**5. Other applications of ultrasound in liver tumor pathology. Technical progress**

Ultrasound has known a great development arising from the need to increase patient access to advanced investigations while avoiding procedures using radiation (CT), contrast agents with allergic potential (iodine substances) and hepatic or renal toxic agents.

*Interventional and intraoperative ultrasound*. Ultrasound exploration by maneuverability of the equipment and dynamic character of the image allows guided interventional procedures or intraoperative examination. Combining ultrasound with such procedures is necessary due to the lack of specificity of the method in case of tumors. Even if tumor markers for defining the nature of some masses are available, their accuracy is not good enough; therefore biological samples from the nodules detected by imaging is often required. Accuracy of ultrasound guided puncture in the diagnosis of liver tumors is dependent on the operator's experience and can reach up to 87.5 - 99% (Horigome et al, 1999). The extracted material can be either a histology fragment or cytology aspiration; in both cases the credibility of the method is sufficient to ensure optimal cancer therapies (Badea R & Badea Gh 1991). Intraoperative ultrasound is also a complementary investigation that allows detection of very small nodules. In addition it allows the characterization of tumor using Doppler and CEUS procedure as well as guided interventional procedures such as intraoperative PEI or RFA.

*Targeted therapy using contrast agents*. The introduction of second generation contrast agents has been a great progress. Diagnostic performance is already proven. A step forward is tumor targeted therapy under ultrasound guidance. The principle is that of transporting chemotherapeutic agents to the target using microbubbles as vectors. Experiments have been made for binding different substances and/or genes to the lesion, with local release by "breaking" and intracellular penetration using the phenomenon of cellular membrane permeability called "sonoporation" (Lindner, 2004, Newman & Bettinger, 2007).

*Image fusion*. Techniques for image fusion obtained by different imaging procedures allow the correlation of real-time ultrasound examination with CT or MRI images, enabling positioning of the needle in relation to the exact position of the tumor. The technique allows a better guidance both for biopsies and percutaneous ablative procedures, replacing CT guidance and thus avoiding irradiation. Combination with CEUS allows a better characterization of lesions as well as successful monitoring of percutaneous procedures or TACE effects (Sandulescu et al, 2011; Ewertsen et al, 2011).

*Elastography*. It was initially introduced in practice to assess the degree of fibrosis in chronic liver disease. In liver tumors it allows detection of liver nodules due to the difference of elasticity between the hepatic nodule and the parenchyma. There are few studies that try to assess the benign or malignant character of the lesion based only on elasticity. By combination with CEUS the method could be beneficial for early detection and characterization of HCC.

*High Intensity Focused Ultrasound (HIFU).* It is a new technique capable of destroying tumor tissue by hyperthermia, allowing percutaneous ablation without requiring tumor puncture. There are studies showing the efficacy of this technique in combination with TACE, with anti-tumor effect and better survival than using TACE alone (Wu, 2005). The method is expected to be an alternative to PEI and RFA because it avoids the puncture of the cirrhotic liver, but more studies are needed to prove its efficacy as a single therapy in the curative treatment of HCC (Maruyama et al, 2008).

Techniques for visualizing blood circulation independently from the angle of insonation based on transversal oscillation of red blood cells groups. This technique is now implemented on conventional transducers and can real time evidence different features of the blood flow visualized so far only on MRI angiography (Hansen et al, 2011).
