Empirical limitations of current low-intensity focused ultrasound simulation platforms

Transcranial low-intensity focused ultrasound (LIFU) is an emerging tool for noninvasive neuromodulation, with potential therapeutic applications across a range of neuropsychiatric disorders. As the field advances toward clinical translation, individualized simulations of sonication parameters are critical for estimating dosing to ensure safety, efficacy, and reproducibility. Currently, <i>k-Plan</i> (Brainbox Ltd.) and <i>BabelBrain</i> (open-source) are two widely used software packages for sonication simulation, yet their outputs have not been empirically compared. In this study, we directly evaluated the consistency of simulation results produced by these two platforms when applied to the same individuals, trajectories, and sonication protocols. We further examined the impact of skull modeling, as accurate estimation of skull bone properties is essential for reliable simulation. While CT scans remain the gold standard for capturing fine anatomical details of the skull, their use carries radiation risk. As an alternative, algorithms generating MRI-based pseudo-CTs have been developed. To assess the validity of using pseudo-CTs for simulations, we compared simulation outputs generated using CT versus pseudo-CT inputs. Our results reveal substantial discrepancies both between software platforms (k-Plan vs. BabelBrain) and between skull modeling approaches (CT vs. pseudo-CT), with differences that were sensitive to individual trajectories. These findings underscore the urgent need for ground-truth validation of current sonication simulation software and highlight the importance of further optimization of pseudo-CT algorithms before widespread clinical adoption.