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

Neuroblastoma is the most common extracranial solid neoplasm in children. This manuscript provides consensus-based imaging recommendations for pediatric neuroblastoma patients at diagnosis and during follow-up.

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

Pediatric thyroid cancer is rare in children; however, incidence is increasing. Papillary thyroid cancer and follicular thyroid cancer are the most common subtypes, comprising about 90% and 10% of cases, respectively. This paper provides consensus imaging recommendations for evaluation of pediatric patients with thyroid cancer at diagnosis and during follow-up.

Magnetic resonance imaging glossary of findings of pediatric pancreatitis and the revised Atlanta classification.

While still uncommon, the incidence of acute pancreatitis in children has been increasing over the last two decades. The Atlanta classification for acute pancreatitis, developed for adults, stratifies cases of acute pancreatitis based on imaging and clinical criteria. This classification scheme allows for standardized use of terminology to facilitate treatment and prognostication. Although US and CT should be used in critical or unstable patients, MRI is an ideal imaging modality in pediatric patients with acute pancreatitis because of its ability to characterize tissue without ionizing radiation. We review MRI examples specific to Atlanta classification terminology in pediatric patients. Chronic pancreatitis has also been increasingly diagnosed in children, and imaging plays a key role in the diagnosis and management of this insidious disease. MRI with magnetic resonance cholangiopancreatography is the optimal modality for assessing the pancreas in a child with known or suspected chronic pancreatitis because it provides tissue characterization and high-contrast imaging of the pancreatic duct without the use of invasive instrumentation or ionizing radiation. We also review and demonstrate accepted MRI findings of chronic pancreatitis.

Liver Doppler Findings in Pediatric Patients After Total Pancreatectomy and Islet Autotransplantation.

OBJECTIVES: This study was intended to establish normal values for velocities in the hepatic artery and portal veins in pediatric patients after total pancreatectomy and islet autotransplantation (TPIAT). METHODS: A retrospective review was performed of liver Doppler studies in pediatric patients after TPIAT over 6 years at an academic children's hospital. Doppler velocities in the liver vasculature and the hepatic artery resistive index were recorded. RESULTS: Sixty-five pediatric patients were evaluated. There were no cases of portal vein thrombosis or other hepatic vascular complications. The mean hepatic artery peak systolic velocity was 157.6 cm/s (SE, 60.9 cm/s), with a mean resistive index of 0.57 (SE, 0.09). The mean main portal vein velocity was 31.9 cm/s (SE, 12.9 cm/s). CONCLUSIONS: Portal vein thrombosis is rare in pediatric patients after TPIAT. A wide range of hepatic artery and portal vein velocities are encountered in children immediately after TPIAT without hepatic vascular complications and can be considered normal.

Fetal MRI: incidental findings in the mother.

BACKGROUND: Fetal magnetic resonance imaging (MRI) is a routinely used tool in prenatal diagnosis; however, there is a lack of studies evaluating incidental findings observed in the mother. OBJECTIVE: This study describes and quantifies incidental findings observed in the mother during fetal MRI. MATERIALS AND METHODS: We reviewed all fetal MRI studies at the University of Minnesota Medical Center from February 2008 to September 2014. Two pediatric radiologists retrospectively conducted a consensus evaluation. The maternal findings were categorized into neurologic, gynecologic, urinary, gastrointestinal and musculoskeletal. Hydronephrosis consistent with the stage of pregnancy was recorded but was not included as an abnormal finding. Abnormal findings were classified into three groups, depending on their clinical significance: level I (low), level II (medium) and level III (high). RESULTS: We evaluated 332 pregnant patients with a mean age of 29.3 years and a mean gestational age of 29 weeks. Of these, 55.4% had at least 1 incidental finding, for a total of 262 incidental maternal findings. Of the 262 abnormalities, 113 (43.1%) were neurologic, 69 were gynecologic (26.3%), 36 (13.7%) urinary, 24 (9.2%) gastrointestinal and 20 (7.6%) musculoskeletal. Of the 262 incidental findings, 237 (90.5%) were level I, 24 (9.2%) were level II and 1 (0.4%) was level III. CONCLUSION: Our results suggest that although the vast majority of incidental maternal findings are benign, more significant findings are still encountered and should be expected.

