European Journal of Pediatrics

, Volume 173, Issue 8, pp 1095–1101 | Cite as

Voiding urosonography with second-generation ultrasound contrast versus micturating cystourethrography in the diagnosis of vesicoureteric reflux

  • L. S. Wong
  • K. S. TseEmail author
  • T. W. Fan
  • K. Y. Kwok
  • T. K. Tsang
  • H. S. Fung
  • W. Chan
  • K. W. Lee
  • M. W. Y. Leung
  • N. S. Y. Chao
  • K. W. Tang
  • S. C. H Chan
Original Article


Vesicoureteric reflux has been associated with paediatric urinary tract infection. Fluoroscopic micturating cystourethrography (MCU) has been the gold standard of diagnostic test for decades; however, it has been criticized owing to its lower detection rate and radiation dose to children. Therefore, new radiation-free reflux imaging modalities have been developed, in which ultrasound-based contrast-enhanced voiding urosonography (ceVUS) is a good example. However, ultrasonography has been considered as an operator-dependent examination. Therefore, our study aimed to examine the inter-observer agreement of this sonographic technique, which has not been evaluated before. Moreover, the second-generation ultrasound contrast SonoVue has been recently marketed, and the data on its efficacy on intravesical use in ceVUS is relatively scarce. Thus, we also aimed to investigate the diagnostic performance and safety profile of SonoVue-enhanced VUS in the diagnosis of vesicoureteric reflux. Our prospective comparative study compared the diagnostic performance of ceVUS with MCU in young children presenting with first episode of urinary tract infection. We performed sequential ceVUS and MCU examinations in 31 patients (62 pelvi-ureter units). Perfect inter-observer agreement (Cohen’s kappa statistics = 1.0, p < 0.001) was achieved in ceVUS, suggesting its good reliability in reflux detection and grading. Using MCU as reference, ceVUS had 100 % sensitivity and 84 % specificity and carried higher reflux detection rate than MCU (p < 0.001). There was no complication encountered. Conclusion: Voiding urosonography is a reliable, sensitive, safe and radiation-free modality in the investigation of vesicoureteric reflux in children. It should be incorporated in the diagnostic algorithm in paediatric urinary tract infection.


Voiding urosonography Micturating cystourethrography Vesicoureteric reflux Urinary tract infection Paediatric 



Voiding urosonography


Micturating cystourethrography


Vesicoureteric reflux


Radionuclide cystography


Urinary tract infection



The authors would like to thank Dr. Kassa Darge for his technical advices in this study.

Supplementary material

Online resource 1

Cine loop of the left kidney shows the influx of moving echogenic particles into the mildly dilated left renal pelvis and calyces during real-time ceVUS examination (grade III reflux). Real-time examination provides definitive evidence to the diagnosis of vesicoureteric reflux (MPG 840 kb)


