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

Malignant primary bone tumors are uncommon in the pediatric population, accounting for 3%-5% of all pediatric malignancies. Osteosarcoma and Ewing sarcoma comprise 90% of malignant primary bone tumors in children and adolescents. This paper provides consensus-based recommendations for imaging in children with osteosarcoma and Ewing sarcoma at diagnosis, during therapy, and after therapy.

Imaging of Peritoneal Dialysis Complications in Children.

Worldwide, peritoneal dialysis (PD) is the preferred renal replacement therapy option for children with end-stage renal disease who are awaiting transplantation. PD involves the instillation of a specifically formulated solution into the peritoneal cavity via a PD catheter, with two-way exchange of solutes and waste products along a concentration gradient. This exchange occurs across the peritoneal membrane. The PD catheter has intraperitoneal, abdominal wall, and external components. Enormous efforts have been directed to augment the efficiency and longevity of the peritoneum as a dialysis system by preventing PD-related infectious and noninfectious complications, which may otherwise result in technique failure and a subsequent temporary or permanent switch to hemodialysis. Imaging has an instrumental role in prompt diagnosis of PD complications and in guiding the management of these complications. The main imaging techniques used in the setting of PD complications-namely, conventional radiography, US, CT, MRI, and peritoneal scintigraphy-as well as the benefits and limitations of these modalities are reviewed. The authors also describe the frequently encountered radiologic findings of each complication. Familiarity with these features enables the radiologist to play a crucial role in early diagnosis of PD complications and aids the pediatric nephrologist in tailoring or discontinuing PD and transitioning to hemodialysis if necessary. Online supplemental material is available for this article. ©RSNA, 2022.

Non-Hodgkin Lymphoma Imaging Spectrum in Children, Adolescents, and Young Adults.

In children, adolescents, and young adults (CAYA), non-Hodgkin lymphoma (NHL) is characterized by various age-related dissimilarities in tumor aggressiveness, prevailing pathologic subtypes, and imaging features, as well as potentially different treatment outcomes. Understanding the imaging spectrum of NHL in CAYA with particular attention to children and adolescents is critical for radiologists to support the clinical decision making by the treating physicians and other health care practitioners. The authors discuss the currently performed imaging modalities including radiography, US, CT, MRI, and PET in the diagnosis, staging, and assessment of the treatment response. Familiarity with diagnostic imaging challenges during image acquisition, processing, and interpretation is required when managing patients with NHL. The authors describe potentially problematic and life-threatening scenarios that require prompt management. Moreover, the authors address the unprecedented urge to understand the imaging patterns of possible treatment-related complications of the therapeutic agents used in NHL clinical trials and in practice. Online supplemental material is available for this article. ©RSNA, 2022.

Artificial intelligence and radiomics in pediatric molecular imaging.

In the past decade, a new approach for quantitative analysis of medical images and prognostic modelling has emerged. Defined as the extraction and analysis of a large number of quantitative parameters from medical images, radiomics is an evolving field in precision medicine with the ultimate goal of the discovery of new imaging biomarkers for disease. Radiomics has already shown promising results in extracting diagnostic, prognostic, and molecular information latent in medical images. After acquisition of the medical images as part of the standard of care, a region of interest is defined often via a manual or semi-automatic approach. An algorithm then extracts and computes quantitative radiomics parameters from the region of interest. Whereas radiomics captures quantitative values of shape and texture based on predefined mathematical terms, neural networks have recently been used to directly learn and identify predictive features from medical images. Thereby, neural networks largely forego the need for so called "hand-engineered" features, which appears to result in significantly improved performance and reliability. Opportunities for radiomics and neural networks in pediatric nuclear medicine/radiology/molecular imaging are broad and can be thought of in three categories: automating well-defined administrative or clinical tasks, augmenting broader administrative or clinical tasks, and unlocking new methods of generating value. Specific applications include intelligent order sets, automated protocoling, improved image acquisition, computer aided triage and detection of abnormalities, next generation voice dictation systems, biomarker development, and therapy planning.

