Evaluation of Transcranial Focused Ultrasound Simulation Accuracy: A Measurement Validation Study

Transcranial focused ultrasound (tFUS) is a promising technique for non-invasive neuromodulation, but accurate estimation of intracranial acoustic fields is hindered by skull-induced distortions. We evaluated the accuracy of CT-informed acoustic simulations against experimental hydrophone measurements in two Thiel-embalmed human skulls. A 680 kHz focused ultrasound transducer was characterized by holography, and simulated and measured fields were compared across multiple regions of interest. In the thinner and denser skull (5.2 ± 1.4 mm, skull density ratio (SDR) 0.74±0.16), simulated transmission (37±5%) closely matched measurement (39±4%), with modest pressure (−5.6±15%) and phase (9±4%) errors. In contrast, the thicker and more porous skull (8.7±2.1 mm, SDR 0.58 ± 0.22) showed lower transmission (measured: 23±7%; simulated: 18±5%) and larger discrepancies (−19±10% pressure error, 20±11% phase error). Across all regions, simulations underestimated transmitted pressures by 2.6 dB, with mean pressure and phase errors of −12±14% and 14±10%, respectively. These results indicate that while simulations can reproduce general field patterns in favorable skull morphologies, predictive accuracy degrades in thick, heterogeneous bone, underscoring the need for refined attenuation models in patient-specific tFUS planning.