Comparison of whole-body DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis.

PURPOSE: To assess and compare the diagnostic accuracy of whole-body (WB) DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis (LCH). METHODS: Twenty-three children with LCH underwent 2-[18F]FDG PET and WB DW-MRI at baseline. Two nuclear medicine physicians and two radiologists independently assessed presence/absence of tumors in 8 anatomical areas. Sixteen children also performed 2-[18F]FDG PET and WB DW-MRI at follow-up. One radiologist and one nuclear medicine physician revised follow-up scans and collected changes in tumor apparent diffusion (ADC) and standardized uptake values (SUV) before and after therapy in all detectable lesions. 2-[18F]FDG PET results were considered the standard of reference for tumor detection and evaluation of treatment response according to Lugano criteria. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of WB DW-MRI at baseline were calculated, and the 95% confidence intervals were estimated by using the Clopper-Pearson (exact) method; changes in tumor SUVs and ADC were compared using a Mann-Whitney U test. Agreement between reviewers was assessed with a Cohen's weighted kappa coefficient. Analyses were conducted using SAS software version 9.4. RESULTS: Agreement between reviewers was perfect (kappa coefficient = 1) for all analyzed regions but spine and neck (kappa coefficient = 0.89 and 0.83, respectively) for 2-[18F]FDG PET images, and abdomen and pelvis (kappa coefficient = 0.65 and 0.88, respectively) for WB DW-MRI. Sensitivity and specificity were 95.5% and 100% for WB DW-MRI compared to 2-[18F]FDG PET. Pre to post-treatment changes in SUVratio and ADCmean were inversely correlated for all lesions (r: -0.27, p = 0·06) and significantly different between responders and non-responders to chemotherapy (p = 0.0006 and p = 0·003 for SUVratio and ADCmean, respectively). CONCLUSION: Our study showed that WB DW-MRI has similar accuracy to 2-[18F]FDG PET for staging and treatment monitoring of LCH in children. While 2-[18F]FDG PET remains an approved radiological examination for assessing metabolically active disease, WB DW-MRI could be considered as an alternative approach without radiation exposure. The combination of both modalities might have advantages over either approach alone.

Role of MRI radiomics for the prediction of MYCN amplification in neuroblastomas.

OBJECTIVES: We evaluate MR radiomics and develop machine learning-based classifiers to predict MYCN amplification in neuroblastomas. METHODS: A total of 120 patients with neuroblastomas and baseline MR imaging examination available were identified of whom 74 (mean age ± standard deviation [SD] of 6 years and 2 months ± 4 years and 9 months; 43 females and 31 males, 14 MYCN amplified) underwent imaging at our institution. This was therefore used to develop radiomics models. The model was tested in a cohort of children with the same diagnosis but imaged elsewhere (n = 46, mean age ± SD: 5 years 11 months ± 3 years 9 months, 26 females and 14 MYCN amplified). Whole tumour volumes of interest were adopted to extract first-order histogram and second-order radiomics features. Interclass correlation coefficient and maximum relevance and minimum redundancy algorithm were applied for feature selection. Logistic regression, support vector machine, and random forest were employed as the classifiers. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic accuracy of the classifiers on the external test set. RESULTS: The logistic regression model and the random forest both showed an AUC of 0.75. The support vector machine classifier obtained an AUC of 0.78 on the test set with a sensitivity of 64% and a specificity of 72%. CONCLUSION: The study provides preliminary retrospective evidence demonstrating the feasibility of MRI radiomics in predicting MYCN amplification in neuroblastomas. Future studies are needed to explore the correlation between other imaging features and genetic markers and to develop multiclass predictive models. KEY POINTS: • MYCN amplification in neuroblastomas is an important determinant of disease prognosis. • Radiomics analysis of pre-treatment MR examinations can be used to predict MYCN amplification in neuroblastomas. • Radiomics machine learning models showed good generalisability to external test set, demonstrating reproducibility of the computational models.