Residual meta-iodobenzyl guanidine (MIBG) positivity following therapy for metastatic neuroblastoma: Patient characteristics, imaging, and outcome.

BACKGROUND: Meta-iodobenzylguanidine(MIBG) scans are used to detect neuroblastoma metastatic lesions at diagnosis and during posttreatment surveillance. MIBG positivity following induction chemotherapy correlates with poor outcome; however, there are reports of patients with progression-free survival despite MIBG positivity at the end of therapy. The factors distinguishing these survivors from patients who progress or relapse are unclear. FDG-positron-emission tomography (PET) scans can also detect metastatic lesions at diagnosis; however, their role in posttherapy surveillance is less well studied. METHODS: We performed a retrospective analysis of International Neuroblastoma Staging System (INSS) stage 4 patients to identify those with residual MIBG-avid metastatic lesions on end-of-therapy scans without prior progression. Data collected included age, disease sites, histopathology, biomarkers, treatment, imaging studies, and response. RESULTS: Eleven of 265 patients met inclusion criteria. At diagnosis three of 11 patients were classified as intermediate and eight of 11 high risk; nine of 11 had documented marrow involvement. Histologic classification was favorable for four of 10 and MYCN amplification was detected in zero of 11 cases. The median time with persistent MIBG positivity following treatment was 1.5 years. Seven patients had at least one PET scan with low or background activity. Biopsies of three of three MIBG-avid residual lesions showed differentiation. All patients remain alive with no disease progression at a median of 4.0 years since end of therapy. CONCLUSION: Persistently MIBG-avid metastatic lesions in subsets of patients following completion of therapy may not represent active disease that will progress. Further studies are needed to determine whether MYCN status or other biomarkers, and/or PET scans, may help identify patients with residual inactive MIBG lesions who require no further therapy.

Posttransplant Lymphoproliferative Disorder in Children: A 360-degree Perspective.

An earlier incorrect version of this article appeared online. This article was corrected on December 17, 2019.

Clinical evaluation of reconstruction and acquisition time for pediatric 18F-FDG brain PET using digital PET/CT.

BACKGROUND: 18F-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) plays an important role in the diagnosis, evaluation and treatment of childhood epilepsy. The selection of appropriate acquisition and reconstruction parameters, however, can be challenging with the introduction of advanced hardware and software functionalities. OBJECTIVE: To quantify the diagnostic performance of a block-sequential regularized expectation maximization (BSREM) tool and reduced effective counts in brain PET/CT for pediatric epilepsy patients on a digital silicon photomultiplier system. MATERIALS AND METHODS: We included 400 sets of brain PET/CT images from 25 pediatric patients (0.5-16 years old) in this retrospective study. Patient images were reconstructed with conventional iterative techniques or BSREM with varied penalization factor (ß), at varied acquisition time (45 s, 90 s, 180 s, 300 s) to simulate reduced count density. Two pediatric nuclear medicine physicians reviewed images in random order - blinded to patient, reconstruction method and imaging time - and scored technical quality (noise, spatial resolution, artifacts), clinical quality (image quality of the cortex, basal ganglia and thalamus) and overall diagnostic satisfaction on a 5-point scale. RESULTS: Reconstruction with BSREM improved quality and clinical scores across all count levels, with the greatest benefits in low-count conditions. Image quality scores were greatest at 300-s acquisition times with ß=500 (overall; noise; artifacts; image quality of the cortex, basal ganglia and thalamus) or ß=200 (spatial resolution). No statistically significant difference in the highest graded reconstruction was observed between imaging at 180 s and 300 s with an appropriately implemented penalization factor (ß=350-500), indicating that a reduction in dose or acquisition time is feasible without reduction in diagnostic satisfaction. CONCLUSION: Clinical evaluation of pediatric 18F-FDG brain PET image quality was shown to be diagnostic at reductions of count density by 40% using BSREM with a penalization factor of ß=350-500. This can be accomplished while maintaining confidence of achieving a diagnostic-quality image.

