Malignant Rhabdoid Tumor and Related Pediatric Tumors: Multimodality Imaging Review with Pathologic Correlation.

Malignant rhabdoid tumors (MRTs) are rare but lethal solid neoplasms that overwhelmingly affect infants and young children. While the central nervous system is the most common site of occurrence, tumors can develop at other sites, including the kidneys and soft tissues throughout the body. The anatomic site of involvement dictates tumor nomenclature and nosology. While the clinical and imaging manifestations of MRTs and other more common entities may overlap, there are some site-specific distinctive imaging characteristics. Irrespective of the site of occurrence, somatic and germline mutations in SMARCB1, and rarely in SMARCA4, underlie the entire spectrum of rhabdoid tumors. MRTs have a simple and remarkably stable genome but can demonstrate considerable molecular and biologic heterogeneity. Related neoplasms encompass an expanding category of phenotypically dissimilar (nonrhabdoid tumors driven by SMARC-related alterations) entities. US, CT, MRI, and fluorodeoxyglucose PET/CT or PET/MRI facilitate diagnosis, initial staging, and follow-up, thus informing therapeutic decision making. Multifocal synchronous or metachronous rhabdoid tumors occur predominantly in the context of underlying rhabdoid tumor predisposition syndromes (RTPSs). These autosomal dominant disorders are driven in most cases by pathogenic variants in SMARCB1 (RTPS type 1) and rarely by pathogenic variants in SMARCA4 (RTPS type 2). Genetic testing and counseling are imperative in RTPS. Guidelines for imaging surveillance in cases of RTPS are based on age at diagnosis. ©RSNA, 2024 Supplemental material is available for this article.

Imaging of Fontan-Associated Liver Disease.

ABSTRACT: The Fontan procedure is the definitive treatment for patients with single-ventricle physiology. Surgical advances have led to a growing number of patients surviving into adulthood. Fontan-associated liver disease (FALD) encompasses a spectrum of pathologic liver changes that occur secondary to altered physiology including congestion, fibrosis, and the development of liver masses. Assessment of FALD is difficult and relies on using imaging alongside of clinical, laboratory, and pathology information. Ultrasound, computed tomography, and magnetic resonance imaging are capable of demonstrating physiologic and hepatic parenchymal abnormalities commonly seen in FALD. Several novel imaging techniques including magnetic resonance elastography are under study for use as biomarkers for FALD progression. Imaging has a central role in detection and characterization of liver masses as benign or malignant. Benign FNH-like masses are commonly encountered; however, these can display atypical features and be mistaken for hepatocellular carcinoma (HCC). Fontan patients are at elevated risk for HCC, which is a feared complication and has a poor prognosis in this population. While imaging screening for HCC is widely advocated, no consensus has been reached regarding an optimal surveillance regimen.

Pilot study to determine whether reduced-dose photon-counting detector chest computed tomography can reliably display Brody II score imaging findings for children with cystic fibrosis at radiation doses that approximate radiographs.

BACKGROUND: The Brody II score uses chest CT to guide therapeutic changes in children with cystic fibrosis; however, patients and providers are often reticent to undergo chest CT given concerns about radiation. OBJECTIVE: We sought to determine the ability of a reduced-dose photon-counting detector (PCD) chest CT protocol to reproducibly display pulmonary disease severity using the Brody II score for children with cystic fibrosis (CF) scanned at radiation doses similar to those of a chest radiograph. MATERIALS AND METHODS: Pediatric patients with CF underwent non-contrast reduced-dose chest PCD-CT. Volumetric inspiratory and expiratory scans were obtained without sedation or anesthesia. Three pediatric radiologists with Certificates of Added Qualification scored each scan on an ordinal scale and assigned a Brody II score to grade bronchiectasis, peribronchial thickening, parenchymal opacity, air trapping and mucus plugging. We report image-quality metrics using descriptive statistics. To calculate inter-rater agreement for Brody II scoring, we used the Krippendorff alpha and intraclass correlation coefficient (ICC). RESULTS: Fifteen children with CF underwent reduced-dose PCD chest CT in both inspiration and expiration (mean age 8.9 years, range, 2.5-17.5 years; 4 girls). Mean volumetric CT dose index (CTDIvol) was 0.07 ± 0.03 mGy per scan. Mean effective dose was 0.12 ± 0.04 mSv for the total examination. All three readers graded spatial resolution and noise as interpretable on lung windows. The average Brody II score was 12.5 (range 4-19), with moderate inter-reader reliability (ICC of 0.61 [95% CI=0.27, 0.84]). Inter-rater reliability was moderate to substantial for bronchiectasis (0.52), peribronchial thickening (0.55), presence of opacity (0.62) and air trapping (0.70) and poor for mucus plugging (0.09). CONCLUSION: Reduced-dose PCD-CT permits diagnostic image quality and reproducible identification of Brody II scoring imaging findings at radiation doses similar to those for chest radiography.

