Thanks to the most recent technological innovations, the ability of grayscale ultrasound (US) in the detection of focal liver lesions (FLLs) has significantly improved, even if small or deeply located. However, the characterization remains a challenge even for experienced sonographers except for hemangiomas with typical US appearance detected in patients with no history of malignancy or chronic liver disease [1].

Both benign and malignant FLLs can present similar aspect at US, thus making really difficult a correct differential diagnosis especially when liver echotexture is altered such as in chronic hepatitis or diffuse fatty infiltration. In particular, this latter, increasing the ultrasound beam attenuation, also hinders lesion’s identification, and the majority of liver masses appear hypoechoic regardless of tumor’s nature.

Moreover, color and power Doppler evaluation slightly improves diagnostic performance of US examination since they visualize large vessels and are limited by motion artifacts, making the analysis often unsatisfactory and thus inconclusive for the differential diagnosis of FLLs.

In the last decades, the development of both second-generation ultrasound contrast media and specific software for contrast agent detection has significantly improved diagnostic accuracy of US in terms of sensitivity and specificity. Nowadays, contrast-enhanced ultrasound (CEUS) represents a reliable, safe, and cost-saving alternative imaging modality able to provide in most cases, in the same US session, a correct characterization of an indeterminate FLL with diagnostic accuracy comparable to CT or MR performed with state-of-the-art scanners thus significantly reducing the number of cases requiring further investigations [2, 3].

CEUS is a real-time technique thus allowing to continuously study microvessels of FLLs adding, with respect to CT and MR examinations (sometimes inconclusive), further useful information that makes it a helpful problem-solving imaging modality.

The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) also recommends CEUS especially in peculiar clinical settings as, for example, in the diagnosis of incidentally discovered FLLs indeterminate at US or in the evaluation of locoregional treatment.

At this regard, a newly developed CEUS technique, three-dimensional CEUS (3D-CEUS) performed by means of a 3D probe, has been reported to improve the study of tumor vascularity in the three orthogonal planes, allowing the visualization of the region of interest from different points of view.

In some cases regarding locoregional treatment CEUS evaluation, an example of a particular 3D reconstruction software called “i-slice” will be showed in this atlas. I-slice provides the capability of displaying the data set in multiple, contiguous, parallel 2D slices, similar to CT and MR, changing the interval (distance between the individual slices) and the depth setting (the position of the slices in the volume) in order to better display the region of interest [4, 5].

So the aim of this atlas is to describe by means of a wide collection of clinical cases the most common imaging patterns of benign and malignant FLLs evaluated by means of CEUS in order to make the specialist who would like to perform it confident in the interpretation of imaging findings and able to provide pivotal information for a definitive characterization during the same session of a baseline US examination avoiding further imaging workup.

The ultrasound contrast agents (UCAs) currently used in diagnostic US are characterized by a microbubble structure consisting of gas bubbles stabilized by a shell. UCAs act as blood pool agents. They strongly increase the US backscatter and therefore are useful in the enhancement of blood echogenicity for the assessment of blood flow in the micro- and macrovessels. SonoVue^© contains low-solubility gas (sulfur hexafluoride) microbubbles surrounded by a flexible phospholipid shell improving microbubble stability. The microbubbles have a mean size of 2.5 μm with 99 % of them smaller than 11 μm allowing a free passage in the capillaries but keeping the contrast medium within the lumen.

The assessment of microbubbles usually requires contrast-specific imaging modes.

Contrast-specific US softwares are generally based on the cancellation and/or separation of linear US signals from tissue and utilization of the nonlinear response from microbubbles.

Nonlinear response from second-generation contrast agents is based on nonlinear response from microbubble oscillations at low acoustic pressure, reducing disruption of the microbubbles.

Due to the flexibility of the microbubbles’ phospholipid shell, the reflectivity of SonoVue is very high with high echo enhancement. On the other hand, due to the poor solubility and diffusivity, this contrast agent is also strongly resistant to pressure. This allows minimally disruptive contrast-specific imaging at mechanical index (MI) set in clinical practice and enables effective investigations over several minutes with the visualization of the dynamic enhancement pattern in real time. Low-MI techniques furthermore lead to effective tissue signal suppression as the nonlinear response from the tissue is minimal when low acoustic pressures are used.

In summary, low-MI imaging with second-generation contrast agent (i.e., SonoVue) allows real-time examination and the evaluation of contrast medium distribution from the beginning of intravenous injection up to 4–5 min.

In our department, CEUS examination involves the use of US scanners equipped with convex probe and Pulse Inversion Harmonic Imaging software, extremely sensitive to microbubble-based US contrast agents. The first part of the study includes a preliminary assessment of hepatic parenchyma in grayscale—including color power Doppler and pulsed Doppler analysis—in order to localize the lesion and select an appropriate scanning plane. Once set, the US scan parameters—such as focal zone, time gain compensation, MI—remain unchanged throughout the study. The US contrast agent (USCA) is sulfur hexafluoride filled microbubble based (SonoVue®, Bracco, Milan, Italy), intravenously injected as a 2.4 mL bolus followed by 10 mL of sterile saline flush by using a 20- or 22-gauge peripheral cannula. In order to minimize microbubble disruption, a low frame rate (5 Hz) and a low MI, usually 0.06, are used for real-time imaging.