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.

Magnetic Resonance Imaging of Lung Perfusion.

"Lung perfusion" in the context of imaging conventionally refers to the delivery of blood to the pulmonary capillary bed through the pulmonary arteries originating from the right ventricle required for oxygenation. The most important physiological mechanism in the context of imaging is the so-called hypoxic pulmonary vasoconstriction (HPV, also known as "Euler-Liljestrand-Reflex"), which couples lung perfusion to lung ventilation. In obstructive airway diseases such as asthma, chronic-obstructive pulmonary disease (COPD), cystic fibrosis (CF), and asthma, HPV downregulates pulmonary perfusion in order to redistribute blood flow to functional lung areas in order to conserve optimal oxygenation. Imaging of lung perfusion can be seen as a reflection of lung ventilation in obstructive airway diseases. Other conditions that primarily affect lung perfusion are pulmonary vascular diseases, pulmonary hypertension, or (chronic) pulmonary embolism, which also lead to inhomogeneity in pulmonary capillary blood distribution. Several magnetic resonance imaging (MRI) techniques either dependent on exogenous contrast materials, exploiting periodical lung signal variations with cardiac action, or relying on intrinsic lung voxel attributes have been demonstrated to visualize lung perfusion. Additional post-processing may add temporal information and provide quantitative information related to blood flow. The most widely used and robust technique, dynamic-contrast enhanced MRI, is available in clinical routine assessment of COPD, CF, and pulmonary vascular disease. Non-contrast techniques are important research tools currently requiring clinical validation and cross-correlation in the absence of a viable standard of reference. First data on many of these techniques in the context of observational studies assessing therapy effects have just become available. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 5.

GOLD stage-specific phenotyping of emphysema and airway disease using quantitative computed tomography.

Background: In chronic obstructive pulmonary disease (COPD) abnormal lung function is related to emphysema and airway obstruction, but their relative contribution in each GOLD-stage is not fully understood. In this study, we used quantitative computed tomography (QCT) parameters for phenotyping of emphysema and airway abnormalities, and to investigate the relative contribution of QCT emphysema and airway parameters to airflow limitation specifically in each GOLD stage. Methods: Non-contrast computed tomography (CT) of 492 patients with COPD former GOLD 0 COPD and COPD stages GOLD 1-4 were evaluated using fully automated software for quantitative CT. Total lung volume (TLV), emphysema index (EI), mean lung density (MLD), and airway wall thickness (WT), total diameter (TD), lumen area (LA), and wall percentage (WP) were calculated for the entire lung, as well as for all lung lobes separately. Results from the 3rd-8th airway generation were aggregated (WT3-8, TD3-8, LA3-8, WP3-8). All subjects underwent whole-body plethysmography (FEV1%pred, VC, RV, TLC). Results: EI was higher with increasing GOLD stages with 1.0 ± 1.8% in GOLD 0, 4.5 ± 9.9% in GOLD 1, 19.4 ± 15.8% in GOLD 2, 32.7 ± 13.4% in GOLD 3 and 41.4 ± 10.0% in GOLD 4 subjects (p < 0.001). WP3-8 showed no essential differences between GOLD 0 and GOLD 1, tended to be higher in GOLD 2 with 52.4 ± 7.2%, and was lower in GOLD 4 with 50.6 ± 5.9% (p = 0.010 - p = 0.960). In the upper lobes WP3-8 showed no significant differences between the GOLD stages (p = 0.824), while in the lower lobes the lowest WP3-8 was found in GOLD 0/1 with 49.9 ± 6.5%, while higher values were detected in GOLD 2 with 51.9 ± 6.4% and in GOLD 3/4 with 51.0 ± 6.0% (p < 0.05). In a multilinear regression analysis, the dependent variable FEV1%pred can be predicted by a combination of both the independent variables EI (p < 0.001) and WP3-8 (p < 0.001). Conclusion: QCT parameters showed a significant increase of emphysema from GOLD 0-4 COPD. Airway changes showed a different spatial pattern with higher values of relative wall thickness in the lower lobes until GOLD 2 and subsequent lower values in GOLD3/4, whereas there were no significant differences in the upper lobes. Both, EI and WP5-8 are independently correlated with lung function decline.

