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Contrast-enhanced ultrasound (CEUS) involves the use of contrast agents and specialised imaging techniques to show blood flow and organs microvascularity and perfusion. US contrast agents are made of microbubbles consisting of gas bubbles stabilised by a shell, with a total diameter smaller than 10 microns. Currently, three contrast agents have been approved for radiological purposes: SonoVue® (Europe, China, India, Korea, Hong Kong, New Zealand, Singapore and Brazil), Definity (Canada and Australia), and Sonazoid (Japan and South Korea). Contrast-specific imaging software is necessary to evaluate the signal obtained by microbubbles, but it is now widely available on US equipment. New technology optimises tissue and contrast agent signals simultaneously, in real time and with excellent spatial resolution. Contrast agents used for US are strictly intravascular and are extremely sensitive to detect microvasculature. They are very well tolerated and only very few cases of adverse events have been described around the world. Other features of CEUS are the absence of exposure to ionising radiation, the absence of nephrotoxicity; the possibility to perform the study at the bedside and the evaluation in real time. The most important limitation of CEUS is the difficulty of performing an optimal study depending on the body habitus and collaboration of the patient, depth of the target studied and bowel gas interposition.
The most targeted organ is the liver, especially to characterise focal liver lesions and evaluation of response to percutaneous tumour ablations. However, the expanding indications of CEUS include the guidance of interventional procedures including biopsies and ablative procedures, characterisation of kidney- and pancreatic masses, and the assessment of disease involving microvascularisation, including ischemic, traumatic, and inflammatory diseases. Nowadays, CEUS is considered a cost-effective tool to characterise abdominal lesions, providing accurate diagnostic information comparable to CT and MRI as has been demonstrated in several studies. In this way, the diagnostic performance of CEUS in the clinical practice was evaluated in a recent multicentre study performed in Spain. For this purpose, 1,786 patients from 42 hospitals, with baseline US studies that were considered inconclusive, were included. All CEUS studies were performed using specific contrast software and the intravenous injection of SonoVue® (Bracco, Italy) and the results were compared with the final diagnosis obtained by reference procedures: surgery, fine needle biopsy or CT/MR with a conclusive diagnosis. The use of CEUS provides a real improvement on clinical practice with an accurate diagnosis in most of the inconclusive baseline US studies, with a significant improvement in the diagnosis confidence in 91.6% of cases, and a conclusive diagnosis in 69.2% of patients.
Baseline US is the preferred imaging technique used to screen for liver lesions, but it has a low specificity in their characterisation. The characterisation needs the administration of a contrast agent (CT, MR or CEUS) and the enhancement behaviour during the arterial, portal and late phases correlates with specific pathologic features such as tumour microvascularisation. The detection of hypovascularisation in portal and late phase is the most specific sign of all malignant lesions (metastases, cholangiocarcinomas and hepatocellular carcinomas) (see figure 1). On the contrary, the typical feature of benign lesions is the presence of isoechogenicity, or even hyperechogenicity, in the late phase. However, there are a few exceptions to this pattern. Small and well-differentiated HCCs may show isoechogenicity in late phase and some benign lesions with intratumoural fibrosis or necrosis will show hypoechogenicity in the late phase. The evaluation in real time during the arterial phase allows the detection of some features that may help in the differential diagnosis; most haemangiomas have a typical peripheral nodular enhancement, followed by centripetal fill-in. On the contrary, focal nodular hyperplasia shows intense enhancement in the arterial phase, with centrifugal enhancement, and in about 40% of cases the presence of a central scar. Several studies have demonstrated the usefulness of CEUS in the characterisation of focal liver lesions with accurate diagnostic information comparable to CT and MRI, thus the use of CEUS as the first imaging technique to characterise a focal liver lesion detected on US, is expanding worldwide.
Characterisation of renal lesions is an increasing indication of CEUS, but it is not routinely recommended to detect and characterise solid masses because there is an overlap of the enhancement pattern between benign and malignant lesions. CEUS main indications are:
1. The differentiation between indeterminated cystic or solid lesions detected with US, CT or MR. Using CEUS, the detection of enhancement is found in solid masses while cystic lesions do not show enhancement
2. The differentiation between real solid masses and pseudotumours, such as prominent Bertin columns and dromedary humps, since pseudotumours have the same enhancing characteristics as the surrounding parenchyma in all phases
3. Characterisation of renal complex cyst. This is one of the well-established indications for CEUS.
The most complex cysts are secondary to the presence of inflammation, infection or haemorrhage. However up to 10% of renal cancers may appear as complex cysts. The presence of a thickened irregular enhancing wall, or septa, or the detection of intracystic enhancing mass independent of the wall or septa, are the most specific signs suggesting malignancy (see figure 2). Due to the evaluation of real time and high sensitivity to depict microvascularisation, CEUS has advantage over CT to detect the presence or absence of abnormal vascularisation of the wall and septa. Moreover, it may be repeated easily with the advantage of absence of radiation, thus CEUS is an excellent tool in the follow-up of cystic lesions managed conservatively.
Indications for CEUS outside the liver and kidney are growing and focal lesions can be evaluated with CEUS in all organs, including pancreas and spleen. Few studies have described the usefulness of CEUS in the characterisation of focal lesions of the pancreas. Most ductal adenocarcinomas hypoenhance with respect the surrounding pancreatic parenchyma in all phases, and CEUS can also help in the differential diagnosis between pseudocysts and cystic tumours of the pancreas demonstrating the presence of vascularisation of intralesional septa or nodules.
CEUS is a very accurate imaging technique in the characterisation of abdominal lesions detected by US and should be considered as an alternative to CT/MR for this purpose. It is also helpful in the characterisation of inconclusive CT/MR studies or when CT and MRI contrasts are contraindicated.
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