Cystic fibrosis hepatobiliary involvement: an update on imaging in diagnosis and monitoring.

Analysis of the liver using imaging for persons with cystic fibrosis (CF) continues to evolve as new medical therapies are developed improving and extending life. In the 2010s, therapies targeted at modulating protein folding became available to those with CF. Therapeutic options have continued to expand, now providing both correction of protein folding and stabilization for most gene mutations that code for the CF transmembrane receptor protein (CFTR). Today, approximately 80% of persons with CF are eligible for highly effective modulator therapy. With these advancements, the impact of CF on the liver has become more complex, adding metabolism of CFTR modulators to intrinsic CF hepatobiliary involvement (CFHBI) and adding not previously appreciated vascular changes within the liver due to increased longevity in persons with CF. A combination of serum biomarkers and imaging is needed to add clarity to the diagnosis and monitoring of the severity of liver disease. A substantial portion of persons with CF will develop at least CFHBI and a subset will develop advanced cystic fibrosis-associated liver disease (aCFLD); therefore, diagnosis and monitoring need to begin in childhood. In this review, we cover the use of and need for imaging, including elastography, ultrasound, and magnetic resonance imaging (MRI), in diagnosing and monitoring CFHBI and its associated complications.

Imaging of pediatric liver tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Primary hepatic malignancies are relatively rare in the pediatric population, accounting for approximately 1%-2% of all pediatric tumors. Hepatoblastoma and hepatocellular carcinoma are the most common primary liver malignancies in children under the age of 5 years and over the age of 10 years, respectively. This paper provides consensus-based imaging recommendations for evaluation of patients with primary hepatic malignancies at diagnosis and follow-up during and after therapy.

Imaging of Right Lower Quadrant Pain in Children and Adolescents: AJR Expert Panel Narrative Review.

Right lower quadrant (RLQ) pain is a common clinical presentation in children, and accurate clinical diagnosis remains challenging given that this nonspecific presentation is associated with numerous surgical and nonsurgical conditions. The broad differential diagnosis varies by patient age and sex. Important considerations in the selection of a diagnostic imaging strategy include the sequencing, performance, and cost of tests. This article provides a comprehensive narrative review of the diagnostic imaging of RLQ pain in children and adolescents, including a discussion of the complementary roles of ultrasound, CT, and MRI; description of key imaging findings based on available evidence; and presentation of salient differential diagnoses. Subspecialized pediatric emergency medicine and surgical perspectives are also provided as further clinical insight into this common, but often challenging, scenario. Finally, the current status of imaging of RLQ pain in children and adolescents is summarized on the basis of expert consensus.

Optimizing Imaging of Pediatric Liver Lesions: Guidelines from the Pediatric LI-RADS Working Group.

A differential diagnosis based on a patient's age, clinical presentation, and serum α-fetoprotein level will help guide the initial imaging workup in children with a liver lesion. Children vary significantly in size, the ability to stay still, and the ability to breath hold for imaging examinations. Choosing and tailoring imaging techniques and protocols for each indication and age group is important for optimal care with minimal invasiveness. The need for sedation or anesthesia can be obviated by using techniques like feed and bundle, distraction, contrast-enhanced US, and motion-insensitive sequences for MRI. US is often the first imaging modality used in children with a suspected abdominal mass. Once a hepatic lesion is confirmed, multiphasic contrast-enhanced MRI is recommended for most lesions as the next imaging modality allowing full characterization of the lesion and assessment of the liver parenchyma. Contrast-enhanced CT can also be performed for assessment of pediatric focal liver lesions, especially in patients who have a contraindication to MRI. Contrast-enhanced US has shown promise to decrease the need for MRI or CT in some lesions such as hemangioma and focal nodular hyperplasia. Children with a history of malignancy can develop multiple types of hepatic lesions at various stages, including infections during an immunocompromised state, manifesting as focal liver lesions. Based on available limited data in the literature and the collective experiences of the Liver Imaging and Reporting Data System Pediatric Working Group, the authors provide guidelines for the imaging workup of pediatric focal liver lesions with an indication- and age-based approach and discuss the selection and performance of various imaging techniques and modalities. ©RSNA, 2022 See the invited commentary by Chojniak and Boaventura in this issue.

Cancer Therapy-related Hepatic Injury in Children: Imaging Review from the Pediatric LI-RADS Working Group.