Quantification of airway wall contrast enhancement on virtual monoenergetic images from spectral computed tomography.

OBJECTIVES: Quantitative computed tomography (CT) plays an increasingly important role in phenotyping airway diseases. Lung parenchyma and airway inflammation could be quantified by contrast enhancement at CT, but its investigation by multiphasic examinations is limited. We aimed to quantify lung parenchyma and airway wall attenuation in a single contrast-enhanced spectral detector CT acquisition. METHODS: For this cross-sectional retrospective study, 234 lung-healthy patients who underwent spectral CT in four different contrast phases (non-enhanced, pulmonary arterial, systemic arterial, and venous phase) were recruited. Virtual monoenergetic images were reconstructed from 40-160 keV, on which attenuations of segmented lung parenchyma and airway walls combined for 5th-10th subsegmental generations were assessed in Hounsfield Units (HU) by an in-house software. The spectral attenuation curve slope between 40 and 100 keV (λHU) was calculated. RESULTS: Mean lung density was higher at 40 keV compared to that at 100 keV in all groups (p < 0.001). λHU of lung attenuation was significantly higher in the systemic (1.7 HU/keV) and pulmonary arterial phase (1.3 HU/keV) compared to that in the venous phase (0.5 HU/keV) and non-enhanced (0.2 HU/keV) spectral CT (p < 0.001). Wall thickness and wall attenuation were higher at 40 keV compared to those at 100 keV for the pulmonary and systemic arterial phase (p ≤ 0.001). λHU for wall attenuation was significantly higher in the pulmonary arterial (1.8 HU/keV) and systemic arterial (2.0 HU/keV) compared to that in the venous (0.7 HU/keV) and non-enhanced (0.3 HU/keV) phase (p ≤ 0.002). CONCLUSIONS: Spectral CT may quantify lung parenchyma and airway wall enhancement with a single contrast phase acquisition, and may separate arterial and venous enhancement. Further studies are warranted to analyze spectral CT for inflammatory airway diseases. KEY POINTS: • Spectral CT may quantify lung parenchyma and airway wall enhancement with a single contrast phase acquisition. • Spectral CT may separate arterial and venous enhancement of lung parenchyma and airway wall. • The contrast enhancement can be quantified by calculating the spectral attenuation curve slope from virtual monoenergetic images.

MDCT-based longitudinal automated airway and air trapping analysis in school-age children with mild cystic fibrosis lung disease.

Objectives: Quantitative computed tomography (QCT) offers some promising markers to quantify cystic fibrosis (CF)-lung disease. Air trapping may precede irreversible bronchiectasis; therefore, the temporal interdependencies of functional and structural lung disease need to be further investigated. We aim to quantify airway dimensions and air trapping on chest CT of school-age children with mild CF-lung disease over two years. Methods: Fully-automatic software analyzed 144 serial spirometer-controlled chest CT scans of 36 children (median 12.1 (10.2-13.8) years) with mild CF-lung disease (median ppFEV1 98.5 (90.8-103.3) %) at baseline, 3, 12 and 24 months. The airway wall percentage (WP5-10), bronchiectasis index (BEI), as well as severe air trapping (A3) were calculated for the total lung and separately for all lobes. Mixed linear models were calculated, considering the lobar distribution of WP5-10, BEI and A3 cross-sectionally and longitudinally. Results: WP5-10 remained stable (P = 0.248), and BEI changed from 0.41 (0.28-0.7) to 0.54 (0.36-0.88) (P = 0.156) and A3 from 2.26% to 4.35% (P = 0.086) showing variability over two years. ppFEV1 was also stable (P = 0.276). A robust mixed linear model showed a cross-sectional, regional association between WP5-10 and A3 at each timepoint (P < 0.001). Further, BEI showed no cross-sectional, but another mixed model showed short-term longitudinal interdependencies with air trapping (P = 0.003). Conclusions: Robust linear/beta mixed models can still reveal interdependencies in medical data with high variability that remain hidden with simpler statistical methods. We could demonstrate cross-sectional, regional interdependencies between wall thickening and air trapping. Further, we show short-term regional interdependencies between air trapping and an increase in bronchiectasis. The data indicate that regional air trapping may precede the development of bronchiectasis. Quantitative CT may capture subtle disease progression and identify regional and temporal interdependencies of distinct manifestations of CF-lung disease.

