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Objectives Bile leakage (BL) is a challenging complication after hepatobiliary surgery and liver trauma. Gadolinium ethoxybenzyl (Gd-EOB-DTPA)–enhanced magnetic resonance cholangiopancreatography (MRCP) is used to diagnose BL non-invasively. We assessed the value of Gd-EOB-DTPA-MRCP in the detection of postoperative and post-traumatic BL hypothesizing that exact identification of the leakage site is pivotal for treatment planning and outcome. Methods We retrospectively enrolled 39 trauma and postoperative patients who underwent Gd-EOB-DTPA-MRCP for suspected BL. Three readers rated the presence of BL and leakage site (intraparenchymal, central, peripheral ± aberrant or disconnected ducts). Imaging findings were compared to subsequent interventional procedures and their complexity and outcome. Results BL was detected in Gd-EOB-DTPA-MRCP in 25 of patients and was subsequently confirmed. Sites of BL differed significantly between postoperative (central [58%] and peripheral [42%]) and trauma patients (intraparenchymal [100%]; p < 0.001). Aberrant or disconnected ducts were diagnosed in 8%/26% of cases in the postoperative subgroup. Inter-rater agreement for the detection and localization of BL was almost perfect (Κ = 0.85 and 0.88; p < 0.001). Intraparenchymal BL required significantly less complex interventional procedures (p = 0.002), whereas hospitalization and mortality did not differ between the subgroups (p > 0.05). Conclusions Gd-EOB-DTPA-MRCP reliably detects and exactly locates BL in postoperative and trauma patients. Exact localization of biliary injuries enables specific treatment planning, as intraparenchymal leakages, which occur more frequently after trauma, require less complex interventions than central or peripheral leaks in the postoperative setting. As a result of specific treatment based on exact BL localization, there was no difference in the duration of hospitalization or mortality. Clinical relevance statement Gd-EOB-DTPA-MRCP is a reliable diagnostic tool for exactly localizing iatrogenic and post-traumatic biliary leakage. Its precise localization helps tailor local therapies for different injury patterns, resulting in comparable clinical outcomes despite varying treatments. Key Points • Gd-EOB-DTPA-MRCP enables adequate detection and localization of bile leakages in both postoperative and post-traumatic patients. • The site of bile leakage significantly impacts the complexity of required additional interventions. • Intraparenchymal bile leakage is commonly seen in patients with a history of liver trauma and requires less complex interventions than postoperative central or peripheral bile leakages, while hospitalization and mortality are similar.

Objectives: Radiography remains the mainstay of diagnostic and follow-up imaging. In view of the risks and the increasing use of ionizing radiation, dose reduction is a key issue for research and development. The introduction of digital radiography and the associated access to image postprocessing have opened up new opportunities to minimize the radiation dosage. These advances are contingent upon quality controls to ensure adequate image detail and maintenance of diagnostic confidence. The purpose of this study was to investigate the clinical applicability of postprocessed low-dose images in skeletal radiography. Methods: In our study setting, the median radiation dose for full dose X-rays was 9.61 dGy*cm2 for pelvis, 1.20 dGy*cm2 for shoulder and 18.64 dGy*cm2 for lumbar spine exams. Based on these values, we obtained 200 radiographs for each anatomic region in four consecutive steps, gradually reducing the dose to 84%, 71%, 60% and 50% of the baseline using an automatic exposure control (AEC). 549 patients were enrolled for a total of 600 images. All X-rays were postprocessed with a spatial noise reduction algorithm. Two radiologists assessed the diagnostic value of the radiographs by rating the visualization of anatomical landmarks and image elements on a five-point Likert scale. A mean-sum score was calculated by averaging the two reader’s total scores. Given the non-parametric distribution, we used the Mann-Whitney U test to evaluate the scores. Results: Median dosage at full dose accounted for 38.4%, 48 and 53.2% of the German reference dose area product for shoulder, pelvis and lumbar spine, respectively. The applied radiation was incrementally reduced to 21.5%, 18.4% and 18.7% of the respective reference value for shoulder, pelvis and lumbar spine. Throughout the study, we observed an estimable tendency of superior quality at higher dosage in overall image quality. Statistically significant differences in image quality were restricted to the 50% dose groups in shoulder and lumbar spine images. Regardless of the applied dosage, 598 out of 600 images were of sufficient diagnostic value. Conclusion: In digital radiography image postprocessing allows for extensive reduction of radiation dosage. Despite a trend of superior image detail at higher dose levels, overall quality and, more importantly, diagnostic utility of low-dose images was not significantly affected. Therefore, our results not only confirm the clinical utility of postprocessed low-dose radiographs, but also suggest a widespread deployment of this advanced technology to ensure further dose limitations in clinical practice. Advances in knowledge: The diagnostic image quality of postprocessed skeletal radiographs is not significantly impaired even after extensive dose reduction by up to 20% of the reference value.

