Impact of Reanalysis of Nitrogen Multiple-Breath Washout on its Relationship with Chest Magnetic Resonance Imaging Findings in Clinically Stable and Pulmonary Exacerbated Children with Cystic Fibrosis.

RATIONALE: Multiple-breath washout (MBW)-derived lung clearance index (LCI) detects lung disease in children with cystic fibrosis (CF). Correction of a cross-talk error in the software of the MBW device Exhalyzer D in a new software version has generated significant interest regarding its impact on previous MBW findings. Since LCI and chest magnetic resonance imaging (MRI) correlated before in CF children, this study aims to reassess previous MBW data after correction. PATIENTS/METHODS: Reanalysis of the main findings from a previously published study comparing MBW and MRI in a pediatric CF cohort by reassessment of nitrogen (N2) MBW of 61 stable children with CF, 75 age-matched healthy controls (HC), and 15 CF children with pulmonary exacerbation (PEx) in the corrected software version. RESULTS: The corrected LCI (N2LCIcor) decreased in the entire cohort (-17.0 (11.2)%), HC (-8.5 (8.2)%), stable CF children (-22.2 (11.1)%), and within the PEx group at baseline, at PEx and after antibiotic therapy (-21.5 (7.3)%; -22.5 (6.1)%; -21.4 (6.6)%; all P<0.01). N2LCIcor and N2LCIpre correlated with chest MRI scores in stable CF (r=0.70 to 0.84; all P<0.01) without a significant difference between N2LCIcor and N2LCIpre. Change in LCI from baseline to PEx and from PEx to after therapy decreased from N2LCIpre to N2LCIcor, but these changes remained significant (all P=0.001). DISCUSSION/CONCLUSIONS: Our results indicate that N2LCIcor is significantly lower than N2LCIpre, but key results published in the original study demonstrating N2MBW and MRI as complementary methods for clinical surveillance in children with CF remain unaffected.

First experience with real-time magnetic resonance imaging-based investigation of respiratory influence on cardiac function in pediatric congenital heart disease patients with chronic right ventricular volume overload.

BACKGROUND: Congenital heart disease (CHD) is often associated with chronic right ventricular (RV) volume overload. Real-time magnetic resonance imaging (MRI) enables the analysis of cardiac function during free breathing. OBJECTIVE: To evaluate the influence of respiration in pediatric patients with CHD and chronic RV volume overload. METHODS AND MATERIALS: RV volume overload patients (n=6) and controls (n=6) were recruited for cardiac real-time MRI at 1.5 tesla during free breathing. Breathing curves from regions of interest reflecting the position of the diaphragm served for binning images in four different tidal volume classes, each in inspiration and expiration. Tidal volumes were estimated from these curves by data previously obtained by magnetic resonance-compatible spirometry. Ventricular volumes indexed to body surface area and Frank-Starling relationships referenced to the typical tidal volume indexed to body height (TTVi) were compared. RESULTS: Indexed RV end-diastolic volume (RV-EDVi) and indexed RV stroke volume (RV-SVi) increased during inspiration (RV-EDVi/TTVi: RV load: + 16 ± 4%; controls: + 22 ± 13%; RV-SVi/TTVi: RV load: + 21 ± 6%; controls: + 35 ± 17%; non-significant for comparison). The increase in RV ejection fraction during inspiration was significantly lower in RV load patients (RV load: + 1.1 ± 2.2%; controls: + 6.1 ± 1.5%; P=0.01). The Frank-Starling relationship of the RV provided a significantly reduced slope estimate in RV load patients (inspiration: RV load: 0.75 ± 0.11; controls: 0.92 ± 0.02; P=0.02). CONCLUSION: In pediatric patients with CHD and chronic RV volume overload, cardiac real-time MRI during free breathing in combination with respiratory-based binning indicates an impaired Frank-Starling relationship of the RV.

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.

[Update on cystic fibrosis : From neonatal screening to causal treatment]. / Update Mukoviszidose : Vom Neugeborenenscreening zur kausalen Therapie.

