Quantifying the effects of standing waves within the skull for ultrasound mediated opening of the blood-brain-barrier

Ultrasound mediated opening of the blood-brain barrier (BBB) has been shown to be effective in enhancing the delivery of therapeutic agents to the brain. However, challenges remain in targeting and specificity of BBB opening due to attenuation, aberration and reverberation of transcranial ultrasound fields. In this study, experimental and numerical assessment was performed of standing waves within an ex vivo human skull when delivering ultrasound pulses of varying lengths at 300 kHz using a large aperture focused ultrasound transducer. Simulations showed minimal distortion of the focal region but low amplitude standing waves were established within the skull with bursts of 50 cycles or more. Under the same conditions, the experimental measurements showed small variations in focal pressure which took 300 to 600 µs to stabilise. The pattern of sidelobes and superimposed standing waves was generally more complex when the focus was placed closer to the side and base of the skull. This data supports the use of large aperture diameter transducers and short pulse lengths for targeted BBB opening.