Background: Bronchopulmonary dysplasia (BPD) is a lung disease of preterm born infants, characterized by alveolar simplification. MicroRNA (miR) are known to be involved in many biological and pathological processes in the lung. Although a changed expression has been described for several miR in BPD, a causal role remains to be established. Results: Our results showed that the expression level of miR-154 increases during lung development and decreases postnatally. Further, hyperoxia treatment maintains high levels of miR-154 in alveolar type 2 cells (AT2). We hypothesized that the decrease in miR-154 expression in AT2 cells is required for normal alveologenesis. To test this hypothesis, we generated a novel transgenic mouse allowing doxycycline-based miR-154 overexpression. Maintenance of miR-154 expression in the postnatal distal lung epithelium under normoxia conditions is sufficient to reproduce the hypoalveologenesis phenotype triggered by hyperoxia. Using a pull-down assay, we identified Caveolin1 as a key downstream target of miR-154. Caveolin1 protein is downregulated in response to overexpression of miR-154. This is associated with increased phosphorylation of Smad3 and Tgf-&szlig, signaling. We found that AT2 cells overexpressing miR-154 display decreased expression of AT2 markers and increased expression of AT1 markers. Conclusion: Our results suggest that down-regulation of miR-154 in postnatal lung may function as an important physiological switch that permits the induction of the correct alveolar developmental program, while conversely, failure to down-regulate miR-154 suppresses alveolarization, leading to the common clinically observed phenotype of alveolar simplification.

Background: Bronchopulmonary dysplasia (BPD) is a lung disease of preterm born infants, characterized by alveolar simplification. MicroRNA (miR) are known to be involved in many biological and pathological processes in the lung. Although a changed expression has been described for several miR in BPD, a causal role remains to be established. Results: Our results showed that the expression level of miR-154 increases during lung development and decreases postnatally. Further, hyperoxia treatment maintains high levels of miR-154 in alveolar type 2 cells (AT2). We hypothesized that the decrease in miR-154 expression in AT2 cells is required for normal alveologenesis. To test this hypothesis, we generated a novel transgenic mouse allowing doxycycline-based miR-154 overexpression. Maintenance of miR-154 expression in the postnatal distal lung epithelium under normoxia conditions is sufficient to reproduce the hypoalveologenesis phenotype triggered by hyperoxia. Using a pull-down assay, we identified Caveolin1 as a key downstream target of miR-154. Caveolin1 protein is downregulated in response to overexpression of miR-154. This is associated with increased phosphorylation of Smad3 and Tgf-ß signaling. We found that AT2 cells overexpressing miR-154 display decreased expression of AT2 markers and increased expression of AT1 markers. Conclusion: Our results suggest that down-regulation of miR-154 in postnatal lung may function as an important physiological switch that permits the induction of the correct alveolar developmental program, while conversely, failure to down-regulate miR-154 suppresses alveolarization, leading to the common clinically observed phenotype of alveolar simplification.

Background: MiR-154 is abundant in neonatal lungs. Experimental evidence for a direct effect of miR-154 on lung development is still lacking. Aims and methods: We aim to investigate the effect of miR-154 by using an in-vivo gain-of-function ( CCSPrtTA/rtTA;tet(O)miR-154/+ ) and an in-vitro loss-of-function (morpholino) approach pre- and postnatally. Results: First, the expression of miR-154 from E10.5-P2 was analyzed by RT-qPCR and FISH. MiR-154 expression increased dynamically from E10.5 and peaks at P2. Attenuation of miR-154 in WT embryonic lung (CD1) harvested at E11.5 and treated with morpholino vs. control reveals a significant decrease in lung branching after 48h of culture. Prenatal overexpression of miR-154 from E7.5-E18.5 in CCSPrtTA/rtTA;tet(O)miR-154/+ mice (lung epithelial specific overexpression) and analysis of the lung structure by using alveolar morphometry shows increased mean linear intercept (MLI) and alveolar airspace but decrease in septal thickness indicating alveolarization defects. RT-qPCR reveals a decrease in Fgf10 signaling as well as markers for alveolar myofibroblast but increase in the epithelial marker EpCAM. In contrast, postnatal overexpression of miR-154 by using CCSPrtTA/rtTA;tet(O)miR-154/+ from P0-P16.5 leads to increased Fgf and Tgf-β signaling in the mutant group as well as increased MLI without changes in airspace and septal thickness. Interestingly, pull-down assay reveals caveolin 1 (Cav1), which is responsible for Tgf-β/Tgf-βR degradation, as a target of miR-154 . Conclusions: MiR-154 plays a crucial role in branching morphogenesis and alveologenesis by mediating Tgf-β signaling through caveolin 1.