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Contrast-enhanced ultrasound (CEUS) utilization is expanding rapidly, particularly in children, in whom the modality offers the important advantages of dynamic evaluation of the vasculature, portability, lack of ionizing radiation, and lack of need for sedation. Accumulating data establish an excellent safety profile of ultrasound contrast agents (UCAs) in children. Although UCAs have been FDA-approved only for IV use in children for characterizing focal liver lesions and for use in children during echocardiography, off-label applications are expanding the diagnostic potential of ultrasound. Focal liver lesion evaluation is the most common use of CEUS, and the American College of Radiology Pediatric LI-RADS Working Group recommends including CEUS for evaluation of a newly discovered focal liver lesion in many circumstances. Data also support the role of CEUS in hemodynamically stable children with blunt abdominal trauma, and CEUS is becoming a potential alternative to CT in this setting. Additional potential applications that require further study include evaluation of pathology in the lung, spleen, brain, pancreas, bowel, kidney, female pelvis, and scrotum. This article explores the implementation of CEUS in children, describing basic principles of UCAs and CEUS technique and summarizing current and potential IV diagnostic applications based on pediatric-specific supporting evidence.

Objective: The objective of this study is to evaluate radial free-breathing (FB) multiecho ultrashort TE (UTE) imaging as an alternative to Cartesian FB multiecho gradient-recalled echo (GRE) imaging for quantitative assessment of hepatic iron content (HIC) in sedated patients and subjects unable to perform breath-hold (BH) maneuvers., Materials and Methods: FB multiecho GRE imaging and FB multiecho UTE imaging were conducted for 46 test group patients with iron overload who could not complete BH maneuvers (38 patients were sedated, and eight were not sedated) and 16 control patients who could complete BH maneuvers. Control patients also underwent standard BH multiecho GRE imaging. Quantitative R2* maps were calculated, and mean liver R2* values and coefficients of variation (CVs) for different acquisitions and patient groups were compared using statistical analysis., Results: FB multiecho GRE images displayed motion artifacts and significantly lower R2* values, compared with standard BH multiecho GRE images and FB multiecho UTE images in the control cohort and FB multiecho UTE images in the test cohort. In contrast, FB multiecho UTE images produced artifact-free R2* maps, and mean R2* values were not significantly different from those measured by BH multiecho GRE imaging. Motion artifacts on FB multiecho GRE images resulted in an R2* CV that was approximately twofold higher than the R2* CV from BH multiecho GRE imaging and FB multiecho UTE imaging. The R2* CV was relatively constant over the range of R2* values for FB multiecho UTE, but it increased with increases in R2* for FB multiecho GRE imaging, reflecting that motion artifacts had a stronger impact on R2* estimation with increasing iron burden., Conclusion: FB multiecho UTE imaging was less motion sensitive because of radial sampling, produced excellent image quality, and yielded accurate R2* estimates within the same acquisition time used for multiaveraged FB multiecho GRE imaging. Thus, FB multiecho UTE imaging is a viable alternative for accurate HIC assessment in sedated children and patients who cannot complete BH maneuvers.

Objective: The purpose of this study was to investigate contrast-enhanced ultrasound assessment of tumor response to antiangiogenic therapy in children and adolescents with solid malignancies., Subjects and Methods: Children with recurrent solid tumors who were enrolled in an institutional phase 1 study of antiangiogenic therapy underwent contrast-enhanced ultrasound of target lesions before therapy, on therapy days 3 and 7, and at the end of course 1. Acoustic data from target lesion ROIs were used to measure peak enhancement, time to peak, rate of enhancement, total AUC, AUC during wash-in (AUC1), and AUC during washout (AUC2). The Cox regression model was used to assess the association between changes in parameters from baseline to follow-up time points and time to tumor progression. Values of p ≤ 0.050 were considered significant., Results: Target lesion sites included liver (n = 3), pleura (n = 2), and supraclavicular mass, soft-tissue component of bone metastasis, lung, retroperitoneum, peritoneum, lymph node, muscle mass, and perineum (n = 1 each). Hazard ratios for changes from baseline to end of course 1 for peak enhancement (1.17, p = 0.034), rate of enhancement (3.25, p = 0.029), and AUC1 (1.02, p = 0.040) were significantly associated with time to progression. Greater decreases in these parameters correlated with longer time to progression., Conclusion: Contrast-enhanced ultrasound measurements of tumor peak enhancement, rate of enhancement, and AUC1 were early predictors of time to progression in a cohort of children and adolescents with recurrent solid tumors treated with antiangiogenic therapy. Further investigation of these findings in a larger population is warranted.

