Top

Published in:

01-09-2013 | Review

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)

Authors: Kassa Darge, Frederica Papadopoulou, Aikaterini Ntoulia, Dorothy I. Bulas, Brian D. Coley, Lynn A. Fordham, Harriet J. Paltiel, Beth McCarville, Frank M. Volberg, David O. Cosgrove, Barry B. Goldberg, Stephanie R. Wilson, Steven B. Feinstein

Published in: Pediatric Radiology | Issue 9/2013

Abstract

The practice of contrast-enhanced ultrasound in children is in the setting of off-label use or research. The widespread practice of pediatric contrast-enhanced US is primarily in Europe. There is ongoing effort by the Society for Pediatric Radiology (SPR) and International Contrast Ultrasound Society (ICUS) to push for pediatric contrast-enhanced US in the United States. With this in mind, the main objective of this review is to describe the status of US contrast agent safety in non-cardiac applications in children. The five published studies using pediatric intravenous contrast-enhanced US comprise 110 children. There is no mention of adverse events in these studies. From a European survey 948 children can be added. In that survey six minor adverse events were reported in five children. The intravesical administration of US contrast agents for diagnosis of vesicoureteric reflux entails the use of a bladder catheter. Fifteen studies encompassing 2,951 children have evaluated the safety of intravesical US contrast agents in children. A European survey adds 4,131 children to this group. No adverse events could be attributed to the contrast agent. They were most likely related to the bladder catheterization. The existing data on US contrast agent safety in children are encouraging in promoting the widespread use of contrast-enhanced US.

The study by Valentini et al. [71] includes 74 patients not identified by gender.

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 259:793–801PubMedCrossRef

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 380:499–505PubMedCrossRef

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

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 5:1200–1205PubMedCrossRef

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

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

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

Piskunowicz M, Kosiak W, Irga N (2011) Primum non nocere? Why can’t we use second generation ultrasound contrast agents for the examination of children? Ultraschall in Med 32:83–85

Nolsoe C, Piscaglia F, Dietrich CF et al (2011) Primum non nocere? Why can’t we use second generation ultrasound contrast agents for the examination of children? Ultraschall Med 32:85–86

10.

Schreiber-Dietrich D, Dietrich CF (2012) Contrast enhanced ultrasound (CEUS) and off-label use (in children). Ultraschall Med 33:295–296PubMedCrossRef

11.

Esposito F, Di Serafino M, Sgambati P et al (2012) Ultrasound contrast media in paediatric patients: is it an off-label use? Regulatory requirements and radiologist’s liability. Radiol Med 117:148–159PubMedCrossRef

12.

Darge K, CEUS task force of the Society for Pediatric Radiology (2011) Contrast-enhanced US (CEUS) in children: ready for prime time in the United States. Pediatr Radiol 41:1486–1488CrossRef

13.

(2012) National Cancer Institute Radiation risks and pediatric computed tomography (CT): a guide for healthcare providers. Available via http://www.cancer.gov/cancertopics/causes/radiation/radiation-risks-pediatric-CT. Accessed 28 Jan 2013

14.

Karcaaltincaba M, Oguz B, Haliloglu M (2009) Current status of contrast-induced nephropathy and nephrogenic systemic fibrosis in children. Pediatr Radiol 39:382–384PubMedCrossRef

15.

Schulte-Uentrop L, Goepfert MS (2010) Anaesthesia or sedation for MRI in children. Curr Opin Anaesthesiol 23:513–517PubMedCrossRef

16.

Slovis TL (2011) Sedation and anesthesia issues in pediatric imaging. Pediatr Radiol 41:514–516PubMedCrossRef

17.

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

18.

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

19.

Conroy S, Choonara I, Impicciatore P et al (2000) Survey of unlicensed and off label drug use in paediatric wards in European countries. European Network for Drug Investigation in Children. BMJ 320:79–82PubMedCrossRef

20.

Lindell-Osuagwu L, Korhonen MJ, Saano S et al (2009) Off-label and unlicensed drug prescribing in three paediatric wards in Finland and review of the international literature. J Clin Pharm Ther 34:277–287PubMedCrossRef

21.

Bazzano AT, Mangione-Smith R, Schonlau M et al (2009) Off-label prescribing to children in the United States outpatient setting. Acad Pediatr 9:81–88PubMedCrossRef

22.

