Biallelic NUDT2 variants defective in mRNA decapping cause a neurodevelopmental disease.

Dysfunctional RNA processing caused by genetic defects in RNA processing enzymes has a profound impact on the nervous system, resulting in neurodevelopmental conditions. We characterized a recessive neurological disorder in 18 children and young adults from 10 independent families typified by intellectual disability, motor developmental delay and gait disturbance. In some patients peripheral neuropathy, corpus callosum abnormalities and progressive basal ganglia deposits were present. The disorder is associated with rare variants in NUDT2, a mRNA decapping and Ap4A hydrolysing enzyme, including novel missense and in-frame deletion variants. We show that these NUDT2 variants lead to a marked loss of enzymatic activity, strongly implicating loss of NUDT2 function as the cause of the disorder. NUDT2-deficient patient fibroblasts exhibit a markedly altered transcriptome, accompanied by changes in mRNA half-life and stability. Amongst the most up-regulated mRNAs in NUDT2-deficient cells, we identified host response and interferon-responsive genes. Importantly, add-back experiments using an Ap4A hydrolase defective in mRNA decapping highlighted loss of NUDT2 decapping as the activity implicated in altered mRNA homeostasis. Our results confirm that reduction or loss of NUDT2 hydrolase activity is associated with a neurological disease, highlighting the importance of a physiologically balanced mRNA processing machinery for neuronal development and homeostasis.

Update on imaging recommendations in paediatric uroradiology: the European Society of Paediatric Radiology workgroup session on voiding cystourethrography.

Voiding cystourethrography (VCUG) is a fluoroscopic technique that allows the assessment of the urinary tract, including the urethra, bladder, and-if vesicoureteral reflux (VUR) is present-the ureters and the pelvicalyceal systems. The technique also allows for the assessment of bladder filling and emptying, providing information on anatomical and functional aspects. VCUG is, together with contrast-enhanced voiding urosonography (VUS), still the gold standard test to diagnose VUR and it is one of the most performed fluoroscopic examinations in pediatric radiology departments. VCUG is also considered a follow-up examination after urinary tract surgery, and one of the most sensitive techniques for studying anatomy of the lower genitourinary tract in suspected anatomical malformations. The international reflux study in 1985 published the first reflux-protocol and graded VUR into five classes; over the following years, other papers have been published on this topic. In 2008, the European Society of Paediatric Radiology (ESPR) Uroradiology Task Force published the first proposed VCUG Guidelines with internal scientific society agreement. The purpose of our work is to create a detailed overview of VCUG indications, procedural recommendations, and to provide a structured final report, with the aim of updating the 2008 VCUG paper proposed by the European Society of Paediatric Radiology (ESPR). We have also compared VCUG with contrast-enhanced VUS as an emergent alternative. As a result of this work, the ESPR Urogenital Task Force strongly recommends the use of contrast-enhanced VUS as a non-radiating imaging technique whenever indicated and possible.

[CF Lung Disease - a German S3 Guideline: Pseudomonas aeruginosa]. / S3-Leitlinie: Lungenerkrankung bei Mukoviszidose ­ Pseudomonas aeruginosa.

Cystic Fibrosis (CF) is the most common autosomal recessive genetic multisystemic disease. In Germany, it affects at least 8000 people. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the airway epithelial lining fluid which leads to reduction of the mucociliary clearance.Even if highly effective, CFTR modulator therapy has been available for some years and people with CF are getting much older than before, recurrent and chronic infections of the airways as well as pulmonary exacerbations still occur. In adult CF life, Pseudomonas aeruginosa (PA) is the most relevant pathogen in colonisation and chronic infection of the lung, leading to further loss of lung function. There are many possibilities to treat PA-infection.This is a S3-clinical guideline which implements a definition for chronic PA-infection and demonstrates evidence-based diagnostic methods and medical treatment in order to give guidance for individual treatment options.

The distal femoral epiphysis in forensic age diagnostics: studies on the evaluation of the ossification process by means of T1- and PD/T2-weighted magnetic resonance imaging.