RINT1 Bi-allelic Variations Cause Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities.

Pediatric acute liver failure (ALF) is life threatening with genetic, immunologic, and environmental etiologies. Approximately half of all cases remain unexplained. Recurrent ALF (RALF) in infants describes repeated episodes of severe liver injury with recovery of hepatic function between crises. We describe bi-allelic RINT1 alterations as the cause of a multisystem disorder including RALF and skeletal abnormalities. Three unrelated individuals with RALF onset ≤3 years of age have splice alterations at the same position (c.1333+1G>A or G>T) in trans with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del) in RINT1. ALF episodes are concomitant with fever/infection and not all individuals have complete normalization of liver function testing between episodes. Liver biopsies revealed nonspecific liver damage including fibrosis, steatosis, or mild increases in Kupffer cells. Skeletal imaging revealed abnormalities affecting the vertebrae and pelvis. Dermal fibroblasts showed splice-variant mediated skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay. Fibroblasts also revealed decreased RINT1 protein, abnormal Golgi morphology, and impaired autophagic flux compared to control. RINT1 interacts with NBAS, recently implicated in RALF, and UVRAG, to facilitate Golgi-to-ER retrograde vesicle transport. During nutrient depletion or infection, Golgi-to-ER transport is suppressed and autophagy is promoted through UVRAG regulation by mTOR. Aberrant autophagy has been associated with the development of similar skeletal abnormalities and also with liver disease, suggesting that disruption of these RINT1 functions may explain the liver and skeletal findings. Clarifying the pathomechanism underlying this gene-disease relationship may inform therapeutic opportunities.

Performing chest computed tomography on pediatric patients on extracorporeal membrane oxygenation (ECMO): a stepwise approach.

Chest CT in pediatric patients on extracorporeal membrane oxygenation (ECMO) can be done safely and provide valuable high-quality diagnostic images to help guide patient management. An understanding of the basics of the ECMO circuit, cannula locations, where and how to inject contrast media, and how to time image acquisition is vital for the radiologist. Additionally, understanding the precautions associated with performing these exams is essential to ensure the safety of the child. This article provides a brief review of pediatric ECMO and its challenges and considerations, as well as a stepwise approach to perform and optimize these exams safely.

Imaging of pre- and post-cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pediatric intraperitoneal malignancy.

Although rare, pediatric peritoneal carcinomatosis does occur in primary abdominopelvic tumors. Additionally, peritoneal carcinomatosis has been described to occur as metastatic disease where the primary tumor is outside the abdominopelvic cavity. Where amenable, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) can be beneficial in disease management. However, favorable outcomes are predicated on specific tumor histology as well as proper patient selection, which significantly relies on preoperative imaging. This review gives a comprehensive, up-to-date summary on pediatric peritoneal carcinomatosis pre-surgical evaluation; where imaging is beneficial and limited; pediatric radiologists' role in helping to quantify disease; and how we, as pediatric radiologists, can help the surgeons and oncologists in the selection of patients for cytoreductive surgery and HIPEC.

Preservation of Renal Function after Major Bleeding Events due to Ultrasound-Guided Parenchymal Renal Biopsy.