The impact of 18F-FDG PET on initial staging and therapy planning of pediatric soft-tissue sarcoma patients.

BACKGROUND: Soft-tissue sarcomas in children are a histologically heterogenous group of malignant tumors accounting for approximately 7% of childhood cancers. There is a paucity of data on the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for initial staging and whether PET influenced management of these patients. OBJECTIVE: The aim of this analysis is to assess the use of 18F-FDG PET exclusively, and as a supplement to cross-sectional imaging in comparison to typical imaging protocols (CT and magnetic resonance imaging [MRI]) for initial staging as well as therapy planning in pediatric soft-tissue sarcoma patients. MATERIALS AND METHODS: The list of 18F-FDG PET/CT performed for soft-tissue sarcoma between March 2007 and October 2017 was obtained from the Hospital Information System database. Twenty-six patients who had received 18F-FDG PET, MRI and/or CT at initial diagnosis were included in the study. 18F-FDG PET and concurrent diagnostic CT and MRI at initial staging were independently reviewed to note the number of primary and metastatic lesions detected by each modality. A chart review was conducted to collect information on final diagnosis, staging and treatment plan. RESULTS: During the study period, 26 patients (15 females) ages 1.3-17.9 years (median age: 6 years) had received 18F-FDG PET/CT at initial diagnosis of soft-tissue sarcoma. Diagnostic CT was available for comparison in all 26 patients and MRI was available in 18 patients. The mean interval between cross-sectional imaging and 18F-FDG PET was 5.9 days (range: 0-30 days). All 26 primary lesions were equally detected by 18F-FDG PET compared to CT and MRI. From 84 metastatic lesions, 16 were detected by PET as well as CT and MRI, 12 by 18F-FDG PET only (included mainly lymph node metastases) and 56 by CT and MRI only (included mainly lung metastases). 18F-FDG PET changed therapy planning in 5 patients out of 26 (19%) by showing additional lesions not detected by CT and MRI. CONCLUSION: 18F-FDG PET proved to be a valuable tool for precise initial staging of pediatric soft-tissue sarcoma patients, especially in detecting lymph node metastasis, and could be included in their initial work-up. Given the relative rarity and heterogeneity of this group of tumors, additional investigations are required to definitely establish a role for 18F-FDG PET in the initial staging and therapy planning of soft-tissue sarcoma in the pediatric population.

Unusual lymphoid malignancy and treatment response in two children with Down syndrome.

BACKGROUND: Lymphoid malignancies other than acute lymphoblastic leukemia (ALL) are rare in children with Down syndrome (DS). Information about the toxicity of chemotherapy and prognosis is largely derived from the experience of children with DS and ALL or children without DS. PROCEDURE: We describe the treatment and outcome of two unusual lymphoid malignancies in children with DS. One patient was diagnosed with Burkitt lymphoma (BL) and the second, after treatment for B precursor ALL, with T-cell EBV-positive proliferative disorder (LPD). RESULTS: BL was treated with standard doses of LMB group B therapy subsequently intensified to group C therapy, including high-dose methotrexate (HD-MTX, 3-8 g/m2 ). The patient did not experience excessive toxicity and remains in complete remission 13 months later. Despite presentation with disseminated disease the patient with T-cell EBV-positive LPD after treatment for B precursor ALL responded to dexamethasone and rituximab and remains in complete remission two years later. CONCLUSIONS: Upfront reduction of the high treatment intensity, which is associated with excellent survival outcomes in BL, may not be warranted in all children with DS. Response to therapy and prognosis of T-cell EBV-positive LPD in a patient with DS was not predicted by reported experience in the absence of DS.

Procedural pain reduction strategies in paediatric nuclear medicine.