The age of majority, which corresponds to the age of 18 years in most European countries, plays a crucial role for a large number of legal decisions. Accordingly, an increasing number of requests by authorities to forensic age estimation experts comprise the question of whether the age of 18 years has been reached by an individual. In recent years, novel study data suggested that magnetic resonance imaging (MRI) of the knee might likewise allow for the determination of majority beyond reasonable doubt. However, the data basis, especially concerning the distal femoral epiphysis (DFE), is still poor. For this reason, 392 routine MRI cases of the knee (204 males and 188 females of a Western Caucasian population, aged between 12 and 25 years) were retrospectively analyzed. T1-weighted and water-selective fat-saturated PD/T2-weighted sequences, generated at 1.5 and 3.0 T clinical MR scanners, were available. Ossification stages of the DFE were determined by means of the classification system by Vieth et al. (Eur Radiol 2018; 28:3255-3262). Both the intra-observer agreement and inter-observer agreement were found to be "very good" (κ = 0.899 and κ = 0.830). The present study confirmed that MRI of the DFE is suitable to determine majority in both sexes when stage 6 is present as the study revealed minimum ages above the age of 18 years for this stage (20.40 years in males and 20.60 years in females). Accordingly, the data represent a strong support for the so far existing database. Hence, the investigation of the knee using routine MRI appears to become a realistic alternative for forensic age estimation practice in the near future.

Amniotic fluid content in children with kidney and urinary tract anomalies determines pre- and postnatal development.

BACKGROUND: Renal oligohydramnios (ROH) describes an abnormally low volume of amniotic fluid (AF) during pregnancy. ROH is mostly caused by congenital fetal kidney anomalies. The ROH diagnosis frequently implies an increased risk of peri- and postnatal fetal mortality and morbidity. The present study aimed to evaluate the impact of ROH on pre-and postnatal development in children with congenital kidney anomalies. METHODS: This retrospective study included 168 fetuses with anomalies in the kidney and urinary tract. Based on the amount of AF measured by ultrasound, patients were divided into three groups: normal amniotic fluid (NAF), amniotic fluid in the lower normal range (LAF), and ROH. These groups were compared with respect to prenatal sonographic parameters, perinatal outcomes, and postnatal outcomes. RESULTS: Among the 168 patients with congenital kidney anomalies, 26 (15%) had ROH, 132 (79%) had NAF, and 10 (6%) had LAF. Of the 26 families affected by ROH, 14 (54%) decided to terminate pregnancy. Of 10 live-born children in the ROH group, 6 (60%) survived the observation time; of these, 5/6 presented with chronic kidney disease, stages I-III, at their last examination. The main differences in postnatal development between the ROH group and the NAF and LAF groups were: restricted height and weight gain, respiratory issues, complicated feeding, and the presence of extrarenal malformations. CONCLUSIONS: ROH is not a mandatory indicator of severe postnatal kidney function impairment. However, children with ROH have complicated peri-and postnatal periods, due to the presence of concomitant malformations, which must be considered in prenatal care. A higher resolution version of the Graphical abstract is available as Supplementary information.

Whole-body diffusion magnetic resonance imaging with simultaneous multi-slice excitation in children and adolescents.