µCT to quantify muco-obstructive lung disease and effects of neutrophil elastase knockout in mice.

Muco-obstructive lung diseases are characterized by airway obstruction and hyperinflation, which can be quantified by imaging. Our aim was to evaluate µCT for longitudinal quantification of muco-obstructive lung disease in ß-epithelial Na+ channel overexpressing (Scnn1b-TG) mice and of the effects of neutrophil elastase (NE) knockout on its progression. Lungs from wild-type (WT), NE-/-, Scnn1b-TG, and Scnn1b-TG/NE-/- mice were scanned with 9-µm resolution at 0, 5, 14, and 60 days of age, and airway and parenchymal disease was quantified. Mucus adhesion lesions (MAL) were persistently increased in Scnn1b-TG compared with WT mice from 0 days (20.25 ± 6.50 vs. 9.60 ± 2.07, P < 0.05), and this effect was attenuated in Scnn1b-TG/NE-/- mice (5.33 ± 3.67, P < 0.001). Airway wall area percentage (WA%) was increased in Scnn1b-TG mice compared with WT from 14 days onward (59.2 ± 6.3% vs. 49.8 ± 9.0%, P < 0.001) but was similar in Scnn1b-TG/NE-/- compared with WT at 60 days (46.4 ± 9.2% vs. 45.4 ± 11.5%, P = 0.97). Air proportion (Air%) and mean linear intercept (Lm) were persistently increased in Scnn1b-TG compared with WT from 5 days on (53.9 ± 4.5% vs. 30.0 ± 5.5% and 78.82 ± 8.44 µm vs. 65.66 ± 4.15 µm, respectively, P < 0.001), whereas in Scnn1b-TG/NE-/-, Air% and Lm were similar to WT from birth (27.7 ± 5.5% vs. 27.2 ± 5.9%, P = 0.92 and 61.48 ± 9.20 µm vs. 61.70 ± 6.73 µm, P = 0.93, respectively). Our results suggest that µCT is sensitive to detect the onset and progression of muco-obstructive lung disease and effects of genetic deletion of NE on morphology of airways and lung parenchyma in Scnn1b-TG mice, and that it may serve as a sensitive endpoint for preclinical studies of novel therapeutic interventions for muco-obstructive lung diseases.

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.

Consolidated lung on contrast-enhanced chest CT: the use of spectral-detector computed tomography parameters in differentiating atelectasis and pneumonia.

OBJECTIVES: To investigate the value of spectral-detector computed tomography (SDCT) parameters for the quantitative differentiation between atelectasis and pneumonia on contrast-enhanced chest CT. MATERIAL AND METHODS: Sixty-three patients, 22 clinically diagnosed with pneumonia and 41 with atelectasis, underwent contrast-enhanced SDCT scans during the venous phase. CT numbers (Hounsfield Units [HU]) were measured on conventional reconstructions (CON120kVp) and the iodine concentration (Ciodine, [mg/ml]), and effective atomic number (Zeff) on spectral reconstructions, using region-of-interest (ROI) analysis. Receiver operating characteristics (ROC) and contrast-to-noise ratios (CNRs) were calculated to assess each reconstruction's potential to differentiate between atelectasis and pneumonia. RESULTS: On contrast-enhanced SDCT, the difference between atelectasis and pneumonia was significant on CON120kVp, Ciodine, and Zeff images (p < 0.001). On CON120kVp images, a threshold of 81 HU achieved a sensitivity of 93 % and a specificity of 95 % for identifying pneumonia, while Ciodine and Zeff images reached the same sensitivity but lower specificities of 85 % and 83 %. CON120kVp images showed significantly higher CNRs between normal lung and atelectasis or pneumonia with 30.63 and 27.69 compared to Ciodine images with 3.54 and 1.27 and Zeff images with 4.22 and 7.63 (p < 0.001). None of the parameters could differentiate atelectasis and pneumonia without contrast media. CONCLUSIONS: Contrast-enhanced SDCT can differentiate atelectasis and pneumonia based on the spectral parameters Ciodine, and Zeff. However, they had no added value compared to CT number measurement on CON120kVp images. Furthermore, contrast media is still needed for a differentiation based on quantitative SDCT parameters.