Objective: The purpose of this study was to determine whether clinical and imaging features can distinguish osteomyelitis from Ewing sarcoma (EWS) and to assess the accuracy of percutaneous biopsy versus open biopsy in the diagnosis of these diseases., Materials and Methods: Three radiologists reviewed the radiographs and MRI examinations of 32 subjects with osteomyelitis and 31 subjects with EWS to determine the presence of 36 imaging parameters. Information on demographic characteristics, history, physical examination findings, laboratory findings, biopsy type, and biopsy results were recorded. Individual imaging and clinical parameters and combinations of these parameters were tested for correlation with findings from histologic analysis. The diagnostic accuracy of biopsy was also determined., Results: On radiography, the presence of joint or metaphyseal involvement, a wide transition zone, a Codman triangle, a periosteal reaction, or a soft-tissue mass, when tested individually, was more likely to be noted in subjects with EWS (p ≤ 0.05) than in subjects with osteomyelitis. On MRI, permeative cortical involvement and soft-tissue mass were more likely in subjects with EWS (p ≤ 0.02), whereas a serpiginous tract was more likely to be seen in subjects with osteomyelitis (p = 0.04). African Americans were more likely to have osteomyelitis than EWS (p = 0). According to the results of multiple regression analysis, only ethnicity and soft-tissue mass remained statistically significant (p ≤ 0.01). The findings from 100% of open biopsies (18/18) and 58% of percutaneous biopsies (7/12) resulted in the diagnosis of osteomyelitis, whereas the findings from 88% of open biopsies (22/25) and 50% of percutaneous biopsies (3/6) resulted in a diagnosis of EWS., Conclusion: Several imaging features are significantly associated with either EWS or osteomyelitis, but many features are associated with both diseases. Other than ethnicity, no clinical feature improved diagnostic accuracy. Compared with percutaneous biopsy, open biopsy provides a higher diagnostic yield but may be inconclusive, especially for cases of EWS. Our findings underscore the need for better methods of diagnosing these disease processes.

Objective: The purpose of this article is to determine the MRI and CT features of low-grade fibromyxoid sarcoma in children., Materials and Methods: We retrospectively analyzed images of 11 pediatric patients with low-grade fibromyxoid sarcoma from a phase 3 clinical trial of nonrhabdomyosarcoma soft-tissue sarcoma (Children's Oncology Group Protocol ARST0332). MRI and CT were performed in 10 and four patients, respectively. Location, size, margin, and composition on imaging were correlated with pathologic findings., Results: Tumors were located in the extremities in nine patients, and one tumor each was located in the tongue and lung. Tumors were deep in seven patients and superficial in four patients. All tumors were well defined, solitary, and nonmetastatic at presentation. Tumors were complex solid-cystic in eight patients and completely solid in three patients. On T1-weighted images, all tumors had at least some areas hypointense to muscles, and six had a split-fat sign. On STIR or T2-weighted images, eight tumors had areas hypointense to adjacent muscle, and eight tumors had fluid signal intensity. On contrast-enhanced MRI studies, eight tumors had thick enhancing internal septations, and three had peripheral nodular gyriform enhancement. When we correlated imaging to pathologic findings, areas with hypointense signal intensity on both T1- and T2-weighted images were likely related to fibrous component; areas with fluid signal intensity on T2-weighted images were likely related to myxoid component. On CT, all four tumors were hypodense to muscle, and one tumor showed punctate calcific foci., Conclusion: Low-grade fibromyxoid sarcoma is hypodense to muscle on CT. MRI may identify both fibrous and myxoid components of this rare pediatric soft-tissue sarcoma.

