Contrast Enhanced Ultrasound in Pediatric Patients: A Real Challenge

Abstract

Ultrasound (US) imaging in the paediatric population has been a routine technique for decades, in part because of the advantages it offers over other imaging modalities. Off-label use (and its funding) is of the utmost importance in paediatrics because many drugs have not been evaluated in randomised trials in children. As a consequence such drugs are not specifically approved for use in children. This is also true for the contrast agents used in CEUS. The off-label use of CEUS in paediatric patients illustrates the need to deal with unresolved legal issues while at the same time balancing this with the need for high diagnostic performance in daily clinical routine. In addition to approved indications with a focus on the liver and Doppler enhancement, CEUS is safe and effective for the examination of many organs, as recently highlighted by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). This article provides a summary of the available literature describing the utility of CEUS in paediatric patients. Furthermore, we suggest the establishment of a registry to collect data on safety and applications of ultrasound contrast agents in children. A paediatric registry has recently been introduced by EFSUMB (www.efsumb.org).

Zusammenfassung

Ultraschall ist ein Standardverfahren in der Pädiatrie. Vorteile gegenüber radiologischen Methoden sind offensichtlich. Die Anwendung nicht speziell für Kinder zugelassener Medikamente und Kontrastmittel stellt ein relevantes Problem in der Pädiatrie dar. Dies gilt ebenfalls für Ultraschallkontrastmittel. Diese Thematik ist brandaktuell und illustriert offensichtliche Schwächen in unserem Gesundheitssystem und den Europäischen Zulassungsprozessen. Die Vorteile und Sicherheitsaspekte von CEUS wurden durch die European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) in Leitlinien publiziert. Dieser Artikel fasst aktuelles Wissen zusammen und fokussiert auf den Nutzen von CEUS in der Kinderheilkunde. Ziel dieses Artikel ist es auch, eine Datensammlung zu generieren, die die Anwendungsmöglichkeiten und Sicherheit von CEUS im Kindesalter abbildet. Die EFSUMB hat eine „Pediatric Registry“ zu diesem Zwecke eingerichtet (www.efsumb.org).