The clinical outcomes of major bleeding events following ultrasound-guided native and allograft parenchymal renal biopsy were evaluated. Forty-eight bleeding complications after biopsy (Society of Interventional Radiology adverse event grade ≥ 2) from 2002 to 2018 were identified. The primary outcome assessed was renal function. The clinical outcomes and interventions performed, including blood transfusion, angiography with or without embolization, nephrostomy tube placement, surgery, nephrectomy, hospitalization, intensive care unit admission, dialysis, and survival, were noted. Renal function may be moderately diminished in the short-term periprocedural setting. None of the patients studied died or required nephrectomy or the initiation of dialysis as a result of a major bleeding complication after the renal biopsy.

Perianal magnetic resonance imaging findings and their potential impact on outcome in children with perianal fistulizing Crohn disease.

BACKGROUND: Children with perianal fistulizing Crohn disease require intensive medical management but also have a higher risk for subsequent surgical interventions. OBJECTIVE: We performed a retrospective study to identify patient factors and perianal anatomical features by pelvic MR that are associated with surgical interventions in these children. MATERIALS AND METHODS: We included children with Crohn disease and perianal fistula who underwent pelvic MR with available, archived images and collected demographic, clinical and laboratory data. Radiologists reviewed pelvic MR exams and identified Park classification and additional anatomical features of perianal fistulas, including fistula branching, horseshoe ramifications, abscess, inflammatory mass, supralevator extension, anal sphincter damage, proctitis and posterior anal space involvement. We performed univariate and subsequent multivariate analysis to determine features associated with subsequent surgical intervention. RESULTS: Ninety-nine children with Crohn disease underwent pelvic MR. In this cohort, 69 children had no surgical interventions prior to baseline MRI, with subsequent median clinical follow-up of 5.5 years. Univariate analysis demonstrated that branching (P=0.009), supralevator extension (P=0.015) and anal sphincter damage (P=0.031) were significantly associated with subsequent surgical intervention. Age at baseline MRI was also associated with intervention (hazard ratio [HR] every 5 years: 2.13; 95% confidence interval [CI]: 1.18-3.83; P=0.012). A multivariable model identified only fistula branching (HR: 2.31; 95% CI: 1.28-4.15; P=0.005) and age (HR: 5.18; CI: 1.57-17.14; P=0.007) as independent predictors of subsequent surgery. No demographic, clinical or laboratory parameter predicted subsequent surgical intervention. CONCLUSION: Age and anatomical MR features indicating fistula complexity (branching, supralevator extension) and sphincter damage confer a higher risk of subsequent surgical intervention in children with perianal Crohn disease.

Procedure for optimal implementation of automatic tube potential selection in pediatric CT to reduce radiation dose and improve workflow.

It is important to employ radiation dose reduction techniques in pediatric computed tomography (CT) to reduce potential risks of radiation-induced malignancy. Automatic tube potential (kV) selection tools have been developed and become available on many CT scanners, which select the optimum kV based on the patient size and clinical task to improve the radiation dose efficiency. However, its use in pediatric CT has been mostly empirical, following manufacturer's default recommendation without solid demonstration for quality improvement. This study aimed to implement an automatic tube potential tool (CAREkV, Siemens Healthcare) into routine pediatric CT practice, using the "Plan-Do-Study-Act" quality improvement process, in place of an existing kV/mAs technique chart. The design of this quality improvement project involved Plan-Do-Study-Act stages. Plan and Do stages identified the criteria for optimal automatic kV selection; a range of phantoms representing typical pediatric groups were scanned on a dual-source 128-slice scanner using a fast-pitch scanning mode. The identified CAREkV settings were implemented into the CT protocol and evaluated after a 6-month period. In the Study stage, an objective evaluation of the image metrics and radiation dose for two similar patient cohorts using CAREkV and the technique-chart, respectively, were compared. The kV selected, image quality and radiation dose determined by CAREkV were comparable to those obtained while using the technique-chart. The CAREkV was successfully implemented into our pediatric abdominopelvic CT practice. By utilizing the "PDSA" process optimal image quality and radiation dose reduction were achieved with an automatic kV selection tool to improve CT workflow.