BACKGROUND: Whole-body magnetic resonance imaging (WB-MRI) is an increasingly used guideline-based imaging modality for oncological and non-oncological pathologies during childhood and adolescence. While diffusion-weighted imaging (DWI), a part of WB-MRI, enhances image interpretation and improves sensitivity, it also requires the longest acquisition time during a typical WB-MRI scan protocol. Interleaved short tau inversion recovery (STIR) DWI with simultaneous multi-slice (SMS) acquisition is an effective way to speed up examinations. OBJECTIVE: In this study of children and adolescents, we compared the acquisition time, image quality, signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) values of an interleaved STIR SMS-DWI sequence with a standard non-accelerated DWI sequence for WB-MRI. MATERIALS AND METHODS: Twenty children and adolescents (mean age: 13.9 years) who received two WB-MRI scans at a maximum interval of 18 months, consisting of either standard DWI or SMS-DWI MRI, respectively, were included. For quantitative evaluation, the signal-to-noise ratio (SNR) was determined for b800 images and ADC maps of seven anatomical regions. Image quality evaluation was independently performed by two experienced paediatric radiologists using a 5-point Likert scale. The measurement time per slice stack, pause between measurements including shim and total measurement time of DWI for standard DWI and SMS-DWI were extracted directly from the scan data. RESULTS: When including the shim duration, the acquisition time for SMS-DWI was 43% faster than for standard DWI. Qualitatively, the scores of SMS-DWI were higher in six locations in the b800 images and four locations in the ADC maps. There was substantial agreement between both readers, with a Cohen's kappa of 0.75. Quantitatively, the SNR in the b800 images and the ADC maps did not differ significantly from one another. CONCLUSION: Whole body-MRI with SMS-DWI provided equivalent image quality and reduced the acquisition time almost by half compared to the standard WB-DWI protocol.

MRI Characteristics of Pediatric Renal Tumors: A SIOP-RTSG Radiology Panel Delphi Study.

BACKGROUND: The SIOP-Renal Tumor Study Group (RTSG) does not advocate invasive procedures to determine histology before the start of therapy. This may induce misdiagnosis-based treatment initiation, but only for a relatively small percentage of approximately 10% of non-Wilms tumors (non-WTs). MRI could be useful for reducing misdiagnosis, but there is no global consensus on differentiating characteristics. PURPOSE: To identify MRI characteristics that may be used for discrimination of newly diagnosed pediatric renal tumors. STUDY TYPE: Consensus process using a Delphi method. POPULATION: Not applicable. FIELD STRENGTH/SEQUENCE: Abdominal MRI including T1- and T2-weighted imaging, contrast-enhanced MRI, and diffusion-weighted imaging at 1.5 or 3 T. ASSESSMENT: Twenty-three radiologists from the SIOP-RTSG radiology panel with ≥5 years of experience in MRI of pediatric renal tumors and/or who had assessed ≥50 MRI scans of pediatric renal tumors in the past 5 years identified potentially discriminatory characteristics in the first questionnaire. These characteristics were scored in the subsequent second round, consisting of 5-point Likert scales, ranking- and multiple choice questions. STATISTICAL TESTS: The cut-off value for consensus and agreement among the majority was ≥75% and ≥60%, respectively, with a median of ≥4 on the Likert scale. RESULTS: Consensus on specific characteristics mainly concerned the discrimination between WTs and non-WTs, and WTs and nephrogenic rest(s) (NR)/nephroblastomatosis. The presence of bilateral lesions (75.0%) and NR/nephroblastomatosis (65.0%) were MRI characteristics indicated as specific for the diagnosis of a WT, and 91.3% of the participants agreed that MRI is useful to distinguish NR/nephroblastomatosis from WT. Furthermore, all participants agreed that age influenced their prediction in the discrimination of pediatric renal tumors. DATA CONCLUSION: Although the discrimination of pediatric renal tumors based on MRI remains challenging, this study identified some specific characteristics for tumor subtypes, based on the shared opinion of experts. These results may guide future validation studies and innovative efforts. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3.

Ultrashort echo time MRI of the lung in children and adolescents: comparison with non-enhanced computed tomography and standard post-contrast T1w MRI sequences.

