There are continuing efforts to reduce radiation exposure in children, and it is widely acknowledged by learned societies dealing with paediatric imaging, that ultrasound (US) and magnetic resonance (MR) imaging need to be used more often. Computed Tomography (CT) has an essential role but overuse and hence increased radiation exposure in children is a recognised problem. There have been a number of studies that point out the long-term detrimental effects of radiation in the young patient 1 2 , with the lifetime risk of a malignancy induced by the radiation of a single CT examination depending on age: 1/1000 at age 15 years and 2.5/1000 at age 1 year. This is not surprising as a single abdominal CT examination may involve a radiation dose of ≅30 mSv (± 12 years of background radiation). Campaigns are in progress to educate physicians of the potential deleterious long-term effects of CT induced radiation in patients, with a particularly concerted effort in progress from paediatric practitioners 3 . Ultimately, pressure from parents will ensure that radiation in children is kept at a minimal level needed for diagnostic requirements. CT examinations work best with a certain amount of body fat surrounding abdominal organs; most children lack this fat distribution, but US thrives on the absence of fat, making US much more suited to abdominal examinations in children. MR imaging is undoubtedly the imaging modality of choice in neuroimaging, but in the child’s abdomen MR imaging may struggle to achieve a diagnosis. This is coupled with the younger child requiring sedation, and the possible administration of a contrast agent, gadolinium, that may have devastating consequences 4 . What is not in doubt is the cost implications of using MR imaging; US remains the least expensive of imaging modalities. Furthermore US succeeds on all occasions as a child-friendly non-intimidating imaging technique. Contrast-enhanced ultrasound (CEUS) is now main-stream in adult imaging, and has proved itself in a number of clinical situations, as a practical, real-time, bed-side problem solving tool, with the European Federation of Societies in Ultrasound in Medicine and Biology (EFSUMB) leading the world in progress on this front and publishing widely accepted guidelines on evidence based CEUS deployment 5 6 . Paediatric imaging with CEUS is mentioned in these guidelines and the implications discussed 7 , with the topic of “off-label” adequately dealt with – there is no legal or regulatory board hindrance to using CEUS in children 8 . Indeed these legal and regulatory board implications in children have been a topic of discussion in the pages of many learned journals, all enthusiastic for the use of CEUS in children, all seemingly un-hampered by physician perceived regulatory and hospital hurdles and impediments 9 10 11 . It is at this point very important to raise two very valid issues with the use of microbubble contrast agents in children. Many drugs are not tested in children and are not licensed to be used to treat children; in one study 67 % of children admitted to five European hospitals were given unlicensed drugs 12 , many of these drugs with known side-effects in adult patients. Secondly, the microbubble contrast agent used in Europe, SonoVue (Bracco, SpA, Milan) has an excellent safety record in adults 13 and a recent survey of the use of paediatric CEUS in Europe recorded a very small number of minor reactions 14 . This agent has a recorded adverse event lower than that seen with iodinated contrast medium used in CT and equivalent to MR agents, widely accepted as essential to many imaging investigations. Historically regulatory procedures for licensing iodinated contrast agents in children followed national approval and was based on studies conducted in a non-controlled fashion, with small patient numbers yet with reported adverse events 15 16 ; there was no central European procedure for performing of clinical evaluation of a new contrast agent. Evaluation of gadolinium based contrast agents in children was performed later, with higher standards but still below of the expectations of today, again obtaining safety data from open-label or even retrospective studies 17 . Current regulatory requirements will imply huge cost necessities to perform prospective, well-controlled studies on microbubble contrast agents in children. Our experience to date in the paediatric patient includes the application of CEUS to interpreting indeterminate focal liver lesions in children with or without underlying chronic liver disease 18 and in the follow-up of blunt abdominal trauma 19 . Both these areas are well established in adult practice, and evidence from the two paediatric studies above confirms a similar usefulness of CEUS in children. Numerous case reports and case series continue to appear in the literature extolling the usefulness of the addition of CEUS to an US examination, with the desired diagnostic outcome achieved with little discomfort to the child, no exposure to radiation, sedation or the effects of iodinated contrast or gadolinium based contrast agents. The physicians involved in reporting what is often assumed as nothing other than a trivial “case-study” are to be congratulated for their desire to advance their clinical practice and directly add to the literature on the subject. By publishing their results a body of evidence builds up, and eventually what was previously a “taboo” area becomes mainstream and readily acceptable. There should be no further delay in introducing paediatric CEUS into routine clinical practice. We have no evidence that the microbubble agent is harmful to the child, but cautiously neither is there substantial evidence that it is safe. The only manner in which we can achieve a database of safety is to prospectively accumulate experience of the use of intra-venous CEUS. The only possibility of achieving this currently is in Europe and with the agent SonoVue (Bracco SpA, Milan). In the United States of America, licensing for adults is an issue, and the prospect of using microbubble contrast agents in paedaitric patients restricted to centers involved in research; it may be a while before any meaningful numbers can be accumulated. The amassing of experience in the Far East and with China in particular is a favorable prospect, but local regulations may be difficult to overcome. Currently, EFSUMB has an established record in pursuing the development of CEUS practice across Europe and to a certain extent across the globe. EFSUMB guidelines are probably the most respected source of knowledge on CEUS and have made the biggest impact on the expanding clinical use of CEUS. To develop a strategy for encouraging physicians involved with the imaging of children, to embrace CEUS into their clinical practice, national and international societies for the care and imaging of children need to be active and enthusiastic participants. Clearly there is a need to work together on this; there will be no assistance from the manufacturers of the microbubble agents as they are constrained by law to restrict their activities to licensed uses of their product. EFSUMB has now established a “registry” on their website which allows data input in a prospective manner and documents any adverse events. A meeting of learned societies to establish a strategy is needed, taking advantage of expertise available in different forums to achieve a rapid and useful outcome. The bottom line is that we owe it to our children to move away from harmful imaging techniques and establish CEUS as the “next-step” imaging modality after an inconclusive B-mode ultrasound examination. There is a risk that we may not get it right with CEUS as an alternative imaging method in children and it may not fulfil its promise – but we have to try and be seen to be trying. We believe that the future of imaging gently in children lies in US with the addition of CEUS a major step in reducing the use of ionizing radiation.
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Sellars et al. (2014) studied this question.
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