Shah SS, Hall M, Goodman DM et al (2007) Off-label drug use in hospitalized children. Arch Pediatr Adolesc Med 161:282–290PubMedCrossRef

23.

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

24.

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 33:33–59PubMedCrossRef

25.

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 38:138–145PubMedCrossRef

26.

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 42:1275–1283PubMedCrossRef

27.

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

28.

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

29.

Levy JA, Noble VE (2008) Bedside ultrasound in pediatric emergency medicine. Pediatrics 121:e1404–e1412PubMedCrossRef

30.

Moore CL, Copel JA (2011) Point-of-care ultrasonography. N Engl J Med 364:749–757PubMedCrossRef

31.

Taylor GA (2000) Potential pediatric applications for US contrast agents: lessons from the laboratory. Pediatr Radiol 30:101–109PubMedCrossRef

32.

Kiessling I, Bzyl J, Kiessling F (2011) Molecular ultrasound imaging and its potential for paediatric radiology. Pediatr Radiol 41:176–184PubMedCrossRef

33.

McCarville MB (2011) Contrast-enhanced sonography in pediatrics. Pediatr Radiol 41:S238–S242PubMedCrossRef

34.

Claudon M, Barnewolt CE, Taylor GA et al (1999) Renal blood flow in pigs: changes depicted with contrast-enhanced harmonic US imaging during acute urinary obstruction. Radiology 212:725–731PubMed

35.

Taylor GA, Barnewolt CE, Claudon M et al (1999) Depiction of renal perfusion defects with contrast-enhanced harmonic sonography in a porcine model. AJR Am J Roentgenol 173:757–760PubMedCrossRef

36.

Farhat W, Traubici J, Sherman C et al (2002) Reliability of contrast enhanced sonography with harmonic imaging for detecting early renal scarring in experimental pyelonephritis in a porcine model: preliminary results. J Urol 168:1114–1117PubMedCrossRef

37.

Paltiel HJ, Kalish LA, Susaeta RA et al (2006) Pulse-inversion US imaging of testicular ischemia: quantitative and qualitative analyses in a rabbit model. Radiology 239:718–729PubMedCrossRef

38.

Paltiel HJ, Padua HM, Gargollo PC et al (2011) Contrast-enhanced, real-time volumetric ultrasound imaging of tissue perfusion: preliminary results in a rabbit model of testicular torsion. Phys Med Biol 56:2183–2197PubMedCrossRef

39.

McCarville MB, Streck CJ, Dickson PV et al (2006) Angiogenesis inhibitors in a murine neuroblastoma model: quantitative assessment of intratumoral blood flow with contrast-enhanced gray-scale US. Radiology 240:73–81PubMedCrossRef

40.

McCarville MB (2008) New frontiers in pediatric oncologic imaging. Cancer Imaging 8:87–92PubMedCrossRef

41.

Barnewolt CE, Jaramillo D, Taylor GA et al (2003) Correlation of contrast-enhanced power Doppler sonography and conventional angiography of abduction-induced hip ischemia in piglets. AJR Am J Roentgenol 180:1731–1735PubMedCrossRef

42.

Taylor GA, Barnewolt CE, Dunning PS (1998) Excitotoxin-induced cerebral hyperemia in newborn piglets: regional cerebral blood flow mapping with contrast-enhanced power Doppler US. Radiology 208:73–79PubMed

43.

Riccabona M, Uggowitzer M, Klein E et al (2000) Echo-enhanced color Doppler sonography in children and adolescents. J Ultrasound Med 19:789–796PubMed

44.

Uggowitzer MM, Kugler C, Riccabona M et al (1999) Cerebral arteriovenous malformations: diagnostic value of echo-enhanced transcranial Doppler sonography compared with angiography. AJNR Am J Neuroradiol 20:101–106PubMed

45.

Doria AS, Guarniero R, Molnar LJ et al (2000) Three-dimensional (3D) contrast-enhanced power Doppler imaging in Legg-Calvé-Perthes disease. Pediatr Radiol 30:871–874PubMedCrossRef

46.

Oldenburg A, Hohmann J, Skrok J et al (2004) Imaging of paediatric splenic injury with contrast-enhanced ultrasonography. Pediatr Radiol 34:351–354PubMedCrossRef

47.