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

Pediatric pulmonary malignancy can be primary or metastatic, with the latter being by far the more common. With a few exceptions, there are no well-established evidence-based guidelines for imaging pediatric pulmonary malignancies, although computed tomography (CT) is used in almost all cases. The aim of this article is to provide general imaging guidelines for pediatric pulmonary malignancies, including minimum standards for cross-sectional imaging techniques and specific imaging recommendations for select entities.

Imaging of pediatric extragonadal pelvic soft tissue tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

The most common pediatric extragonadal pelvic cancers include germ cell tumors, sacrococcygeal teratomas, and rhabdomyosarcomas (arising from the urinary bladder, prostate, paratesticular tissues, vagina, uterus, and perineum). This paper describes the radiological and nuclear medicine features of these entities and provides consensus-based recommendations for the assessment at diagnosis, during, and after treatment.

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

Primary pancreatic tumors in children are rare with an overall age-adjusted incidence of 0.018 new cases per 100,000 pediatric patients. The most prevalent histologic type is the solid pseudopapillary neoplasm, followed by pancreatoblastoma. This paper describes relevant imaging modalities and presents consensus-based recommendations for imaging at diagnosis and follow-up.

Neuroblastic Tumor Recurrence Associated With Opsoclonus Myoclonus Ataxia Syndrome Relapse a Decade After Initial Resection and Treatments.

Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare disorder that causes significant neurodevelopmental sequelae in children. Approximately half of pediatric OMAS cases are paraneoplastic, typically associated with localized neuroblastic tumors. Since early persistence or relapse of OMAS symptoms is common even after tumor resection, OMAS relapses may not routinely prompt reevaluation for recurrent tumors. We report a 12-year-old girl with neuroblastic tumor recurrence associated with OMAS relapse a decade after initial treatment. Providers should be aware of tumor recurrence as a trigger for distant OMAS relapse, raising intriguing questions about the role of immune surveillance and control of neuroblastic tumors.

Whole-tumour apparent diffusion coefficient (ADC) histogram analysis to identify MYCN-amplification in neuroblastomas: preliminary results.

OBJECTIVES: To determine the role of apparent diffusion coefficient (ADC) histogram analysis in the identification of MYCN-amplification status in neuroblastomas. METHODS: We retrospectively evaluated imaging records from 62 patients with neuroblastomas (median age: 15 months (interquartile range (IQR): 7-24 months); 38 females) who underwent magnetic resonance imaging at our institution before the initiation of any therapy or biopsy. Fourteen patients had MYCN-amplified (MYCNA) neuroblastoma. Histogram parameters of ADC maps from the entire tumour was obtained from the baseline images and the normalised images. The Mann-Whitney U test was used to compare the absolute and normalised histogram parameters amongst neuroblastomas with and without MYCN-amplification. Receiver operating characteristic (ROC) curves and area under the curves (AUC) were generated for the statistically significant histogram parameters. Cut-offs obtained from the ROC curves were evaluated on an external validation set (n-15, MYCNA-6, F-7, age 24 months (10-60)). A logistic regression model was trained to predict MYCNA by combining statistically significant histogram parameters and was evaluated on the validation set. RESULTS: MYCN-amplified neuroblastomas had statistically significant higher maximum ADC and lower minimum ADC than non-amplified neuroblastomas. They also demonstrated higher entropy, variance, energy, and lower uniformity than non-amplified neoplasms (p > 0.05). Energy, entropy, and maximum ADC had AUC of 0.85, 0.79, and 0.82, respectively. CONCLUSIONS: Whole tumour ADC histogram analysis of neuroblastomas can differentiate between tumours with and without MYCN-amplification. These parameters can help identify areas for targeted biopsies or can be used to predict subtypes of these high-risk tumours before biopsy results are available. KEY POINTS: • MYCN-amplification significantly affects treatment decisions in neuroblastomas. • MYCN-amplified neuroblastomas had significantly different ADC histogram metrics as compared to tumours without amplification. • ADC histogram metrics can be used to predict MYCN-amplification status based on imaging.

