Multifocal acoustic holograms for deep-brain neuromodulation and BBB opening

Single-element focused ultrasound devices have demonstrated its ability to non-invasively open the Blood Brain Barrier. However, skull irregularities and absorption produce strong aberrations in the ultrasound focus. Recently, 3D-printed acoustic holograms were used to compensate aberrations and to produce a sharp focus. In addition, using this technology the geometry of the ultrasonic focus can be matched to the shape of the brain structure of interest. In this work, we experimentally and numerically report 3D-printed acoustic holograms for bilateral focusing through an ex-vivo human skull. Using holograms, we target different cerebral nuclei and the ultrasonic focuses are adapted to the target volumes, minimizing the acoustic field outside. Simultaneously, skull aberrations are corrected using phased-conjugation methods. The holographic surfaces were manufactured for a 100-mm aperture and 140-mm focal focused transducer at 500 kHz to focus through an ex-vivo human skull. Numerical and experimental results agree targeting several deep-brain nuclei: left-and-right putamen, caudate nuclei, and hippocampi, showing the potential of this low-cost technology to optimize BBBO or neuromodulation treatments.