Impact of acoustic property uncertainty on transcranial ultrasound simulation

Subject-specific simulations of wave propagation are commonly used to plan and report acoustic and thermal exposure during transcranial ultrasound (TUS) interventions. Their accuracy depends on acoustic and thermal tissue property assumptions, including sound speed, density, and attenuation. Reported property measurements vary widely across the literature, precluding consensus point estimates for simulation. How this property uncertainty affects estimated exposure has not been quantified. We compile literature-based bounds for seven acoustic and thermal properties of skull and brain tissue and assess their individual impact on simulated intensity and temperature rise using two independent simulation platforms (PRESTUS/k-Wave and BabelBrain). Variations in skull attenuation and absorption produced the largest outcome uncertainty: peak intensity in the brain varied roughly threefold across the reported range of skull attenuation alone, while absorption most strongly affected temperature rise within the skull. The direction of each parameter's effect was consistent across platforms and, with one exception, across skull thickness. This allowed bounds to be combined into setups that bracket transmission and temperature rise. Compared to these extremes, default property sets of three simulation toolboxes (k-Plan, BabelBrain, PRESTUS) yielded similar brain intensity but divergent skull heating, driven mainly by differing assumptions on skull absorption and heat capacity. These results indicate that uncertainty in skull acoustic properties is a major source of variability in TUS exposure estimates, and that refined measurements of these properties, together with explicit reporting of exposure uncertainty, are needed to support safe, effective, and reproducible transcranial ultrasound planning.