Cystic fibrosis (CF) is a multiorgan disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Approximately 90% of the morbidity and mortality are caused by pulmonary involvement. The mean life expectancy of patients with CF in 2020 was more than 52 years in Germany. The introduction of neonatal screening for CF and the development of a causally acting CFTR modulator treatment have clearly improved the prognosis of these patients. As an introduction, this article describes important aspects of CF in this context in order to go into details of the CF neonatal screening which was introduced in Germany in 2016.

Imaging Biomarkers in Thoracic Oncology: Current Advances in the Use of Radiomics in Lung Cancer Patients and its Potential Use for Therapy Response Prediction and Monitoring.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. The development of therapies targeting molecular alterations has significantly improved the treatment of NSCLC patients. To identify these targets, tumor phenotyping is required, with tissue biopsies and molecular pathology being the gold standard. Some patients do not respond to targeted therapies and many patients suffer from tumor recurrence, which can in part be explained by tumor heterogeneity. This points out the need for new biomarkers allowing for better tumor phenotyping and monitoring during treatment to assess patient outcome. METHOD: The contents of this review are based on a literature search conducted using the PubMed database in March 2021 and the authors' experience. RESULTS AND CONCLUSION: The use of radiomics and artificial intelligence-based approaches allows for the identification of imaging biomarkers in NSCLC patients for tumor phenotyping. Several studies show promising results for models predicting molecular alterations, with the best results being achieved by combining structural and functional imaging. Radiomics could help solve the pressing clinical need for assessing and predicting therapy response. To reach this goal, advanced tumor phenotyping, considering tumor heterogeneity, is required. This could be achieved by integrating structural and functional imaging biomarkers with clinical data sources, such as liquid biopsy results. However, to allow for radiomics-based approaches to be introduced into clinical practice, further standardization using large, multi-center datasets is required. KEY POINTS: · Some NSCLC patients do not benefit from targeted therapies, and many patients suffer from tumor recurrence, pointing out the need for new biomarkers allowing for better tumor phenotyping and monitoring during treatment.. · The use of radiomics-based approaches allows for the identification of imaging biomarkers in NSCLC patients for tumor phenotyping.. · A multi-omics approach integrating not only structural and functional imaging biomarkers but also clinical data sources, such as liquid biopsy results, could further enhance the prediction and assessment of therapy response.. CITATION FORMAT: · Kroschke J, von Stackelberg O, Heußel CP et al. Imaging Biomarkers in Thoracic Oncology: Current Advances in the Use of Radiomics in Lung Cancer Patients and its Potential Use for Therapy Response Prediction and Monitoring. Fortschr Röntgenstr 2022; 194: 720 - 727.

Acquisition of a Dose Management System with Consideration of Medico-Legal and Economic Aspects. / Beschaffung eines Dosismanagementsystems unter mediko-legalen und ökonomischen Aspekten.

BACKGROUND: New radiation protection regulation encompassing additional obligations for monitoring, reporting and recording of radiation exposure, was enacted on December 31, 2018. As a consequence, dose management systems (DMS) are necessary to fulfill the requirements. The process of selection, acquisition and implementation of a suitable IT solution for this purpose is a challenge that all X-ray-applying facilities, including hospitals and private practices, are currently facing. METHOD: A target/actual-analysis as well as a cost-utility analysis is presented for this specific case as a foundation for the acquisition decision-making process. RESULT: An actual analysis is necessary in order to record the current status of dose documentation. An interdivisional approach is recommended to include all imaging modalities and devices. An interdisciplinary steering committee can be helpful in enabling consensus and rapid action. A target analysis includes additional criteria with respect to ease of operation, technical feasibility, process optimization and research opportunities to consider in addition to the statutory requirements. By means of a cost-benefit analysis, considerations between costs and the individually weighted advantages and disadvantages of eligible DMS result in a ranking of preference for the available solutions. CONCLUSION: Requirements of a DMS can be summarized in a specification sheet. Deploying an actual condition analysis, target state analysis and cost-utility analysis can help to identify a suitable DMS to achieve rapid commissioning and highest possible user acceptance while optimizing costs at the same time. KEY POINTS: · An actual analysis reveals optimization and standardization needs in examination protocols and technical coding of dose data that can be addressed before or during the acquisition process.. · A specification sheet covers all functional, technical, and financial aspects of a target analysis.. · A cost-utility analysis is useful for exploring an appropriate dose management system with high user acceptance, rapid implementation, and low cost.. · An interdisciplinary steering committee can be helpful to enable early consensus building and fast action.. CITATION FORMAT: · Do TD, Melzig C, Kauczor H et al. Acquisition of a Dose Management System with Consideration of Medico-Legal and Economic Aspects. Fortschr Röntgenstr 2022; 194: 363 - 372.

