Objective To conduct a dose testing analysis of perfluorobutane microbubble (NC100100) contrast-enhanced ultrasound (CEUS) to determine the optimal dose for detection of liver metastases in patients with extra-hepatic primary malignancy. Methods 157 patients were investigated with conventional US and CEUS. CEUS was performed following intravenous administration of perfluorobutane microbubbles (using one dose of either 0.008, 0.08, 0.12 or 0.36 μL/kg body weight). Three blinded off-site readers recorded the number and locations of metastatic lesions detected by US and CEUS. Contrast enhanced CT and MRI were used as the "Standard Of Reference" (SOR). Sensitivity, specificity and accuracy of liver metastasis detection with US versus CEUS, for each dose group were obtained. Dose group analysis was performed using the Chi-square test. Results 165 metastases were present in 92 patients who each had 1-7 lesions present on the SOR. Sensitivity of US versus CEUS (for all doses combined) was 38% and 67% (p=0.0001). The 0.12 dose group with CEUS (78%) had significantly higher sensitivity and accuracy (70%) compared to other dose groups (p<0.05). Conclusion The diagnostic performance of CEUS is dose dependent with the 0.12 μL/kg NC100100 dose group showing the greatest sensitivity and accuracy in detection of liver metastases. © European Society of Radiology 2011.