BACKGROUND: In paediatric nuclear medicine, the majority of the scans require intravenous (IV) access to deliver the radiotracers. Children and parents often cite procedural pain as the most distressing part of their child's hospitalization. In our department, various pain management strategies including physical and psychological distraction methods and pharmacological intervention have been implemented to reduce procedural pain. OBJECTIVE: The purpose of this study was to evaluate and compare different pain reduction strategies used in our paediatric nuclear medicine department. MATERIALS AND METHODS: The charts of 196 children (114 female) were reviewed retrospectively (median age: 8 months; interquartile range [IQR]: 33.1). Children were categorized into five groups: (1) Maxilene (topical liposomal lidocaine; n=50), (2) Pain Ease (vapocoolant; n=69), (3) oral sucrose (n=48), (4) Maxilene and Pain Ease combined (n=10), and (5) no pharmacological/adjuvant intervention (n=19). Physical and psychological distraction were used in all patients. Therefore, Group 5 only received physical and psychological strategies. Physical methods included supportive positioning, deep breathing, temperature considerations, massage pressure or vibration and neonatal development strategies (e.g., non-nutritive sucking, facilitated tucking, swaddling, rocking). Psychological strategies included education, distraction with movies, books or storytelling, and relaxation techniques. The pain perceived by the children after the IV access was compared in these five groups. Two types of pain assessment were used in this study: self-reporting pain scale and behavioural observational pain rating scale. Pain was reported on a scale of 1 to 10. The average pain score was also compared between patients who had one or two attempts for IV access and those who had more than two attempts. RESULTS: The average pain score was 2.8 (mean±standard error [SE]=0.4) in Maxilene, 2.1 (SE=0.3) in Pain Ease, 2.7 (SE=0.3) in sucrose, 1.6 (SE=0.5) in combined Maxilene and Pain Ease and 3.4 (SE=0.6) in "no pharmacology/adjuvant" groups. There was no statistically significant difference between the four pharmacology groups of Maxilene, Pain Ease, sucrose and no pharmacology/adjuvant intervention group. However, the pain score was significantly reduced in patients who received both Maxilene and Pain Ease combined compared with the patients who didn't have any pharmacological/adjuvant intervention (P=0.041). The average pain was 2.2 (SE=0.1) with one attempt at IV access, 3.0 (SE=0.5) with two attempts and 5.1 (SE=0.9) with three attempts. CONCLUSION: A combination of two pharmacological/adjuvant interventions may be more effective in reducing procedural pain compared with a single intervention. A comprehensive pain management program should consider all available interventions - pharmacological, adjuvant, physical and psychological. Further randomized clinical trials are needed to evaluate if a combination of two or more methods of pharmacological and adjuvant interventions are more effective to reduce procedural pain compared with only one method.

Correction to: FDG uptake in cervical lymph nodes in children without head and neck cancer.

The original version of this article unfortunately contained a mistake. Author name Alaa Bakkari was incorrect. The correct spelling is given above.

Correlation of PET/CT and Image-Guided Biopsies of Pediatric Malignancies.

OBJECTIVE: The purpose of this study was to evaluate an early experience with correlation of PET/CT findings and image-guided biopsy results in pediatric patients. MATERIALS AND METHODS: In a single-center retrospective case series, the inclusion criterion was performance of image-guided biopsy within 6 weeks of PET/CT, either before or after the biopsy. RESULTS: Forty-five patients (23 boys, 22 girls; age range, 4-17 years; median, 10.5 years; weight range, 14.6-86.2 kg; median, 48 kg) underwent 47 PET/CT examinations and biopsies. Nineteen patients (20 biopsies) had known malignancy, and 26 patients had suspected malignancy. The results were malignant in 24 cases, benign in 16, and inadequate or normal in 7 cases. Thirty-nine of 47 PET/CT examinations had positive results, and eight had negative results. Final analysis of 37 of the 47 cases (confounders excluded) showed concordant results between biopsy and PET in 36 cases and discordant results in one case. CONCLUSION: PET/CT can be used for disease staging and follow-up. In the future PET/CT can play a valuable role in directing image-guided biopsies of children.

The clinical impact of 18F-FDG PET/CT in extracranial pediatric germ cell tumors.