The liver is the primary organ for the metabolism of many chemotherapeutic agents. Treatment-induced liver injury is common in children undergoing cancer therapy. Hepatic injury occurs due to various mechanisms, including biochemical cytotoxicity, hepatic vascular injury, radiation-induced cytotoxicity, and direct hepatic injury through minimally invasive and invasive surgical treatments. Treatment-induced liver injury can be seen contemporaneous with therapy and months to years after therapy is complete. Patients can develop a combination of hepatic injuries manifesting during and after treatment. Acute toxic effects of cancer therapy in children include hepatitis, steatosis, steatohepatitis, cholestasis, hemosiderosis, and vascular injury. Longer-term effects of cancer therapy include hepatic fibrosis, chronic liver failure, and development of focal liver lesions. Quantitative imaging techniques can provide useful metrics for disease diagnosis and monitoring, especially in treatment-related diffuse liver injury such as hepatic steatosis and steatohepatitis, hepatic iron deposition, and hepatic fibrosis. Focal liver lesions, including those developing as a result of treatment-related vascular injury such as focal nodular hyperplasia-like lesions and hepatic perfusion anomalies, as well as hepatic infections occurring as a consequence of immune suppression, can be anxiety provoking and confused with recurrent malignancy or hepatic metastases, although there often are imaging features that help elucidate the correct diagnosis. Radiologic evaluation, in conjunction with clinical and biochemical screening, is integral to diagnosing and monitoring hepatic complications of cancer therapy in pediatric patients during therapy and after therapy completion for long-term surveillance. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material See the invited commentary by Ferraciolli and Gee in this issue.

Imaging Features of Hepatocellular Carcinoma in Children With and Without Underlying Risk Factors.

BACKGROUND. Pediatric hepatocellular carcinoma (HCC) is an aggressive malignancy for which imaging findings remain poorly described. In comparison with adult HCC, pediatric HCC more commonly occurs without underlying risk factors, and standardized surveillance guidelines for those with predispositions are lacking. OBJECTIVE. The purpose of this article was to evaluate imaging findings of nonfibrolamellar pediatric HCC and to identify associations between these imaging findings and the presence of predisposing factors. METHODS. This retrospective study included children (≤ 18 years) with histologically confirmed nonfibrolamellar HCC who underwent multiphase CT or MRI at one of four academic children's hospitals between July 2009 and April 2019. Surveillance regimens in children with predispositions were at the discretion of treating physicians. Clinical characteristics were recorded. Scan indications were classified as surveillance versus clinical signs and symptoms. Images from all sites were submitted to a cloud-based server. Two radiologists independently assessed imaging features of HCC, including tumor size, tumor in vein, Pre-Treatment Extent of Tumor (PRETEXT) stage, and LI-RADS major features of adult HCC. Imaging findings were compared between patients with and without predispositions. RESULTS. The study included 39 patients: 17 with predispositions (mean age, 10.5 ± 4.5 years; nine boys, eight girls) and 22 without predispositions (mean age, 11.3 ± 5.1 years; 12 boys, 10 girls). Scan indication was surveillance in 14/17 patients with predispositions versus 0/22 patients without predispositions (p < .001). Patients with versus those without predispositions had smaller tumor size (reader 1: 6.0 vs 11.9 cm [p = .003]; reader 2: 6.0 vs 12.9 cm [p < .001]) and less frequent tumor in vein (reader 1: 0% vs 41% [p = .002]; reader 2: 0% vs 36% [p = .006]). PRETEXT stage IV disease was observed in 18% (both readers) of patients with predispositions versus 50-55% of patients without predispositions. No LI-RADS major feature of adult HCC showed a significant difference in frequency between patients with and without predispositions for either reader (all p > .05). CONCLUSION. Among children with HCC, those with predispositions exhibited smaller and lower-stage tumors and less frequent tumor in vein, likely because of surveillance imaging. CLINICAL IMPACT. The study supports the role of routine surveillance imaging in children with HCC predispositions to facilitate earlier detection. Standardization of surveillance guidelines remains needed.

Hepatic manifestations of systemic disease: an imaging-based review.

The liver is responsible for many processes that maintain human metabolic homeostasis and can be affected by several pediatric systemic diseases. In this manuscript, we explore key pathological findings and imaging features across multiple modalities of a spectrum of congenital, metabolic and autoimmune disorders. Strengthening the radiologists' knowledge regarding potential hepatic manifestations of these systemic diseases will ultimately lead to improved care for pediatric patients.

Pediatric electronic cigarette or vaping product use-associated lung injury (EVALI): updates in the coronavirus disease 2019 (COVID-19) pandemic era.