The transverse diameter of the chest on routine radiographs reliably estimates gestational age and weight in premature infants.

BACKGROUND: Prior to digital radiography it was possible for a radiologist to easily estimate the size of a patient on an analog film. Because variable magnification may be applied at the time of processing an image, it is now more difficult to visually estimate an infant's size on the monitor. Since gestational age and weight significantly impact the differential diagnosis of neonatal diseases and determine the expected size of kidneys or appearance of the brain by MRI or US, this information is useful to a pediatric radiologist. Although this information may be present in the electronic medical record, it is frequently not readily available to the pediatric radiologist at the time of image interpretation. OBJECTIVE: To determine if there was a correlation between gestational age and weight of a premature infant with their transverse chest diameter (rib to rib) on admission chest radiographs. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, which waived informed consent. The maximum transverse chest diameter outer rib to outer rib was measured on admission portable chest radiographs of 464 patients admitted to the neonatal intensive care unit (NICU) during the 2010 calendar year. Regression analysis was used to investigate the association between chest diameter and gestational age/birth weight. Quadratic term of chest diameter was used in the regression model. RESULTS: Chest diameter was statistically significantly associated with both gestational age (P < 0.0001) and birth weight (P < 0.0001). CONCLUSION: An infant's gestational age and birth weight can be reliably estimated by comparing a simple measurement of the transverse chest diameter on digital chest radiograph with the tables and graphs in our study.

Beyond acute appendicitis: imaging of additional pathologies of the pediatric appendix.

Primary acute appendicitis is by far the most common pathological condition affecting the appendix. There are differential diagnoses, however, when an abnormal appendix is found by imaging. The purpose of this paper is to highlight the imaging and clinical manifestations of less common appendiceal abnormalities in children. Familiarity with these alternative diagnoses might be particularly helpful in guiding management of the child whose clinical presentation is not typical for primary acute appendicitis.

Anti-MDA5 juvenile idiopathic inflammatory myopathy with second-degree heart block but no skin or lung involvement: a case report.

BACKGROUND: Patients with idiopathic inflammatory myopathy and autoantibodies directed against melanoma differentiation-associated protein 5 (MDA5) characteristically have interstitial lung disease, severe cutaneous involvement, arthritis, and relatively mild myositis. Cardiac involvement in idiopathic inflammatory myopathy can occur and has been associated with anti-signal recognition particle and anti-polymyositis-scleroderma autoantibodies, but not with anti-MDA5 autoantibodies. CASE PRESENTATION: A 14-year-old male presented with weakness, second-degree heart block, arthritis, and hematologic cytopenias. Imaging and biopsies confirmed the diagnosis of juvenile idiopathic inflammatory myopathy, and he had high titer anti-MDA5 autoantibodies. There were no cutaneous or pulmonary abnormalities. While on prednisone and methotrexate, the patient's heart block improved from second- to first-degree and the cytopenias resolved. Persistent myositis prompted the addition of intravenous immunoglobulin. Seven months into the disease course, the arthritis and myositis are in remission and the patient is no longer taking corticosteroids. CONCLUSIONS: We report a novel case of a patient with juvenile idiopathic myositis who lacked the typical cutaneous and pulmonary findings associated with anti-MDA5 positivity, but who had cardiac conduction defects. This report broadens the clinical spectrum of anti-MDA5-associated inflammatory myopathy.

Adrenalectomy improves diabetes in A-ZIP/F-1 lipoatrophic mice by increasing both liver and muscle insulin sensitivity.