Spirometry-based reconstruction of real-time cardiac MRI: Motion control and quantification of heart-lung interactions.

PURPOSE: To test the feasibility of cardiac real-time MRI in combination with retrospective gating by MR-compatible spirometry, to improve motion control, and to allow quantification of respiratory-induced changes during free-breathing. METHODS: Cross-sectional real-time MRI (1.5T; 30 frames/s) using steady-state free precession contrast during free-breathing was combined with MR-compatible spirometry in healthy adult volunteers (n = 4). Retrospective binning assigned images to classes that were defined by electrocardiogram and spirometry. Left ventricular eccentricity index as an indicator of septal position and ventricular volumes in different respiratory phases were calculated to assess heart-lung interactions. RESULTS: Real-time MRI with MR-compatible spirometry is feasible and well tolerated. Spirometry-based binning improved motion control significantly. The end-diastolic epicardial eccentricity index increased significantly during inspiration (1.04 ± 0.04 to 1.19 ± 0.05; P < .05). During inspiration, right ventricular end-diastolic volume (79 ± 17 mL/m2 to 98 ± 18 mL/m2 ), stroke volume (41 ± 8 mL/m2 to 59 ± 11 mL/m2 ) and ejection fraction (53 ± 3% to 60 ± 1%) increased significantly, whereas the end-systolic volume remained almost unchanged. Left ventricular end-diastolic volume, left ventricular stroke volume, and left ventricular ejection fraction decreased during inspiration, whereas the left ventricular end-systolic volume increased. The relationship between stroke volume and end-diastolic volume (Frank-Starling relationship) based on changes induced by respiration allowed for a slope estimate of the Frank-Starling curve to be 0.9 to 1.1. CONCLUSION: Real-time MRI during free-breathing combined with MR-compatible spirometry and retrospective binning improves image stabilization, allows quantitative image analysis, and importantly, offers unique opportunities to judge heart-lung interactions.

Simultaneous presence of the "bullseye" and "reversed halo" sign at CT of COVID-19 pneumonia: A case report.

The "bullseye" sign has been exclusively reported in patients suffering from coronavirus disease 2019 (COVID-19) pneumonia. It is theorized that this newly recognized computed tomography (CT) feature represents a sign of organizing pneumonia. Well established signs of organizing pneumonia also reported in COVID-19 patients include linear opacities, the "reversed halo" sign (or "atoll" sign), and a perilobular distribution of abnormalities. These findings are usually present on imaging in the intermediate and late stage of the disease. This is a case of simultaneous presence of the "bullseye" and the "reversed halo" sign on chest CT images of a COVID-19 patient examined 22 days after symptom onset.

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.

Prognostic Impact of CT-Quantified Muscle and Fat Distribution before and after First-Line-Chemotherapy in Lung Cancer Patients.

