Numerical and experimental evaluation of low-intensity transcranial focused ultrasound wave propagation using human skulls for brain neuromodulation

Abstract

Background: Low-intensity transcranial focused ultrasound (tFUS) has gained considerable attention as a promising noninvasive neuromodulatory technique for human brains. However, the complex morphology of the skull hinders scholars from precisely predicting the acoustic energy transmitted and the region of the brain impacted during the sonication. This is due to the fact that different ultrasound frequencies and skull morphology variations greatly affect wave propagation through the skull.

Purpose: Although the acoustic properties of human skull have been studied for tFUS applications, such as tumor ablation using a multielement phased array, there is no consensus about how to choose a single-element focused ultrasound (FUS) transducer with a suitable frequency for neuromodulation. There are interests in exploring the magnitude and dimension of tFUS beam through human parietal bone for modulating specific brain lobes. Herein, we aim to investigate the wave propagation of tFUS on human skulls to understand and address the concerns above.

Methods: Both experimental measurements and numerical modeling were conducted to investigate the transmission efficiency and beam pattern of tFUS on five human skulls (C3 and C4 regions) using single-element FUS transducers with six different frequencies (150-1500 kHz). The degassed skull was placed in a water tank, and a calibrated hydrophone was utilized to measure acoustic pressure past it. The cranial computed tomography scan data of each skull were obtained to derive a high-resolution acoustic model (grid point spacing: 0.25 mm) in simulations. Meanwhile, we modified the power-law exponent of acoustic attenuation coefficient to validate numerical modeling and enabled it to be served as a prediction tool, based on the experimental measurements.

Results: The transmission efficiency and -6 dB beamwidth were evaluated and compared for various frequencies. An exponential decrease in transmission efficiency and a logarithmic decrease of -6 dB beamwidth with an increase in ultrasound frequency were observed. It is found that a >750 kHz ultrasound leads to a relatively lower tFUS transmission efficiency (<5%), whereas a <350 kHz ultrasound contributes to a relatively broader beamwidth (>5 mm). Based on these observations, we further analyzed the dependence of tFUS wave propagation on FUS transducer aperture size.

Conclusions: We successfully studied tFUS wave propagation through human skulls at different frequencies experimentally and numerically. The findings have important implications to predict tFUS wave propagation for ultrasound neuromodulation in clinical applications, and guide researchers to develop advanced ultrasound transducers as neural interfaces.

Keywords: human skull; transcranial focused ultrasound; ultrasonic neuromodulation; ultrasound transducer.

FIGURE 1

Typical schematic and key parameters of pulsed ultrasound sequences for neuromodulation. Here, FF represents the fundamental frequency; PD represents the pulse duration; PRP is the pulse repetition period, which equals the inverse of pulse repetition frequency (PRF); SD is the sonication duration.

FIGURE 2

Experiment setup: (a) a schematic diagram for all apparatuses; (b) side view of focused ultrasound (FUS) transducer, human skull, and hydrophone

FIGURE 3

Experimental results of the dependence of the transcranial focused ultrasound (tFUS) transmission efficiency on various ultrasound frequencies, including (a) intensity ratio and (b) pressure ratio (n = 10)

FIGURE 4

Comparison between experiment and simulation results in terms of the transcranial focused ultrasound (tFUS) transmission efficiency for various ultrasound frequencies, including (a) intensity ratio and (b) pressure ratio. The standard deviation refers to the different skulls. The p‐values (*) of one‐sample t‐test are larger than 0.05. (n = 10)

FIGURE 5

Simulation results of transcranial focused ultrasound (tFUS) pressure distribution over human skull #3, C4 region, for (a) 150 kHz, (b) 350 kHz, (c) 500 kHz, (d)750 kHz, (e) 1000 kHz, and (f) 1500 kHz

FIGURE 6

Simulation results of the −6 dB beamwidth (i.e., full width at half maximum, FWHM) of transcranial focused ultrasound (tFUS) beam pattern and free water focused ultrasound (FUS) beam pattern for various ultrasound frequencies (n = 10)

FIGURE 7

The dependence of acoustic pressure ratio on aperture size of the 350 kHz focused ultrasound (FUS) transducer (n = 1)

FIGURE 8

The dependence of acoustic attenuation power‐law exponent of human skulls on ultrasound frequency (n = 10)