Contrast-enhanced ultrasound (CEUS) is reliable, safe and non-ionising, and these benefits make it very interesting for examining children. However, intravenous application for assessment of focal liver lesions in children is currently off-label in Europe and paediatric radiologists must advocate for its approval, experts will argue in a Special Focus session.

Dr. Damjana Ključevšek from the University Medical Centre Children’s Hospital in Ljubljana, Slovenia, will speak about liver and extrahepatic intravenous applications of CEUS in children.

There is mounting evidence backing the use of contrast-enhanced ultrasound (CEUS) in children and the technique is now widely recognised in many fields, according to Dr. Damjana Ključevšek from the University Medical Centre Children’s Hospital in Ljubljana, Slovenia. “CEUS is particularly beneficial for children: baby habitus is ideal for ultrasonography, due to the small body size and tissue composition, and CEUS is easily repeatable and can be performed in a variety of settings. It is cost effective, radiation-free and requires no sedation. Ultrasound contrast agents also have fewer adverse effects than iodine or paramagnetic contrast agents. For example, ultrasound contrast agents are not excreted by the kidneys, so they are not nephrotoxic. Paediatric radiologists have to advocate for these new methods to make them available for children,” she said.

A new era of CEUS imaging is beginning with the recent approval of SonoVue®/Lumason® for paediatric intravesical applications in the United States, Europe and Asia. However, paediatric intravenous (IV) application specifically for assessment of focal liver lesions is approved only in the United States, while in Europe it is still off-label. This situation is confusing to say the least, according to Ključevšek.

“When a contrast agent is administered intravenously, it passes through all the organs in the body. So it does not matter which organ is evaluated during the contrast agent distribution. When looking at the liver, why not look at the kidney, spleen, bowel and soft tissue as well? This really makes no sense. The sensitivity, specificity and diagnostic accuracy of CEUS in different fields is a matter of clinical guidelines. Even if IV CEUS examinations are currently off-label, it does not mean that they are banned. Many reports from different abdominal organs, tumours and scrotum have proved that CEUS has much greater capability than officially allowed,” she argued.

A three-year-old girl with an incidental focal liver lesion finding on ultrasound (US) examination: (A) native US showed a well-defined lesion in liver parenchyma, (B–F) focal liver lesion is well depicted during contrast-enhanced ultrasonography (CEUS): (B) entering artery (arrow), (C–E) lesion enhancement (arrowheads) during arterial phases of CEUS showed first hyperenhancement of the lesion, which becomes iso-enhanced during venous phase (F). This is a typical enhancement pattern for focal nodular hyperplasia. The diagnosis was made, and no further imaging is necessary (provided by Dr. Damjana Ključevšek).

Dynamic CEUS is a real step forward in quantitative evaluation of tissue perfusion. A video clip is recorded in continuum for 100 to 180 seconds at the same location, and then analysed using special post-processing software to obtain a time-intensity curve and calculate different time and intensity parameters. “Dynamic CEUS allows objective evaluation of the examined organ or tumour perfusion. These tissue perfusion studies are more frequent in oncologic patients and in the evaluation of degree of inflammation in, for example, inflammatory bowel diseases in children,” she said.

In recent years, new guidelines and good clinical practice recommendations for the use of ultrasound contrast agents in children have been published by the European Federation of Societies for Ultrasound in Medicine and Biology and the European Society of Paediatric Radiology.

“CEUS has a number of well-known advantages over CT and MR, particularly in children, and IV applications may influence clinical management,” said Ključevšek.

Prof. Goran Roić from the Children’s Hospital in Zagreb, Croatia, will talk about vesicoureteral (VU) reflux (© Luka Stanzl / PIXSELL).

Contrast-enhanced voiding urosonography (ceVUS) is a relatively new dynamic imaging technique that enables the morphological and functional evaluation of the entire urinary tract by introducing an ultrasonographic (US) contrast agent into the bladder. CeVUS is most often indicated to depict vesicoureteral reflux (VUR), the most common urinary tract abnormality in children, as the method is diagnostically more reliable than x-ray voiding cystourethrography (VCUG) and radionuclide voiding cystography (RNVC), according to Prof. Goran Roić from the Children’s Hospital in Zagreb, Croatia, who will also speak in the session.