Doria AS, Kiss MH, Lotito AP et al (2001) Juvenile rheumatoid arthritis of the knee: evaluation with contrast-enhanced color Doppler ultrasound. Pediatr Radiol 31:524–531PubMedCrossRef

48.

Doria AS, Guarniero R, Cunha FG et al (2002) Contrast-enhanced power Doppler sonography: assessment of revascularization flow in Legg-Calvé-Perthes’ disease. Ultrasound Med Biol 28:171–182PubMedCrossRef

49.

Bonini G, Pezzotta G, Morzenti C et al (2007) Contrast-enhanced ultrasound with SonoVue in the evaluation of postoperative complications in pediatric liver transplant recipients. J Ultrasound 10:99–106PubMedCrossRef

50.

Valentino M, Serra C, Pavlica P et al (2008) Blunt abdominal trauma: diagnostic performance of contrast-enhanced US in children – initial experience. Radiology 246:903–909PubMedCrossRef

51.

Riccabona M (2012) Application of a second-generation US contrast agent in infants and children – a European questionnaire-based survey. Pediatr Radiol 42:1471–1480PubMedCrossRef

52.

Claudon M, Dietrich CF, Choi BI et al (2013) Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver – update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultraschall Med 39:187–210

53.

Darge K (2002) Diagnosis of vesicoureteral reflux with ultrasound. Pediatr Nephrol 17:52–60PubMedCrossRef

54.

Duran C, del Riego J, Riera L et al (2012) Voiding urosonography including urethrosonography: high-quality examinations with an optimised procedure using a second-generation US contrast agent. Pediatr Radiol 42:660–667PubMedCrossRef

55.

Darge K, Troeger J (2002) Vesicoureteral reflux grading in contrast-enhanced voiding urosonography. Eur J Radiol 43:122–128PubMedCrossRef

56.

Robrecht J, Darge K (2007) In-vitro comparison of a 1st and a 2nd generation US contrast agent for reflux diagnosis. Rofo 179:818–825PubMedCrossRef

57.

Ascenti G, Zimbaro G, Mazziotti S et al (2004) Harmonic US imaging of vesicoureteric reflux in children: usefulness of a second generation US contrast agent. Pediatr Radiol 34:481–487PubMedCrossRef

58.

Darge K, Beer M, Gordjani N et al (2004) Contrast-enhanced voiding urosonography with the use of a 2nd generation US contrast medium: preliminary results. Pediatr Radiol 34:S97CrossRef

59.

Papadopoulou F, Anthopoulou A, Siomou E et al (2009) Harmonic voiding urosonography with a second-generation contrast agent for the diagnosis of vesicoureteral reflux. Pediatr Radiol 39:239–244PubMedCrossRef

60.

Kis E, Nyitrai A, Várkonyi I et al (2010) Voiding urosonography with second-generation contrast agent versus voiding cystourethrography. Pediatr Nephrol 25:2289–2293PubMedCrossRef

61.

Ključevšek D, Battelino N, Tomažič M et al (2012) A comparison of echo-enhanced voiding urosonography with X-ray voiding cystourethrography in the first year of life. Acta Paediatr 101:e235–e239PubMedCrossRef

62.

Papadopoulou F, Evangelou E, Riccabona M et al (2012) Contrast-enhanced voiding urosonography for diagnosis of vesicoureteric reflux in comparison to conventional methods: a meta-analysis. ECR Book of Abstracts, Insights Imaging 3:SS 1712, B-0860

63.

O’Hara SM (2001) Vesicoureteral reflux: latest option for evaluation in children. Radiology 221:283–284PubMedCrossRef

64.

Piscaglia F, Bolondi L, Italian Society for Ultrasound in Medicine and Biology (SIUMB) Study Group on Ultrasound Contrast Agents (2006) The safety of SonoVue in abdominal applications: retrospective analysis of 23,188 investigations. Ultrasound Med Biol 32:1369–1375CrossRef

65.

Zilberman MV, Witt SA, Kimball TR (2003) Is there a role for intravenous transpulmonary contrast imaging in pediatric stress echocardiography? J Am Soc Echocardiogr 16:9–14PubMedCrossRef

66.

