Experimental Validation of Skull Acoustic Modelling Strategies for Transcranial Focused Ultrasound Simulation: A Cross-Comparison Study

Abstract: Accurate acoustic modelling of the skull is essential for simulation-guided transcranial focused ultrasound (tFUS), but commonly used skull parameterisation strategies differ in complexity and reported accuracy. This study experimentally compared five k-Wave skull models: two voxel-wise linear mapping models, two three-layer models, and one single-layer fixed-parameter model. Nineteen regions of interest from five historical and two Thiel-embalmed human skulls were tested at 220 kHz, 680 kHz, and 1000 kHz. Bowl-surface source fields were reconstructed using acoustic holography, and simulated intracranial pressure fields were benchmarked against needle-hydrophone measurements. Across frequencies, mean peak-pressure errors ranged from 20% to 31%, whereas intensity errors reached 41% to 77%. Errors in -6 dB focal volume ranged from 11% to 67%, and focal-position discrepancies were typically several millimetres. Simulations generally predicted smaller insertion losses than measured, indicating a tendency to underestimate skull-related attenuation and overestimate transmitted intracranial exposure. The linear mapping model with fixed attenuation gave the lowest frequency-averaged pressure error, but no model showed a consistent advantage across all metrics. These results show that current skull models can reproduce gross intracranial beam patterns while retaining substantial quantitative uncertainty in exposure, focal coverage, and target localisation.