Molecular Imaging with PET-CT and PET-MRI in Pediatric Musculoskeletal Diseases.

Molecular imaging has emerged as an integral part of oncologic imaging. Given the physiologic changes that precede anatomic changes, molecular imaging can enable early detection of disease and monitoring of response. [18F] Fluorodeoxyglucose (FDG) Positron emission tomography (PET) is the predominant molecular imaging modality used in oncologic assessment and can be performed using PET/CT or PET/MR. In pediatric patients, PET/MRI imaging is generally preferred due to low radiation exposure and PET/MRI is particularly advantageous for imaging musculoskeletal (MSK) diseases, as MRI provides superior characterization of tissue changes as compared to CT. In this article, we provide an overview of the typical role of PET CT/MRI in assessment of some common pediatric malignancies and benign MSK diseases with case examples. We also discuss the relative advantages of PET/MRI compared to PET/CT, and review published data with a primary focus on the use of PET/MR.

Comparison of the different imaging modalities used to image pediatric oncology patients: A COG diagnostic imaging committee/SPR oncology committee white paper.

Diagnostic imaging is essential in the diagnosis and management, including surveillance, of known or suspected cancer in children. The independent and combined roles of the various modalities, consisting of radiography, fluoroscopy, ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine (NM), are both prescribed through protocols but also function in caring for complications that may occur during or subsequent to treatment such as infection, bleeding, or organ compromise. Use of a specific imaging modality may be based on situational circumstances such as a brain CT or MR for a new onset seizure, chest CT for respiratory signs or symptoms, or US for gross hematuria. However, in many situations, there are competing choices that do not easily lend themselves to a formulaic approach as options; these situations depend on the contributions of a variety of factors based on a combination of the clinical scenario and the strengths and limitations of the imaging modalities. Therefore, an improved understanding of the potential influence of the imaging decision pathways in pediatric cancer care can come from comparison among the individual diagnostic imaging modalities. The purpose of the following material to is to provide such a comparison. To do this, pediatric imaging content experts for the individual modalities of radiography and fluoroscopy, US, CT, MRI, and NM will discuss the individual modality strengths and limitations.

Serial Lung Perfusion Scintigraphy After Unifocalization and Repair of Tetralogy of Fallot With Major Aortopulmonary Collaterals.

BACKGROUND: In patients with tetralogy of Fallot and major aortopulmonary collaterals (MAPCAs), pulmonary blood supply is highly variable. Our approach to this condition emphasizes complete unifocalization of the pulmonary circulation, incorporating all lung segments and addressing stenoses out to the segmental level. Post-repair, we recommend serial lung perfusion scintigraphy (LPS) to assess short-term changes in pulmonary blood flow distribution. METHODS: We reviewed post-discharge and follow-up LPS performed through three years post-repair and analyzed serial changes in perfusion, risk factors for change, and the relationship between LPS parameters and pulmonary artery reintervention. RESULTS: Of 543 patients who had postoperative LPS results in our system, 317 (58%) had only a predischarge LPS available for review, while 226 had 1 (20%) or more (22%) follow-up scans within three years. Overall, pulmonary flow distribution prior to discharge was balanced, and there was minimal change over time; however, there was considerable patient-to-patient variation in both metrics. On multivariable mixed modeling, time after repair (P = .025), initial anatomy consisting of a ductus arteriosus to one lung (P < .001), and age at repair (P = .014) were associated with changes on serial LPS. Patients who had follow-up LPS were more likely to undergo pulmonary artery reintervention, but within that cohort, LPS parameters were not associated with reintervention risk. CONCLUSION: Serial LPS during the first year after MAPCAs repair is a noninvasive method of screening for significant post-repair pulmonary artery stenosis that occurs in a small but important minority of patients. In patients who received follow-up LPS beyond the perioperative period, there was minimal change over time in the population overall, but large changes in some patients and considerable variability. There was no statistical association between LPS findings and pulmonary artery reintervention.

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.

ACR Appropriateness Criteria® Crohn Disease-Child.

