Air-filled ultrasound contrast agents do not damage the cerebral microvasculature or brain tissue in rats
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Updated: Oct 30, 2026
Monitoring Blood-Brain Barrier Opening in Rats with a Preclinical Focused Ultrasound System
Published on: September 13, 2024
K J Haggag1, D Russell, P Walday
1Department of Neurology, The National Hospital, University of Oslo, Norway. n.k.j.haggag@klinmed.uio.no
Rationale And Objectives:
Air microemboli may damage the cerebral microvasculature. The aim of this study was to evaluate the safety of ultrasound contrast agents composed of air microspheres with regard to cerebral damage when administered into the arterial system (ie, when not filtered by the capillary system of the lungs).
Methods:
Three experimental methods were used in 75 rats after injection of either Albunex, Echovist, or Levovist into the left heart ventricle. The alkaline phosphatase (ALP) method to demonstrate small segmental brain capillary and arteriolar dilatations (SCADs), intravenous injections of Evans blue and fluorescence microscopy to detect increased vascular permeability (blood-brain barrier damage), and histologic examination of the brain to detect microinfarction. Intracardiac injections of saline, air, and corn oil were used as controls.
Results:
Brain microinfarcts and SCADs formation of the brain microvasculature occurred only after control injections with corn oil. None of the brains from animals that received ultrasound contrast agent showed gross discoloration, as an indication of increased vascular permeability, with the Evans blue/fluorescence microscopy method. Definite leakage of Evans blue occurred only after large doses (150 microL) of air.
Conclusions:
This study indicates that ultrasound contrast media composed of air microspheres do not cause lesions of the brain microvasculature or parenchyma.