INTRODUCTION: Cachexia and sarcopenia are associated with poor outcome and increased chemotherapy-induced toxicity in lung cancer patients. However, the complex interplay of obesity, sarcopenia and cachexia, and its impact on survival in the context of first-line-chemotherapy is not yet understood. METHODS: In 200 consecutively recruited lung cancer patients (70 female, mean age 62y; mean BMI 25 kg/m2; median follow-up 15.97 months) with routine staging-CT before and after chemotherapy (CTX, mean interval: 4.3 months), densitometric quantification of total (TFA), visceral (VFA), and subcutaneous-fat-area (SFA), inter-muscular-fat-area (IMFA), muscle-density (MD), muscle-area (MA) and skeletal-muscle-index (SMI) was performed retrospectively to evaluate changes under chemotherapy and the impact on survival. RESULTS: We observed increases in TFA, VFA, SFA, VFA/SFA, and IMFA (p<0.05-0.001), while there were decreases in MA, MD and BMI (p<0.05-0.001) after chemotherapy. High pre-therapeutic VFA/SFA was a predictive factor for poor survival (HR = 1.272; p = 0.008), high pre-therapeutic MD for improved survival (HR = 0.93; p<0.05). Decrease in BMI (HR = 1.303; p<0.001), weight (HR = 1.067; p<0.001) and SMI (HR = 1.063; p<0.001) after chemotherapy were associated with poor survival. Patients with ≥4 CTX-cycles showed increased survival (17.6 vs. 9.1months), less muscle depletion (SMIdifference: p<0.05) and no BMI loss (BMIdifference: p<0.001). CONCLUSIONS: After chemotherapy, patients exhibited sarcopenia with decreased muscle and increased adipose tissue compartments, which was not adequately mirrored by BMI and weight loss but by imaging. Particularly sarcopenic patients received less CTX-cycles and had poorer survival. As loss of BMI, weight and muscle were associated with poor survival, early detection (via imaging) and prevention (via physical exercise and nutrition) of sarcopenia may potentially improve outcome and reduce chemotherapy-induced toxicity.

Automatic lung segmentation method for MRI-based lung perfusion studies of patients with chronic obstructive pulmonary disease.

PURPOSE: A novel fully automatic lung segmentation method for magnetic resonance (MR) images of patients with chronic obstructive pulmonary disease (COPD) is presented. The main goal of this work was to ease the tedious and time-consuming task of manual lung segmentation, which is required for region-based volumetric analysis of four-dimensional MR perfusion studies which goes beyond the analysis of small regions of interest. METHODS: The first step in the automatic algorithm is the segmentation of the lungs in morphological MR images with higher spatial resolution than corresponding perfusion MR images. Subsequently, the segmentation mask of the lungs is transferred to the perfusion images via nonlinear registration. Finally, the masks for left and right lungs are subdivided into a user-defined number of partitions. Fourteen patients with two time points resulting in 28 perfusion data sets were available for the preliminary evaluation of the developed methods. RESULTS: Resulting lung segmentation masks are compared with reference segmentations from experienced chest radiologists, as well as with total lung capacity (TLC) acquired by full-body plethysmography. TLC results were available for thirteen patients. The relevance of the presented method is indicated by an evaluation, which shows high correlation between automatically generated lung masks with corresponding ground-truth estimates. CONCLUSION: The evaluation of the developed methods indicates good accuracy and shows that automatically generated lung masks differ from expert segmentations about as much as segmentations from different experts.

Incomplete pulmonary fissures evaluated by volumetric thin-section CT: semi-quantitative evaluation for small fissure gaps identification, description of prevalence and severity of fissural defects.

OBJECTIVE: To assess the interobserver agreement for a semi-quantitative evaluation of the interlobar fissures integrity in volumetric thin-section CT images, looking for more detailed information regarding fissural defects; and describe prevalence and severity of fissural defects between the different functional groups of subjects. MATERIALS AND METHODS: Volumetric scans of 247 individuals exposed to tobacco with different functional status (normal to severe COPD), were retrospectively and independently evaluated by 2 chest radiologists, with a consensual reading additionally with a third reader in disagreement cases. Right oblique (RO), right horizontal (RH) and left oblique fissures (LO) integrity was estimated using a 5% scale. GOLD classification was available for all subjects. RESULTS: Interobserver agreement (weighted Kappa-index) for fissural categorization was 0.76, 0.70 and 0.75, for RO, RH and LO, respectively. Final evaluation found 81%, 89% and 50% of RO, RH and LO to be incomplete, with respective mean integrity of 80%, 58% and 80%. Small fissure gaps (<10%) were present in 30% of patients. Prevalence and severity of fissural defects were not different between the GOLD categories. CONCLUSIONS: A substantial agreement between readers was found in the analysis of interlobar fissures integrity. The semi-quantitative method allowed a detailed description of the fissural defects, information that can be important, for example, in endoscopic lung volume reduction therapies for emphysema. Small fissure gaps, overlooked in previous studies, were found in almost a third of the patients. A higher than previously described prevalence of fissural defects was described, but without significant differences among the distinct functional groups.