Schlüsselwörter

Leber - Charakterisierung - Microbubble - Richtlinien - Register

Key words

liver - characterization - microbubble - guidelines - registry

• References

• 1 Piskunowicz M, Kosiak W, Irga N. Primum non nocere? Why can't we use second generation ultrasound contrast agents for the examination of children?. Ultraschall in der Medizin 2011; 32: 83-86
• 2 Nolsoe C, Piscaglia F, Dietrich CF et al. Why Can't We Use Second Generation Ultrasound Contrast Agents for the Examination of Children?. Ultraschall in der Medizin 2011; 32: 83-86
• 3 Schreiber-Dietrich D, Dietrich CF. Contrast enhanced ultrasound (CEUS) and off-label use (in children). Ultraschall in der Medizin 2012; 33: 295-296
• 4 Claudon M, Cosgrove D, Albrecht T et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) – update 2008. Ultraschall in der Medizin 2008; 29: 28-44
• 5 Claudon M, Dietrich CF, Choi BI et al. 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 in der Medizin 2013; 34: 11-29
• 6 Dietrich CF, Averkiou MA, Correas JM et al. An EFSUMB introduction into Dynamic Contrast-Enhanced Ultrasound (DCE-US) for quantification of tumour perfusion. Ultraschall in der Medizin 2012; 33: 344-351
• 7 Piscaglia F, Nolsoe C, Dietrich CF et al. The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast Enhanced Ultrasound (CEUS): update 2011 on non-hepatic applications. Ultraschall in der Medizin 2012; 33: 33-59
• 8 Piskunowicz M, Kosiak W, Batko T. Intravenous application of second-generation ultrasound contrast agents in children: a review of the literature. Ultraschall in der Medizin 2012; 33: 135-140
• 9 Akgur FM, Aktug T, Olguner M et al. Prospective study investigating routine usage of ultrasonography as the initial diagnostic modality for the evaluation of children sustaining blunt abdominal trauma. The Journal of trauma 1997; 42: 626-628
• 10 Patel JC, Tepas 3rd JJ. The efficacy of focused abdominal sonography for trauma (FAST) as a screening tool in the assessment of injured children. Journal of pediatric surgery 1999; 34: 44-47 discussion 52–44
• 11 Rossi D, de Ville de Goyet J, Clement de Clety S et al. Management of intra-abdominal organ injury following blunt abdominal trauma in children. Intensive care medicine 1993; 19: 415-419
• 12 Soudack M, Epelman M, Maor R et al. Experience with focused abdominal sonography for trauma (FAST) in 313 pediatric patients. Journal of clinical ultrasound: JCU 2004; 32: 53-61
• 13 Benya EC, Lim-Dunham JE, Landrum O et al. Abdominal sonography in examination of children with blunt abdominal trauma. Am J Roentgenol American journal of roentgenology 2000; 174: 1613-1616
• 14 Coley BD, Mutabagani KH, Martin LC et al. Focused abdominal sonography for trauma (FAST) in children with blunt abdominal trauma. The Journal of trauma 2000; 48: 902-906
• 15 Emery KH, McAneney CM, Racadio JM et al. Absent peritoneal fluid on screening trauma ultrasonography in children: a prospective comparison with computed tomography. Journal of pediatric surgery 2001; 36: 565-569
• 16 McGahan JP, Horton S, Gerscovich EO et al. Appearance of solid organ injury with contrast-enhanced sonography in blunt abdominal trauma: preliminary experience. Am J Roentgenol American journal of roentgenology 2006; 187: 658-666
• 17 Valentino M, Serra C, Pavlica P et al. Blunt abdominal trauma: diagnostic performance of contrast-enhanced US in children--initial experience. Radiology 2008; 246: 903-909
• 18 Oldenburg A, Hohmann J, Skrok J et al. Imaging of paediatric splenic injury with contrast-enhanced ultrasonography. Pediatric radiology 2004; 34: 351-354
• 19 Thorelius L. Emergency real-time contrast-enhanced ultrasonography for detection of solid organ injuries. European radiology 2007; 17 (Suppl. 06) F107-F111
• 20 Valentino M, Galloni SS, Rimondi MR et al. Contrast-enhanced ultrasound in non-operative management of pancreatic injury in childhood. Pediatric radiology 2006; 36: 558-560
• 21 Cleper R, Krause I, Eisenstein B et al. Prevalence of vesicoureteral reflux in neonatal urinary tract infection. Clinical pediatrics 2004; 43: 619-625
• 22 Jacobson SH, Hansson S, Jakobsson B. Vesico-ureteric reflux: occurrence and long-term risks. Acta paediatrica 1999; 88: 22-30
