Contrast-enhanced ultrasound (CEUS) is a safe, reliable and relatively low cost diagnostic tool with special advantages for use in pediatric imaging. In particular, CEUS does not expose patients to ionizing radiation — which can increase a patient’s lifetime risk of cancer; this presents special concerns in pediatric imaging since children are considerably more sensitive to ionizing radiation than adults, and some children may require repeat imaging over a longer lifetime. CEUS also is child-friendly and does not require sedation. CEUS may be performed in a variety of clinical settings using relatively low cost and widely available ultrasound equipment. Further, ultrasound contrast agents (UCAs) do not contain dye — which can increase the risk of kidney complications. Nor do UCAs contain radioactive material. A considerable body of scientific literature describes the increasing use of CEUS in children to diagnose a range of medical abnormalities with a high degree of accuracy and an extremely low rate or absence of contrast-related adverse events. UCAs are biocompatible solutions that are generally administered intravenously or intravesically in children. UCAs have been used in pediatric patients since the late 1990s. Because they often improve the accuracy and reliability of an initial US diagnosis, UCAs may reduce the need for downstream CT, MR and other unnecessary diagnostic procedures. Growing interest in pediatric CEUS is due, in part, to concerns relating to the use of CT and MR in children. Although CT can be an important diagnostic option for some patients including children, CT represents the largest single contributor to medical radiation exposure in the US. While MR is radiation free, its use in children frequently requires sedation. In addition, one MR contrast agent, gadolinium, can increase a child’s risk of nephrogenic systemic fibrosis, presenting potentially heightened concerns in newborns and infants because their kidneys have not reached full maturity. The US Food and Drug Administration has approved LUMASON^® (SonoVue^®) for pediatric liver and intravesical applications.

Three routes of US contrast agent administration have been described in children: intravenous (IV), intracavitary and oral.

• IV administration is typically used for characterization and detection of solid organ pathology, analogous to established IV uses in adults [6].
• Intracavitary contrast-enhanced US utilizes catheterization and includes intravesical administration for diagnosis of vesicoureteric reflux (VUR) and contrast-enhanced genitography for eval¬uation of ambiguous genitalia and cloacal malformations, both pediatric-specific indications [5, 8, 9, 14].
• Oral US contrast agent administration has only been described in one study involving the diagnosis of gastroesophageal reflux [15]. The procedures, uses and safety of IV and intravesical contrast-enhanced US in children are described below.

European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB): An Update on the Pediatric CEUS Registry on Behalf of the “EFSUMB Pediatric CEUS Registry Working Group”

Prof. Christoph F. Dietrich, Department Allgemeine Innere Medizin (DAIM), Kliniken

Hirslanden Beau Site, Salem und Permanence, Bern, Switzerland

The European Federation of Societies of Ultrasound in Medicine and Biology (EFSUMB) first incorporated pediatric CEUS in its 2008 updated clinical practice guidelines and recommendations for CEUS: 

Claudon M, Cosgrove D, Albrecht T et al (2008) Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) – update 2008. Ultraschall Med 29:28–44.

EFSUMB’s current guidelines also address pediatric CEUS:

Piscaglia, F., et al., The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast Enhanced Ultrasound (CEUS): update 2011 on non-hepatic applications. Ultraschall Med, 2012. 33(1): p. 33-59.

The European Society of Paediatric Radiology (ESPR) Uroradiology Task Force and the European Society of Urogenital Radiology (ESUR) Paediatric Working Group issued recommendations for pediatric CEUS imaging, primarily for intravesical administration, in 2008 and 2012:

Riccabona M, Avni FE, Blickman JG et al (2008) Imaging recommendations in paediatric uroradiology: minutes of the ESPR workgroup session on urinary tract infection, fetal hydronephrosis, urinary tract ultrasonography and voiding cystourethrography, Barcelona,Spain, June 2007. Pediatr Radiol 38:138–145

Riccabona M, Avni FE, Damasio MB et al (2012) ESPR Uroradiology Task Force and ESUR Paediatric Working Group – Imaging recommendations in paediatric uroradiology, part V: childhood cystic kidney disease, childhood renal transplantation and contrast-enhanced ultrasonography in children. Pediatr Radiol 42:1275–1283

1. Larson DB, Johnson LW, Schnell BM et al (2011) Rising use of CT in child visits to the emergency department in the United States, 1995–2008. Radiology 259:793–801

2. Pearce MS, Salotti JA, Little MP et al (2012) Radiation exposure from CT scans in childhood and subsequent risk of leukemia and brain tumors: a retrospective cohort study. Lancet 380:499–505

3. Brenner D, Elliston C, Hall E et al (2001) Estimated risks of radiation-induced fatal cancer from pediatric CT. AJR Am J Roentgenol 176:289–296

4. Goske MJ, Applegate KE, Boylan J et al (2008) Image Gently®: a national education and communication campaign in radiology using the science of social marketing. J Am Coll Radiol 5:1200–1205

5. Darge K (2010) Voiding urosonography with US contrast agent for the diagnosis of vesicoureteric reflux in children: an update. Pediatr Radiol 40:956–962

6. Piskunowicz M, Kosiak W, Batko T (2012) Intravenous application of second-generation ultrasound contrast agents in children: a review of the literature. Ultraschall Med 33:135–140

7. Papadopoulou F, Ntoulia A, Siomou E et al (2011) Safety of intravesical use of a second generation US contrast agent in children for vesicoureteric reflux detection. ECR Book of Abstracts, Insights Imaging 3:SS 1612, B-736

8. Darge K (2008) Voiding urosonography with ultrasound contrast agents for the diagnosis of vesicoureteric reflux in children. I. Procedure. Pediatr Radiol 38:40–53

9. Darge K (2008) Voiding urosonography with US contrast agents for the diagnosis of vesicoureteric reflux in children. II. Comparison with radiological examinations. Pediatr Radiol 38:54–63

10. Claudon M, Cosgrove D, Albrecht T et al (2008) Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) – update 2008. Ultraschall Med 29:28–44

11. Piscaglia F, Nolsøe C, Dietrich CF et al (2012) The EFSUMB guidelines and recommendations on the clinical practice of contrast enhanced ultrasound (CEUS): update 2011 on non-hepatic applications. Ultraschall Med 33:33–59

12. Riccabona M, Avni FE, Blickman JG et al (2008) Imaging recommendations in paediatric uroradiology: minutes of the ESPR workgroup session on urinary tract infection, fetal hydronephrosis, urinary tract ultrasonography and voiding cystourethrography, Barcelona, Spain, June 2007. Pediatr Radiol 38:138–145

13. Riccabona M, Avni FE, Damasio MB et al (2012) ESPR Uroradiology Task Force and ESUR Paediatric Working Group – Imaging recommendations in paediatric uroradiology, part V: childhood cystic kidney disease, childhood renal transplantation and contrast-enhanced ultrasonography in children. Pediatr Radiol 42:1275–1283

14. Kopac M, Riccabona M, Haim M (2009) Contrast-enhanced voiding urosonography and genitography in a baby with ambiguous genitalia and urogenital sinus. Ultraschall Med 30:299–300

15. Farina R, Pennisi F, La Rosa M et al (2008) Contrast-enhanced colour-Doppler sonography versus pH-metry in the diagnosis of gastrooesophageal reflux in children. Radiol Med 113:591–598

16. Darge K, Papadopoulou F, et al (2013) Safety of contrast-enhanced ultrasound in children for non-cardiac applications: a review by the Society for Pediatric Radiology (SPR) and the International Contrast Ultrasound Society (ICUS). Pediatr Radiol. 2013 Sep;43(9):1063-73.