Julia Ley-Zaporozhan

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.

International management platform for children’s interstitial lung disease (chILD-EU)

Background Children’s interstitial lung diseases (chILD) cover many rare entities, frequently not diagnosed or studied in detail. There is a great need for specialised advice and for internationally agreed subclassification of entities collected in a register. Our objective was to implement an international management platform with independent multidisciplinary review of cases at presentation for long-term follow-up and to test if this would allow for more accurate diagnosis. Also, quality and reproducibility of a diagnostic subclassification system were assessed using a collection of 25 complex chILD cases. Methods A web-based chILD management platform with a registry and biobank was successfully designed and implemented. Results Over a 3-year period, 575 patients were included for observation spanning a wide spectrum of chILD. In 346 patients, multidisciplinary reviews were completed by teams at five international sites (Munich 51%, London 12%, Hannover 31%, Ankara 1% and Paris 5%). In 13%, the diagnosis reached by the referring team was not confirmed by peer review. Among these, the diagnosis initially given was wrong (27%), imprecise (50%) or significant information was added (23%). The ability of nine expert clinicians to subcategorise the final diagnosis into the chILD-EU register classification had an overall exact inter-rater agreement of 59% on first assessment and after training, 64%. Only 10% of the ‘wrong’ answers resulted in allocation to an incorrect category. Subcategorisation proved useful but training is needed for optimal implementation. Conclusions We have shown that chILD-EU has generated a platform to help the clinical assessment of chILD. Trial registration number Results, NCT02852928.

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.

Pulmonary interstitial glycogenosis – A systematic analysis of new cases

BACKGROUND Pulmonary interstitial glycogenosis (PIG) is a rare paediatric interstitial lung disease of unknown cause. The diagnosis can only be made by lung biopsy. Less than 100 cases have been reported. Clinical features, treatment and outcomes have rarely been assessed systematically in decent cohorts of patients. METHODS In this retrospective multicentre study, the clinical presentation, radiologic findings, pattern of lung biopsy, extrapulmonary comorbidities, treatment and outcome of eleven children with PIG were collected systematically. RESULTS 10/11 children presented with respiratory distress immediatly after birth and 8/11 needed invasive ventilation. In 8/11 children extrapulmonary comorbidities were present, congenital heart defects being the most common. 7/11 children received systemic glucocorticoids and of these four showed a clear favorable response. During a median follow-up of 3.0 years (range 0.42-12.0) one child died, while 10 patients improved. Chest CT-scans showed ground-glass opacities (7/10), consolidations (6/10), linear opacities (5/10) and mosaic attenuation (4/10) without uniform pattern. Besides interstitial thickening related to undifferentiated glycogen positive mesenchymal cells all tissue samples showed growth abnormalities with reduced alveolarization. CONCLUSIONS PIG is associated with alveolar growth abnormalities and has to be considered in all newborns with unexplained respiratory distress. Apparent treatment benefit of glucocorticosteroids needs to be evaluated systematically.

Management of Spontaneous Pneumothorax and Post-Interventional Pneumothorax: German S3 Guideline

In Germany, 10,000 cases of spontaneous pneumothorax are treated inpatient every year. The German Society for Thoracic Surgery, in co-operation with the German Society for Pulmonology, the German Radiological Society, and the German Society of Internal Medicine has developed an S3 guideline on spontaneous pneumothorax and post-interventional pneumothorax moderated by the German Association of Scientific Medical Societies. Method: Based on the source guideline of the British Thoracic Society (2010) for spontaneous pneumothorax, a literature search on spontaneous pneumothorax was carried out from 2008 onwards, for post-interventional pneumothorax from 1960 onwards. Evidence levels according to the Oxford Center for Evidence-Based Medicine (2011) were assigned to the relevant studies found. Recommendations according to grade (A: “we recommend”/“we do not recommend,” B: “we suggest”/“we do not suggest”) were determined in 3 consensus conferences by the nominal group process. Results: The algorithms for primary and secondary pneumothorax differ in the indication for CT scan as well as in the indication for chest drainage application and video-assisted thoracic surgery. Indication for surgery is recommended individually taking into account the risk of recurrence, life circumstances, patient preferences, and procedure risks. For some forms of secondary pneumothorax, a reserved indication for surgery is recommended. Therapy of post-interventional spontaneous pneumothorax is similar to that of primary spontaneous pneumothorax. Discussion: The recommendations of the S3 Guideline provide assistance in managing spontaneous pneumothorax and post-interventional pneumothorax. Whether this will affect existing deviant diagnostic and therapeutic measures will be demonstrated by future epidemiological studies.

Chest CT Imaging in Children

The major airway diseases in children (cystic fibrosis, primary cilia dyskinesia, asthma, bronchiolitis obliterans, and Swyer–James) are being discussed in the Chapter Airways.

Epstein–Barr Virus+ Smooth Muscle Tumors as Manifestation of Primary Immunodeficiency Disorders

Epstein–Barr virus positive (EBV+) smooth muscle tumors (SMTs) constitute a very rare oncological entity. They usually develop in the context of secondary immunodeficiency caused by human immunodeficiency virus infection or immunosuppressive treatment after solid organ transplantation. However, in a small fraction of predominantly pediatric patients, EBV+ SMTs may occur in patients with primary immunodeficiency disorders (PIDs), such as GATA2 and CARMIL2 deficiency. In secondary immunodeficiencies and when the underlying condition can not be cured, the treatment of EBV+ SMTs is based on surgery in combination with antiretroviral and reduced or altered immunosuppressive pharmacotherapy, respectively. Importantly, without definitive reconstitution of cellular immunity, long-term survival is poor. This is particularly relevant for patients with EBV+ SMTs on the basis of PIDs. Recently, allogeneic hematopoietic stem cell transplantation resulted in cure of immunodeficiency and EBV+ SMTs in a GATA2-deficient patient. We propose that in the absence of secondary immunodeficiency disorders patients presenting with EBV+ SMTs should be thoroughly evaluated for PIDs. Allogeneic hematopoietic stem cell transplantation should be taken into consideration, ideally in the setting of a prospective clinical trial.

MRI of Chronic Obstructive Pulmonary Disease

MRI is becoming increasingly useful for imaging of lung structure and function, in terms of airway imaging, assessment of ventilation, and evaluation of lung perfusion and right heart function. This modality is highly versatile and capable of generating a range of inherent and exogenously introduced contrast mechanisms while maintaining high resolution as well as incredible speed of data acquisition.

Changes of Emphysema Parameters over the Respiratory Cycle During Free Breathing: Preliminary Results Using Respiratory Gated 4D-CT

ABSTRACT The purpose of this research was to evaluate respiratory gated CT of the lung in patients with COPD for analysis of parenchymal characteristics who were potential candidates for volume reduction surgery. Eleven patients with clinically known emphysematous disease underwent a respiratory gated, free-breathing 64-multislice-CT (Aquilion 64, Toshiba). Retrospective image reconstruction was performed similar to cardiac CT at every 10% of the respiratory loop, resulting in 10 complete volumetric datasets at 10 equidistant time points. All images were transferred onto a PC for calculation of the total lung volume, emphysema volume, emphysema index, and mean lung density. Complete datasets could be successfully reconstructed in all patients. The mean lung volume increased from 6.9 L to 7.5 L over the respiratory cycle. Emphysema volume increased from 1.6 L to 2.0 L and emphysema index from 22.6% to 26.5% from expiration to inspiration. In conclusion, respiratory gated chest 4D-CT allows for combined morphologic and functional image analysis, which can provide new insight into functional impairment and individual treatment planning.