Congenital hyperinsulinism: localization of a focal lesion with 18F-FDOPA positron emission tomography.

Hyperinsulinemic hypoglycemia of infancy, also known as congenital hyperinsulinism, is a group of disorders characterized by dysregulated insulin release. Neonates with severe, persistent hyperinsulinemic hypoglycemia who are unresponsive to medical therapy require pancreatectomy to prevent brain damage from hypoglycemia. To date, multiple genetic mutations and syndromes and several unique histopathological entities have been identified in children with hyperinsulinism. Histopathology is characterized as diffuse, focal or atypical. Surgical resection of a focal lesion results in a cure in up to 97% of these children. Imaging with 6-fluoro-(18F)-L-3,4-dihydroxyphenylalanine (18F-FDOPA) positron emission tomography (PET) is the test of choice for identifying and localizing a focal lesion and has proved to be an invaluable guide for surgical resection. Genetic evaluation is essential for determining who will benefit from PET imaging. This article provides an approach to determine who should be imaged, how to set up a protocol and how to interpret the imaging findings. The diagnosis and management of this disorder require a multidisciplinary approach to prevent brain damage from hypoglycemia.

Working from home during the COVID-19 pandemic: surveys of the Society for Pediatric Radiology and the Society of Chiefs of Radiology at Children's Hospitals.

BACKGROUND: Due to the COVID-19 pandemic, some pediatric radiologists have shifted to working from home; the long-term ramifications for pediatric radiologists and departments have not yet been defined. OBJECTIVE: To characterize experiences of working from home associated with the COVID-19 pandemic and guide expectations after the pandemic is controlled, via separate surveys of Society for Pediatric Radiology (SPR) and Society of Chiefs of Radiology at Children's Hospitals (SCORCH) members. MATERIALS AND METHODS: Two separate surveys were conducted. In the first, SPR members were surveyed Jan. 11 through Feb. 8, 2021. The response rate was 17.0% (255 of 1,501). Survey questions included demographics, information on the ability to work from home and subjective experiences ranked on a scale of 0 to 10. The survey enabled segregation and comparison of responses between those with and without home PACS. In the second survey, SCORCH members were surveyed Dec. 8, 2020, through Jan. 8, 2021. The response rate was 51.5% (51/99). Survey questions included the logistics of working from home, technical specifications and the expectations on clinical duties performed from home. The Wilcoxon rank test was used to determine statistical significance of compared variables between respondents with and without home PACS in SPR members, and expectations between SPR and SCORCH members. Descriptive statistics summarized demographic questions and free text responses. RESULTS: The majority of member respondents (81.2%, 207/255) had a home PACS and most departments provided home PACS to faculty (94.1%, 48/51). Overall, radiologists who could work from home were satisfied with their ability to work from home (mean rating: 8.3/10) and were significantly more satisfied than predicted by those without home PACS (5.9/10, P<0.0001). Respondents overwhelmingly indicated they were less able to teach trainees (mean rating: 2.7/10) and had decreased emotional engagement (mean rating: 4.4/10), but had improved research productivity and cognitive ability for research when working from home (mean rating for both: 5.3/10). Regarding the expectations of the ability to work from home after no longer needing to address the pandemic, department chairs generally favored fewer rotations from home, with 97.9% (47/48) indicating working from home should be 60% or fewer assignments, compared with 84.1% (164/195) of individual radiologists (P=0.071). CONCLUSIONS: Due to the COVID-19 pandemic, there has been a shift to working from home using PACS. Results of these SPR and SCORCH member surveys can help inform future decisions regarding pediatric radiologists working from home once the pandemic has been controlled.

Pediatric Lung MRI: Currently Available and Emerging Techniques.

