Update on Pediatric Nuclear Medicine in Acute Care.

Various radiopharmaceuticals are available for imaging pediatric patients in the acute care setting. This article focuses on the common applications used on a pediatric patient in acute care. To confirm the clinical diagnosis of brain death, brain scintigraphy is considered accurate and has been favorably compared with other methods of detecting the presence or absence of cerebral blood flow. Ventilation-perfusion lung scans are easy and safe to perform with less radiation exposure than computed tomography pulmonary angiography and remain an appropriate procedure to perform on children with suspected pulmonary embolism as a first imaging test in a hemodynamically stable patient with no history of lung disease and normal chest radiograph. 99mTc-pertechnetate scintigraphy (Meckel's scan) is the best noninvasive procedure to establish the diagnosis of ectopic gastric mucosa in Meckel's diverticulum. 99mTcred blood cell scintigraphy generally is useful for assessing lower GI bleeding in patients from any cause. Hepatobiliary scintigraphy is the most accurate diagnostic imaging modality for acute cholecystitis. 99mTc-dimercaptosuccinic acid scintigraphy is the simplest, and the most reliable and sensitive method for the early diagnosis of focal or diffuse functional cortical damage. 99mTcmercaptoacetyltriglycine scintigraphy is used to evaluate for early and late complications of renal transplantation. Bone scintigraphy is a sensitive and noninvasive technique for diagnosis of bone disorders such as osteomyelitis and fracture. 18F-fluorodeoxyglucose-positron emission tomography could be valuable in the evaluation of fever of unknown origin in pediatric patients, with better sensitivity and significantly less radiation exposure than a gallium scan. Moving forward, further refinement of pediatric radiopharmaceutical administered activities, including dose reduction, greater radiopharmaceutical applications, and updated consensus guidelines is warranted, with the use of radionuclide imaging likely to increase.

Relationship between risk factors for impaired bone health and HR-pQCT in young adults with type 1 diabetes.

Objective: In type 1 diabetes, risk factors associated with impaired bone health contribute to increased risk of fracture. The aim of this study was to (1): compare the high-resolution peripheral quantitative computed tomography (HR-pQCT) parameters of young adults with type 1 diabetes with those of healthy controls (2), identify sex differences, and (3) evaluate the association between diabetes and bone health risk factors, with HR-pQCT. Methods: This is a cross-sectional study in young Canadian adults with childhood onset type 1 diabetes. Z-scores were generated for HR-pQCT parameters using a large healthy control database. Diet, physical activity, BMI, hemoglobin A1C (A1C) and bone health measures were evaluated, and associations were analyzed using multivariate regression analysis. Results: Eighty-eight participants (age 21 ± 2.2 years; 40 males, 48 females, diabetes duration 13.9 ± 3.4 years) with type 1 diabetes were studied. Low trabecular thickness and elevated cortical geometry parameters were found suggesting impaired bone quality. There were no sex differences. Significant associations were found: Vitamin D (25(OH)D) with trabecular parameters with possible synergy with A1C, parathyroid hormone with cortical parameters, BMI with cortical bone and failure load, and diabetes duration with trabecular area. Conclusions: Our data suggests impairment of bone health as assessed by HR-pQCT in young adults with type 1 diabetes. Modifiable risk factors were associated with trabecular and cortical parameters. These findings imply that correction of vitamin D deficiency, prevention and treatment of secondary hyperparathyroidism, and optimization of metabolic control may reduce incident fractures.

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.

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.

The role of renal contour change in the diagnosis of cortical scarring after urinary tract infection.

Urinary tract infections in children can lead to permanent renal scarring in approximately 15% of cases. Technetium-99m (99mTc)-dimercaptosuccinic acid (DMSA) scintigraphy is the gold standard for identifying renal scarring. Using data and scans from children enrolled at our center in a 2-year prospective clinical trial (RIVUR study), we included children with radiologically confirmed pyelonephritis who exhibited renal scarring on their 1 and/or 2-year follow-up scans and asked 3 blinded pediatric nuclear medicine physicians to reexamine the renal contours in these scans. Five girls met all eligibility criteria (each had two late 99mTc-DMSA scans 1 and 2 years after index UTI). Of the 20 kidneys imaged, 10 exhibited renal scarring and of these, 7 exhibited renal contour abnormalities. These findings suggest that the presence of abnormalities of the renal contour is not necessary for diagnosis of renal scarring.

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.

Pediatric Nephro-Urology: Overview and Updates in Diuretic Renal Scans and Renal Cortical Scintigraphy.