Sheil ML, Cartmill TB, Nunn GR et al (2003) Contrast echocardiography: potential for the in-vivo study of pediatric myocardial preservation. Ann Thorac Surg 75:1542–1548PubMedCrossRef

67.

McMahon CJ, Ayres NA, Bezold LI et al (2005) Safety and efficacy of intravenous contrast imaging in pediatric echocardiography. Pediatr Cardiol 26:413–417PubMedCrossRef

68.

McCarville MB, Kaste SC, Hoffer FA et al (2012) Contrast-enhanced sonography of malignant pediatric abdominal and pelvic solid tumors: preliminary safety and feasibility data. Pediatr Radiol 42:824–833PubMedCrossRef

69.

Darge K, Troeger J, Duetting T et al (1999) Reflux in young patients: comparison of voiding US of the bladder and retrovesical space with echo enhancement versus voiding cystourethrography for diagnosis. Radiology 210:201–207PubMed

70.

Berrocal T, Gayá F, Arjonilla A et al (2001) Vesicoureteral reflux: diagnosis and grading with echo-enhanced cystosonography versus voiding cystourethrography. Radiology 221:359–365PubMedCrossRef

71.

Valentini AL, Salvaggio E, Manzoni C et al (2001) Contrast-enhanced gray-scale and color Doppler voiding urosonography versus voiding cystourethrography in the diagnosis and grading of vesicoureteral reflux. J Clin Ultrasound 29:65–71PubMedCrossRef

72.

Mentzel HJ, Vogt S, John U et al (2002) Voiding urosonography with ultrasonography contrast medium in children. Pediatr Nephrol 17:272–276PubMedCrossRef

73.

Galia M, Midiri M, Pennisi F et al (2004) Vesicoureteral reflux in young patients: comparison of voiding color Doppler US with echo enhancement versus voiding cystourethrography for diagnosis or exclusion. Abdom Imaging 29:303–308PubMedCrossRef

74.

Papadopoulou F, Tsampoulas C, Siomou E et al (2006) Cyclic contrast-enhanced harmonic voiding urosonography for the evaluation of reflux. Can we keep the cost of the examination low? Eur Radiol 16:2521–2526PubMedCrossRef

75.

Piscitelli A, Galiano R, Serrao F et al (2008) Which cystography in the diagnosis and grading of vesicoureteral reflux? Pediatr Nephrol 23:107–110PubMedCrossRef

76.

Kljucevsek D, Kljucevsek T, Kersnik Levart T et al (2009) Ureteric jet Doppler waveform: is it a reliable predictor of vesicoureteric reflux in children? Pediatr Nephrol 24:313–318PubMedCrossRef

77.

Zerin JM, Shulkin BL (1992) Postprocedural symptoms in children who undergo imaging studies of the urinary tract: is it the contrast material or the catheter? Radiology 182:727–730PubMed

78.

Kljucevsek D, Kljucevsek T, Kersnik Levart T et al (2010) Catheter-free methods for vesicoureteric reflux detection: our experience and a critical appraisal of existing data. Pediatr Nephrol 25:1201–1206PubMedCrossRef

79.

Snow BW (2011) New noninvasive methods to diagnose vesicoureteral reflux. Curr Opin Urol 21:339–342PubMedCrossRef

Title: 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)
Authors: Kassa Darge
Frederica Papadopoulou
Aikaterini Ntoulia
Dorothy I. Bulas
Brian D. Coley
Lynn A. Fordham
Harriet J. Paltiel
Beth McCarville
Frank M. Volberg
David O. Cosgrove
Barry B. Goldberg
Stephanie R. Wilson
Steven B. Feinstein
Publication date: 01-09-2013
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Radiology / Issue 9/2013
Print ISSN: 0301-0449
Electronic ISSN: 1432-1998
DOI: https://doi.org/10.1007/s00247-013-2746-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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)

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 9/2013

Clinical and MRI features of neurological complications after influenza A (H1N1) infection in critically ill children

Diffusion-weighted imaging to assess treatment response in a child with trilateral retinoblastoma

Fetal MRI on a multi-element digital coil platform

Hermes

Alveolar soft part sarcoma—radiologic patterns in children and adolescents

Comparison of respiratory-triggered 3-D fast spin-echo and single-shot fast spin-echo radial slab MR cholangiopancreatography images in children