Multi-centre clinical study evaluating the efficacy of SonoVue™ (BR1), a new ultrasound contrast agent in Doppler investigation of focal hepatic lesions

Objectives: SonoVue(TM) 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(TM) 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 till 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 (TM) is effective in improving the display of tumoral vascularisation and may be useful in the characterisation of focal liver lesions. (C) 2002 Published by Elsevier Science Ireland Ltd.