Nuclear medicine offers several diagnostic scans for the evaluation of congenital and acquired conditions of the kidneys and urinary track in children. Tc-99m-MAG 3 diuretic renal scans are most commonly used in the evaluation and follow up of urinary track dilatations. They provide functional information on the differential renal function and on drainage quality which is allows distinction between obstructed and non-obstructed kidneys and the need for surgical correction vs conservative management in kidneys with impaired drainage. Standardized imaging and processing protocols are essential for correct interpretation and for meaningful comparisons between follow up scans. Different approaches and conceptions led to some contradicting recommendations between SNMMI and EANM guidelines on diuretic renography in children which caused confusion and to the emergence of self-made institutional protocols. In Late 2018 the two societies published joint procedural guidelines on diuretic renography in infants and children which hopefully will end the confusion. Tc-99m DMSA scans provide important information about the function of the renal cortex allowing detection of acute pyelonephritis, renal scars dysplasia and ectopy as well as accurate determination of the differential renal function. They are commonly used in the evaluation of children with urinary tract infections and affect clinical management. A standardized imaging and processing protocol improves the diagnostic accuracy of these studies. SPECT or pinhole images should be a routine part of the imaging protocol. This is one of the recommendations in the new EANM and SNMMI procedural guidelines for renal cortical scintigraphy in children available online on the SNMMI website and is under publication. This article provides an overview on the clinical role of diuretic renography and cortical scintigraphy in children and describes the imaging protocols focusing on the new recommendations in the procedural guidelines.

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.

Theranostics in Neuroblastoma.

Theranostics combines diagnosis and targeted therapy, achieved by the use of the same or similar molecules labeled with different radiopharmaceuticals or identical with different dosages. One of the best examples is the use of metaiodobenzylguanidine (MIBG). In the management of neuroblastoma-the most common extracranial solid tumor in children. MIBG has utility not only for diagnosis, risk-stratification, and response monitoring but also for cancer therapy, particularly in the setting of relapsed/refractory disease. Improved techniques and new emerging radiopharmaceuticals likely will strengthen the role of nuclear medicine in the management of neuroblastoma.

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.

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.

Severe Primary Hyperparathyroidism Caused by Parathyroid Carcinoma in a 13-Year-Old Child; Novel Findings From HRpQCT.

Primary hyperparathyroidism is a condition that occurs infrequently in children. Parathyroid carcinoma, as the underlying cause of hyperparathyroidism in this age group, is extraordinarily rare, with only a few cases reported in the literature. We present a 13-year-old boy with musculoskeletal pain who was found to have brown tumors from primary hyperparathyroidism caused by parafibromin-immunodeficient parathyroid carcinoma. Our patient had no clinical, biochemical, or radiographic evidence of pituitary adenomas, pancreatic tumors, thyroid tumors, pheochromocytoma, jaw tumors, renal abnormalities, or testicular lesions. Germline testing for AP2S1, CASR, CDC73/HRPT2, CDKN1B, GNA11, MEN1, PTH1R, RET, and the GCM2 gene showed no pathological variants, and a microarray of CDC73/HRPT2 did not reveal deletion or duplication. He was managed with i.v. fluids, calcitonin, pamidronate, and denosumab prior to surgery to stabilize hypercalcemia. After removal of a single parathyroid tumor, he developed severe hungry bone syndrome and required 3 weeks of continuous i.v. calcium infusion, in addition to oral calcium and activated vitamin D. Histopathological examination identified an angioinvasive parathyroid carcinoma with global loss of parafibromin (protein encoded by CDC73/HRPT2).HRpQCT and DXA studies were obtained prior to surgery and 18-months postsurgery. HRpQCT showed a resolution of osteolytic lesions combined with structural improvement of cortical porosity and an increase in both cortical thickness and density compared with levels prior to treatment. These findings highlight the added value of HRpQCT in primary hyperparathyroidism. In addition to our case, we have provided a review of the published cases of parathyroid cancer in children. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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.

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.

Evaluation of the pulmonary radioaerosol mucociliary clearance scan as an adjunctive test for the diagnosis of primary ciliary dyskinesia in children.

INTRODUCTION: The accuracy of primary ciliary dyskinesia (PCD) diagnosis has improved but no single test is diagnostic and some cases remain unsolved. Data regarding the accuracy of pulmonary radioaerosol mucociliary clearance scan (PRMCC) for the diagnosis of PCD are limited to predominantly adults using a 24-hour test. This study was performed to determine the accuracy of a 60-minute PRMCC test for diagnosing PCD in children. METHODS: Children with suspected PCD and inconclusive clinical diagnostic testing in an expert center were selected for PRMCC testing. Nebulized 99m Tc sulfur colloid was inhaled and dynamic imaging acquired for 60 to 120 minutes. Two independent radiologists blinded to the clinical diagnosis and health records overread PRMCC studies. The PRMCC result was compared with the reference standard diagnosis of PCD made by two physicians using the cumulative health record, blinded to PRMCC results. RESULTS: From 2008 to 2018, 57 patients (6-17 years) participated, of which 16 met criteria for the reference diagnosis of PCD. The PRMCC test was conclusive in 54 patients (94.7%) and had a sensitivity of 100% (95% confidence interval [CI] = 78.2-100), specificity of 85.7% (95% CI = 69.7-95.2), positive predictive value of 75% (95% CI = 57.1-87.1), negative predictive value of 100% (95% CI = 90.2-100), and accuracy of 90% (95% CI = 78.2-96.7). CONCLUSION: The 60-minute PRMCC test is noninvasive and feasible in children with a high negative predictive value for PCD. It may be a helpful adjunctive test to rule out PCD when clinical suspicion remains after guideline recommended first-line clinical testing.

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.

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.

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.