Endocavitary contrast enhanced ultrasound (CEUS): a novel problem solving technique
Contrast-enhanced ultrasound (CEUS) is a technique that has developed as an adjunct to conventional ultrasound. CEUS offers a number of benefits over conventional axial imaging with computerised tomography and magnetic resonance imaging, primarily as a “beside” test, without ionising radiation or the safety concerns associated with iodinated/gadolinium-based contrast agents. Intravascular use of ultrasound contrast agents (UCAs) is widespread with extensive evidence for effective use. Despite this, the potential utility of UCAs in physiological and non-physiological cavities has not been fully explored. The possibilities for endocavitary uses of CEUS are described in this review based on a single-centre experience including CEUS technique and utility in confirming drain placement, as well as within the biliary system, urinary system, gastrointestinal tract and intravascular catheters.
• CEUS offers an excellent safety profile, spatial resolution and is radiation free.
• Endocavitary CEUS provides real-time imaging similar to fluoroscopy in a portable setting.
• Endocavitary CEUS can define internal architecture of physiological cavities.
• Endocavitary CEUS can confirm drain position in physiological and non-physiological cavities.
KeywordsUltrasound imaging Contrast agents Microbubbles Diagnostic ultrasound Ultrasound, interventional
Contrast-enhanced ultrasound (CEUS) has developed as a technique with increasing acceptance in recent years. Although the most widespread use of CEUS has been in the characterisation of focal liver lesions , many other uses have been developed including renal, aortic, bowel and testicular evaluation . CEUS is expected to gain further popularity following the recent Food and Drug Administration approval in the USA of Lumason™/SonoVue™ (Bracco, Milan) for hepatic and paediatric hepatic use . The rapidly increasing myriad uses of CEUS have led to the development of guidelines, issued by the European Federation and Society of Ultrasound in Medicine and Biology (EFSUMB) examining both hepatic and non-hepatic applications [1, 2]. These guidelines are based almost entirely on conventional intravascular use. The EFSUMB guidelines do acknowledge the use of ultrasound contrast agents (UCAs) in the assessment of non-physiological cavities and state that in theory this should be safe, based on the excellent safety profile from intravascular use in both adults and paediatrics [4, 5]. Despite intra-cavitary usage being reported, the EFSUMB refrains from making recommendations other than use on a case-by-case basis given the lack of experience in this area .
CEUS is an adjunctive technique to conventional B-mode and Doppler ultrasound (US), giving rise to the term multiparametric ultrasound (MPUS) . The microbubble ultrasound contrast agent (UCA) most often used in Europe, SonoVue™, consists of sulphur hexafluoride, an inert gas, enveloped in a phospholipid shell and is a truly intravascular agent with pulmonary excretion of the gas and hepatic clearance of the phospholipid shell . At low acoustic pressure microbubbles resonate, giving rise to non-linear signals, which are detected by modifications of the conventional ultrasound machine. Following cancellation of the linear signal from normal tissue, the non-linear signal provides a contrast image with dynamic assessment on a macro- and microvascular scale when used intravenously. These properties make CEUS appropriate for endocavitary use, with excellent spatial and temporal resolution in real time, akin to fluoroscopic imaging but without the need for iodinated contrast or ionising radiation. There are also the traditional advantages of US imaging, including the ability to perform imaging at the bedside, in immobile patients, particularly important in an intensive care setting. As a result CEUS offers an alternative means of dynamic imaging in the population potentially at increased risk from conventional means such as paediatric patients, renal failure patients and those for whom transport to a radiology department would be impractical or unsafe. Many individual case reports and case series on the utilisation of endocavitary CEUS exist [8, 9], but there is no unifying technique or definitive list of applications. Generally endocavitary CEUS is used for confirming catheter drain placement, tracking the course of a physiological or non-physiological cavity, identifying filling defects and the presence of fistulation. This review article aims to describe the myriad uses implemented in a single centre and to consider the recent literature on the utility of endocavitary CEUS.
