A New Versatile System for 3D Steered LIFU Based on 2D Matrix Arrays.

<b><i>Introduction:</i></b> Ultrasound is a promising new approach for noninvasive brain stimulation. Low-intensity focused ultrasound (LIFU) allows targeting the deep brain with high spatial and temporal resolution. For clinical use, ultrasound systems must fulfill specific requirements. Three-dimensional (3D) steering and focusing either requires mechanical displacement of (focused) transducers or multielement arrays and corresponding multichannel electronics. Since the waveform has an impact of the induced neurostimulation effect, electronics need sufficient flexibility for generating arbitrary temporal signal patterns. For compensation of skull aberration artifacts, elements must be excited with defined phase resulting of phase aberration correction (PAC) algorithms. Finally, for being clinically usable, systems must be combined with planning hardware and software. <b><i>Methods:</i></b> A versatile system for 3D steered LIFU based on two-dimensional matrix arrays was designed, fabricated, and characterized in terms of focusing, steering, and output of temporal patterns. Our PAC algorithm was validated on an <i>ex vivo</i> skull. The system was tested for compliance with defined medical device standard by accredited laboratories, and an initial Magnetic resonance imaging (MRI) phantom study was performed. <b><i>Results:</i></b> Our system allows 3D beam steering and focusing with lateral focus sizes down to 4 mm, which is less than the size of a human gyrus, such that detailed targeting is possible. Arbitrary temporal signal patterns (different wave forms, pulse length, duty cycle, and ramping) were generated. Different software interfaces allow patient-specific planning with a Magnetic resonance Tomograph (MR)- or neuronavigation-based workflow, in which a custom-developed PAC algorithm allows compensation of the skull bone. The absence of transducer susceptibility artifacts was shown in the MRI phantom study, and the acoustic focus was localized using magnetic resonance acoustic radiation force imaging. <b><i>Discussion:</i></b> Our new versatile ultrasound neuromodulation platform represents a compromise between conformal helmet-like systems and single element transducer setups. It is flexible in terms of spatiotemporal stimulation patterns and can be accommodated to different workflows. Impact Statement Progress in the field of ultrasound neurostimulation is depending on the availability of suitable hardware fulfilling a range of practical, technical, safety, and regulatory requirements. Systems must fit in established clinical workflows (e.g., usable with MR and/or neuronavigation systems), allow accessing deep brain regions, and generate defined spatiotemporal ultrasound patterns. Furthermore, basic regulatory constraints (e.g., IEC 60601-1) must be fulfilled. Our new low-intensity focused ultrasound (LIFU) system addresses these requirements and is flexible enough for use in a research environment. It was developed for facilitating the clinical transfer of LIFU and helping to gain a better understanding of underlying effects in ultrasound neurostimulation.