Mesopolysaccharides: The extracellular surface layer of visceral organs.

The mesothelium is a dynamic and specialized tissue layer that covers the somatic cavities (pleural, peritoneal, and pericardial) as well as the surface of the visceral organs such as the lung, heart, liver, bowel and tunica vaginalis testis. The potential therapeutic manipulation of visceral organs has been complicated by the carbohydrate surface layer-here, called the mesopolysaccharide (MPS)-that coats the outer layer of the mesothelium. The traditional understanding of MPS structure has relied upon fixation techniques known to degrade carbohydrates. The recent development of carbohydrate-preserving fixation for high resolution imaging techniques has provided an opportunity to re-examine the structure of both the MPS and the visceral mesothelium. In this report, we used high pressure freezing (HPF) as well as serial section transmission electron microscopy to redefine the structure of the MPS expressed on the murine lung, heart and liver surface. Tissue preserved by HPF and examined by transmission electron microscopy demonstrated a pleural MPS layer 13.01±1.1 um deep-a 100-fold increase in depth compared to previously reported data obtained with conventional fixation techniques. At the base of the MPS were microvilli 1.1±0.35 um long and 42±5 nm in diameter. Morphological evidence suggested that the MPS was anchored to the mesothelium by microvilli. In addition, membrane pits 97±17 nm in diameter were observed in the apical mesothelial membrane. The spatial proximity and surface density (29±4.5%) of the pits suggested an active process linked to the structural maintenance of the MPS. The striking magnitude and complex structure of the MPS indicates that it is an important consideration in studies of the visceral mesothelium.

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

INTRODUCTION: Quantitative analysis of multi-detector computed tomography (MDCT) plays an increasingly important role in assessing airway disease. Depending on the algorithms used, airway dimensions may be over- or underestimated, primarily if contrast material was used. Therefore, we tested a modified integral-based method (IBM) to address this problem. METHODS: Temporally resolved cine-MDCT was performed in seven ventilated pigs in breath-hold during iodinated contrast material (CM) infusion over 60s. Identical slices in non-enhanced (NE), pulmonary-arterial (PA), systemic-arterial (SA), and venous phase (VE) were subjected to an in-house software using a standard and a modified IBM. Total diameter (TD), lumen area (LA), wall area (WA), and wall thickness (WT) were measured for ten extra- and six intrapulmonary airways. RESULTS: The modified IBM significantly reduced TD by 7.6%, LA by 12.7%, WA by 9.7%, and WT by 3.9% compared to standard IBM on non-enhanced CT (p<0.05). Using standard IBM, CM led to a decrease of all airway parameters compared to NE. For example, LA decreased from 80.85±49.26mm2 at NE, to 75.14±47.96mm2 (-7.1%) at PA (p<0.001), 74.96±48.55mm2 (-7.3%) at SA (p<0.001), and to 78.95±48.94mm2 (-2.4%) at VE (p = 0.200). Using modified IBM, the differences were reduced to -3.1% at PA, -2.9% at SA and -0.7% at VE (p<0.001; p<0.001; p = 1.000). CONCLUSIONS: The modified IBM can optimize airway wall segmentation and reduce the influence of CM on quantitative CT. This allows a more precise measurement as well as potentially the comparison of enhanced with non-enhanced scans in inflammatory airway disease.

Conditional deletion of Nedd4-2 in lung epithelial cells causes progressive pulmonary fibrosis in adult mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by patchy scarring of the distal lung with limited therapeutic options and poor prognosis. Here, we show that conditional deletion of the ubiquitin ligase Nedd4-2 (Nedd4l) in lung epithelial cells in adult mice produces chronic lung disease sharing key features with IPF including progressive fibrosis and bronchiolization with increased expression of Muc5b in peripheral airways, honeycombing and characteristic alterations in the lung proteome. NEDD4-2 is implicated in the regulation of the epithelial Na+ channel critical for proper airway surface hydration and mucus clearance and the regulation of TGFß signaling, which promotes fibrotic remodeling. Our data support a role of mucociliary dysfunction and aberrant epithelial pro-fibrotic response in the multifactorial disease pathogenesis. Further, treatment with the anti-fibrotic drug pirfenidone reduced pulmonary fibrosis in this model. This model may therefore aid studies of the pathogenesis and therapy of IPF.