Objective: There are few studies in the literature regarding the imaging features of alveolar soft-part sarcoma (ASPS). We performed a comprehensive assessment of the imaging characteristics of this rare tumor to determine whether there are features that suggest the diagnosis., Materials and Methods: Twenty-two subjects with ASPS underwent pretherapy imaging as part of enrollment in Children's Oncology Group protocol ARST0332 for the treatment of nonrhabdomyosarcoma soft-tissue sarcomas: 16 patients underwent MRI; three, CT; and three, both MRI and CT. Two radiologists retrospectively reviewed the imaging studies by consensus and recorded tumor location, size, contour, internal architecture, signal characteristics, presence of flow voids, and enhancement patterns., Results: The 12 females and 10 males in the study group ranged in age from 8 to 23 years 7 months (mean, 15 years 8 months). The most common anatomic site was the lower extremity (12/22, 55%) followed by the upper extremity (4/22, 18%). The maximal tumor diameter ranged from 2.3 to 20.0 cm (median, 5.9 cm). All tumors imaged with MRI had flow voids (19/19, 100%), and 19 (19/22, 86%) had large peripheral vessels, lobulated margins, and nodular internal architecture. Unenhanced T1-weighted MRI was available for 18 tumors: 14 (14/18, 78%) appeared slightly hyperintense to muscle. Of the 16 tumors imaged with contrast material, 11 (11/16, 69%) showed intense enhancement and five (5/16, 31%), moderate enhancement. Six tumors (6/16, 38%) had a thick enhancing peripheral rim with a nonenhancing center consistent with necrosis., Conclusion: The imaging features of ASPS include flow voids, large peripheral vessels, internal nodularity, and lobulated margins. Contrast administration produces intense to moderate enhancement, sometimes with a thick enhancing peripheral rim around central necrosis. Extremity tumors with these imaging features in a child or young adult should suggest the diagnosis of ASPS.

Objective: Little information is available regarding the safety of ultrasound contrast agents in children. The purpose of this article was to assess the safety profile of the i.v. administration of ultrasound contrast agents in the pediatric oncology population., Materials and Methods: Patients with pediatric solid malignancies who were enrolled on institutional clinical trials conducted between June 2003 and January 2013 and who met our institutional screening criteria for contrast-enhanced ultrasound (CEUS) were eligible. After providing informed consent or assent for CEUS, subjects received i.v. bolus injections of one of two contrast agents for imaging of the primary tumor or a metastatic target lesion. Hemodynamic parameters, including heart rate, cardiac rhythm, and oxygen saturation, were monitored immediately before and for 30 minutes after the administration of the contrast agent. Interviews with the subject or a guardian were conducted by the principal investigator or a radiologist coinvestigator before and after the examination to assess for any adverse effects., Results: Thirty-four subjects (21 male and 13 female) ranging in age from 8 months to 20.7 years (median, 8.7 years) underwent 134 CEUS. No detrimental change in hemodynamic status occurred in any subject. Three subjects (3/134, 2.2%) reported mild transient side effects on one occasion each, two (2/134, 1.5%) had taste alteration, and one (1/134, 0.8%) reported mild transient tinnitus and lightheadedness. These reactions did not recur in these subjects on subsequent CEUS examinations., Conclusion: The i.v. administration of ultrasound contrast agents is safe and well tolerated in the pediatric oncology population. Further studies in children are needed to confirm our findings.