OBJECTIVES: To compare the diagnostic value of ultrashort echo time (UTE) magnetic resonance imaging (MRI) for the lung versus the gold standard computed tomography (CT) and two T1-weighted MRI sequences in children. METHODS: Twenty-three patients with proven oncologic disease (14 male, 9 female; mean age 9.0 + / - 5.4 years) received 35 low-dose CT and MRI examinations of the lung. The MRI protocol (1.5-T) included the following post-contrast sequences: two-dimensional (2D) incoherent gradient echo (GRE; acquisition with breath-hold), 3D volume interpolated GRE (breath-hold), and 3D high-resolution radial UTE sequences (performed during free-breathing). Images were evaluated by considering image quality as well as distinct diagnosis of pulmonary nodules and parenchymal areal opacities with consideration of sizes and characterisations. RESULTS: The UTE technique showed significantly higher overall image quality, better sharpness, and fewer artefacts than both other sequences. On CT, 110 pulmonary nodules with a mean diameter of 4.9 + / - 2.9 mm were detected. UTE imaging resulted in a significantly higher detection rate compared to both other sequences (p < 0.01): 76.4% (84 of 110 nodules) for UTE versus 60.9% (67 of 110) for incoherent GRE and 62.7% (69 of 110) for volume interpolated GRE sequences. The detection of parenchymal areal opacities by the UTE technique was also significantly higher with a rate of 93.3% (42 of 45 opacities) versus 77.8% (35 of 45) for 2D GRE and 80.0% (36 of 45) for 3D GRE sequences (p < 0.05). CONCLUSION: The UTE technique for lung MRI is favourable in children with generally high diagnostic performance compared to standard T1-weighted sequences as well as CT. Key Points • Due to the possible acquisition during free-breathing of the patients, the UTE MRI sequence for the lung is favourable in children. • The UTE technique reaches higher overall image quality, better sharpness, and lower artefacts, but not higher contrast compared to standard post-contrast T1-weighted sequences. • In comparison to the gold standard chest CT, the detection rate of small pulmonary nodules small nodules ≤ 4 mm and subtle parenchymal areal opacities is higher with the UTE imaging than standard T1-weighted sequences.

Magnetic resonance imaging of the proximal tibial epiphysis is suitable for statements as to the question of majority: a validation study in forensic age diagnostics.

Determining majority plays a key role for forensic age diagnostics in living individuals. Recent data suggest that magnetic resonance imaging (MRI) of the proximal tibial epiphysis (PTE) may be a suitable alternative or at least an additional tool to clarify whether an individual has reached majority. However, the reference data situation is still sparse. Hence, the present dual center study retrospectively analyzed routine MRI of the knee in 413 cases (214 males and 199 females) of a Western Caucasian population aged between 12 and 25 years. MRI was performed at 1.5 and 3.0 T clinical scanners using T1- and T2-weighted sequences. The classification system by Vieth et al. (Eur Radiol 2018; 28:3255-3262) was applied for determining the ossification stages of the PTE. Intra-observer agreement was "very good" (κ = 0.931), and inter-observer agreement was "good" (κ = 0.798). Minimum ages above the age of 18 years were observed with the final stage (stage 6) in either sex (20.27 years in males and 18.55 years in females). The results are not in contradiction with the previous data and can be considered a strong and valuable support of the so far existing database. Therefore, the investigation of the PTE using routine MRI (either at 1.5 or 3.0 T) could be taken into consideration for application in forensic age estimation practice in near future.

Two Cases of Veno-occlusive Disease/Sinusoidal Obstruction Syndrome After Thioguanine Treatment for Acute Lymphoblastic Leukemia.

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation conditioning or high-dose chemotherapy. The underlying pathogenesis involves toxic injury to hepatocytes and sinusoidal endothelial cells. Presenting symptoms include ascites, weight gain, hepatomegaly, and hyperbilirubinemia. Severe VOD/SOS with multiorgan failure has a mortality rate of >80% if left untreated. Thioguanine, a chemotherapy drug used to treat acute lymphoblastic leukemia, has been shown to cause VOD/SOS. Here, we describe cases of 2 patients who developed very severe VOD/SOS after starting thioguanine for acute lymphoblastic leukemia; both achieved complete remission with defibrotide and experienced no defibrotide-related adverse events.

In vitro measurements of radiation exposure with different modalities (computed tomography, cone beam computed tomography) for imaging the petrous bone with a pediatric anthropomorphic phantom.