The value of chest magnetic resonance imaging compared to chest radiographs with and without additional lung ultrasound in children with complicated pneumonia.

INTRODUCTION: In children with pneumonia, chest x-ray (CXR) is typically the first imaging modality used for diagnostic work-up. Repeated CXR or computed tomography (CT) are often necessary if complications such as abscesses or empyema arise, thus increasing radiation exposure. The aim of this retrospective study was to evaluate the potential of radiation-free chest magnetic resonance imaging (MRI) to detect complications at baseline and follow-up, compared to CXR with and without additional lung ultrasound (LUS). METHODS: Paired MRI and CXR scans were retrospectively reviewed by two blinded readers for presence and severity of pulmonary abscess, consolidation, bronchial wall thickening, mucus plugging and pleural effusion/empyema using a chest MRI scoring system. The scores for MRI and CXR were compared at baseline and follow-up. Furthermore, the MRI scores at baseline with and without contrast media were evaluated. RESULTS: 33 pediatric patients (6.3±4.6 years), who had 33 paired MRI and CXR scans at baseline and 12 at follow-up were included. MRI detected significantly more lung abscess formations with a prevalence of 72.7% compared to 27.3% by CXR at baseline (p = 0.001), whereas CXR+LUS was nearly as good as MRI. MRI also showed a higher sensitivity in detecting empyema (p = 0.003). At follow-up, MRI also showed a slightly better sensitivity regarding residual abscesses. The overall severity of disease was rated higher on MRI. Contrast material did not improve detection of abscesses or empyema by MRI. CONCLUSION: CXR and LUS seem to be sufficient in most cases. In cases where LUS cannot be realized or the combination of CXR+LUS might be not sufficient, MRI, as a radiation free modality, should be preferred to CT. Furthermore, the admission of contrast media is not mandatory in this context.

Quantitative CT detects progression in COPD patients with severe emphysema in a 3-month interval.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by variable contributions of emphysema and airway disease on computed tomography (CT), and still little is known on their temporal evolution. We hypothesized that quantitative CT (QCT) is able to detect short-time changes in a cohort of patients with very severe COPD. METHODS: Two paired in- and expiratory CT each from 70 patients with avg. GOLD stage of 3.6 (mean age = 66 ± 7.5, mean FEV1/FVC = 35.28 ± 7.75) were taken 3 months apart and analyzed by fully automatic software computing emphysema (emphysema index (EI), mean lung density (MLD)), air-trapping (ratio expiration to inspiration of mean lung attenuation (E/I MLA), relative volume change between - 856 HU and - 950 HU (RVC856-950)), and parametric response mapping (PRM) parameters for each lobe separately and the whole lung. Airway metrics measured were wall thickness (WT) and lumen area (LA) for each airway generation and the whole lung. RESULTS: The average of the emphysema parameters (EI, MLD) increased significantly by 1.5% (p < 0.001) for the whole lung, whereas air-trapping parameters (E/I MLA, RVC856-950) were stable. PRMEmph increased from 34.3 to 35.7% (p < 0.001), whereas PRMNormal decrased from 23.6% to 22.8% (p = 0.012). WT decreased significantly from 1.17 ± 0.18 to 1.14 ± 0.19 mm (p = 0.036) and LA increased significantly from 25.08 ± 4.49 to 25.84 ± 4.87 mm2 (p = 0.041) for the whole lung. The generation-based analysis showed heterogeneous results. CONCLUSION: QCT detects short-time progression of emphysema in severe COPD. The changes were partly different among lung lobes and airway generations, indicating that QCT is useful to address the heterogeneity of COPD progression. KEY POINTS: • QCT detects short-time progression of emphysema in severe COPD in a 3-month period. • QCT is able to quantify even slight parenchymal changes, which were not detected by spirometry. • QCT is able to address the heterogeneity of COPD, revealing inconsistent changes individual lung lobes and airway generations.

Influence of Inspiratory/Expiratory CT Registration on Quantitative Air Trapping.

