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.

A clinical perspective on imaging in juvenile idiopathic arthritis.

In recent years, imaging has become increasingly important to confirm diagnosis, monitor disease activity, and predict disease course and outcome in children with juvenile idiopathic arthritis (JIA). Over the past few decades, great efforts have been made to improve the quality of diagnostic imaging and to reach a consensus on which methods and scoring systems to use. However, there are still some critical issues, and the diagnosis, course, and management of JIA are closely related to clinical assessment. This review discusses the main indications for conventional radiography (XR), musculoskeletal ultrasound (US), and magnetic resonance imaging (MRI), while trying to maintain a clinical perspective. The diagnostic-therapeutic timing at which one or the other method should be used, depending on the disease/patient phenotype, will be assessed, considering the main advantages and disadvantages of each imaging modality according to the currently available literature. Some brief clinical case scenarios on the most frequently and severely involved joints in JIA are also presented.

The role of radiography in diagnosing, monitoring and prognosing juvenile idiopathic arthritis.

The current role of conventional radiography in the diagnosis, monitoring and prognosis of juvenile idiopathic arthritis (JIA) is reviewed, as its role has changed with the increasing use of ultrasound and magnetic resonance imaging, as well as with the introduction of biological drugs. Conventional radiography does not play an important role in the diagnosis of JIA, as this is based on history, clinical examination and laboratory findings. The main role of conventional radiography is in the detection and monitoring of growth disorders and chronic structural and morphological changes of the affected joints and bones, in addition to helping with the differential diagnosis of conditions that mimic JIA. Radiographic changes of the joints depend on the age of the child, the type and duration of arthritis and the specific joints affected. There are no standard protocols for arthritis monitoring and most indications for imaging are based on individual case-by-case decisions. The development of degenerative joint changes is considered a poor predictive factor, but there are no clear studies that more precisely define the predictive value of radiographic changes. Conventional radiography remains an important imaging modality in narrowing the differential diagnosis and in evaluating growth disorders and the developing destructive joint changes.

Diagnostic Value of Quantitative Contrast-Enhanced Ultrasound in Comparison to Endoscopy in Children With Crohn's Disease.

OBJECTIVE: Quantitative contrast-enhanced US (CEUS) provides objective evaluation of bowel wall perfusion and has been reported as a useful method for evaluating Crohn's disease (CD) activity in children. We tested its' diagnostic accuracy in comparison to endoscopy and evaluated its' usefulness in comparison to Pediatric Crohn's Disease Activity Index (PCDAI) and fecal Calprotectin (FC). MATERIALS AND METHODS: Children with CD and thickened bowel wall on abdominal US were prospectively enrolled. Disease activity was evaluated with quantitative CEUS, PCDAI and FC and compared to a simple endoscopic score for Crohn's disease (SES-CD). Spearman's correlation and Cohen's kappa statistic between the SES-CD and other disease activity measures were performed and diagnostic accuracies calculated. RESULTS: 36 children 3.5-18 years old (mean age 14 years) were included. The quantitative CEUS had 78.57% sensitivity (95%CI 0.59-0.92), 100% specificity (95%CI 0.63-1.0) and 83.33% diagnostic accuracy (95% CI 0.67-0.94). The concordance remission agreement with endoscopy was substantial for quantitative CEUS and PCDAI (quantitative CEUS: κ = 0.62; 95% CI 0.363-0.877; PCDAI: κ = 0.615; 95% CI 0.311-0.920), but only fair for FC (κ = 0.389; 95% CI 0.006-0.783). Correlation between all measures and endoscopy was moderate and statistically significant (quantitative CEUS: rs  = 0.535, PCDAI: rs  = 0.543, FC: rs  = 0.497). CONCLUSIONS: Quantitative CEUS has a potential of becoming a complementary method for evaluation of CD activity in children due to its' high specificity in comparison to endoscopy. Lower sensitivity makes it deficient as a single measure and further management should be guided by PCDAI and FC results as well.

Contrast-enhanced ultrasound in detection and follow-up of focal renal infections in children.

OBJECTIVE: Focal renal infections in children have to be diagnosed early in order to enable an appropriate antibiotic treatment. The purpose of this paper was to investigate the efficacy and clinical utility of intravenous renal contrast-enhanced ultrasound (CEUS) as an alternative imaging method for the diagnosis and follow-up of focal renal infections in children. METHODS: Fourteen children aged from 6 months to 17 years (mean 6.5 years) in whom focal renal infection was suspected were included in this retrospective study. All data were obtained from medical and imaging records of the patients. RESULTS: CEUS was performed for the diagnosis in all 14 children and then also for follow-up in seven children with renal abscess. In three children enhancement pattern was concordant with focal nephritis and in four children CEUS excluded focal renal infection and the diagnosis of pseudolesion was confirmed. CONCLUSION: Renal CEUS was proven to be an efficient and self-sufficient imaging in diagnosis and further follow-up of focal renal infections in children. CEUS patterns of focal renal infections are described as well as relevant CEUS enhancement patterns important for differential diagnosis. Renal abscess follow-up algorithm with CEUS is suggested. ADVANCES IN KNOWLEDGE: All clinically relevant imaging data was obtained by CEUS and no other imaging was necessary for the diagnosis and follow-up.