BACKGROUND: Extracranial germ cell tumors are an uncommon pediatric malignancy with limited information on the clinical impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the literature. OBJECTIVE: The purpose of this study was to evaluate and compare the clinical impact on management of 18F-FDG PET/CT with diagnostic computed tomography (CT) in pediatric extracranial germ cell tumor. MATERIALS AND METHODS: The list of 18F-FDG PET/CT performed for extracranial germ cell tumor between May 2007 and November 2015 was obtained from the nuclear medicine database. 18F-FDG PET/CT and concurrent diagnostic CT were obtained and independently reviewed. Additionally, the patients' charts were reviewed for duration of follow-up and biopsy when available. The impact of 18F-FDG PET/CT compared with diagnostic CT on staging and patient management was demonstrated by chart review, imaging findings and follow-up studies. RESULTS: During the study period, 9 children (5 males and 4 females; age range: 1.6-17 years, mode age: 14 years) had 11 18F-FDG PET/CT studies for the evaluation of germ cell tumor. Diagnostic CTs were available for comparison in 8 patients (10 18F-FDG PET/CT studies). The average interval between diagnostic CT and PET/CT was 7.2 days (range: 0-37 days). In total, five lesions concerning for active malignancy were identified on diagnostic CT while seven were identified on PET/CT. Overall, 18F-FDG PET/CT resulted in a change in management in 3 of the 9 patients (33%). CONCLUSION: 18F-FDG PET/CT had a significant impact on the management of pediatric germ cell tumors in this retrospective study. Continued multicenter studies are required secondary to the rarity of this tumor to demonstrate the benefit of 18F-FDG PET/CT in particular clinical scenarios.

FDG uptake in cervical lymph nodes in children without head and neck cancer.

BACKGROUND: Reactive cervical lymphadenopathy is common in children and may demonstrate increased 18F-fluoro-deoxyglucose (18F-FDG) uptake on positron emission tomography/computed tomography (PET/CT). OBJECTIVE: We sought to evaluate the frequency and significance of 18F-FDG uptake by neck lymph nodes in children with no history of head and neck cancer. MATERIALS AND METHODS: The charts of 244 patients (114 female, mean age: 10.4 years) with a variety of tumors such as lymphoma and post-transplant lymphoproliferative diseases (PTLD), but no head and neck cancers, who had undergone 18F-FDG PET/CT were reviewed retrospectively. Using the maximum standardized uptake value (SUVmax), increased 18F-FDG uptake by neck lymph nodes was recorded and compared with the final diagnosis based on follow-up studies or biopsy results. RESULTS: Neck lymph node uptake was identified in 70/244 (28.6%) of the patients. In 38 patients, the lymph nodes were benign. In eight patients, the lymph nodes were malignant (seven PTLD and one lymphoma). In 24 patients, we were not able to confirm the final diagnosis. Seven out of the eight malignant lymph nodes were positive for PTLD. The mean SUVmax was significantly higher in malignant lesions (4.2) compared with benign lesions (2.1) (P = 0.00049). CONCLUSION: 18F-FDG uptake in neck lymph nodes is common in children and is frequently due to reactive lymph nodes, especially when the SUVmax is <3.2. The frequency of malignant cervical lymph nodes is higher in PTLD patients compared with other groups.

Variants and pitfalls on radioiodine scans in pediatric patients with differentiated thyroid carcinoma.