OBJECTIVE. The purpose of this article is to assess the feasibility and utility of PET/CT in distinguishing benign from malignant pulmonary nodules in patients with solid childhood malignancies. SUBJECTS AND METHODS. This prospective study was conducted between March 2008 and August 2010. We enrolled 25 subjects 21 years old or younger with solid childhood malignancies and at least one pulmonary nodule measuring 0.5-3.0 cm. PET/CT was performed within 3 weeks of diagnostic chest CT. Three panels of three reviewers each reviewed diagnostic CT only (panel 1), PET/CT only (panel 2), or diagnostic CT and PET/CT concurrently (panel 3) and predicted each nodule's histologic diagnosis as benign, malignant, or indeterminate. Interreviewer agreement was assessed with the kappa statistic. Using nodule biopsy or clinical follow-up as reference standards, the sensitivity, specificity, and accuracy for each panel was assessed. Logistic regression was used to assess the nodule's maximum standardized uptake value (SUVmax) association with its histologic diagnosis. RESULTS. There were 75 nodules with a median size of 0.74 cm (range, 0.18-2.38 cm); 48 nodules were malignant. Sensitivity was 85% (41/48) for panel 1, 60% (29/48) for panel 2, and 67% (32/48) for panel 3. All panels had poor specificities. Interreviewer agreement was moderate for panel 1 (0.43) and poor for panels 2 (0.22) and 3 (0.33). SUVmax was a significant predictor of histologic diagnosis (p = 0.004). CONCLUSION. PET/CT assessment of pulmonary nodules is feasible in children with solid malignancies but may not reliably improve our ability to predict a nodule's histologic diagnosis. The SUVmax may improve the performance of PET/CT in this setting.

Objective: The purpose of this study is to perform and evaluate baseline abdominal ultrasound in infants with sickle cell anemia who participated in the BABY HUG multiinstitutional randomized placebo-controlled trial of hydroxyurea therapy and to examine the potential relationships among ultrasound results and clinical, nuclear medicine, and laboratory data., Subjects and Methods: After local institutional review board approval and with informed guardian consent, 116 girls and 87 boys (age range, 7.5-18 months) with sickle cell anemia underwent standardized abdominal sonography at 14 institutions. Imaging was centrally reviewed by one radiologist who assessed and measured the spleen, kidneys, gallbladder, and common bile duct. Baseline physical assessment of spleen size, serum alanine aminotransferase and bilirubin levels, (99m)Tc sulfur colloid liver-spleen scans, and (99m)Tc diethylenetriaminepentaacetic acid clearance glomerular filtration rates (GFRs) were obtained. Analysis of variance and the Student test were performed to compare sonographic findings to published results in healthy children and to clinical and laboratory findings., Results: The mean (± SD) spleen volume (108 ± 47 mL) was significantly greater than published normal control values (30 ± 14 mL; p < 0.0001). There was no correlation between spleen volume and function assessed by liver-spleen scan. The mean GFR (125 ± 34 mL/min/1.73 m(2)) was elevated compared with control GFRs (92 ± 18 mL/min/1.73 m(2)). Renal volumes (right kidney, 29 ± 8 mL; left kidney, 31 ± 9 mL) were significantly greater than control volumes (right kidney, 27 ± 3 mL; left kidney, 27 ± 3 mL; p < 0.0001) and were positively correlated with GFR (p = 0.0009). Five percent of patients had sonographic biliary abnormalities (sludge, n = 6; dilated common bile duct, n = 2; and cholelithiasis and thickened gallbladder wall, n = 1 each). There was no correlation between biliary sonographic findings and laboratory results., Conclusion: In infants with sickle cell anemia, sonographic spleen volume does not reflect function, but increased renal volume correlates with GFR and is consistent with hyperfiltration. Sonographic biliary abnormalities can occur early in life, while remaining clinically silent.