OBJECTIVE. The purpose of this article is to review currently available and emerging techniques for pediatric lung MRI for general radiologists. CONCLUSION. MRI is a radiation-free alternative to CT, and clearly understanding the strengths and limitations of established and emerging techniques of pediatric lung MRI can allow practitioners to select and combine the optimal techniques, apply them in clinical practice, and potentially improve early diagnostic accuracy and patient management.

Imaging sedation and anesthesia practice patterns in pediatric radiology departments - a survey of the Society of Chiefs of Radiology at Children's Hospitals (SCORCH).

BACKGROUND: There are few data describing practice patterns related to the use of sedation/anesthesia for diagnostic imaging in pediatric radiology departments. OBJECTIVE: To understand current practice patterns related to imaging with sedation/anesthesia in pediatric radiology departments based on a survey of the Society of Chiefs of Radiology at Children's Hospitals (SCORCH) in conjunction with the American College of Radiology's Pediatric Imaging Sedation and Anesthesia Committee. MATERIALS AND METHODS: A multi-question survey related to imaging with sedation/anesthesia in pediatric radiology departments was distributed to SCORCH member institutions in January 2019. A single reminder email was sent. Descriptive statistical analyses were performed. RESULTS: Of the 84 pediatric radiology departments, 23 (27%) completed the survey. Fifty-seven percent of the respondents self-identified as academic/university-affiliated and 13% as a division/section in an adult radiology department. Imaging sedation (excluding general anesthesia) is commonly performed by pediatric anesthesiologists (76%) and intensive care unit physicians (intensivists, 48%); only 14% of departments expect their pediatric radiologists to supervise imaging sedation. Ninety-six percent of departments use child life specialists for patient preparation. Seventy percent of departments have preparatory resources available on a website, including simulation videos (26%) and audio clips (17%). Nearly half (48%) of the departments have a mock scanner to aid in patient preparation. Imaging sedation/anesthesia is most often scheduled at the request of ordering clinicians (65%), while 57% of departments allow schedulers to place patients into imaging sedation/anesthesia slots based on specified criteria. CONCLUSION: Imaging sedation/anesthesia practice patterns vary among pediatric radiology departments, and understanding current approaches can help with standardization and practice improvement.

Biliary Excretion Noted on Hepatobiliary Iminodiacetic Acid Scan Does Not Exclude Diagnosis of Biliary Atresia.

A hepatobiliary iminodiacetic acid (HIDA) scan is frequently used in an attempt to exclude biliary atresia in infants who are cholestatic. We present 6 cases of confirmed biliary atresia in infants who had biliary patency reported on HIDA scan. We demonstrate that misinterpreted HIDA scans led to delayed diagnosis and surgical intervention for biliary atresia.

Whole-Body PET/MRI Applications in Pediatric Oncology.

OBJECTIVE. Fluorine-18-labeled FDG PET/CT and MRI are current imaging standards for staging and assessing tumor response and recurrence of pediatric extracranial solid tumors. PET/MRI combines anatomic and physiologic imaging in a single session with reduced radiation compared with CT. Pediatric protocols are primarily whole-body protocols because of the behavior and type of cancers unique to children. This article will focus on the practice and utility of whole-body PET/MRI for pediatric oncologic imaging. CONCLUSION. The strengths of PET/MRI over PET/CT are compelling and include decreased radiation exposure, decreased number of sedation and general anesthesia events, single-day one-stop visits, and simultaneous imaging with two stand-alone advanced imaging techniques essential to staging and assessing treatment response in pediatric oncology.

Current trends in pediatric nuclear medicine: a Society for Pediatric Radiology membership survey.