• 23 Jakobsson B, Jacobson SH, Hjalmas K. Vesico-ureteric reflux and other risk factors for renal damage: identification of high- and low-risk children. Acta paediatrica 1999; 88: 31-39
• 24 Wennerstrom M, Hansson S, Jodal U et al. Disappearance of vesicoureteral reflux in children. Archives of pediatrics & adolescent medicine 1998; 152: 879-883
• 25 Riccabona M, Avni FE, Dacher JN et al. ESPR uroradiology task force and ESUR paediatric working group: imaging and procedural recommendations in paediatric uroradiology, part III. Minutes of the ESPR uroradiology task force minisymposium on intravenous urography, uro-CT and MR-urography in childhood. Pediatric radiology 2010; 40: 1315-1320
• 26 Riccabona M, Avni FE, Damasio MB et al. 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. Pediatric radiology 2012; 42: 1275-1283
• 27 Riccabona M, Lobo ML, Papadopoulou F et al. ESPR uroradiology task force and ESUR paediatric working group: imaging recommendations in paediatric uroradiology, part IV: Minutes of the ESPR uroradiology task force mini-symposium on imaging in childhood renal hypertension and imaging of renal trauma in children. Pediatric radiology 2011; 41: 939-944
• 28 Darge K, Ghods S, Zieger B et al. Reduction in voiding cystourethrographies after the introduction of contrast enhanced sonographic reflux diagnosis. Pediatric radiology 2001; 31: 790-795
• 29 Giordano M, Marzolla R, Puteo F et al. Voiding urosonography as first step in the diagnosis of vesicoureteral reflux in children: a clinical experience. Pediatric radiology 2007; 37: 674-677
• 30 Piaggio G, Degl' Innocenti ML, Toma P et al. Cystosonography and voiding cystourethrography in the diagnosis of vesicoureteral reflux. Pediatric nephrology 2003; 18: 18-22
• 31 Berrocal T, Gaya F, Arjonilla A. Vesicoureteral reflux: can the urethra be adequately assessed by using contrast-enhanced voiding US of the bladder?. Radiology 2005; 234: 235-241
• 32 Duran C, Valera A, Alguersuari A et al. Voiding urosonography: the study of the urethra is no longer a limitation of the technique. Pediatric radiology 2009; 39: 124-131
• 33 Darge K, Troeger J. Vesicoureteral reflux grading in contrast-enhanced voiding urosonography. European journal of radiology 2002; 43: 122-128
• 34 Darge K, Zieger B, Rohrschneider W et al. Contrast-enhanced harmonic imaging for the diagnosis of vesicoureteral reflux in pediatric patients. Am J Roentgenol American journal of roentgenology 2001; 177: 1411-1415
• 35 Duran C, del Riego J, Riera L et al. Voiding urosonography including urethrosonography: high-quality examinations with an optimised procedure using a second-generation US contrast agent. Pediatric radiology 2012; 42: 660-667
• 36 Riccabona M. Ultrasound of the chest in children (mediastinum excluded). European radiology 2008; 18: 390-399
• 37 Riccabona M, Mache CJ, Lindbichler F. Echo-enhanced color Doppler cystosonography of vesicoureteral reflux in children. Improvement by stimulated acoustic emission. Acta radiologica 2003; 44: 18-23
• 38 Ascenti G, Zimbaro G, Mazziotti S et al. Harmonic US imaging of vesicoureteric reflux in children: usefulness of a second generation US contrast agent. Pediatric radiology 2004; 34: 481-487
• 39 Kis E, Nyitrai A, Varkonyi I et al. Voiding urosonography with second-generation contrast agent versus voiding cystourethrography. Pediatric nephrology 2010; 25: 2289-2293
• 40 Papadopoulou F, Anthopoulou A, Siomou E et al. Harmonic voiding urosonography with a second-generation contrast agent for the diagnosis of vesicoureteral reflux. Pediatric radiology 2009; 39: 239-244
• 41 Darge K. Voiding urosonography with ultrasound contrast agents for the diagnosis of vesicoureteric reflux in children. I. Procedure. Pediatric radiology 2008; 38: 40-53
• 42 Spinazzi A. Emerging clinical applications for contrast-enhanced ultrasonography. European radiology 2001; 11 (Suppl. 03) E7-E12
• 43 Zimbaro G, Ascenti G, Visalli C et al. Contrast-enhanced ultrasonography (voiding urosonography) of vesicoureteral reflux: state of the art. La Radiologia medica 2007; 112: 1211-1224
• 44 Darge K. Voiding urosonography with US contrast agents for the diagnosis of vesicoureteric reflux in children. II. Comparison with radiological examinations. Pediatric radiology 2008; 38: 54-63 quiz 126–127