  1. 1.
    Ascenti G, Zimbaro G, Mazziotti S, Chimenz R, Fede C, Visalli C, Scribano E (2004) Harmonic US imaging of vesicoureteric reflux in children: usefulness of a second generation US contrast agent. Pediatr Radiol 34:481–487PubMedCrossRefGoogle Scholar
  2. 2.
    Atala A, Ellsworth P, Share J, Paltiel H, Walker RD, Retik AB (1998) Comparison of sonicated albumin enhanced sonography to fluoroscopic and radionuclide voiding cystography for detecting vesicoureteral reflux. J Urol 160:1820–1822PubMedCrossRefGoogle Scholar
  3. 3.
    Bosio M (1998) Cystosonography with echocontrast: a new imaging modality to detect vesicoureteral reflux in children. Pediatr Radiol 28:250–255PubMedCrossRefGoogle Scholar
  4. 4.
    Cleper R, Krause I, Eisenstein B, Davidovits M (2004) Prevalence of vesicoureteral reflux in neonatal urinary tract infection. Clin Pediatr (Phila) 43(7):619–625CrossRefGoogle Scholar
  5. 5.
    Darge K (2008) Voiding urosonography with ultrasound contrast agents for the diagnosis of vesicoureteric reflux in children. I. Procedure. Pediatr Radiol 38:40–53PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Darge K (2008) Voiding urosonography with US contrast agents for the diagnosis of vesicoureteric reflux in children. II. Comparison with radiological examinations. Pediatr Radiol 38:54–63PubMedCrossRefGoogle Scholar
  7. 7.
    Darge K, Troeger J (2002) Vesicoureteral reflux grading in contrast-enhanced voiding urosonography. Eur J Radiol 43:122–128PubMedCrossRefGoogle Scholar
  8. 8.
    Darge K, Dutting T, Zieger B, Mohring K, Rohrschneider W, Troger J (1998) Diagnosis of vesicoureteral reflux with echo-enhanced micturition urosonography. Radiologe 38(5):405–409PubMedCrossRefGoogle Scholar
  9. 9.
    Darge K, Beer M, Gordjani N, Riedmiller H (2004) Contrast-enhanced voiding urosonography with the use of a 2nd generation US contrast medium: preliminary results. Pediatr Radiol 34:S97CrossRefGoogle Scholar
  10. 10.
    Darge K, Papadopoulou F, Ntoulia A 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 43(9):1063–1073PubMedCrossRefGoogle Scholar
  11. 11.
    Duran C, Valera A, Alguersuari A, Ballesteros E, Riera L, Martin C, Puig J (2009) Voiding urosonography: the study of the urethra is no longer a limitation of the technique. Pediatr Radiol 39:124–131PubMedCrossRefGoogle Scholar
  12. 12.
    Duran C, del Riego J, Riera L, Martin C, Serrano C, Palana P (2012) Voiding urosonography including urethrosonography: high-quality examinations with an optimised procedure using a second-generation US contrast agent. Pediatr Radiol 42:660–667PubMedCrossRefGoogle Scholar
  13. 13.
    Galloy MA, Guillemin F, Couture A et al (2008) Voiding ultrasonography: evaluation of the detection of vesicoureteral reflux based on the review of digital ultrasound clips. Ultraschall Med 29(1):53–59PubMedCrossRefGoogle Scholar
  14. 14.
    Greenbaum LA, Mesrobian HGO (2006) Vesicoureteral reflux. Pediatr Clin N Am 53:413–427CrossRefGoogle Scholar
  15. 15.
    Greenfield SP, Wan J (1996) Vesicoureteral reflux: practical aspects of evaluation and management. Pediatr Nephrol 10(6):789–794PubMedCrossRefGoogle Scholar
  16. 16.
    Hellerstein S (1995) Urinary tract infections—old and new concepts. Pediatr Clin N Am 42(6):1433–1457Google Scholar
  17. 17.
    Kis E, Nyitrai A, Varkonyi I, Mattyus I, Cseprekal O, Reusz G, Szabo A (2010) Voiding urosonography with second-generation contrast agent versus voiding cystourethrography. Pediatr Nephrol 25:2289–2293PubMedCrossRefGoogle Scholar
  18. 18.
    Kljucevsek D, Battelino N, Tomazic M, Levart TK (2012) A comparison of echo-enhanced voiding urosonography with X-ray voiding cystourethrography in the first year of life. Acta Paediatr 101:e235–e239PubMedCrossRefGoogle Scholar
  19. 19.
    Koff SA (1983) Estimating bladder capacity in children. Urology 21(3):248PubMedCrossRefGoogle Scholar
  20. 20.
    Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM, Tamminen-Mobius TE (1985) International system of radiographic grading of vesicoureteric reflux. Pediatr Radiol 15:105–109PubMedCrossRefGoogle Scholar
  21. 21.
    Lim R (2009) Vesicoureteral reflux and urinary tract infection: evolving practices and current controversies in pediatric imaging. AJR 192(5):1197–1208PubMedCrossRefGoogle Scholar
  22. 22.
    Papadopoulou F, Katzioti F, Arkoumani E et al (2005) Voiding urosonography harmonic imaging with 2nd generation contrast agent for the diagnosis of reflux (abstract O 110). Pediatr Radiol S35:130Google Scholar
  23. 23.
    Papadopoulou F, Anthopoulou A, Siomou E, Efremidis S, Tsamboulas C, Darge K (2009) Harmonic voiding urosonography with a second-generation contrast agent for the diagnosis of vesicoureteral reflux. Pediatr Radiol 39(3):239–244PubMedCrossRefGoogle Scholar
  24. 24.
    Papadopoulou F, Ntoulia A, Siomou E, Darge K (2014). Contrast-enhanced voiding urosonography with intravesical administration of a second-generation ultrasound contrast agent for diagnosis of vesicoureteral reflux: prospective evaluation of contrast safety in 1,010 children. Pediatr Radiol. 2014 Jan 18Google Scholar
  25. 25.
    Prasad MM, Cheng EY (2012) Radiographic evaluation of children with febrile urinary tract infection: bottom-up, top-down, or none of the above? Adv Urol 2012:716739PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Riccabona M (2012) Application of a second-generation US contrast agent in infants and children—a European questionnaire-based survey. Pediatr Radiol 42(12):1471–1480PubMedCrossRefGoogle Scholar
  27. 27.
    Riccabona M, Avni FE, Blickman JG, Dacher JN, Darge K, Lobo ML, Willi U (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 38:138–145PubMedCrossRefGoogle Scholar
  28. 28.
    Riccabona M, Avni FE, Damasio MB, Ording-Muller LS, Blickman JG, Darge K, Lobo ML, Papadopoulou F, Vivier PH, Willi U (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(10):1275–1283PubMedCrossRefGoogle Scholar
  29. 29.
    Rushton HG (1997) Urinary tract infections in children. Epidemiology, evaluation, and management. Pediatr Clin N Am 44:1133–1169CrossRefGoogle Scholar
  30. 30.
    Schneider M (1999) SonoVue, a new ultrasound contrast agent. Eur Radiol 9(S3):S347–S348PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • L. S. Wong
    • 1
  • K. S. Tse
    • 1
    Email author
  • T. W. Fan
    • 2
  • K. Y. Kwok
    • 1
  • T. K. Tsang
    • 3
  • H. S. Fung
    • 1
  • W. Chan
    • 4
  • K. W. Lee
    • 5
  • M. W. Y. Leung
    • 6
  • N. S. Y. Chao
    • 6
  • K. W. Tang
    • 1
  • S. C. H Chan
    • 1
  1. 1.Department of Radiology and ImagingQueen Elizabeth HospitalKowloonHong Kong
  2. 2.Scanning DepartmentSt Teresa’s Medical CentreKowloonHong Kong
  3. 3.Department of RadiologyEvangelist HospitalKowloonHong Kong
  4. 4.Department of PaediatricsQueen Elizabeth HospitalKowloonHong Kong
  5. 5.Department of PaediatricsSt Teresa’s Medical CentreKowloonHong Kong
  6. 6.Division of Paediatric Surgery, Department of SurgeryQueen Elizabeth HospitalKowloonHong Kong

Personalised recommendations