The virtually fatless A-ZIP/F-1 mouse is profoundly insulin resistant, diabetic, and a good model for humans with severe generalized lipoatrophy. Like a number of other mouse models of diabetes, the A-ZIP/F-1 mouse has elevated serum corticosterone levels. Leptin infusion lowers the corticosterone levels, suggesting that leptin deficiency contributes to the hypercorticosteronemic state. To test the hypothesis that the increased glucocorticoids contribute to the diabetes and insulin resistance, we examined the effect of adrenalectomy on A-ZIP/F-1 mice. Adrenalectomy significantly decreased the blood glucose, serum insulin, and glycated hemoglobin levels. Hyperinsulinemic-euglycemic clamps were performed to characterize the changes in whole-body and tissue insulin sensitivity. The adrenalectomized A-ZIP/F-1 mice displayed a marked improvement in insulin-induced suppression of endogenous glucose production, indicating increased hepatic insulin sensitivity. Adrenalectomy also increased muscle glucose uptake and glycogen synthesis. These results suggest that the chronically increased serum corticosterone levels contribute to the diabetes of the A-ZIP/F-1 mice and that removal of the glucocorticoid excess improves the insulin sensitivity in both muscle and liver.

Genetic background (C57BL/6J versus FVB/N) strongly influences the severity of diabetes and insulin resistance in ob/ob mice.

We studied the effects of genetic background on the phenotype of ob/ob mice, a model of severe obesity, insulin resistance, and diabetes caused by leptin deficiency. Despite a comparable degree of obesity and hyperinsulinemia, C57BL/6J ob/ob mice had much milder hyperglycemia and, surprisingly, normal circulating adiponectin levels despite still-prominent signs of insulin resistance. Hyperinsulinemic-euglycemic clamp revealed relatively less whole-body and muscle insulin resistance in C57BL/6J ob/ob mice, whereas liver insulin resistance tended to be more severe than in FVB/N ob/ob mice. C57BL/6J ob/ob mice had also more rapid clearance of circulating triglycerides and more severe hepatic steatosis. We suggest that strain-related distinction in lipid handling is the most important player in the differences in diabetic phenotype and insulin sensitivity, whereas the impact of circulating adiponectin levels on the overall phenotype of ob/ob mice is less important.

Increased insulin sensitivity in paternal Gnas knockout mice is associated with increased lipid clearance.

The G protein alpha-subunit Gsalpha is required for hormone-stimulated cAMP generation. The Gsalpha gene Gnas is a complex gene with multiple imprinted gene products. Mice with heterozygous disruption of the Gnas paternal allele (+/p-) are partially Gsalpha deficient and totally deficient in XLalphas, a neuroendocrine-specific Gsalpha isoform that is expressed only from the paternal Gnas allele. We previously showed that these mice are hypermetabolic and lean and have increased insulin sensitivity. We now performed hyperinsulinemic-euglycemic clamp studies, which confirmed the markedly increased whole body insulin sensitivity in +/p- mice. +/p- mice had 1.4-, 7- and 3.8-fold increases in insulin-stimulated glucose uptake in muscle and white and brown adipose tissue, respectively, and markedly suppressed endogenous glucose production from the liver. This was associated with increased phosphorylation of insulin receptor and a downstream effector (Akt kinase) in both liver and muscle in response to insulin. Triglycerides cleared more rapidly in +/p- mice after a bolus administered by gavage. This was associated with decreased liver and muscle triglyceride content and increased muscle acyl-CoA oxidase mRNA expression. Resistin and adiponectin were overexpressed in white adipose tissue of +/p- mice, although there was no difference in serum adiponectin levels. The lean phenotype and increased insulin sensitivity observed in +/p- mice is likely a consequence of increased lipid oxidation in muscle and possibly other tissues. Further studies will clarify whether XLalphas deficiency is responsible for these effects and if so, the mechanism by which XLalphas deficiency leads to this metabolic phenotype.

WY14,643, a peroxisome proliferator-activated receptor alpha (PPARalpha ) agonist, improves hepatic and muscle steatosis and reverses insulin resistance in lipoatrophic A-ZIP/F-1 mice.

