Simulation, Implementation and Measurement of Defined Sound Fields for Blood-Brain Barrier Opening in Rats

Area of Science:

• Neuroscience
• Biomedical Engineering
• Pharmacology

Background:

• The blood-brain barrier (BBB) impedes central nervous system (CNS) drug delivery.
• Low-intensity pulsed focused ultrasound (FUS) with microbubbles offers a non-invasive method for BBB opening (BBBo).
• Standardized FUS protocols are lacking, especially considering species-specific skull properties.

Purpose of the Study:

• To measure ultrasound attenuation through the Wistar rat skull.
• To assess the safety and efficacy of a targeted FUS system for BBBo.
• To investigate the relationship between FUS pressure and BBBo-induced hyperintense MRI signals and potential hemorrhages.

Main Methods:

• Utilized a targeted FUS system to examine ultrasound attenuation in Wistar rat skulls.
• Modified transducer elements and simulated acoustic fields to measure skull attenuation (~60%).
• Performed histological and MRI analyses on healthy animals to evaluate safety at varying pressures.

Main Results:

• Measured approximately 60% ultrasound attenuation by the Wistar rat skull.
• Observed increased hyperacute bleeds with increasing focal pressure.
• Found no induced bleeds at 0.4 MPa, but with a reduced hyperintense MRI signal post-BBBo.

Conclusions:

• Skull attenuation significantly affects FUS parameters for BBBo.
• FUS pressure is a critical factor influencing BBBo extent and potential for hemorrhage.
• Optimizing FUS pressure is essential for safe and effective therapeutic delivery across the BBB.