Observation on the integrity of the blood-brain barrier after microbubble destruction by diagnostic transcranial color-coded sonography.

Abstract

To investigate alteration of the blood-brain barrier from ultrasonic contrast agent destruction by diagnostic transcranial color-coded sonography using gadolinium-enhanced magnetic resonance imaging. Healthy male volunteers received 10 mL (400 mg/dL) of Levovist (SH U 508A; Schering AG, Berlin, Germany; n = 6) or 3 mL of Optison (FS069; Mallinckrodt Inc, St Louis, MO; n = 4) followed by 0.3 mmol/kg magnetic resonance imaging contrast agent (Magnevist; Schering) intravenously. Then transcranial color-coded sonography was performed with a conventional color duplex sonographic system, which insonated the brain in a slightly angulated axial plane with temporal average intensity of less than 700 mW/cm2 or acoustic pressure amplitude of less than 2.69 MPa, attenuated by the temporal bone. Before, immediately after, and 2 hours after insonation, T1-weighted axial magnetic resonance imaging was performed. All magnetic resonance images were individually assessed, and T1 signal intensities were measured in 2 regions of interest in both hemispheres at the 3 time points. No focal contrast enhancement or damage to the brain and no significant difference between T1 signal intensities in the right and left brain regions could be detected during early or late phases when either ultrasonic contrast agent was used. This bioeffects study gives further evidence of the safety of ultrasonic destruction of Levovist and Optison microbubbles by diagnostic transcranial color-coded sonography. However, more subtle local effects may have been missed by gadolinium-enhanced magnetic resonance imaging. Studies on diagnostic contrast-enhanced transcranial color-coded sonography as well as microbubble-based drug delivery strategies should consider ultrasonic contrast agent microbubble characteristics and concentration as well as ultrasound transmission power levels.