Endocavitary CEUS technique
Endocavitary CEUS is a developing technique and a methodology for general use remains undefined. Conventionally intravenous use of CEUS requires 1.2 ml – 4.8 ml of SonoVue™ depending on the organ or site examined. Endocavitary CEUS differs in that the volume of the solvent, the fluid within a cavity, is much smaller than the volume of circulating blood in the vascular tree, and a considerably lower dose of UCA is required. In vitro studies have shown SonoVue™ to be stable in a diluted state providing sufficient backscatter for endocavitary use . In addition, the lack of circulation of the UCA results in a greater degree of stability, with the UCA estimated to remain within a collection for up to 20–30 min [10, 11]. Prior feasibility studies and case reports suggest 0.1 ml SonoVue™ diluted in 10-20 ml 0.9 % saline is sufficient for intra-cavitary use, whilst for oral administration 1 drop of the UCA is diluted in 50 ml water . The authors use a dilution of 0.1 ml SonoVue™ in 50 ml 0.9 % saline routinely. The administered volume of the solution varies on a case-by-case basis, as high-frequency linear transducers may require higher concentrations of UCA, given the optimal imaging for CEUS is 2–3 MHz . For studies of the gastrointestinal tract where a larger volume would be potentially needed, the ratio can be extrapolated in up to 200 ml of solution.
Adverse reactions to intravenous CEUS have been rarely described and UCAs have been shown to have an excellent safety profile [4, 5]. Due to the absence of contact with the systemic circulation, endocavitary CEUS is expected to have a lower rate of adverse incidents, but this has not yet been proven and access to resuscitation equipment must be considered essential. Contraindications to endocavitary CEUS are not yet available given that it is a technique in its infancy. Contraindications to intravenous CEUS are severe cardiopulmonary dysfunction and known hypersensitivity, whilst it has been deemed preferable to avoid intravenous CEUS in pregnancy because of an absence of clinical data.
Endocavitary CEUS is performed following optimised greyscale and Doppler imaging using contrast-specific software with a low mechanical index (< 0.2). Either high frequency linear transducers or a low frequency curvilinear transducer can be used for imaging with no adjustment of contrast volume or concentration required.
Endocavitary CEUS has limitations. Traditional factors that hinder ultrasound remain a factor in endocavitary CEUS and may include body habitus, bowel gas and operator skill. In addition, it is important to use larger volumes of UCA solution in endocavitary use to prevent pooling of contrast, rather than dynamic free diffusion, within a space that may not have any active flow movement. At the same time the volume of UCA must be reduced to prevent artefact from excessive signal, which can lead to loss of detail and posterior acoustic shadowing. In the experience of the authors the same concentration can be utilised regardless of whether a high frequency linear or curvilinear transducer is used. A further limiting factor is the ability to access the targeted cavity. Often this is via an invasive technique (e.g. nephrostomy, biliary drainage or catheterisation); the additional procedural risk may not be preferable. The invasive element and the recent development of endocavitary CEUS mean direct comparative studies with non-invasive techniques have not been performed in many areas such as with MR imaging. The dynamic nature of the studies involved, however, likens endocavitary CEUS more to fluoroscopy but without the need for a dedicated suite or use of radiation.
Conventional CEUS is a technique gaining rapid popularity owing to its excellent safety profile, spatial and temporal resolution whilst also being portable and free of ionising radiation. Extrapolation of traditional intravascular use of CEUS allows for a range of endocavitary CEUS uses in diagnostic radiology particularly for the assessment of drain positions and evaluation of loculation, strictures and fistulae. The detailed resolution and real-time imaging also allow for myriad interventional uses of endocavitary CEUS.
Endocavitary CEUS is a novel technique and offers a dynamic modality assessment in real time, with operator discretion for visualisation of specified anatomy. The size of UCA microbubbles combined with both exquisite temporal and spatial resolution means it is ideally suited to endoluminal delineation with uses described above in the biliary and collecting systems as well as established intrauterine use and utility in interventional radiology. Experimental use for non-physiological cavities, vascular lines and bowel implementations have been performed at our institution and, although feasible, formal studies have not yet been conducted despite anecdotal benefit, as befits a new technique.
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