BACKGROUND: Various imaging modalities, such as multi-detector computed tomography (CT) and cone beam CT are commonly used in infants for the diagnosis of hearing loss and surgical planning of implantation hearing aid devices, with differing results. OBJECTIVE: We compared three different imaging modalities available in our institution, including a high-class CT scanner, a mid-class CT scanner and an angiography system with a cone beam CT option, for image quality and radiation exposure in a phantom study. MATERIALS AND METHODS: While scanning an anthropomorphic phantom imitating a 1-year-old child with vendor-provided routine protocols, organ doses, surface doses and effective doses were determined for these three modalities with thermoluminescent dosimeters. The image quality was evaluated using the signal difference to noise ratio (SDNR) and the spatial resolution of a line-pair insert in the phantom head. The dose efficiency, defined as the ratio of SDNR and effective dose, was also compared. RESULTS: The organ and surface doses were lowest with the high-class CT protocol, but the image quality was the worst. Image quality was best with the cone beam CT protocol, which, however, had the highest radiation exposure in this study, whereas the mid-class CT was in between. CONCLUSION: Based on our results, high-end CT should be used for surgical planning because it has the lowest dose, while the image quality is still sufficient for this purpose. However, if highest image quality is needed and required, e.g., by ENT surgeons, the other modalities should be considered.

Evaluation of the post-processing algorithms SimGrid and S-Enhance for paediatric intensive care patients and neonates.

BACKGROUND: Post-processing software can be used in digital radiography to achieve higher image quality, especially in cases of scattered radiation. SimGrid is a grid-like software based on a Convolutional Neuronal Network that estimates the distribution and degree of scattered radiation in radiographs and thus improves image quality by simulating an anti-scatter grid. S-Enhance is an algorithm programmed to improve contrast visibility of foreign material. OBJECTIVE: The objective of this study was to evaluate the SimGrid and S-Enhance digital radiography post-processing methods for neonatology and paediatric intensive care. MATERIALS AND METHODS: Two hundred and ten radiographs from the neonatal (n = 101, 0 to 6 months of age) and paediatric (n = 109, 6 months to 18 years of age) intensive care units performed in daily clinical routine using a mobile digital radiography system were post-processed with one of the algorithms, anonymized and then evaluated comparatively by two experienced paediatric radiologists. For every radiograph, patient data and exposure data were collected and analysed. RESULTS: Analysis of different radiographs showed that SimGrid significantly improves image quality for patients with a weight above 10 kg (range: 10-30 kg: odds ratio [OR] = 6.683, P < 0.0001), especially regarding the tracheobronchial system, intestinal gas, and bones. Utilizing S-Enhance significantly advances the assessment of foreign material (OR = 136.111, P < 0.0001) and bones (OR = 34.917, P < 0.0001) for children of all ages and weight, whereas overall image quality decreases. CONCLUSION: SimGrid offers a differentiated spectrum in image improvement for children beyond the neonatal period whereas S-Enhance especially improves visibility of foreign material and bones for all patients.

Imaging of anorectal malformations: where are we now? Abdominal imaging task force of the European Society of Paediatric Radiology.

Anorectal and cloacal malformations are a broad mix of congenital abnormalities related to the distal rectum and anus. Confusion exists between all the forms in this large and heterogeneous group. The spectrum includes everything from anal stenosis, ventral anus, anal atresia (with and without fistula) and the full spectrum of cloacal malformations. Imaging in these conditions is done through the whole armamentarium of radiologic modalities, with very different imaging strategies seen across the centres where these conditions are managed. In 2017, the European Society of Paediatric Radiology (ESPR) abdominal imaging task force issued recommendations on the imaging algorithm and standards for imaging anorectal malformations. This was followed by further letters and clarifications together with an active multispecialty session on the different imaging modalities for anorectal malformations at the 2018 ESPR meeting in Berlin. Through this paper, the abdominal task force updates its guidelines and recommended imaging algorithm for anorectal malformations.

Contrast-enhanced ultrasound of pediatric lungs.

