Safety and ultrasound-enhancing potentials of a new sulfur hexafluoride-containing agent in the cerebral circulation

Insufficient ultrasound penetration through the temporal bone is a serious limitation of transcranial ultrasound diagnostics. In a phase I study, the authors studied safety and ultrasound enhancing potentials of the new trans pulmonary ultrasound contrast agent SonoVue, which contains sulfur hexafluo ride gas microbubbles stabilized by a phospholipid shell. Twelve healthy vo lunteers received four different doses of SonoVue (0.3 ml, 0.6 ml, 1.2 ml, and 2.4 ml) intravenously. The duration of ultrasound contrast enhancement was measured by transcranial Doppler sonography (TCD) and transcranial colo r-coded sonography (TCCS). Safety and tolerability was monitored during the study and for 24 hours after contrast agent administration. TCD: Duration of spectral enhancement (signal intensity of 5 dB over baseline) was observ ed dose-related (p<0,0001; Friedman-test) for (0.3 ml) 136 +/- 63.4 seconds ; (0.6 ml) 191 +/- 63.3 seconds; (1.2 ml) 314 +/- 88 seconds; (2.4 ml) 434 +/- 168 seconds [mean +/- SD]. Dependent on dosage, the peak signal amplifi cation in TCD was significantly different (p<0.001; Friedman-test) as well: (0.3 ml) 24.5 +/- 2:0 dB; (0.6 ml) 26.0 +/- 1.6 dB; (1.2 ml) 27.6 +/- 2.2 dB; (2.4 ml) 28.4 +/- 2.2 dB (mean +/- SD). TCCS: Mean time of optimal enha ncement increased from 214 +/- 73 seconds (0.3 ml) to 356 +/- 14 seconds (2 .4 ml) in a dose-dependent manner. In TCCS, signal amplification appeared t o be stronger with increasing doses. Adverse events were not observed durin g the study. This investigation describes the ultrasound enhancing potentia l of SonoVue in the intracranial cerebral circulation. SonoVue proved to be well tolerated and provided a long-lasting ultrasound contrast enhancement that supports an optimal transcranial ultrasound diagnostic.