Crohn disease is an inflammatory condition of the gastrointestinal tract with episodes of exacerbation and remission occurring in children, adolescents, and adults. Crohn disease diagnosis and treatment depend upon a combination of clinical, laboratory, endoscopic, histological, and imaging findings. Appropriate use of imaging provides critical information in the settings of diagnosis, assessment of acute symptoms, disease surveillance, and therapy monitoring. Four variants are discussed. The first variant discusses the initial imaging for suspected Crohn disease before established diagnosis. The second variant pertains to appropriateness of imaging modalities during suspected acute exacerbation. The third variant is a substantial discussion of recommendations related to disease surveillance and monitoring of Crohn disease. Finally, panel recommendations and discussion of perianal fistulizing disease imaging completes the document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

The Utility of PET/CT in Guiding Radiotherapy Reduction for Children With Hodgkin Lymphoma Treated With ABVD.

ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is standard upfront chemotherapy for adults diagnosed with Hodgkin lymphoma (HL), but positron emission tomography (PET)-based response data following ABVD is lacking for pediatrics. Among children who received ABVD for HL, we document interim and end of therapy PET-computed tomography (CT) response by Deauville criteria, and survival outcomes following a response-based reduction in involved field radiotherapy (IFRT). Children 18 years of age or below with HL treated with ABVD between 2006 and 2015 who had interim PET/CT scans after 2 cycles of chemotherapy were included. Interim and end of therapy PET/CT scans were retrospectively re-evaluated using Deauville criteria by 3 radiologists. Among 45 children, 32 (71%) met criteria for intermediate risk, 86% achieved rapid early response (RER) and only 4 (9%) received upfront IFRT. Patients achieving RER had superior 5-year event-free survival (EFS) 95%±4% versus 50%±18% (P≤0.001) and overall survival (OS) 100% versus 83%±15% (P=0.025). Patients with bulk who achieved RER and received no IFRT achieved 5-year EFS of 92%±6% and OS 100%. Low, intermediate, and high risk patients had 5-year EFS of 100%, 94%±4%, and 50%±18% (P=0.002) and 5-year OS of 100%, 100%, and 75%±15% (P=0.03). RER following 2 cycles of ABVD is predictive of survival outcomes in children and adolescents with HL and may identify a group who may omit IFRT.

Imaging for diagnosis, staging and response assessment of Hodgkin lymphoma and non-Hodgkin lymphoma.

Hodgkin lymphoma and non-Hodgkin lymphoma are common malignancies in children and are now highly treatable. Imaging plays a major role in diagnosis, staging and response using conventional CT and MRI and metabolic imaging with positron emission tomography (PET)/CT and PET/MRI. Cross-sectional imaging has replaced staging laparotomy and splenectomy by demonstrating abdominal nodal groups and organ involvement. [F-18]2-fluoro-2-deoxyglucose (FDG) PET provides information on bone marrow involvement, and MRI elucidates details of cortical bone and confirmation of bone marrow involvement. The staging system for Hodgkin lymphoma is the Ann Arbor system with Cotswald modifications and is based on imaging, whereas the non-Hodgkin staging system is the St. Jude Classification by Murphy or the more recent revised International Pediatric Non-Hodgkin Lymphoma Staging System (IPNHLSS). Because all pediatric lymphomas are metabolically FDG-avid and identify all nodal, solid organ, cortical bone and bone marrow disease, staging evaluations require FDG PET as PET/CT or PET/MRI in both Hodgkin and non-Hodgkin lymphoma. Both diseases have in common issues of airway compromise at presentation demonstrated by imaging. Differences exist in that Hodgkin lymphoma has several independent poor prognostic factors seen by imaging such as large mediastinal adenopathy, Stage IV disease, systemic symptoms, pleural effusion and pericardial effusion. Non-Hodgkin lymphoma includes more organ involvement such as renal, ovary, central nervous system and skin. Early or interim PET-negative scans are a reliable indicator of improved clinical outcome and optimize risk-adapted therapy and patient management; imaging may not, however, predict who will relapse. A recent multicenter trial has concluded that it is usually sufficient for pediatric lymphoma at staging and interim assessment to evaluate children with PET imaging from skull base to mid-thigh. Various systems of assessment of presence of disease or response are used, including the Deauville visual scale, where avidity is compared to liver; Lugano, which includes size change as part of response; or quantitative PET, which uses standardized uptake values to define more accurate response. Newer methods of immunotherapy can produce challenges in FDG PET evaluation because of inflammatory changes that may not represent disease.

Assessment of the Reconstructed Pulmonary Circulation With Lung Perfusion Scintigraphy After Unifocalization and Repair of Tetralogy of Fallot With Major Aortopulmonary Collaterals.