• 45 Barreiros AP, Piscaglia F, Dietrich CF. Contrast enhanced ultrasound for the diagnosis of hepatocellular carcinoma (HCC): comments on AASLD guidelines. Journal of hepatology 2012; 57: 930-932
• 46 Claudon M, Dietrich CF, Choi BI et al. 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. Ultrasound in medicine & biology 2013; 39: 187-210
• 47 Dietrich CF, Cui XW, Boozari B et al. Contrast-enhanced ultrasound (CEUS) in the diagnostic algorithm of hepatocellular and cholangiocellular carcinoma, comments on the AASLD guidelines. Ultraschall in der Medizin 2012; 33 (Suppl. 01) S57-S66
• 48 Dietrich CF. Liver tumor characterization--comments and illustrations regarding guidelines. Ultraschall in der Medizin 2012; 33 (Suppl. 01) S22-S30
• 49 Dietrich CF, Ignee A, Trojan J et al. Improved characterisation of histologically proven liver tumours by contrast enhanced ultrasonography during the portal venous and specific late phase of SHU 508A. Gut 2004; 53: 401-405
• 50 Dietrich CF, Maddalena ME, Cui XW et al. Liver tumor characterization--review of the literature. Ultraschall in der Medizin 2012; 33 (Suppl. 01) S3-S10
• 51 Dietrich CF, Schuessler G, Trojan J et al. Differentiation of focal nodular hyperplasia and hepatocellular adenoma by contrast-enhanced ultrasound. The British journal of radiology 2005; 78: 704-707
• 52 Jang HJ, Yu H, Kim TK. Contrast-enhanced ultrasound in the detection and characterization of liver tumors. Cancer imaging: the official publication of the International Cancer Imaging Society 2009; 9: 96-103
• 53 Luo XL, Liu D, Yang JJ et al. Primary gastrointestinal stromal tumor of the liver: a case report. World journal of gastroenterology: WJG 2009; 15: 3704-3707
• 54 Mandry D, Bressenot A, Galloy MA et al. Contrast-enhanced ultrasound in fibro-lamellar hepatocellular carcinoma: a case report. Ultraschall in der Medizin 2007; 28: 547-552
• 55 Bonini G, Pezzotta G, Morzenti C et al. Contrast-enhanced ultrasound with SonoVue in the evaluation of postoperative complications in pediatric liver transplant recipients. Journal of ultrasound 2007; 10: 99-106
• 56 de Perrot T, Righini M, Bounameaux H et al. Contrast-enhanced sonographic diagnosis of unsuspected internal iliac vein thrombosis. Journal of clinical ultrasound: JCU 2011; 39: 553-555
• 57 D'Onofrio M, Malago R, Vecchiato F et al. Contrast-enhanced ultrasonography of small solid pseudopapillary tumors of the pancreas: enhancement pattern and pathologic correlation of 2 cases. Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 2005; 24: 849-854
• 58 Groth KA, Hoyer S, Klaaborg KE et al. Get closer to the diagnosis in a flash. Circulation Cardiovascular imaging 2012; 5: 280-282
• 59 Svensson JF, Larsson A, Uusijarvi J et al. Oophoropexy, hyperbaric oxygen therapy, and contrast-enhanced ultrasound after asynchronous bilateral ovarian torsion. Journal of pediatric surgery 2008; 43: 1380-1384
• 60 Dietrich CF, Cui XW, Barreiros AP et al. EFSUMB guidelines 2011: comment on emergent indications and visions. Ultraschall in der Medizin 2012; 33 (Suppl. 01) S39-S47
• 61 Dietrich CF, Cui XW, Schreiber-Dietrich DG et al. EFSUMB guidelines 2011: comments and illustrations. Ultraschall in der Medizin 2012; 33 (Suppl. 01) S11-S21
• 62 Dietrich CF, Schreiber-Dietrich D, Hocke M. Comments on the EFSUMB non-liver Guidelines 2011. Praxis 2012; 101: 1175-1181
• 63 Piscaglia F, Bolondi L. Italian Society for Ultrasound in M et al. The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations. Ultrasound in medicine & biology 2006; 32: 1369-1375
• 64 Henschel AD, Rothenberger LG, Boos J. Randomized clinical trials in children--ethical and methodological issues. Current pharmaceutical design 2010; 16: 2407-2415
• 65 Rothenberger LG, Henschel AD, Schrey D et al. Methodological and ethical aspects of randomized controlled clinical trials in minors with malignant diseases. Pediatric blood & cancer 2011; 57: 599-605
• 66 Conroy S, Choonara I, Impicciatore P et al. Survey of unlicensed and off label drug use in paediatric wards in European countries. European Network for Drug Investigation in Children. Bmj 2000; 320: 79-82
• 67 Conroy S, McIntyre J, Choonara I. Unlicensed and off label drug use in neonates. Archives of disease in childhood Fetal and neonatal edition 1999; 80: F142-F144 discussion F144–F145