BACKGROUND: Potentially false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma can mimic functioning thyroid tissue and functioning thyroid carcinomatous tissue. Such false-positive findings comprise variants and pitfalls that can vary slightly in children as compared with adults. OBJECTIVE: To determine the patterns and frequency of these potential false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma. MATERIALS AND METHODS: We reviewed a total of 223 radioiodine scans from 53 pediatric patients (mean age 13.3 years, 37 girls) with differentiated thyroid carcinoma. Focal or regional activity that likely did not represent functioning thyroid tissue or functioning thyroid carcinomatous tissue were categorized as variants or pitfalls. The final diagnosis was confirmed by reviewing the concurrent and follow-up clinical data, correlative ultrasonography, CT scanning, serum thyroglobulin and antithyroglobulin antibody levels. We calculated the frequency of these variants and pitfalls from diagnostic and post-therapy radioiodine scans. RESULTS: The most common variant on the radioiodine scans was the thymic activity (24/223, 10.8%) followed by the cardiac activity (8/223, 3.6%). Salivary contamination and star artifact, caused by prominent thyroid remnant, were the most important observed pitfalls. CONCLUSION: Variants and pitfalls that mimic functioning thyroid tissue or functioning thyroid carcinomatous tissue on radioiodine scan in children with differentiated thyroid carcinoma are not infrequent, but they decrease in frequency on successive radioiodine scans. Potential false-positive findings can be minimized with proper knowledge of the common variants and pitfalls in children and correlation with clinical, laboratory and imaging data.

False-positive In-111 DTPA octreotide scintigraphy in bilateral tibial insufficiency fracture.

We present a case of bilateral tibial insufficiency fracture in which indium (In)-111 diethylenetriamine pentaacetic acid (DTPA) octreotide scan showed increased activity in the region of the fracture. The scan was performed in a 5-year-old girl with severe refractory hypertension and elevated plasma metanephrines for evaluation of possible neuroendocrine tumor. Octreotide scan is usually positive in neuroendocrine and some other tumors but also shows positive results in a number of other conditions. However insufficiency fracture has not been reported as a positive finding on octreotide scan in children. This may relate to the expression of somatostatin membrane receptor in activated white blood cells or expression of somatostatin receptors by bone cells.

The value of repeat scintigraphy in patients with a high clinical suspicion for Meckel diverticulum after a negative or equivocal first Meckel scan.

BACKGROUND: Technetium (99m)Tc-pertechnetate is the most common and accurate noninvasive method of preoperative investigation for Meckel diverticulum. Despite introducing various methods to increase the sensitivity of the study, there are many case reports of false-negative Meckel scans. A repeat scan is sometimes requested in patients with a high suspicion for Meckel diverticulum and negative or equivocal first Meckel scan. OBJECTIVES: The purpose of this retrospective study is to evaluate the value of repeat scintigraphy for these patients. MATERIALS AND METHODS: Seven hundred fifty-three Meckel scans were recorded retrospectively. In 33 cases (22 male and 11 female; mean age: 6.8 years), the Meckel scintigraphy was repeated either due to a high clinical suspicion of Meckel diverticulum and a negative study (n = 21) or due to equivocal findings in the first scan (n = 12). The study was interpreted as positive if an abnormal focal activity was identified in the abdomen and pelvis during the procedure. The results were correlated with pathology and clinical symptoms. RESULTS: Seven out of 12 (58%) equivocal studies were positive on the second study. Six of them were proven to be positive at operation (confirmed by pathology) while one of them was negative on laparoscopy. From 21 negative first scans with a high suspicion for Meckel diverticulum, three (14%) were positive on the second study. All three were proven to be Meckel diverticulum on pathology. CONCLUSION: Repeat Meckel scans in patients with equivocal findings on the first study or a negative result with a high clinical suspicion for a Meckel diverticulum are useful especially in cases in which the first study had been done without appropriate preparation.

Neuroendocrine tumor in liver with positive ACTH receptor: a case report.

A rare case of possible primary ectopic adrenocorticotropic hormone (ACTH)-producing tumor in the liver mimicking a liver hemangioma is reported. A 9-year-old boy, with Cushing syndrome, was referred for the assessment of ectopic ACTH-producing tumor. Ultrasound, CT scan, and MRI of the abdomen revealed a liver lesion suggestive of a hemangioma. (111)In-octreotide scintigraphy revealed focal activity in the liver, indicative of a somatostatin-positive lesion. (99m)Tc-labeled RBC scintigraphy was negative for hemangioma. After surgical resection of the tumor, the cortisol level converted to a normal range indicative of a rare possible primary ACTH-producing tumor in the liver, which was confirmed by histopathology.