Fig. A: Contrast-enhanced voiding ultrasonography (ceVUS): transverse sonogram – bladder completely filled with ultrasound contrast medium.
Fig. B: Contrast-enhanced voiding ultrasonography (ceVUS): reflux of the contrast media into the ureter and kidney collecting system.
Fig. C: Contrast-enhanced voiding ultrasonography (ceVUS): Grade 5 vesicoureteral reflux (VUR).
Fig. D: Contrast-enhanced voiding ultrasonography (ceVUS): Grade 2 vesicoureteral reflux (VUR).
Fig. E: Contrast-enhanced voiding ultrasonography (ceVUS): suprapubic approach – the neck of the bladder, male urethra.
Fig. F: Contrast-enhanced voiding ultrasonography (ceVUS): intrarenal reflux (IRR) – hyperechoic contrast foci in the renal parenchyma.
(Images provided by Prof. Goran Roić)

“CeVUS provides important morphological and functional information regarding the urinary tract and allows the diagnosis of reflux, to help prevent the spread of infection from the lower urinary tract to the kidneys. Recently, many comparative studies have shown that ceVUS is not only more sensitive, but also detects higher grades of reflux compared with VCUG. In addition, ceVUS can be used to differentiate obstructive from non-obstructive urethral pathologic conditions, as well as normal variants, on high-quality diagnostic images,” Roić explained.

In addition, ceVUS does not use ionising radiation and can be combined with urodynamic investigation in a so-called videourodynamics study, which has become a gold standard for functional and anatomic evaluation of the urinary tract.

Consequently, ceVUS use is increasing, but slowly. Many hospitals have no skilled paediatric radiologists, who are paramount to such a system. “CeVUS requires a skilled medical team, state-of-the-art ultrasound equipment, ultrasound machines with contrast-enhanced software and second-generation ultrasound contrast,” he said.

The technique has a long learning curve, but with experience, it becomes easier and examination times can be reduced. Diagnosis can be more difficult in certain uncommon pathologic conditions, such as severe scoliosis or renal ectopia, that make it difficult to locate and depict the kidneys. Furthermore, ceVUS is not recommended in cases of active, untreated urinary tract infection.

Besides the off-label status for liver IV application, CEUS has a high safety profile – the contrast agent is safer than iodine or paramagnetic contrast agents with transient light side effects like headache, tinnitus, urticaria, rash, taste alteration and hyperventilation.

However, there are a few reports of anaphylactoid reactions after IV application, also in children. “Resuscitation equipment should therefore always be ready in the ultrasound examination room and radiologists should be prepared to act appropriately,” Ključevšek said.

One last limitation is if the lesion is not well depicted on native ultrasound, when it is located too deeply to evaluate it properly, in obese children, or when there is superposition of bowel air – just as with native or Doppler ultrasound.

Special Focus Session, Tuesday, October 20, 17:00–18:00
SF 1b CEUS in children

  • Chairperson’s introduction
    Magdalena Wozniak; Lublin/PL
  • Liver and extrahepatic intravenous applications
    Damjana Kljucevsek; Ljubljana/SI
  • Vesicoureteral (VU) reflux
    Goran Roić; Zagreb/HR
  • Traumas
    Hans-Joachim Mentzel; Jena/DE
  • Live Q&A: Is off-label use of CEUS in children a cause for concern?


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Wozniak MM, Pawelec A, Wieczorek AP, Zajączkowska MM, Nachulewicz P, Borzęcka H (2014) The usefulness of 3D/4D techniques during voiding urosonography (VUS) in the diagnostics and monitoring of treatment of vesicoureteral reflux in children. ECR 2014 / C-0344:

Duran Feliubadaló C, Beltrán Salazar VP, Martin C et al (2015) Tips and tricks to evaluate the urethra through serial voiding urosonography (VUS): making it easy. ECR 2015 / C-1387: