Review finds substantial discrepancies in LIFU simulation software and skull modeling approaches

Background: 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, k-Plan (Brainbox Ltd.) and BabelBrain (open-source) are two widely used software packages for sonication simulation, yet their outputs have not been empirically compared. 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 approximate skull bone properties. Objective: In this study, we directly evaluated the consistency of simulation results from the two platforms, k-Plan and BabelBrain. We also examined the impact of skull modeling using CT vs. pseudo-CT on LIFU simulation results. Methods: We compared LIFU simulation results between the two platforms when applied to the same individuals, trajectories, and using the same sonication protocol parameters. To assess the validity of using pseudo-CTs for simulations, we also compared simulation outputs generated using CT versus pseudo-CT inputs. Results: Our results reveal substantial discrepancies both between software platforms (k-Plan vs. BabelBrain) and between skull modeling approaches (CT vs. pseudo-CT). 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.