BACKGROUND: Pulmonary vascular supply in tetralogy of Fallot (TOF) with major aortopulmonary collaterals (MAPCAs) is highly variable. Our approach to surgical management of this condition emphasizes early repair including unifocalization and reconstruction of the pulmonary circulation, incorporating all lung segments and addressing stenoses both proximal to and within the lung, in addition to ventricular septal defect closure. At our institution, we have over 15 years of experience using lung perfusion scintigraphy (LPS) to assess the distribution of pulmonary blood flow after complete unifocalization and repair. METHODS: We reviewed clinical and quantitative LPS data in 310 patients who underwent complete unifocalization and repair of TOF/MAPCAs from 2003 to 2018 at our institution. Postrepair relative lung perfusion distributions were determined from LPS initially obtained at our institution within 60 days after repair and thereafter. RESULTS: Total lung perfusion to the right and left lungs was 58.0% ± 14.2% and 42.0% ± 14.2%, respectively. Perfusion was balanced in 75% of patients and unbalanced in 25%, including 11% in whom it was extremely unbalanced. On multivariable analysis, older age at repair, surgery other than a single-stage complete unifocalization, and native anatomy consisting of unilateral pulmonary blood supply through a ductus arteriosus were associated with unbalanced perfusion. CONCLUSION: We present our experience using LPS as an outcome measure after surgical repair of TOF/MAPCAs. Balanced lung perfusion was present in the majority of patients who had complete repair of TOF/MAPCAs performed at our center.

Nivolumab in the Treatment of Refractory Pediatric Hodgkin Lymphoma.

The programmed death-1 (PD-1) pathway of immune evasion is exploited by many malignancies to limit host T-cell-mediated immune responses. Nivolumab is a PD-1-blocking monoclonal antibody that disrupts this pathway and is FDA approved for the treatment of metastatic melanoma, renal cell carcinoma, and squamous non-small cell lung cancer. In this case report, we describe the first published pediatric experience of nivolumab in refractory classic Hodgkin lymphoma. In this patient with primary refractory disease and high disease burden, cytokine release syndrome requiring inotropic support developed following the first infusion of nivolumab. The patient subsequently demonstrated a dramatic clinical response with resolution of fevers, transfusion independence, improvement in functional status, and very good partial response on PET/CT following a single dose. Nivolumab was continued with corticosteroid and antihistamine premedication without further adverse events and clinical benefit was sustained at 11 months after therapy initiation, despite evidence of slow radiographic disease progression.

SPECT/CT in pediatric patient management.

Hybrid SPECT/CT imaging is becoming the standard of care in pediatric imaging. Indications are mainly for oncologic imaging including mIBG scintigraphy for neuroblastoma and I-123 post surgical imaging of children with thyroid carcinoma, bone scintigraphy for back pain, children referred from sports medicine and neurodevelopmentally delayed children presenting with pain symptoms. The studies provide improved diagnostic accuracy, and oncologic imaging that includes optimized CT as part of the SPECT/CT study may decrease the number of studies and sedation procedures an individual child may need. The studies, however, must be tailored on an individual basis as the addition of the CT study can increase exposure to the child and should only be performed after appropriate justification and with adherence to optimized low dose pediatric protocols.

Novel use of F-DOPA PET/CT imaging in a child with paraganglioma/pheochromocytoma syndrome.

We report the use of F-DOPA PET/CT imaging in the evaluation of a teenager with marked hypertension and right pararenal, left adrenal and left para-aortic mass lesions. The use of the modality for this clinical application has not been described previously within the pediatric imaging literature. The value of this technique relative to conventional imaging modalities is discussed and warrants consideration of its use, if available, for evaluating children with suspected paragangliomas/pheochromocytomas.

FDG positron emission tomography/computed tomography studies of Wilms' tumor.