WY14,643 is a specific peroxisome proliferator-activated receptor alpha (PPARalpha) agonist with strong hypolipidemic effects. Here we have examined the effect of WY14,643 in the A-ZIP/F-1 mouse, a model of severe lipoatrophic diabetes. With 1 week of treatment, all doses of WY14,643 that were tested normalized serum triglyceride and fatty acid levels. Glucose and insulin levels also improved but only with high doses and longer treatment duration. WY14,643 reduced liver and muscle triglyceride content and increased levels of mRNA encoding fatty acid oxidation enzymes. In liver, the elevated lipogenic mRNA profile (including PPARgamma) in A-ZIP/F-1 mice remained unchanged. These results suggest that WY14,643 acts by increasing beta-oxidation rather by than decreasing lipogenesis or lipid uptake. Hyperinsulinemic euglycemic clamp studies indicated that WY14,643 treatment improved liver more than muscle insulin sensitivity and that hepatic mRNA levels of gluconeogenic enzymes were reduced. Combination treatment with both WY14,643 and a PPARgamma ligand, rosiglitazone, did not lower glucose levels more effectively than did treatment with WY14,643 alone. These data support the hypothesis that reducing intracellular triglycerides in non-adipose tissues improves insulin sensitivity and suggest that further investigation of the role of PPARalpha agonists in the treatment of lipoatrophic diabetes is warranted.

Opposite effects of background genotype on muscle and liver insulin sensitivity of lipoatrophic mice. Role of triglyceride clearance.

The metabolic phenotype of the A-ZIP/F-1 (AZIP) lipoatrophic mouse is different depending on its genetic background. On both the FVB/N (FVB) and C57BL/6J (B6) backgrounds, AZIP mice have a similarly severe lack of white adipose tissue and comparably increased insulin levels and triglyceride secretion rates. However, on the B6 background, the AZIP mice have less hyperglycemia, lower circulating triglyceride and fatty acid levels, and lower mortality. AZIP characteristics that are more severe on the B6 background include increased liver size and liver triglyceride content. A unifying hypothesis is that the B6 strain has higher triglyceride clearance into the liver, with lower triglyceride levels elsewhere. This may account for the observation that the B6 AZIP mice have less insulin-resistant muscles and more insulin-resistant livers, than do the FVB AZIP mice. B6 wild type, as well as B6 AZIP, mice have increased triglyceride clearance relative to FVB, which may be explained in part by higher serum lipase levels and liver CD36/fatty acid translocase mRNA levels. Thus, it is likely that increased triglyceride clearance in B6, as compared with FVB, mice contributes to the strain differences in insulin resistance and lipid metabolism.

Liver peroxisome proliferator-activated receptor gamma contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor that mediates the antidiabetic effects of thiazolidinediones. PPAR gamma is present in adipose tissue and becomes elevated in fatty livers, but the roles of specific tissues in thiazolidinedione actions are unclear. We studied the function of liver PPAR gamma in both lipoatrophic A-ZIP/F-1 (AZIP) and wild type mice. In AZIP mice, ablation of liver PPAR gamma reduced the hepatic steatosis but worsened the hyperlipidemia, triglyceride clearance, and muscle insulin resistance. Inactivation of AZIP liver PPAR gamma also abolished the hypoglycemic and hypolipidemic effects of rosiglitazone, demonstrating that, in the absence of adipose tissue, the liver is a primary and major site of thiazolidinedione action. In contrast, rosiglitazone remained effective in non-lipoatrophic mice lacking liver PPAR gamma, suggesting that adipose tissue is the major site of thiazolidinedione action in typical mice with adipose tissue. Interestingly, mice without liver PPAR gamma, but with adipose tissue, developed relative fat intolerance, increased adiposity, hyperlipidemia, and insulin resistance. Thus, liver PPAR gamma regulates triglyceride homeostasis, contributing to hepatic steatosis, but protecting other tissues from triglyceride accumulation and insulin resistance.