RATIONALE AND OBJECTIVES: The aim of this study was to assess variability in quantitative air trapping (QAT) measurements derived from spatially aligned expiration CT scans. MATERIALS AND METHODS: Sixty-four paired CT examinations, from 16 school-age cystic fibrosis subjects examined at four separate time intervals, were used in this study. For each pair, visually inspected lobe segmentation maps were generated and expiration CT data were registered to the inspiration CT frame. Measurements of QAT, the percentage of voxels on the expiration CT scan below a set threshold were calculated for each lobe and whole-lung from the registered expiration CT and compared to the true values from the unregistered data. RESULTS: A mathematical model, which simulates the effect of variable regions of lung deformation on QAT values calculated from aligned to those from unaligned data, showed the potential for large bias. Assessment of experimental QAT measurements using Bland-Altman plots corroborated the model simulations, demonstrating biases greater than 5% when QAT was approximately 40% of lung volume. These biases were removed when calculating QAT from aligned expiration CT data using the determinant of the Jacobian matrix. We found, by Dice coefficient analysis, good agreement between aligned expiration and inspiration segmentation maps for the whole-lung and all but one lobe (Dice coefficient > 0.9), with only the lingula generating a value below 0.9 (mean and standard deviation of 0.85 ± 0.06). CONCLUSION: The subtle and predictable variability in corrected QAT observed in this study suggests that image registration is reliable in preserving the accuracy of the quantitative metrics.

Towards synchrotron phase-contrast lung imaging in patients - a proof-of-concept study on porcine lungs in a human-scale chest phantom.

In-line free propagation phase-contrast synchrotron tomography of the lungs has been shown to provide superior image quality compared with attenuation-based computed tomography (CT) in small-animal studies. The present study was performed to prove the applicability on a human-patient scale using a chest phantom with ventilated fresh porcine lungs. Local areas of interest were imaged with a pixel size of 100 µm, yielding a high-resolution depiction of anatomical hallmarks of healthy lungs and artificial lung nodules. Details like fine spiculations into surrounding alveolar spaces were shown on a micrometre scale. Minor differences in artificial lung nodule density were detected by phase retrieval. Since we only applied a fraction of the X-ray dose used for clinical high-resolution CT scans, it is believed that this approach may become applicable to the detailed assessment of focal lung lesions in patients in the future.

Quantitative CT detects changes in airway dimensions and air-trapping after bronchial thermoplasty for severe asthma.

OBJECTIVES: Bronchial thermoplasty (BT) can be considered in the treatment of severe asthma to reduce airway smooth muscle mass and bronchoconstriction. We hypothesized that BT may thus have long-term effects on airway dimensions and air-trapping detectable by quantitative computed tomography (QCT). METHODS: Paired in- and expiratory CT and inspiratory CT were acquired in 17 patients with severe asthma before and up to two years after bronchial thermoplasty and in 11 additional conservatively treated patients with serve asthma, respectively. A fully automatic software calculated the airways metrics for wall thickness (WT), wall percentage (WP), lumen area (LA) and total diameter (TD). Furthermore, lung air-trapping was quantified by determining the quotient of mean lung attenuation in expiration vs. inspiration (E/I MLA) and relative volume change in the Hounsfield interval -950 to -856 in expiration to inspiration (RVC856-950) in a generation- and lobe-based approach, respectively. RESULTS: BT reduced WT for the combined analysis of the 2nd-7th airway generation significantly by 0.06 mm (p = 0.026) and WP by 2.05% (p < 0.001), whereas LA and TD did not change significantly (p = 0.147, p = 0.706). No significant changes were found in the control group. Furthermore, E/I MLA and RVC856-950 decreased significantly after BT by 12.65% and 1.77% (p < 0.001), respectively. CONCLUSION: BT significantly reduced airway narrowing and air-trapping in patients with severe asthma. This can be interpreted as direct therapeutic effects caused by a reduction in airway-smooth muscle mass and changes in innervation. A reduction in air-trapping indicates an influence on more peripheral airways not directly treated by the BT procedure.

Similarities in the Computed Tomography Appearance in α1-Antitrypsin Deficiency and Smoking-Related Chronic Obstructive Pulmonary Disease in a Smoking Collective.

