Abstract
The development of large-aperture multiple-source transducer arrays for ultrasound transmission through the human skull has demonstrated the possibility of controlled and substantial acoustic energy delivery into the brain parenchyma without the necessitation of a craniotomy. The individual control of acoustic parameters from each ultrasound source allows for the correction of distortions arising from transmission through the skull bone and also opens up the possibility for electronic steering of the acoustic focus within the brain. In addition, the capability to adjust the frequency of insonation at different locations on the skull can have an effect on ultrasound transmission. To determine the efficacy and applicability of a multiple-frequency approach with such a device, this study examined the frequency dependence of ultrasound transmission in the range of 0.6-1.4 MHz through a series of 17 points on four ex vivo human skulls. Effects beyond those that are characteristic of frequency-dependent attenuation were examined. Using broadband pulses, it was shown that the reflected spectra from the skull revealed information regarding ultrasound transmission at specific frequencies. A multiple-frequency insonation with optimized frequencies over the entirety of five skull specimens was found to yield on average a temporally brief 230% increase in the transmitted intensity with an 88% decrease in time-averaged intensity transmission within the focal volume. This finding demonstrates a potential applicability of a multiple-frequency approach in transcranial ultrasound transmission.