Harmonic power-based duplex sonography is a new ultrasound method that improves the signal-to-noise ratio of extracranial vascular imaging. The authors evaluated this new method for transtemporal imaging of the basal cerebral arteries. Fundamental power-based duplex sonography (p-TCCS) and harmonic power-based duplex sonography (HI-p-TCCS) in combination with a novel perfluoropropane-containing ultrasound contrast agent (Optison) were investigated for the evaluation of the basal cerebral arteries in 12 healthy volunteers. The number of identified vascular segments and the blood flow velocities in the middle and posterior cerebral arteries were determined for p-TCCS and for two doses of Optison (0.5 and 1.5 mL) using HI-p-TCCS. Furthermore, the authors determined the time course of signal enhancement after Optison bolus injections. The results were compared using Friedman two-way ANOVA test. Significantly more arterial segments were visualized using HI-p-TCCS with enhancement of either 0.5 mL or 1.5 mL Optison (p < 0.01, each) than using p-TCCS. The spatial resolution was markedly increased with HI-p-TCCS, resulting in a striking difference in the detection of distal arterial segments and cortical and parenchymal branches. Except for the diastolic blood flow velocities (BFVs) in the M1 segment, the BFVs did not differ significantly between p-TCCS and HI-p-TCCS. Comparing HI-p-TCCS with 0.5 mL and 1.5 mL Optison, the authors found a small but significant reduction of the latency period (18.2 vs. 15.9 seconds, respectively; p < 0.01), a significant increase of the blooming phase (62.7 vs. 99.8 seconds, respectively; p < 0.0006) and a significant prolongation of the diagnostically useful signal enhancement (233.7 vs. 427.6 seconds, respectively; p < 0.004).