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.

Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi-Goutières syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency.

Aicardi-Goutières syndrome (AGS) is a genetically determined early-onset progressive encephalopathy caused by mutations leading to overexpression of type I interferon (IFN) and resulting in various clinical phenotypes. A gain-of-function (GOF) mutation in the IFIH1 gene is associated with robust production of type I IFN and activation of the Janus kinase (JAK) signal transducer and activator of the transcription (STAT) pathway, which can cause AGS type 7. We detail the clinical case of an infant who initially presented with Pneumocystis jirovecii pneumonia (PCP), had recurrent respiratory infections, and was later treated with a JAK inhibitor, baricitinib, because of a genetically confirmed GOF mutation in the IFIH1 gene. This spectrum of IFIH1 GOF mutations with overlapping features of hyperinflammation and severe opportunistic infection, which mimics combined immunodeficiency (CID), has not been described before. In this case, therapy with baricitinib effectively blocked IFN-α activation and reduced STAT1 signaling but had no effect on the progression of the neurological disease.

Case Report: Necrotizing Stomatitis as a Manifestation of COVID-19-Associated Vasculopathy.

Necrotizing stomatitis is a rare, acute-onset disease that is usually associated with severely malnourished children or diminished systemic resistance. We describe a 1-year-old girl who developed necrotizing stomatitis, vasculitic rash, skin desquamation on the fingers and toes, and persistent hypertension after serologically confirmed SARS-CoV-2 infection. Her laboratory investigations revealed positive IgG anticardiolipin and IgG anti-ß2 glycoprotein antibodies, and biopsy of the mucosa of the lower jaw showed necrosis and endothelial damage with mural thrombi. Swollen endothelial cells of small veins in the upper dermis were confirmed also by electron microscopy. As illustrated by our case, necrotizing stomatitis may develop as a rare complication associated with SARS-CoV-2 infection and can be considered as a part of the clinical spectrum of COVID-19 vasculopathy. The pathogenic mechanism could involve a consequence of inflammatory events with vasculopathy, hypercoagulability, and damage of endothelial cells as a response to SARS-CoV-2 infection.

Surveillance of Fontan-associated liver disease: current standards and a proposal from the European Society of Paediatric Radiology Abdominal Task Force.

Since Francis Fontan first introduced the eponymous technique, the Fontan procedure, this type of surgical palliation has allowed thousands of children affected by specific heart malformations to reach adulthood. Nevertheless, abdominal, thoracic, lymphatic and neurologic complications are the price that is paid by these patients. Our review focuses on Fontan-associated liver disease; the purpose is to summarize the current understanding of its physiopathology, the aim of follow-up and the specific radiologic follow-up performed in Europe. Finally, we as members of the Abdominal Task Force of the European Society of Paediatric Radiology propose a consensus-based imaging follow-up algorithm.

Radiologic follow-up in Fontan-associated liver disease in Europe: European Society of Paediatric Radiology survey demonstrates the need for a consensus protocol.

Fontan surgery is a life-saving procedure for newborns with complex cardiac malformations, but it originates complications in different organs. The liver is also affected, with development of fibrosis and sometimes cirrhosis and hepatocellular carcinoma. There is no general agreement on how to follow-up these children for the development of liver disease. To understand the current practice on liver follow-up, we invited members of the European Society of Paediatric Radiology (ESPR) to fill out an online questionnaire. The survey comprised seven questions about when and how liver follow-up is performed on Fontan patients. While we found some agreement on the use of US as screening tool, and of MRI for nodule characterization, the discrepancies on timing and the lack of a shared protocol make it currently impossible to compare data among centers.

Quantitative contrast-enhanced ultrasound for the differentiation of kidney allografts with significant histopathological injury.

OBJECTIVE: To identify specific quantitative contrast-enhanced ultrasound (CEUS) parameters that could distinguish kidney transplants with significant histopathological injury. METHODS: Sixty-four patients were enrolled in this prospective observational study. Biopsies were performed following CEUS and blood examination. RESULTS: 28 biopsy specimens had minimal changes (MC group), while 36 had significant injury (SI group). Of these, 12 had rejection (RI group) and 24 non-rejection injury (NRI group). In RI and NRI groups, temporal difference in time to peak (TTP) between medulla and cortex (ΔTTPm-c) was significantly shorter compared to the MC group (5.77, 5.92, and 7.94 s, P = 0.048 and 0.026, respectively). Additionally, RI group had significantly shorter medullary TTP compared to the MC group (27.75 vs. 32.26 s; P = 0.03). In a subset of 41 patients with protocol biopsy at 1-year post-transplant, ΔTTPm-c was significantly shorter in the SI compared to the MC group (5.67 vs. 7.67 s; P = 0.024). Area under receiver operating characteristic curves (AUROCs) for ΔTTPm-c was 0.69 in all patients and 0.71 in patients with protocol biopsy. CONCLUSIONS: RI and NRI groups had shorter ΔTTPm-c compared to the MC group. AUROCs for both patient groups were good, making ΔTTPm-c a promising CEUS parameter for distinguishing patients with significant histopathological injury.

