Optison (FS069) Disrupts the Blood-Brain Barrier in Rats

Abstract

Optison is a new echocardiographic contrast agent, designed for IV injection, that is very useful in delineating cardiac structures during ultrasound examination. Because Optison could be a valuable adjunct in the diagnosis and evaluation of congenital heart disease, this study was undertaken to assess its effects on the blood-brain barrier when introduced directly in the cerebral circulation, as might occur with some congenital lesions. In this study, Sprague-Dawley rats were anesthetized, and Optison, at various dosages, was injected into the carotid artery. After this, Evans blue dye, a marker for blood-brain barrier disruption, was injected at different time intervals. Gross and histologic examination of the animals' brains revealed disruption of the blood-brain barrier that appeared to be Optison-dosage-dependent. Although the mechanism for this disruption is unclear, it may be related to the use of octofluoropropane gas used in the Optison as a contrast medium. Further studies are necessary to determine the pathologic consequences of Optison's effects on the blood-brain barrier.

Safety of ultrasound contrast agents

“…Disruption of the blood-brain barrier may occur in rats after intravenous injection of ultrasound contrast media [17,18].…”

Development of efficient plasmid DNA transfer into adult rat central nervous system using microbubble-enhanced ultrasound

“…Since previous studies showed destruction of the blood-brain barrier (BBB) several hours after injection of Optison into the carotid artery 14 or insonation after intravenous injection of Optison, 15 we carefully evaluated the safety aspect of the present gene transfer method. We first evaluated the change in body weight, tissue damage by hematoxylin and eosin (HE) staining, and destruction of the BBB by microangiography using albumin-fluorescein isothiocyanate (FITCalbumin), 16 as the microbubble-enhanced ultrasound Figure 4 Local gene expression produced by plasmid DNA transfer using microbubble-enhanced ultrasound as assessed by luciferase expression.…”

Ultrasound Contrast Agents in Ischemic Stroke

“…In these studies, Doppler-based nonlinear imaging technologies with higher receiving frequencies seem to be superior to grey scale harmonic imaging [69]. In theory, when using high MI imaging, the direct contrast-enhanced insonation of the brain without the skull (which reduces the actual energy that has an effect on the tissue) could be harmful because of cavitation and capillary rupture [80,81,82,83]. …”