Electronic cigarette or vaping product use-associated lung injury (EVALI) is a toxic inhalational injury that surged in late 2019 and early 2020, immediately prior to the coronavirus disease 2019 (COVID-19) pandemic. Although EVALI cases have significantly decreased, they are still encountered, especially among adolescents. While several characteristic imaging findings and patterns of EVALI have been described, some of them can overlap with the imaging features of COVID-19 pneumonia. We provide a comprehensive review of EVALI that includes the latest updates and highlight the important role of radiologists as contributors to the appropriate and timely care of pediatric patients with this diagnosis.

Assessing and conveying risks and benefits of imaging in neonates using ionizing radiation and sedation/anesthesia.

Neonates represent a unique subset of the pediatric population that requires special attention and careful thought when implementing advanced cross-sectional imaging with CT or MRI. The ionizing radiation associated with CT and the sedation/anesthesia occasionally required for MRI present risks that must be balanced against the perceived benefit of the imaging examination in the unique and particularly susceptible neonatal population. We review the perceived risks of ionizing radiation and the more concrete risks of sedation/anesthesia in term and preterm neonates in the context of an imaging paradigm. When the expected diagnostic yield from CT and MRI is similar, and sedation is required for MRI but not for CT, CT likely has the higher benefit-to-risk ratio in the neonate. However, despite the risks, the most appropriate imaging modality should always be chosen after thoughtful consideration is given to each unique patient and informed discussions including radiology, anesthesia, neonatology and the parents/caregivers are pursued.

Diagnostic Performance of LI-RADS Version 2018 for Evaluation of Pediatric Hepatocellular Carcinoma.

Background The Liver Imaging Reporting and Data System (LI-RADS) has standardized the evaluation of adult but not pediatric hepatocellular carcinoma (HCC). Purpose To evaluate the performance of LI-RADS version 2018 for diagnosis of pediatric HCC. Materials and Methods This multi-institution retrospective study evaluated all available dynamic CT and/or MRI scans of pediatric (≤18 years) HCC from five institutions between July 2009 and April 2019. The control group included an equal number of other enhancing hepatic lesions. Blinded to final diagnosis, three radiologists independently applied LI-RADS version 2018 criteria. The reference standard was pathologic examination or more than 1 year follow-up. Sensitivity and specificity of LI-RADS were computed using a dichotomous classification of LR-1, LR-2, or LR-3 versus LR-4, LR-5, LR-TIV (tumor in vein), or LR-M (probably or definitely malignant but not HCC-specific) for predicting hepatic malignancy in the entire cohort and in patients at risk for HCC. Results The cohort consisted of 116 children: 58 with HCC (mean age, 12 years ± 5; 31 girls) and 58 with other enhancing hepatic masses (mean age, 12 years ± 5; 42 girls). Frequencies of major criteria in classic HCC for the three readers were as follows: nonrim arterial phase hyperenhancement, 49%-62% (19-24 of 39 patients); nonperipheral "washout," 36%-59% (14-23 of 39 patients); and enhancing "capsule," 28%-38% (11-15 of 39 patients). For the full cohort, the sensitivity of LR-4, LR-5, LR-TIV, or LR-M for malignancy among the three readers ranged from 85% (95% CI: 76, 94) to 88% (95% CI: 80, 96); specificity of LR-1, LR-2, or LR-3 for benignity ranged from 54% (95% CI: 40, 68) to 70% (95% CI: 57, 83). In the at-risk subgroup, sensitivity ranged from 58% (95% CI: 36, 80) to 68% (95% CI: 48, 89); specificity ranged from 56% (95% CI: 37, 74) to 63% (95% CI: 45, 81). All lesions categorized as LR-TIV (n = 10-13) were HCCs. Conclusion Liver Imaging Reporting and Data System version 2018 had moderate sensitivity but low specificity for the diagnosis of pediatric hepatocellular carcinoma (HCC), which had low frequencies of the major criteria used for adult HCC diagnosis. © RSNA, 2021 See also the editorial by Paltiel in this issue.

Hepatic vascular malignancies in children are associated with increased rates of surgical resection and improved overall survival compared with adults.