Contrast-enhanced voiding urosonography part 2: urethral imaging.

Ultrasound (US) has been increasingly used as an important imaging tool to assess the urethra in children. The earliest reports of pediatric urethral sonography involved imaging the urethra in a non-voiding state, during physiological voiding of urine, and after instillation of saline. The introduction of US contrast agents has continued to improve visualization of urethral anatomy. Contrast-enhanced US of the urethra can be performed during the voiding phase of a standard contrast-enhanced voiding urosonography (ceVUS) exam or with retrograde instillation of a contrast agent, depending on the exam indication. Both techniques are well tolerated by children and provide accurate information about urethral pathology and periurethral soft tissues. This article reviews the technical aspects and imaging findings of urethral pathologies in children using contrast-enhanced US, both by the voiding and retrograde instillation techniques.

Contrast-enhanced ultrasound of blunt abdominal trauma in children.

Trauma is the leading cause of morbidity and mortality in children, and rapid identification of organ injury is essential for successful treatment. Contrast-enhanced ultrasound (CEUS) is an appealing alternative to contrast-enhanced CT in the evaluation of children with blunt abdominal trauma, mainly with respect to the potential reduction of population-level exposure to ionizing radiation. This is particularly important in children, who are more vulnerable to the hazards of ionizing radiation than adults. CEUS is useful in hemodynamically stable children with isolated blunt low- to moderate-energy abdominal trauma to rule out solid organ injuries. It can also be used to further evaluate uncertain contrast-enhanced CT findings, as well as in the follow-up of conservatively managed traumatic injuries. CEUS can be used to detect abnormalities that are not apparent by conventional US, including infarcts, pseudoaneurysms and active bleeding. In this article we present the current experience from the use of CEUS for the evaluation of pediatric blunt abdominal trauma, emphasizing the examination technique and interpretation of major abnormalities associated with injuries in the liver, spleen, kidneys, adrenal glands, pancreas and testes. We also discuss the limitations of the technique and offer a review of the major literature on this topic in children, including an extrapolation of experience from adults.

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 kidneys and adrenals in children.

Pediatric applications of contrast-enhanced ultrasound (CEUS) are growing. Evaluation of the kidneys and adrenal glands in children using intravenous administration of US contrast agents, however, is still an off-label indication. Pediatric CEUS applications for kidneys are similar to those in adults, including ischemic disorders, pseudo- versus real tumors, indeterminate lesions, complex cystic lesions, complicated pyelonephritis, and abscesses. CEUS applications for evaluation of adrenal glands in children are limited, mainly focusing on the assessment and follow-up of adrenal trauma and the differentiation between an adrenal hemorrhage and a mass. This review addresses the current experience in pediatric CEUS of the kidneys and adrenal glands. By extrapolating the established knowledge for US contrast evaluations in the adult kidney to the pediatric context we can note opportunities for CEUS clinical use in children.

Contrast-enhanced ultrasound of transplant organs - liver and kidney - in children.

Ultrasound (US) is the first-line imaging tool for evaluating liver and kidney transplants during and after the surgical procedures. In most patients after organ transplantation, gray-scale US coupled with color/power and spectral Doppler techniques is used to evaluate the transplant organs, assess the patency of vascular structures, and identify potential complications. In technically difficult or inconclusive cases, however, contrast-enhanced ultrasound (CEUS) can provide prompt and accurate diagnostic information that is essential for management decisions. CEUS is indicated to evaluate for vascular complications including vascular stenosis or thrombosis, active bleeding, pseudoaneurysms and arteriovenous fistulas. Parenchymal indications for CEUS include evaluation for perfusion defects and focal inflammatory and non-inflammatory lesions. When transplant rejection is suspected, CEUS can assist with prompt intervention by excluding potential underlying causes for organ dysfunction. Intracavitary CEUS applications can evaluate the biliary tract of a liver transplant (e.g., for biliary strictures, bile leak or intraductal stones) or the urinary tract of a renal transplant (e.g., for urinary obstruction, urine leak or vesicoureteral reflux) as well as the position and patency of hepatic, biliary and renal drains and catheters. The aim of this review is to present current experience regarding the use of CEUS to evaluate liver and renal transplants, focusing on the examination technique and interpretation of the main imaging findings, predominantly those related to vascular complications.

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.

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.