Reproducibility of Lung and Liver Volume Measurements on Fetal Magnetic Resonance Imaging in Left-Sided Congenital Diaphragmatic Hernia.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) affects 1 in 3,000 live births and is associated with significant morbidity and mortality. METHODS: A review of fetal magnetic resonance imaging (MRI) examinations was performed for fetuses with left CDH and normal lung controls. Image review and manual tracings were performed by 4 pediatric radiologists; right and left lung volumes in the coronal and axial planes as well as liver volume above and below the diaphragm in the coronal plane were measured. Intra- and interreviewer reproducibility was assessed using intraclass correlation coefficient (ICC) and Bland-Altman analysis. RESULTS: Excellent intra- and interreviewer reproducibility of the right and left lung volume measurements was observed in both axial planes (interreviewer ICC: right lung: 0.97, 95% CI: 0.95-0.99; left lung: 0.97, 95% CI: 0.95-0.98) and coronal planes (interreviewer ICC: right lung: 0.97, 95% CI: 0.95-0.98; left lung: 0.96, 95% CI: 0.93-0.98). Moderate-to-good interreviewer reproducibility was observed for liver volume above the diaphragm (ICC 0.7, 95% CI: 0.59-0.81). Liver volume below the diaphragm had a good-to-excellent interreviewer reproducibility (ICC 0.88, 95% CI: 9.82-0.93). CONCLUSIONS: The present study demonstrated an excellent intra- and interreviewer reproducibility of MRI lung volume measurements and good-to-moderate inter- and intrareviewer reproducibility of liver volume measurements after standardization of the methods at our fetal center.

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.

Awareness of implicit bias mitigates discrimination in radiology resident selection.

OBJECTIVES: Implicit bias is common and is thought to drive discriminatory behaviour. Having previously demonstrated discrimination against specific applicant demographics by academic radiology departments in a simulated resident selection process, the authors sought to better understand the relationship between implicit bias and discrimination, as well as the potential and mechanisms for their mitigation. METHODS: A total of 51 faculty reviewers at three academic radiology departments, who had participated in a 2017 audit study in which they were shown to treat applicants differently based on race or ethnicity and physical appearance, were invited to complete testing for implicit racial and weight bias using the Implicit Association Test in 2019. Respondents were also surveyed regarding awareness of their own personal racial and weight biases, as well as any prior participation in formal diversity training. Comparisons were made between implicit bias scores and applicant ratings, as well as between diversity training and self-awareness of bias. RESULTS: A total of 31 out of 51 faculty reviewers (61%) completed and submitted results of race and weight Implicit Association Tests. A total of 74% (23/31) reported implicit anti-obese bias, concordant with discrimination demonstrated in the resident selection simulation, in which obese applicants were rated 0.40 standard deviations (SDs) lower than non-obese applicants (P < .001). A total of 71% (22/31) reported implicit anti-Black bias, discordant with application ratings, which were 0.47 SDs higher for Black than for White applicants (P < .001). A total of 84% (26/31) of participants reported feeling self-aware of potential racial bias at the time of application review, significantly higher than the 23% (7/31) reporting self-awareness of potential anti-obese bias (P < .001). Participation in formal diversity training was not associated with implicit anti-Black or anti-fat bias, nor with self-reported awareness of potential racial or weight-based bias (all P > .2). CONCLUSIONS: These findings suggest that implicit bias, as measured by the Implicit Association Test, does not inevitably lead to discrimination, and that personal awareness of implicit biases may allow their mitigation.

The Milk Protein Alpha-Casein Suppresses Triple Negative Breast Cancer Stem Cell Activity Via STAT and HIF-1alpha Signalling Pathways in Breast Cancer Cells and Fibroblasts.