BACKGROUND: Pediatric nuclear medicine is evolving, and its practice patterns are uncertain. Knowledge of the current trends in pediatric nuclear medicine might be helpful to direct local decisions, including expectations for patient care, needs for capital acquisitions, and staffing recruitment strategies. OBJECTIVE: To provide data regarding the current practice of pediatric nuclear medicine via a Society for Pediatric Radiology (SPR) membership survey. MATERIALS AND METHODS: The SPR emailed our 25-question survey to all 1,847 SPR members in August 2018 and we accepted responses until April 2019. Questions focused on nuclear medicine staffing, positron emission tomography (PET) utilization, and radiotherapy availability. Respondents could indicate their affiliated hospital, which we used for data cataloguing only. Analysis of survey responses was blinded to reported institution. We analyzed response data using contingency tables. Independence testing between categorical variables based on proportions of physicians with additional nuclear medicine board certification was performed on a subset of questions regarding PET and therapy practices. RESULTS: Sixty-seven people from at least 29 hospitals responded to the survey, including all 10 of the 2018-2019 U.S. News & World Report best children's hospitals. The majority (48/67, 71.6%) of respondents indicated that pediatric nuclear medicine examinations were interpreted in the pediatric radiology department by pediatric radiologists and that most physicians interpreting the exams (43/67, 64.2%) did not have subspecialty certification in nuclear medicine or nuclear radiology. Most facilities offered PET/CT (57/67, 85.1%); few offered PET/MRI (12/67, 17.9%). Most facilities offered radiotherapies (57/67, 85.1%) but at most of these facilities (30/57, 52.6%), fewer than half the physicians who cover nuclear medicine were approved to administer therapies. In the subset analyses based on proportion of physicians with additional nuclear medicine board certification, there were statistically significant differences between the groups in availability of PET/MRI, lutetium-177 dotatate therapy programs, and percentages of physicians approved to administer therapies. CONCLUSION: Pediatric nuclear medicine is largely practiced by pediatric radiologists without subspecialty certification. Staffing, PET practices and therapies vary among practices, in part associated with the number of radiologists with nuclear medicine board certification.

Pediatric applications of Dotatate: early diagnostic and therapeutic experience.

In recent years, new somatostatin receptor agents (SSTRs) have become available for diagnostic imaging and therapy in neuroendocrine tumors. The novel SSTR ligand DOTA-DPhel-Tyr3-octreotate (Dotatate) in particular can be linked with 68Gallium for diagnostic imaging purposes, and with the ß-emitter 177Lutetium for radiotherapy in the setting of neuroendocrine tumors. Dotatate imaging offers distinct advantages in the evaluation of neuroendocrine tumors compared to standard techniques, including greater target-to-background ratio and lesion conspicuity, high sensitivity/specificity, improved spatial resolution with positron emission tomography (PET)/CT or PET/MR, and decreased radiation exposure. Although currently off-label in pediatrics, Dotatate theranostics in children are being explored, most notably in the setting of neuroblastoma and hereditary neuroendocrine syndromes. This article provides a multicenter case series of Dotatate imaging and therapy in pediatric patients in order to highlight the spectrum of potential clinical applications.

Clinical pediatric positron emission tomography/magnetic resonance program: a guide to successful implementation.

Children with malignancies undergo recurrent imaging as part of tumor diagnosis, staging and therapy response assessment. Simultaneous positron emission tomography (PET) and magnetic resonance (MR) allows for decreased radiation exposure and acts as a one-stop shop for disease in which MR imaging is required. Nevertheless, PET/MR is still less readily available than PET/CT across institutions. This article serves as a guide to successful implementation of a clinical pediatric PET/MR program based on our extensive clinical experience. Challenges include making scanners more affordable and increasing patient throughput by decreasing total scan time. With improvements in workflow and robust acquisition protocols, PET/MR imaging is expected to play an increasingly important role in pediatric oncology.

Rachitic change and vitamin D status in young children with fractures.

