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 lungMRI 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 (kappa = 0.86, 95% CI = 0.81-0.91). Most subscores showed at least "substantial" agreement of MRI1 and MRI2 (kappa = 0.64-1.00),whereas the agreement for the diagnosis of dystelectasis/effusion (kappa = 0.42, 95% CI = 0.00-0.93) was "moderate" and of tracheal abnormalities (kappa = 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 end-points 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 (Delta T1) 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 Delta T1 were highly prevalent in the patient cohort. T1 and Delta T1 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 Delta T1 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), T1 (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

Relationship of spirometric, body plethysmographic, and diffusing capacity parameters to emphysema scores derived from CT scans

Phenotyping of chronic obstructive pulmonary disease (COPD) with computed tomography (CT) is used to distinguish between emphysema- and airway-dominated type. The phenotype is reflected in correlations with lung function measures. Among these, the relative value of body plethysmography has not been quantified. We addressed this question using CT scans retrospectively collected from clinical routine in a large COPD cohort. Three hundred and thirty five patients with baseline data of the German COPD cohort COPD and Systemic Consequences-Comorbidities Network were included. CT scans were primarily evaluated using a qualitative binary emphysema score. The binary score was positive for emphysema in 52.5% of patients, and there were significant differences between the positive/negative groups regarding forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), intrathoracic gas volume (ITGV), residual volume (RV), specific airway resistance (sRaw), transfer coefficient (KCO), transfer factor for carbon monoxide (TLCO), age, pack-years, and body mass index (BMI). Stepwise discriminant analyses revealed the combination of FEV1/FVC, RV, sRaw, and KCO to be significantly related to the binary emphysema score. The additional positive predictive value of body plethysmography, however, was only slightly higher than that of the conventional combination of spirometry and diffusing capacity, which if taken alone also achieved high predictive values, in contrast to body plethysmography. The additional information on the presence of CT-diagnosed emphysema as conferred by body plethysmography appeared to be minor compared to the well-known combination of spirometry and CO diffusing capacity. </jats:p

Echo Time-Dependent Observed Lung T-1 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 T-1 (T-1(TE)) depends on the echo-time (TE) and reflects regional pulmonary function. Purpose To investigate the potential diagnostic value of T-1(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 T-1(TE) mapping at TE1-5 = 70 mu sec, 500 mu sec, 1200 mu sec, 1650 mu sec, and 2300 mu sec. Assessment Perfusion images were scored by three radiologists. T-1(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 (rho) were calculated between T-1(TE) and perfusion scores, clinical parameters and qCT. A P-value -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 T-1(TE) with TE occurred at shorter TEs than previously found in healthy subjects. Together with the lack of correlation between T-1 and clinical parameters of disease at longer TEs, this suggests that T-1(TE) quantification in COPD patients requires shorter TEs. The TE-dependence of correlations implies that T-1(TE) mapping might be developed further to provide diagnostic information beyond T-1 at a single TE. Level of Evidence 2 Technical Efficacy Stage

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 80(th) 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

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

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, O-2) 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 O-2 with RA conditions, PBF and PBV were found to be significantly lower at O-2, 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 O-2, 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

Reproducibility and comparison of oxygen-enhanced T-1 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 Delta T1, 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 T-1,T-RA = 1206ms (room air) was reduced to T-1,T-O2 = 1141ms under oxygen conditions (Delta T1 = 5.3%, p < 5.10(-4)), while in COPD patients both native T-1,T-RA = 1125ms was significantly shorter (p < 10(-3)) and the relative reduction to T-1,T-O2 = 1081ms on average Delta T1 = 4.2%(p < 10(-5)). On the second day, with T-1,T-RA = 1186ms in asthma and T-1,T-RA = 1097ms in COPD, observed values were slightly shorter on average in all patient groups. Delta T1 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 Delta T1 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