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Contrast-enhanced voiding urosonography

Kassa Darge
Professor of Radiology
Department of Pediatric Radiology
Institute of Radiodiagnostic
E: [email protected]

Voiding urosonography (VUS) is an US examination of the bladder, ureters and kidneys (± urethra) utilising intravesically administered US contrast media with the primary purpose to exclude or diagnose reflux into the ureters and pelvic calyces. Vesicoureteral reflux (VUR) is a common paediatric problem that can, particularly in the presence of urinary tract infection, result in renal damage and consequently hypertension and renal function impairment. Three different imaging modalities are currently employed for the diagnosis of VUR. The two radiological modalities, voiding cystourethrography (VCUG) and radionuclide cystography (RNC), have been in use for several decades.

In 1976, the first report appeared on the use of US for diagnosis of VUR. Further attempts to implement US for reflux diagnosis in children have been underway in two directions.(1) The indirect methods were based on US of the urinary tract, without administration of any kind of substance into the bladder. The direct means used to diagnose VUR involved instilling various substances intravesically. The most frequently administered fluid was physiological saline solution. Application of air bubbles or adding carbon dioxide has also been tried. US studies were also carried out in which the empty bladder was solely filled with air. In addition to low diagnostic accuracy, all the above methods have major limitations, making them impractical for use in routine imaging.

The use of a US contrast agent consisting of sonicated albumin (Albunex(®); Molecular Biosystems) for the diagnosis of VUR in a child was reported in Japan in 1994.(1) A further US contrast medium used in the past was a galactose- based microbubbles-containing agent (Echovist(®), Schering). The comparison of VCUG with VUS using this US contrast medium showed high diagnostic concordance. However, its very short imaging window of approximately five minutes hindered its routine use.(1) The “breakthrough” in the US diagnosis of reflux in children came about in the mid-1990s, with the availability of US contrast agents containing stabilised microbubbles. The US contrast medium Levovist(®) (Schering, Berlin) was the first such contrast agent that became available for clinical use in Europe. It is a galactose-based contrast agent that contains microbubbles stabilised with a layer of palmitic acid. In a large number of studies incorporating hundreds of children, the diagnostic accuracy of VUS with the use of Levovist has been compared with that of VCUG.(1–4) There is a significant correlation between the two imaging modalities, with the concordance rate ranging from 89% to 97% and more refluxes being detected in the VUS (approximately 10%).(4) Moreover, up to 90% of grade I refluxes in the VCUG are found to be grade II or higher in the VUS.(3) The VUS examination incorporates four basic steps:(2,3)

  • Precontrast examination: standard US of the urinary tract in supine (± prone) positions.
  • Catheterisation or suprapubic puncture of the bladder under sterile condition and administration of normal saline and the US contrast medium.
  • Postcontrast examination: a repeat of the standard US of the urinary tract.
  • Postcontrast voiding examination: US of the renal pelves and terminal ureters (± urethra) during and after micturition.

It is crucial that the normal saline instilled into the bladder is not from a container sealed under vacuum. All plastic containers are not sealed under vacuum, but almost all glass containers are. The normal saline in the latter is desaturated, and the air in the microbubbles diffuses very rapidly in the solution with the consequence of fast decrease of echo-enhancement. Reflux is diagnosed when echogenic microbubbles are detected in the ureters or pelvic calyces. During the postcontrast examinations, the right and left renal pelves are scanned alternatively. The scan during voiding can be carried out when the patient is lying or sitting on a pan or standing and voiding into a urine bottle. The severity of reflux is graded in a similar manner as the international reflux grading system in VCUG from grade I to V. Comparative studies have shown the high concordance rate of over 85% between the reflux grading systems in VCUG and VUS.(1,3)

Depending on the availability, different US imaging modalities are employed in VUS to depict the refluxing microbubbles. These imaging options affect not only the conspicuity of the microbubbles but also the overall diagnostic accuracy of the examination. The most widely employed modality for VUS is conventional (ie, fundamental) US. This can be combined with colour Doppler to enhance the detection of reflux. A recent innovation in US, and one that will have major impact on the application of US contrast media, is harmonic imaging. When using harmonic imaging for VUS, not only do the microbubbles become strikingly conspicuous compared with the fundamental mode but the sensitivity is also significantly increased (see Figure 1).(5) Furthermore, it is possible to visualise intrarenal reflux. Advanced contrast-specific imaging modalities tuned for individual contrast medium (eg, “agent detection imaging” [Sequoia, Siemens] have brought about a profound improvement in detecting refluxing microbubbles). Not only are the microbubbles are enhanced and colour-coded, but it is also possible to visualise only the refluxing microbubbles blocking out the background greyscale image (see Figure 2).



Currently, the US contrast medium Levovist is the most widely used and the one approved for use in VUS. The concentration of Levovist used for VUS is 300mg/ml. The dose administered depends on the imaging modality being employed. For fundamental US, the volume of Levovist administered is 5%–10% of the filling volume of the bladder.(1–3) In the case of harmonic imaging or advanced contrast-specific imaging modalities, 3%–5% of the filling volume of the bladder suffices (ie, for one cycle of examination just one 2.5g flask of Levovist will be adequate).(5) Recently, a second-generation US contrast agent, SonoVue(®) (Bracco), has become available in Europe.

Preliminary comparative studies have revealed that the dose of this contrast medium for intravesical use is less than 1% of the bladder filling.(1) This will have a huge potential in the future not only in reducing the amount of contrast medium necessary for an examination but also in markedly lowering the cost for a VUS. With the introduction of VUS in a paediatric radiology department as an alternative reflux imaging modality, it is possible to reduce significantly the VCUGs by over half, consequently curtailing radiation exposure of paediatric patients.


  1. Darge K,Riedmiller H. Current status of vesicoureteral reflux diagnosis. World J Urol 2004;22:88-95.
  2. Darge K, Troeger J, Duetting T, et al. Reflux in young patients:comparison of voiding US of the bladder and retrovesical space with echo enhancement versus voiding cystourethrography for diagnosis. Radiology 2001;210:201-7.
  3. Berrocal T, Gaya F, Arjonilla A, Lonergan GJ. Vesicoureteral reflux: diagnosis and grading with echo-enhanced cystosonography versus voiding cystourethrography.Radiology 2001;221:359-65.
  4. Valentini AL, De Gaetano AM, Destito C, et al. The accuracy of voiding urosonography in detecting vesico-ureteral reflux: a summary of existing data. Eur J Pediatr 2002;161:380-4.
  5. Darge K, Zieger B, Rohrschneider W, et al. Contrast-enhanced harmonic imaging for the diagnosis of vesicoureteral reflux. AJR 2001;177:1411-5.