In addition to radiography, ultrasound (US) has long proved to be a valuable imaging modality to evaluate the pediatric lung and pleural cavity. Its many inherent advantages, including real-time performance, high spatial resolution, lack of ionizing radiation and lack of need for sedation make it preferable over other imaging modalities such as CT. Since the introduction of ultrasound contrast agents (UCAs), contrast-enhanced ultrasound (CEUS) has become a valuable complementary US technique, with many well-established uses in adults and evolving uses in children. Lung CEUS applications are still not licensed and are performed off-label, although the added value of CEUS in certain clinical scenarios is increasingly reported. The limited evidence of CEUS in the evaluation of pediatric lungs focuses primarily on community-acquired pneumonia and its complications. In this clinical setting, CEUS is used to confidently and accurately diagnose necrotizing pneumonia and to delineate pleural effusions and empyema. In addition to intravenous use, UCAs can be administered directly into the pleural cavity through chest catheters to improve visualization of loculations within a complex pleural effusion, which might necessitate fibrinolytic therapy. The purpose of this paper is to present the current experience on pediatric lung CEUS and to suggest potential additional uses that can be derived from adult studies.

Contrast-enhanced ultrasound for musculoskeletal indications in children.

The increasing use of contrast-enhanced ultrasound (CEUS) has opened exciting new frontiers for musculoskeletal applications in adults and children. The most common musculoskeletal-related CEUS applications in adults are for detecting inflammatory joint diseases, imaging skeletal muscles and tendon perfusion, imaging postoperative viability of osseous and osseocutaneous tissue flaps, and evaluating the malignant potential of soft-tissue masses. Pediatric musculoskeletal-related CEUS has been applied for imaging juvenile idiopathic arthritis and Legg-Calvé-Perthes disease and for evaluating femoral head perfusion following surgical hip reduction in children with developmental hip dysplasia. CEUS can improve visualization of the capillary network in superficial and deep tissues and also in states of slow- or low-volume blood flow. In addition, measurements of blood flow imaging parameters performed by quantitative CEUS are valuable when monitoring the outcome of treatment interventions. In this review article we present current experience regarding a wide range of CEUS applications in musculoskeletal conditions in adults and children, with emphasis on the latter, and discuss imaging techniques and CEUS findings in musculoskeletal applications.

Contrast-enhanced ultrasound of the pediatric bowel.

Contrast-enhanced ultrasound (CEUS) has emerged as a valuable modality for bowel imaging in adults and children. CEUS enables visualization of the perfusion of the bowel wall and of the associated mesentery in healthy and disease states. In addition, CEUS images can be used to make quantitative measurements of contrast kinetics, allowing for objective assessment of bowel wall enhancement. Bowel CEUS is commonly applied to evaluate inflammatory bowel disease and to monitor treatment response. It has also been applied to evaluate necrotizing enterocolitis, intussusception, appendicitis and epiploic appendagitis, although experience with these applications is more limited. In this review article, we present the current experience using CEUS to evaluate the pediatric bowel with emphasis on inflammatory bowel disease, extrapolating the established experience from adult studies. We also discuss emerging applications of CEUS as an adjunct or problem-solving tool for evaluating bowel perfusion.

Contrast-enhanced ultrasound of the spleen, pancreas and gallbladder in children.

Gray-scale and color/power Doppler ultrasound (US) are the first-line imaging modalities to evaluate the spleen, gallbladder and pancreas in children. The increasing use of contrast-enhanced ultrasound (CEUS) as a reliable and safe method to evaluate liver lesions in the pediatric population promises potential for imaging other internal organs. Although CEUS applications of the spleen, gallbladder and pancreas have been well described in adults, they have not been fully explored in children. In this manuscript, we present an overview of the applications of CEUS for normal variants and diseases affecting the spleen, gallbladder and pancreas. We highlight a variety of cases as examples of how CEUS can serve in the diagnosis and follow-up for such diseases in children. Our discussion includes specific examination techniques; presentation of the main imaging findings in various benign and malignant lesions of the spleen, gallbladder and pancreas in children; and acknowledgment of the limitations of CEUS for these organs.