OBJECTIVE: To examine the association between rachitic changes and vitamin D levels in children less than 2 years old with fractures. METHODS: Children less than 2 years old who were admitted to a large children's hospital for a fracture and underwent a skeletal survey were included. Two pediatric radiologists blinded to the children's vitamin D levels independently reviewed the skeletal surveys for the following rachitic findings: demineralization, widened sutures, rachitic rosary, Looser zones, and metaphyseal changes. Kappa coefficients were calculated to assess inter-rater agreement. Logistic regression was used to test the association between vitamin D level and rachitic findings. RESULTS: There were 79 subjects (40 female and 39 male) with a median age of 4 months. Vitamin D levels ranged from 11.6 to 88.9 ng/ml and were low in 27. Questionable demineralization was noted in seven subjects; mild to moderate demineralization was observed in four subjects. Widened sutures were noted in seven subjects, many also with concurrent intracranial hemorrhage. Lower vitamin D levels were associated with increased odds of demineralization after adjusting for age, gender, and prematurity (P < 0.015). An association was not found between the vitamin D level and suture widening (P = 0.07). None of the cases demonstrated Looser zones, rachitic rosary, or metaphyseal changes of rickets. CONCLUSIONS: Infants and toddlers with fractures frequently have suboptimal vitamin D levels, but radiographic evidence of rickets is uncommon in these children.

Androgenetic chimerism as an etiology for Beckwith-Wiedemann syndrome: diagnosis and management.

PURPOSE: Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder characterized by lateralized overgrowth, macroglossia, abdominal wall defects, congenital hyperinsulinism, and predisposition to embryonal tumors. One of the molecular etiologies underlying BWS is paternal uniparental isodisomy of chromosome 11p15.5 (pUPD11). About 8% of pUPD11 cases are due to genome-wide paternal uniparental isodisomy (GWpUPD). About 30 cases of live-born patients with GWpUPD have been described, most of whom were mosaic and female. We present male patients with BWS due to GWpUPD, elucidate the underlying mechanism, and make recommendations for management. METHODS: Three male patients with GWpUPD underwent clinical and molecular evaluation by single-nucleotide polymorphism (SNP) microarrays in different tissues. Previously published cases of GWpUPD were reviewed. RESULTS: SNP microarray demonstrated a GWpUPD cell population with sex chromosomes XX and biparental cell population with sex chromosomes XY, consistent with dispermic androgenetic chimerism. CONCLUSION: SNP microarray is necessary to distinguish GWpUPD cases and the underlying mechanisms. The percentage of GWpUPD cell population within a specific tissue type correlated with the amount of tissue dysplasia. Males with BWS due to GWpUPD are important to distinguish from other molecular etiologies because the mechanism indicates risk for germ cell tumors and autosomal recessive diseases in addition to other BWS features.

Imaging surveillance for children with predisposition to renal tumors.

Effective surveillance is necessary for early detection of tumors in children with cancer predisposition syndromes. Instituting a surveillance regimen in children comes with practical challenges that include determining imaging modality and timing, and considering cost efficiency, accessibility, and the significant consequences of false-positive and false-negative results. To address these challenges, the American Association for Cancer Research has recently published consensus recommendations that focus on surveillance of cancer predisposition syndromes in children. This review condenses the imaging surveillance recommendations for syndromes that carry a predisposition to renal tumors in childhood, and includes summaries of the predisposition syndromes and discussion of considerations of available imaging modalities.

Whole-body magnetic resonance imaging of pediatric cancer predisposition syndromes: special considerations, challenges and perspective.

Cancer predisposition syndromes increase the incidence of tumors during childhood and are associated with significant morbidity and mortality. Imaging is paramount for ensuring early detection of neoplasms, impacting therapeutic interventions and potentially improving outcome. While conventional imaging techniques involve considerable exposure to ionizing radiation, whole-body MRI is a radiation-free modality that allows continuous imaging of the entire body and has increasingly gained relevance in the surveillance, diagnosis, staging and monitoring of pediatric patients with cancer predisposition syndromes. Nevertheless, widespread implementation of whole-body MRI faces several challenges as a screening tool. Some of these challenges include developing clinical indications, variability in protocol specifications, image interpretation as well as coding and billing practices. These factors impact disease management, patient and family experience and research collaborations. In this discussion we review the aforementioned special considerations and the potential direction that might help overcome these challenges and promote more widespread use of whole-body MRI in children with cancer predisposition syndromes.