Spatially broad opening of the blood-brain barrier with an unfocused ultrasound transducer in rabbits
Year: 2012
Type: conference-paper
Abstract: The aim of this work was to study the opening of the blood-brain barrier (BBB) over a large volume using an unfocused ultrasound device in the presence of ultrasound contrast agents in rabbits. A mono-element planar 1MHz ultrasound transducer was used to perform burst sonications in 24 healthy New-Zealand white rabbits after craniectomy and during intravenous injection of Sonovue®. The transducer was operated with a pulse repetition frequency of 1Hz, and a range of pulses lengths and in situ acoustic pressures (10-35ms and 0.3-1MPa respectively). Opening of the BBB was observed in contrast-enhanced images in a 4.7T MRI, through blue dye extravasation and with confocal microscopy. Adverse effects were analyzed on histology. A significant BBB opening limited spatially to the extent of the ultrasound field was observed. BBB opening appeared during the sonication and lasted for several hours. Monitoring was possible on MRI sequences as a significant gadolinium contrast enhancement (p<0.0001). BBB opening was associated with perivascular blood red cell extravasation and transient vascular spasm. In conclusion, the BBB can be opened in large areas of the brain with low power unfocused ultrasound, with limited tissue damage, and could permit safe drug delivery in the brain. Work supported by CarThera and Région Ile-de-France.
Source: HAL
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W2247279736