Contrast-enhanced ultrasound of the small organs in children.

In pediatric and adult populations, intravenous contrast-enhanced ultrasound (CEUS) remains off-label for imaging of organs other than the liver and heart. This limited scope inhibits potential benefits of the new modality from a more widespread utilization. Yet, CEUS is potentially useful for imaging small organs such as the thyroid gland, lymph nodes, testes, ovaries and uterus, with all having locations and vasculature favorable for this type of examination. In the adult population, the utility of CEUS has been demonstrated in a growing number of studies for the evaluation of these small organs. The aim of this article is to present a review of pediatric CEUS of the thyroid gland, lymph nodes, testes, ovaries and uterus as well as to draw from the adult literature indications for possible applications in children.

Practical approach for the diagnosis of biliary atresia on imaging, part 2: magnetic resonance cholecystopancreatography, hepatobiliary scintigraphy, percutaneous cholecysto-cholangiography, endoscopic retrograde cholangiopancreatography, percutaneous liver biopsy, risk scores and decisional flowchart.

We aim to present a practical approach to imaging in suspected biliary atresia, an inflammatory cholangiopathy of infancy resulting in progressive fibrosis and obliteration of extrahepatic and intrahepatic bile ducts. Left untreated or with failure of the Kasai procedure, biliary atresia progresses to biliary cirrhosis, end-stage liver failure and death within the first years of life. Differentiating biliary atresia from other nonsurgical causes of neonatal cholestasis is difficult as there is no single method for diagnosing biliary atresia and clinical, laboratory and imaging features of this disease overlap with those of other causes of neonatal cholestasis. In this second part, we discuss the roles of magnetic resonance (MR) cholecystopancreatography, hepatobiliary scintigraphy, percutaneous biopsy and percutaneous cholecysto-cholangiography. Among imaging techniques, ultrasound (US) signs have a high specificity, although a normal US examination does not rule out biliary atresia. Other imaging techniques with direct opacification of the biliary tree combined with percutaneous liver biopsy have roles in equivocal cases. MR cholecystopancreatography and hepatobiliary scintigraphy are not useful for the diagnosis of biliary atresia. We propose a decisional flowchart for biliary atresia diagnosis based on US signs, including elastography, percutaneous cholecysto-cholangiography or endoscopic retrograde cholangiopancreatography and liver biopsy.

Practical approach to imaging diagnosis of biliary atresia, Part 1: prenatal ultrasound and magnetic resonance imaging, and postnatal ultrasound.

We present a practical approach to imaging in suspected biliary atresia, an inflammatory cholangiopathy of infancy resulting in progressive fibrosis and obliteration of extrahepatic and intrahepatic bile ducts. Left untreated or with failure of the Kasai procedure, biliary atresia progresses towards biliary cirrhosis, end-stage liver failure and death by age 3. Differentiation of biliary atresia from other nonsurgical causes of neonatal cholestasis is challenging because there is no single method for diagnosing biliary atresia, and clinical, laboratory and imaging features of this disease overlap with those of other causes of neonatal cholestasis. Concerning imaging, our systematic literature review shows that ultrasonography is the main tool for pre- and neonatal diagnosis. Key prenatal features, when present, are non-visualisation of the gallbladder, cyst in the liver hilum, heterotaxy syndrome and irregular gallbladder walls. Postnatal imaging features have a very high specificity when present, but a variable sensitivity. Triangular cord sign and abnormal gallbladder have the highest sensitivity and specificity. The presence of macro- or microcyst or polysplenia syndrome is highly specific but less sensitive. The diameter of the hepatic artery and hepatic subcapsular flow are less reliable. When present in the context of acholic stools, dilated intrahepatic bile ducts rule out biliary atresia. Importantly, a normal US exam does not rule out biliary atresia. Signs of chronic hepatopathy and portal hypertension (portosystemic derivations such as patent ductus venosus, recanalised umbilical vein, splenomegaly and ascites) should be actively identified for - but are not specific for - biliary atresia.