Triple negative breast cancer (TNBC) is the most lethal breast cancer subtype. Extended periods of lactation protect against breast cancer development, but the mechanisms underlying this protection are unknown. We examined the effects of the milk protein alpha-casein over expression in the triple negative MDA-MB-231 breast cancer cell line. The effects of recombinant alpha-casein added exogenously to MDA-MB-231 breast cancer cells, and immortalised human fibroblasts were also investigated. We used transcriptional reporters to understand the signalling pathways downstream of alpha-casein in breast cancer cells and these fibroblasts that were activated by breast cancer cells. To extend our findings to the clinical setting, we analysed public gene expression datasets to further understand the relevance of these signalling pathways in triple negative breast cancer cells and patient samples. Finally, we used small molecular inhibitors to target relevant pathways and highlight these as potential candidates for the treatment of TN breast cancer. High levels of alpha-casein gene expression were predictive of good prognosis across 263 TNBC patient tumour samples. Alpha-casein over expression or exogenous addition reduces cancer stem cell (CSC) activity. HIF-1alpha was identified to be a key downstream target of alpha-casein, in both breast cancer cells and activated fibroblasts, and STAT transcription factors to be upstream of HIF-1alpha. Interestingly, HIF-1alpha is regulated by STAT3 in breast cancer cells, but STAT1 is the regulator of HIF-1alpha in activated fibroblasts. In analysis of 573 TNBC patient samples, alpha-casein expression, inversely correlated to HIF-1alpha, STAT3 and STAT1. STAT1 and STAT3 inhibitors target HIF-1alpha signalling in activated fibroblasts and MDA-MB-231 breast cancer cells respectively, and also abrogate CSC activities. Our findings provide an explanation for the protective effects of lactation in TNBC. Clinical data correlates high alpha-casein expression with increased recurrence-free survival in TNBC patients. Mechanistically, alpha-casein reduces breast cancer stem cell activity in vitro, and STAT3 and STAT1 were identified as regulators of pro-tumorigenic HIF-1alpha signalling in breast cancer cells and fibroblasts respectively.

Pediatric ileocolic intussusception: new observations and unexpected implications.

BACKGROUND: Ileocolic intussusception occurs when the terminal ileum "telescopes" into the colon. We observed that ileocolic intussusception lengths are similar regardless of location in the colon. OBJECTIVE: To examine the uniformity of ileocolic intussusception length and its relationship to colon location, symptom duration and reducibility. MATERIALS AND METHODS: We retrospectively reviewed ultrasound-diagnosed pediatric ileocolic intussusceptions initially treated with pneumatic reduction at the Mayo Clinic or Texas Children's Hospital. We recorded demographic, imaging and surgical findings including age, gender, symptom duration, location of the ileocolic intussusception, reducibility with air enema and, if fluoroscopically irreducible, surgical findings. RESULTS: We identified 119 ileocolic intussusceptions (64% boys), with 81% in the right colon. There was no significant relationship between ileocolic intussusception length and colon location (P=0.15), nor ileocolic intussusception length and symptom duration (P=0.36). Ileocolic intussusceptions were more distal with increasing symptom duration (P=0.016). Successful reductions were unrelated to symptom duration (P=0.84) but were more likely with proximal versus distal locations (P=0.02). CONCLUSION: Ileocolic intussusception lengths are relatively uniform regardless of location along the course of the colon where they present. Our findings suggest that most of the apparent distal propagation of ileocolic intussusceptions is not caused by increasing telescoping of small bowel across the ileocecal valve but rather by foreshortening of the right colon. This implies poor cecal fixation and confirms fluoroscopic and surgical observations of cecal displacement from the right lower quadrant with ileocolic intussusceptions. The movement of the leading edge of the ileocolic intussusception during reduction is first due to "relocating" the cecum into the right lower quadrant after which the reduction of small bowel back across the ileocecal valve then occurs.

Correction to: Pediatric ileocolic intussusception: new observations and unexpected implications.

In this article, the fourth author's name is misspelled. The correct spelling, as shown above, should be "Nadia F. Mahmood."

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

The published version of this article incorrectly lists the authors' affiliations. The correct affiliations are given below. The Publisher regrets this mistake.

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.