Objective: Little information is available regarding doses of ionizing radiation from medical imaging in the growing population of children undergoing therapy for cancer who are at risk of developing second cancers. The purpose of our study was to estimate the potential excess lifetime cancer incidence and mortality associated with thallium bone imaging in pediatric patients., Materials and Methods: We retrospectively reviewed the medical records of pediatric patients treated between August 1991 and December 2003 for newly diagnosed osteosarcoma who underwent 201Tl imaging as part of the treatment protocol. According to age at diagnosis and doses of 201Tl, we estimated the excess cancer incidence and cancer mortality for boys and girls at 5 and 15 years old., Results: The study cohort consisted of 73 patients, 32 males (median age at diagnosis, 14.8 years; age range, 8.1-20.1 years) and 41 females (median age at diagnosis, 13.3 years; age range, 6.0-20.7 years). Patients underwent a total of three 201Tl studies with a median dose of 4.4 mCi (162.8 MBq) (range, 2.2-8.4 mCi [81.4-310.8 MBq]) per study. Total median cumulative patient radiation dose for 201Tl studies was 18.6 rem (186 mSv) (range, 8.4-44.2 rem [84-442 mSv]) for males and 21.5 rem (215 mSv) (range, 7.0-43.8 rem [70-438 mSv]) for females. Estimated excess cancer incidence was 6.0 per 100 (male) and 13.0 per 100 (female) if exposed by 5 years of age; 2.0 per 100 (male) and 3.1 per 100 (female) by 15 years of age. Estimated excess cancer mortality was 3.0 per 100 for males and 5.2 per 100 for females at 5 years of age; 1.0 per 100 (male) and 1.4 per 100 (female) exposed at 15 years of age., Conclusion: Further reduction of doses in younger patients is needed to consider 201Tl a viable option for imaging osteosarcoma.

Objective: The outcome of desmoid tumor in children cannot be reliably predicted on the basis of histologic findings. We sought to determine whether the postoperative presence of residual or recurrent tumor can be predicted on the basis of demographic variables and baseline MRI features of the tumor. We also aimed to determine how imaging features change during adjuvant treatment and how the imaging features relate to the histologic features., Materials and Methods: Two radiologists retrospectively reviewed images from 281 MRI examinations performed at baseline and during postoperative therapy for desmoid tumor. The examinations had been performed on 17 children treated between September 1991 and March 2003. Tumor volume; distinctness of margins; involvement of bone and neurovascular bundle; and T1-weighted, T2-weighted, and STIR signal intensity and contrast enhancement pattern were recorded. Baseline imaging and demographic features were correlated with the postoperative presence of residual or recurrent tumor. Imaging changes during follow-up were compared with treatment response and outcome. The imaging features of eight tumors were compared with percentage cellularity and collagen deposition in biopsy samples obtained within 30 days of imaging., Results: Baseline involvement of the neurovascular bundle approached significance as a predictor of the presence of residual or recurrent tumor (p = 0.08). Other baseline imaging and demographic features were not predictive (p > or = 0.4). Changes in imaging features were variable during follow-up. T2-weighted and STIR signal intensity may be correlated with percentage cellularity and collagen deposition., Conclusion: MRI has limited value in prediction of the postoperative presence of residual or recurrent desmoid tumor in children. It is useful, however, for detecting disease and monitoring postoperative adjuvant therapy.

Objective: The objectives of our study were to determine whether central tumor photopenia on thallium-201 (201Tl) scintigraphy of primary osteosarcoma results from central tumor necrosis or dense central tumor ossification and to determine the relation of this finding to tumor response to chemotherapy and to patient survival., Materials and Methods: After the institutional review board approved our study and waived the need for patient or parental consent, two radiologists independently reviewed 201Tl scans, conventional radiographs, and MR images of 57 patients obtained at diagnosis of extremity primary nonmetastatic osteosarcoma to detect the presence of central tumor photopenia on 201Tl scintigraphy and estimate outer tumor ossification versus inner tumor ossification and enhancement. The dynamic enhanced MRI parameters dynamic vector magnitude (DVM) and k(ep) (measure of the exchange rate between plasma and extracellular fluid space) were compared for outer tumor versus inner tumor, and the relation among 201Tl scintigraphy, conventional radiography, MRI, and the dynamic enhanced MRI parameters was analyzed. We examined whether central tumor photopenia on 201Tl imaging was related to histologic response or to patient survival., Results: Thirty-three patients (58%) had central tumor photopenia on 201Tl imaging that was not associated with central tumor ossification (p = 0.8) or with the difference between outer tumor and inner tumor contrast enhancement (p = 0.4). Central tumor photopenia on 201Tl scintigraphy was significantly associated with an increasing difference between outer tumor DVM and inner tumor DVM (i.e., outer tumor DVM minus inner tumor DVM) (p = 0.05), an increasing difference between outer tumor k(ep) and inner tumor k(ep) (i.e., outer k(ep) minus inner k(ep)) (p = 0.01), and an increasing outer k(ep)-inner k(ep) ratio (p = 0.02). We found no relation between central tumor photopenia and histologic response (p > or = 0.2). Older patients (age, > or = 13 years) with central tumor photopenia were least likely to survive, whereas younger patients (age, < 13 years) without central tumor photopenia were most likely to survive (p = 0.07)., Conclusion: Central tumor photopenia on 201Tl scintigraphy of primary osteosarcoma is unlikely to reflect central ossification but may be due to central necrosis reflected by higher outer tumor DVM and k(ep) than inner tumor DVM and k(ep) and may be negatively associated with survival in older patients. Prospective studies are needed to determine the value of this information in planning treatment.

