number of detected airway segments, most peripheral airway generation detected, generation-specific airway wall thickness (WT), total diameter (TD) and normalized wall thickness (pi10) were compared. RESULTS: The number of detected airway segments decreased slightly with dose (324.8±118 at 120kV/120mAs vs. 288.9±130 at 80kV/30mAs with FBP, p<0.05) and was not changed by IR. The 20th generation was constantly detected as most peripheral. WT did not change significantly with exposure parameters and reconstruction algorithm across all generations: range 1st generation 2.4-2.7mm, 5th 1.0-1.1mm, and 10th 0.7mm with FBP; 1st 2.3-2.4mm, 5th 1.0-1.1mm, and 10th 0.7-0.8mm with IR. pi10 was not affected as well (range 0.32-0.34mm). CONCLUSIONS: Exposure parameters and IR had no relevant influence on measured airway parameters even for WT <1mm. Thus, no systematic errors would be expected using automatic airway analysis with low-dose MDCT and IR.

Reproducibility and comparison of oxygen-enhanced T1 quantification in COPD and asthma patients.

T1 maps have been shown to yield useful diagnostic information on lung function in patients with chronic obstructive pulmonary disease (COPD) and asthma, both for native T1 and ΔT1, the relative reduction while breathing pure oxygen. As parameter quantification is particularly interesting for longitudinal studies, the purpose of this work was both to examine the reproducibility of lung T1 mapping and to compare T1 found in COPD and asthma patients using IRSnapShotFLASH embedded in a full MRI protocol. 12 asthma and 12 COPD patients (site 1) and further 15 COPD patients (site 2) were examined on two consecutive days. In each patient, T1 maps were acquired in 8 single breath-hold slices, breathing first room air, then pure oxygen. Maps were partitioned into 12 regions each to calculate average values. In asthma patients, the average T1,RA = 1206ms (room air) was reduced to T1,O2 = 1141ms under oxygen conditions (ΔT1 = 5.3%, p < 5⋅10-4), while in COPD patients both native T1,RA = 1125ms was significantly shorter (p < 10-3) and the relative reduction to T1,O2 = 1081ms on average ΔT1 = 4.2%(p < 10-5). On the second day, with T1,RA = 1186ms in asthma and T1,RA = 1097ms in COPD, observed values were slightly shorter on average in all patient groups. ΔT1 reduction was the least repeatable parameter and varied from day to day by up to 23% in individual asthma and 30% in COPD patients. While for both patient groups T1 was below the values reported for healthy subjects, the T1 and ΔT1 found in asthmatics lies between that of the COPD group and reported values for healthy subjects, suggesting a higher blood volume fraction and better ventilation. However, it could be demonstrated that lung T1 quantification is subject to notable inter-examination variability, which here can be attributed both to remaining contrast agent from the previous day and the increased dependency of lung T1 on perfusion and thus current lung state.

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.

Functional lung MRI in chronic obstructive pulmonary disease: comparison of T1 mapping, oxygen-enhanced T1 mapping and dynamic contrast enhanced perfusion.

PURPOSE: Monitoring of regional lung function in interventional COPD trials requires alternative endpoints beyond global parameters such as FEV1. T1 relaxation times of the lung might allow to draw conclusions on tissue composition, blood volume and oxygen fraction. The aim of this study was to evaluate the potential value of lung Magnetic resonance imaging (MRI) with native and oxygen-enhanced T1 mapping for the assessment of COPD patients in comparison with contrast enhanced perfusion MRI. MATERIALS AND METHODS: 20 COPD patients (GOLD I-IV) underwent a coronal 2-dimensional inversion recovery snapshot flash sequence (8 slices/lung) at room air and during inhalation of pure oxygen, as well as dynamic contrast-enhanced first-pass perfusion imaging. Regional distribution of T1 at room air (T1), oxygen-induced T1 shortening (ΔT1) and peak enhancement were rated by 2 chest radiologists in consensus using a semi-quantitative 3-point scale in a zone-based approach. RESULTS: Abnormal T1 and ΔT1 were highly prevalent in the patient cohort. T1 and ΔT1 correlated positively with perfusion abnormalities (r = 0.81 and r = 0.80; p&0.001), and with each other (r = 0.80; p<0.001). In GOLD stages I and II ΔT1 was normal in 16/29 lung zones with mildly abnormal perfusion (15/16 with abnormal T1). The extent of T1 (r = 0.45; p<0.05), ΔT1 (r = 0.52; p<0.05) and perfusion abnormalities (r = 0.52; p<0.05) showed a moderate correlation with GOLD stage. CONCLUSION: Native and oxygen-enhanced T1 mapping correlated with lung perfusion deficits and severity of COPD. Under the assumption that T1 at room air correlates with the regional pulmonary blood pool and that oxygen-enhanced T1 reflects lung ventilation, both techniques in combination are principally suitable to characterize ventilation-perfusion imbalance. This appears valuable for the assessment of regional lung characteristics in COPD trials without administration of i.v. contrast.

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.