Acoustic holographic lenses for transcranial focusing in an <i>ex vivo</i> human skull

The skull has long been an obstacle for transcranial ultrasound therapy and neuromodulation, leading to waveform distortion and focal points misalignment. In this work, we propose a dual-focus transcranial ultrasound focusing method for ex vivo human skulls to bridge this barrier, which is demonstrated by using a 2 MHz single-element transducer placed outside the occipital bone, coupled to a 3D-printed acoustic holographic lens. The experimental results show that the proposed method allows for achieving high-precision single- and dual-focus ultrasound focusing through human skulls with the maximum target registration error less than one wavelength in water. The in-target ratio spans a range from 72% to 92%, with an average of 80.7%, while the out-of-target ratio varies from 0% to 43.9%, with an average of 18.3%. Additionally, the focal spots are substantially free of the skull-induced distortion, closely matching the ideal ones, and maintain a clearly identifiable circular focus shape. The method opens up a route toward the subsequent applications in clinical research and may enable to implement transcranial ultrasound therapy and neuromodulation.