BACKGROUND: Hepatic vascular malignancies (HVMs) are rare malignancies, with no standardized treatment regimens. The most common HVMs, angiosarcoma and malignant epithelioid hemangioendothelioma (EHE), are often grouped together in the literature complicating our ability to achieve reliable survival data and treatment strategies. OBJECTIVE: To compare the disease characteristics of HVMs, with a subanalysis on pediatric patients. METHODS: The 2016 National Cancer Database was queried for patients with HVMs using international classification of diseases-oncology-3 (ICD-O-3) codes yielding 699 patients. Descriptive statistics, chi-square, Kaplan-Meier, and log-rank analyses were performed. RESULTS: We found 478 patients (68%) with angiosarcoma and 221 (32%) with EHE. The median (Q1, Q3) age for angiosarcoma patients was 65 years (56, 75) versus 54 years (37, 65) in EHE patients (P < .001). The rate of resection was lower in patients with angiosarcoma than EHE (13% vs 32%, P < .001). The mean 1-, 3-, and 5-year overall survival for angiosarcoma patients was 17%, 8%, and 6%, respectively, versus 80%, 65%, and 62% in EHE patients (P < .0001). A subgroup analysis was performed on pediatric patients demonstrating six with angiosarcoma and 10 with EHE. The mean 1-, 3-, and 5-year overall survival for pediatric angiosarcoma patients was 67%, 50%, and 50%, respectively, and 90%, 90%, and 90% for pediatric EHE patients. CONCLUSION: In the largest study of HVMs to date, we found angiosarcoma has significantly worse overall survival than EHE. Pediatric patients appear to have improved survival and higher rates of resection. Larger studies of HVMs are needed to clearly differentiate tumor types, standardize care, and improve survivorship.

Imaging for Staging of Pediatric Abdominal Tumors: An Update, From the AJR Special Series on Cancer Staging.

The three most common pediatric solid tumors of the abdomen are neuroblastoma, Wilms tumor, and hepatoblastoma. These embryonal tumors most commonly present in the first decade of life. Each tumor has unique imaging findings, including locoregional presentation and patterns of distant spread. Neuroblastoma, Wilms tumor, and hepatoblastoma have unique staging systems that rely heavily on imaging and influence surgical and oncologic management. The staging systems include image-defined risk factors for neuroblastoma, the Children's Oncology Group staging system for Wilms tumor, and the pretreatment extent of tumor system (PRETEXT) for hepatoblastoma. It is important for radiologists to be aware of these staging systems to optimize image acquisition and interpretation. This article provides a practical and clinically oriented approach to the role of imaging in the staging of these common embryonal tumors of childhood. The selection among imaging modalities, key findings for determining tumor stage, and the role of imaging in posttreatment response evaluation and surveillance are discussed. Recent updates to the relevant staging systems are highlighted with attention to imaging findings of particular prognostic importance. The information presented will help radiologists tailor the imaging approach to the individual patient and guide optimal oncologic management.

Pediatric Hepatoblastoma, Hepatocellular Carcinoma, and Other Hepatic Neoplasms: Consensus Imaging Recommendations from American College of Radiology Pediatric Liver Reporting and Data System (LI-RADS) Working Group.

Appropriate imaging is imperative in evaluating children with a primary hepatic malignancy such as hepatoblastoma or hepatocellular carcinoma. For use in the adult patient population, the American College of Radiology created the Liver Imaging Reporting and Data System (LI-RADS) to provide consistent terminology and to improve imaging interpretation. At present, no similar consensus exists to guide imaging and interpretation of pediatric patients at risk for developing a liver neoplasm or how best to evaluate a pediatric patient with a known liver neoplasm. Therefore, a new Pediatric Working Group within American College of Radiology LI-RADS was created to provide consensus for imaging recommendations and interpretation of pediatric liver neoplasms. The article was drafted based on the most up-to-date existing information as interpreted by imaging experts comprising the Pediatric LI-RADS Working Group. Guidance is provided regarding appropriate imaging modalities and protocols, as well as imaging interpretation and reporting, with the goals to improve imaging quality, to decrease image interpretation errors, to enhance communication with referrers, and to advance patient care. An expanded version of this document that includes broader background information on pediatric hepatocellular carcinoma and rationale for recommendations can be found in Appendix E1 (online).

Hepatobiliary MRI Contrast Agents: Pattern Recognition Approach to Pediatric Focal Hepatic Lesions.

OBJECTIVE. The purposes of this article are to review currently available hepatobiliary contrast agents, discuss techniques for optimization of pediatric liver MRI with hepatobiliary contrast agents, and review the imaging features of several pediatric hepatic lesions, focusing on their assessment with hepatobiliary contrast agents. CONCLUSION. MRI is the preferred imaging modality for complete assessment of focal liver lesions in the pediatric population. Imaging with gadolinium-based hepatobiliary contrast agents yields beneficial information about many focal liver lesions encountered in pediatric patients.

Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring.