PURPOSE: The purpose of this analysis was to evaluate the utility of FDG PET/CT scanning in patients with Wilms' tumors. METHODS: A total of 58 scans were performed in 27 patients (14 male, 13 female; ages: 1.9-23 years, median: 7 years) with proven Wilms' tumor. Twenty-six patients (56 scans) were studied at the time of suspected relapse, progressive disease, persistent disease, or for monitoring of therapy. RESULTS: In the 27 patients with Wilms' tumor, 34 scans showed areas of abnormal uptake consistent with metabolically active tumors. Of the patients, 8 (24 scans) had pulmonary metastases larger than 10 mm in diameter, 10 (12 scans) had hepatic metastases, 11 (11 scans) had regional nodal involvement, 3 (3 scans) had bone metastases, 1 (1 scan) had chest wall involvement, 2 (2 scans) had pancreatic metastasis, and 5 (5 scans) had abdominal and pelvic soft tissue involvement. Two of eight patients with lung metastases had variable uptakes. Lung lesions 10 mm or smaller were not consistently visualized on PET scans. One patient with a liver metastasis showed no uptake on PET scan after treatment (size decreased from 45 to 15 mm). CONCLUSION: Most Wilms' tumors concentrate FDG. However, small pulmonary metastases may be better visualized with CT. FDG PET/CT appears useful for defining the extent of involvement and assessing the response to treatment.

Pediatric bone scintigraphy update.

Bone scintigraphy is a sensitive tool to evaluate the musculoskeletal system in children. Hybrid imaging using computed tomography (CT) in combination with conventional bone scan and single photon emission computed tomography improves specificity and diagnostic accuracy. It also improves laboratory efficiency and may save the patient an additional visit to the hospital for a separate cross-sectional imaging study. We have found this technique to be particularly helpful in localizing a cause for pain in children who are nonverbal and to better delineate small bone and soft-tissue lesions that can occur with diagnoses of trauma, infection, and tumor. Special attention to technique of positioning the patient for potential CT examination is an adaptation that must be made by the technologist. Because of radiation concerns of the additional CT, obviously these examinations should be tailored to the individual child and be performed for limited sites directed to the abnormality observed on the associated single photon emission computed tomography examination or directed by the appropriate history.

Pediatric positron emission tomography-computed tomography protocol considerations.

Pediatric body oncology positron emission tomography-computed tomography studies require special considerations for optimal diagnostic performance while limiting radiation exposure to young patients. Differences from routine adult procedures include the patient preparation phase, radiopharmaceutical dose, computed tomography acquisition parameters, and approach to computed tomography contrast materials and imaging sequence. Attention to these differences define the best practice for positron emission tomography-computed tomography examinations of children with cancer contributing to optimal care of these patients.

Embryonal rhabdomyosarcoma as a second malignancy following multimodal therapy for advanced-stage neuroblastoma.

Second malignancy as a long-term complication in survivors of advanced-stage neuroblastoma is rare, but it is becoming recognized more frequently. We report an unusual case of a soft-tissue sarcoma developing within a retroperitoneal primary following previous extensive treatment for metastatic neuroblastoma using multimodality imaging including PET/CT.

Imaging guidelines for children with Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group Bone Tumor Committee.

The Children's Oncology Group (COG) is a multi-institutional cooperative group dedicated to childhood cancer research that has helped to increase the survival of children with cancer through clinical trials. These clinical trials include a standardized regimen of imaging examinations performed prior to, during, and following therapy. This article presents imaging guidelines developed by a multidisciplinary group from the COG Bone Tumor Committee. These guidelines provide both required and recommended studies. Recommended examinations may become required in the future. These guidelines should be considered a work in progress that will evolve with advances in imaging and childhood cancer research.

Bone scan update.

The radionuclide bone scan is one of the most commonly performed pediatric nuclear medicine procedures. Bone scintigraphy is used as the diagnostic procedure of choice for diagnosis of bone and soft-tissue infection and can aid in the diagnosis of occult trauma without radiographic findings. There is a complimentary role for bone scintigraphy in the assessment of a child with suspected nonaccidental injury. The use of bone scan in a child with unexplained bone pain or limp may provide a diagnosis that could be related to trauma, tumor, or inflammation. A negative bone scan can help relieve concern for significant pathology. Bone scans in children require careful attention to technique to obtain high-quality diagnostic images. Routine whole-body imaging, magnification, additional views, and the use of single-photon emission computed tomography also are a routine part of this examination in children. Correlation with conventional radiographs is mandatory, and the judicious use of hybrid imaging with the addition of computed tomography may further improve diagnostic acumen, confidence and accuracy. New radiopharmaceuticals such as fluorine-18 may also play a role in changing techniques for pediatric bone scintigraphy.