A library of acoustic holograms for precise targeting of murine brain regions

This work aims to produce a library of acoustic holograms, which will precisely target brain regions of varying shapes, sizes, and focal depths through the aberrating murine skull. K-wave was used to simulate an isotropic grid for a focused single-element transducer (H-204, 1.68 MHz, 82-mm aperture; Sonic Concepts) using 6 points per wavelength. A time reversal method was used to design a phase-only holographic lens in clear resin. Binary matrices of a single mouse skull and brain were used as background media to account for tissue inhomogeneity and varying speed of sound. The Allen Brain Atlas was used to identify and select the regions for targeting. Four different brain regions were selected: the substantia nigra, the subthalamic nucleus (both relevant to Parkinson’s disease), the central lateral thalamic nucleus (chronic pain), and the hippocampus (Alzheimer’s disease). With the top of the mouse head positioned at a distance of 60 mm, these regions required a focal depth of 62.4, 62.1, 60.6, and 60.2 mm, respectively. The successful in-target focusing was 50%, 87.5%, 84%, and 38% of the ROI, respectively. This work demonstrates that acoustic holograms can improve targeting accuracy and reduce out-of-target effects, thereby improving the efficiency of drug delivery to the brain.