Objective: The purpose of this study was to characterize the anatomic appearance and metabolic activity of nonossifying fibromas, fibrous cortical defects, and cortical desmoids on PET/CT images., Conclusion: Over a 14-month period, we identified eight nonossifying fibromas, four fibrous cortical defects, and two cortical desmoids in 330 children who underwent PET/CT for the evaluation of a known or suspected malignancy. CT, conventional radiography, MRI, or clinical follow-up was used to confirm the diagnoses of these fibroosseous lesions. Eleven of the 14 children underwent multiple PET/CT examinations; thus, 34 studies were included. The lesions showed variable metabolic activity as indicated by 18F-FDG uptake: 19 PET/CT examinations showed lesions with mild 18F-FDG uptake, eight showed moderate 18F-FDG uptake, and seven showed intense uptake. When PET reveals metabolically active osseous abnormalities in children who are at risk for bone metastases, benign fibroosseous lesions should be considered in the differential diagnosis before additional diagnostic procedures are undertaken. Benign fibroosseous lesions may be metabolically active and thus mimic metastatic osseous disease in children with underlying malignancies. Correlative CT or other anatomic imaging can confirm the benign nature of these lesions.

Objective: Our objective was to review our preliminary experience with PET/CT in evaluating childhood sarcomas including rhabdomyosarcoma (n = 28), the Ewing's sarcoma family of tumors (n = 14), nonrhabdomyosarcoma soft-tissue sarcoma (n = 9), osteosarcoma (n = 8), chondrosarcoma (n = 1), and embryonal sarcoma (n = 1)., Conclusion: We found PET/CT useful in depicting an unknown primary rhabdomyosarcoma and detecting unsuspected and unusual metastatic sites of childhood sarcomas. It was useful in monitoring response to chemotherapy, radiation therapy, and radiofrequency ablation and aided the postoperative evaluation of tumor resection sites.

Objective: High blood flow velocity in the middle cerebral artery or distal internal carotid artery, as measured by nonduplex transcranial Doppler sonography, predicts stroke in children with sickle cell anemia. However, velocities measured using the more widely available duplex transcranial Doppler imaging equipment may not be comparable. We sought to determine the magnitude and significance of the potential differences., Subjects and Methods: We performed 55 paired examinations with duplex imaging and nonduplex nonimaging sonography machines on 53 children with sickle cell anemia. Examinations were performed consecutively by three sonographers blinded to the results of the opposing study. Velocities were measured in five clinically relevant vessels., Results: Time-averaged mean maximum (TAMx) velocity measurements obtained with the duplex equipment were significantly lower than those made with the nonduplex equipment for all vessels except the posterior cerebral artery. The mean differences were 10.9% (p < 0.0001) in the middle cerebral artery, 12.7% (p = 0.002) in the anterior cerebral artery, 2.2% (p = 0.69) in the posterior cerebral artery, 21.0% (p < 0.0001) in the distal internal carotid artery, and 15.3% (p < 0.0001) at the bifurcation of the distal internal carotid artery., Conclusion: If TAMx velocities measured with duplex equipment are used to assign stroke risk in children with sickle cell anemia, we suggest that 180 cm/sec or more should be considered abnormal, and 153-179 cm/sec, as conditional. These values are 10% lower than those obtained from the nonduplex equipment used in the Stroke Prevention Trial in Sickle Cell Anemia study.