Rapid optimization of focused ultrasound for complex targeting with phased array transducers and precomputed propagation operators.

Low-intensity focused ultrasound has emerged as a versatile tool for various applications including noninvasive neuromodulation and blood-brain barrier (BBB) opening. To achieve precise individual targeting, phase aberration correction (PAC) is essential to compensate for the heterogeneities introduced by the skull. Traditional methods for PAC are restricted to single point-based targets, resulting in elongated, cigar-shaped focal beams that often fail to align with the geometry of the intended target. Additionally, these approaches demand lengthy simulation times, making the simultaneous sonication of multiple targets within a reasonable timeframe infeasible. This work introduces real-time optimization-based sonication of volumetric brain targets. By leveraging a pair of linear phased array transducers aligned orthogonally over the skull, the approach is capable of optimizing phase and amplitude parameters within seconds to focus acoustic pressure at multiple targets inside target volumes while limiting potential off-target activation. Three brain areas were targeted under different orthogonal transducer alignments, enforcing the desired intracranial peak pressure at a minimum of three target points in each region. Further results demonstrate the sensitivity of transducer displacements, particularly with translational and rotational misalignments. A ray tracing correction scheme was employed, restoring the peak pressure at the intended target region while keeping the increase in off-target pressure below 20%. Overall, these advancements hold promise for enhancing targeting in Focused Ultrasound-guided BBB opening and neuromodulatory applications, expanding the utility of ultrasound in clinical and experimental settings.