Safety and UltrasoundEnhancing Potentials of a New Sulfur Hexafluoride‐Containing Agent in the Cerebral Circulation

Abstract

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 transpulmonary ultrasound contrast agent SonoVue, which contains sulfur hexafluoride gas microbubbles stabilized by a phospholipid shell. Twelve healthy volunteers 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 color-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 observed 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 amplification 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 enhancement 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 to be stronger with increasing doses. Adverse events were not observed during the study. This investigation describes the ultrasound enhancing potential 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.