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Objectives: SonoVue is a new ultrasound contrast agent, which consists of stabilised microbubbles of a sulphur hexafluoride gas. The aim of the study was to assess its efficacy in the Doppler investigation of focal hepatic lesions., Materials and Methods: Seventy patients with focal liver tumours were studied. Four doses (0.3, 0.6, 1.2 and 2.4 ml) of SonoVue were administered intravenously with at least 10 min delay between each injection. A complete colour/power and spectral Doppler imaging investigation of the lesions was performed at baseline pre-dosing and after each SonoVue injection. All examinations were recorded on SVHS videotapes. Baseline and post contrast videotapes were reviewed by the on-site (un-blinded) investigators and by two off-site blinded readers (a) to grade the global quality of the Doppler scans of the focal lesions vascularity and the normal parenchymal vessels (b) to measure the duration of clinically useful Doppler signal enhancement and (c) to determine the diagnostic accuracy and performance of the enhanced versus unenhanced scans using histopathology, tumour markers, CT and/or MR as the reference standard., Results: A statistically significant improvement was observed at all four SonoVue doses in the off site assessment of global quality of the Doppler examination of tumoral and normal parenchymal vessels in comparison with the baseline (P < 0.05). The median duration of clinically useful enhancement was significantly increased with increasing doses (P < 0.001), ranging between 1.4-2.2 min for the lowest dose and 3.2-3.8 min for the highest dose for the off-site readers. On-site assessment of diagnostic accuracy showed a significant increase in the specificity of the Doppler diagnoses (P < 0.0016) with an increase in the positive and negative predictive values and in the likelihood ratio in differentiating between benign and malignant lesions. Off-site evaluation showed a significant increase in the accuracy of enhanced Doppler diagnosis in comparison with the baseline performance., Conclusion: The results suggest that SonoVue is effective in improving the display of tumoral vascularisation and may be useful in the characterisation of focal liver lesions.

Considering the several suggestions regarding the future developments of echocontrast agents, there is a striking difference between the few compounds actually available on the market and used in clinical practice and those undergoing experimental clinical trials. It is therefore difficult to predict what will be the actual impact of these agents in the next future. Future developments will probably go beyond color enhancement which was the end-point till a very short time ago. They can be schematically summarized as follows: (1) development of new substances which enhance both color and gray scales; (2) use of new-generation substances, such as BR1 (Bracco, Milan, Italy) and EchoGen (Sonus, Bothell, WA), which use a gas other than air, such as perfluorate compounds which are more stable and guarantee longer and stronger effects; (3) use of more complex compounds acting at different levels. For example, SHU 536A (Sonovist) produces resonance phenomena with the second and third harmonics, and also stimulated acoustic emission which permits the morphological study of liver parenchyma. Other promising compounds are liposomes and aerosomes. Among the new possibilities in recording and observing phenomena, we can distinguish two main application fields: one is based on the physics of ultrasound and related to the presence of microbubbles in an acoustic field. These phenomena are generally obtained increasing the emission acoustic pressure, which eventually results in microbubble destruction and they are called nonlinear because there is no direct relationship between emission and return frequencies. These phenomena, which are detectable only with dedicated equipment, include: the resonance phenomenon with harmonic emission; intermittent harmonic emission and stimulated acoustic emission. The other application field is not strictly related to ultrasound physics and includes all the systems which can detect the presence of microbubles qualitatively or quantitatively. Other possible applications are related to the possibility of acquiring not only morphological but also functional data, especially in cardiology and neurology. Finally, targeted agents are potentially capable of demonstrating receptor sites or specific molecules, which may open very interesting therapeutic routes.

The differential diagnosis of focal hepatic lesions is a current problem even though many study methods are available. Color Doppler US has been recently suggested as a diagnostic technique capable of depicting lesion vascularization patterns to better understand lesion nature. However, this examination is often difficult and long. In this study, we investigated the role of a US contrast agent SH U 508 A (Levovist) enhancing the color Doppler signals for easier and better depiction of lesion vascularization. Seventy-four patients with one or more focal hepatic lesions (mean diameter: 5.6 cm) were examined. The lesions were 38 HCCs, 4 cholangiocarcinomas, 1 intrahepatic biliary duct carcinoma, 1 case of multiple adenomas, 2 regenerations nodules in cirrhosis, 2 cases of FNH, 18 metastases and 8 hemangiomas. In 54 cases the US contrast agent allowed the visualization of some vessels inside the lesions which had been missed at baseline examinations. Moreover, the vessels which had been depicted on baseline images were better demonstrated. In all but one patient with severe hepatic steatosis, normal parenchymal vessels were markedly enhanced. Our results in the different kinds of tumors are here reported.