BACKGROUND: Emphysematous destruction of lung parenchyma visible in computed tomography (CT) can be attributed to chronic obstructive pulmonary disease (COPD) or to α1-antitrypsin deficiency (AATD). OBJECTIVES: We evaluated if visual semiquantitative phenotyping of CT data helps identifying individuals with AATD in a group of smokers with severe emphysema and airflow limitation. METHOD: n = 14 patients with AATD and n = 15 with COPD and a minimum of 10 pack years underwent CT, clinical assessment, and full-body plethysmography. The extent and type of emphysema as well as large and small airway changes were rated semiquantitatively for each lobe using a standardized previously published scoring system. Lastly, a final diagnosis for each patient was proposed. RESULTS: AATD had a significantly lower mean emphysema score than COPD, with 8.9 ± 3.4 versus 11.9 ± 3.2 (p < 0.001), respectively. Within both groups, there was significantly more emphysema in the lower lobes (p < 0.05-0.001). The COPD group showed an upper- and middle-lobe predominance of emphysema distribution when compared to the AATD group (p < 0.001). Centrilobular (CLE) and panlobular (PLE) emphysema patterns showed a uniform distribution within both groups, with a CLE predominance in the upper lung and a PLE predominance in the lower lung regions. AATD and COPD both showed significantly more airway changes in lower lobes compared to upper lobes (p = 0.05-0.001), without significant differences between both groups. CONCLUSION: The typical emphysema distribution patterns seen on CT traditionally assigned to AATD and COPD were of little use in discriminating both entities. Also, airway changes could not contribute to a more precise differentiation. We conclude that a concise standardized phenotyping-driven approach to chest CT in emphysema is not sufficient to identify patients with AATD in a cohort of smokers with advanced emphysema.

Validation of automated lobe segmentation on paired inspiratory-expiratory chest CT in 8-14 year-old children with cystic fibrosis.

OBJECTIVES: Densitometry on paired inspiratory and expiratory multidetector computed tomography (MDCT) for the quantification of air trapping is an important approach to assess functional changes in airways diseases such as cystic fibrosis (CF). For a regional analysis of functional deficits, an accurate lobe segmentation algorithm applicable to inspiratory and expiratory scans is beneficial. MATERIALS AND METHODS: We developed a fully automated lobe segmentation algorithm, and subsequently validated automatically generated lobe masks (ALM) against manually corrected lobe masks (MLM). Paired inspiratory and expiratory CTs from 16 children with CF (mean age 11.1±2.4) acquired at 4 time-points (baseline, 3mon, 12mon, 24mon) with 2 kernels (B30f, B60f) were segmented, resulting in 256 ALM. After manual correction spatial overlap (Dice index) and mean differences in lung volume and air trapping were calculated for ALM vs. MLM. RESULTS: The mean overlap calculated with Dice index between ALM and MLM was 0.98±0.02 on inspiratory, and 0.86±0.07 on expiratory CT. If 6 lobes were segmented (lingula treated as separate lobe), the mean overlap was 0.97±0.02 on inspiratory, and 0.83±0.08 on expiratory CT. The mean differences in lobar volumes calculated in accordance with the approach of Bland and Altman were generally low, ranging on inspiratory CT from 5.7±52.23cm3 for the right upper lobe to 17.41±14.92cm3 for the right lower lobe. Higher differences were noted on expiratory CT. The mean differences for air trapping were even lower, ranging from 0±0.01 for the right upper lobe to 0.03±0.03 for the left lower lobe. CONCLUSIONS: Automatic lobe segmentation delivers excellent results for inspiratory and good results for expiratory CT. It may become an important component for lobe-based quantification of functional deficits in cystic fibrosis lung disease, reducing necessity for user-interaction in CT post-processing.

Occlusion of a Long-Term Transpleural Biliary Drainage Tract Using a Gelatin Pledget (Hep-Plug™).

This case describes a technique used to close a long-term 14F transpleural biliary drainage catheter tract to prevent biliopleural fistula and further complications. We deployed a compressed gelatin foam pledget provided in a pre-loaded delivery device (Hep-Plug™) along the intrahepatic tissue tract for sealing it against the pleural cavity. The device used is easy to handle and gives the Interventional Radiologist the possibility to safely manage and prevent complications after percutaneous transhepatic interventions.