PURPOSE: In glycogen storage disease type III (GSD III), liver aminotransferases tend to normalize with age giving an impression that hepatic manifestations improve with age. However, despite dietary treatment, long-term liver complications emerge. We present a GSD III liver natural history study in children to better understand changes in hepatic parameters with age. METHODS: We reviewed clinical, biochemical, histological, and radiological data in pediatric patients with GSD III, and performed a literature review of GSD III hepatic findings. RESULTS: Twenty-six patients (median age 12.5 years, range 2-22) with GSD IIIa (n = 23) and IIIb (n = 3) were enrolled in the study. Six of seven pediatric patients showed severe fibrosis on liver biopsy (median [range] age: 1.25 [0.75-7] years). Markers of liver injury (aminotransferases), dysfunction (cholesterol, triglycerides), and glycogen storage (glucose tetrasaccharide, Glc4) were elevated at an early age, and decreased significantly thereafter (p < 0.001). Creatine phosphokinase was also elevated with no significant correlation with age (p = 0.4). CONCLUSION: Liver fibrosis can occur at an early age, and may explain the decrease in aminotransferases and Glc4 with age. Our data outlines the need for systematic follow-up and specific biochemical and radiological tools to monitor the silent course of the liver disease process.

Free-breathing unsedated MRI in children: Justification and techniques.

One of the more common and important challenges in the imaging of children is minimizing image degradation caused by motion. This is especially important in MRI, which is often preferable in the pediatric population due to better tissue characterization and lack of ionizing radiation. However, due to the length of time needed for most examinations, MRI is among the most sensitive to disruption by patient motion. Traditionally, deep conscious sedation or general anesthesia was the most common method of reducing motion in children who are unable or unwilling to follow direction. As the drawbacks and risks of anesthesia in children become more known and accepted, the development and optimization of means of mitigating motion and anxiety in children without the use of sedation or anesthesia becomes more urgent. In this article we describe the risks of sedation in the pediatric population and explore current methods of reducing both patient anxiety and imaging degradation from motion in the unsedated, free-breathing child. Level of Evidence: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;50:365-376.

Current utilization and procedural practices in pediatric whole-body MRI.

BACKGROUND: Whole-body magnetic resonance imaging (MRI) is an evolving and increasingly powerful imaging tool with a variety of applications in the pediatric patient population. Variability exists among radiology practices in how this MRI tool is used and how it is performed. OBJECTIVE: Our objective was to gain an improved understanding of technical and utilization practices in pediatric whole-body MRI across North America by exploring indications for exam performance, determining referral patterns, and assessing technical protocols and procedures. MATERIALS AND METHODS: A 19-question survey was generated in Survey Monkey and distributed in 2016 to the Society for Pediatric Radiology membership. The survey asked questions that included practice type, imaging modality preferences for diseases commonly evaluated with whole-body MRI, MRI field strength and sequence selection, and billing practices. RESULTS: Data were obtained from 62 unique responses to the survey, representing 471 physicians. The majority (93%) practice in an academic institution or private practice with academic affiliation and most practices have utilized whole-body MRI for less than 6 years. Whole-body MRI is performed in pediatric patients 0 to 18 years of age, and was the preferred imaging modality for diagnosis/staging/follow-up in neurofibromatosis, type 1 (75%), chronic recurrent multifocal osteomyelitis (CRMO) (74%), cancer predisposition syndromes (75%), vasculopathies (50%) and disseminated/multifocal infection (49%). The most commonly utilized sequences are coronal short tau inversion recovery (STIR) (90%), coronal T1 with or without fat saturation (65%), and axial diffusion-weighted imaging (DWI) (48%). No preference was shown for either 1.5-T or 3-T systems. Wide variability was seen in preference for billing code utilization, though the majority use chest/abdomen/pelvis (57%) or unlisted MRI (37%) codes. CONCLUSION: Radiology practitioners - represented by the Society for Pediatric Radiology pediatric radiologists - are using whole-body MRI in the imaging care of pediatric patients for a variety of indications. Survey results reveal some variability in exam utilization and technical performance practices among those pediatric radiologists who perform whole-body MRI.

Chest computed tomography angiography in children on extracorporeal membrane oxygenation (ECMO).

Performing chest CT angiography on pediatric patients on extracorporeal membrane oxygenation (ECMO) can be challenging. Successfully performing CT angiography in these children requires substantial communication and coordination between the radiologists and clinical care providers. Additionally, the radiologist must understand the child's anatomy and disease pathophysiology, flow dynamics of the ECMO circuit, image acquisition timing, contrast injection site, and volume, rate and duration of contrast administration. In this article we highlight the vital factors the radiologist needs to consider to optimize the chest CT angiography in pediatric patients on ECMO.