Design and Holographic Field Reconstruction of Ultrasonic Lenses for Drug Delivery in non-Human Primates

The aim of this work is to design and employ a large-aperture focused transducer with a holographic lens to selectively sonicate small deep-brain structures in non-human primates, such as the left post-commissural putamen, correcting skull aberrations and obtaining a good quality focal spot. Acoustic hologram was designed with time-reversal methods and numerical simulations with a k-space pseudospectral method. Its performance was experimentally evaluated with an ex-vivo macaque skull in water with direct measurements. To avoid undesired artefacts and retrieve the whole acoustic field, the focal region was also reconstructed by holographic projections of measurements taken at a 2D plane. Simulation, direct measurements and holographic projection results are in good agreement, with the focus lying into the therapeutical target location. We experimentally obtained that 38% of the target volume is sonicated with a pressure higher than half the focus maximum, getting more than 0.5 MPa rarefaction pressure. We present that holographic lenses coupled to large-aperture focused transducers allow for precise targeting of small deep brain structures at sufficient amplitudes to generate cavitation. This technology is presented as a low-cost system for preclinical localized drug delivery.

Automated summary

The aim of this study is to design and utilize a large-aperture focused transducer with a holographic lens to selectively sonicate small deep-brain structures in non-human primates. Through experimental evaluation and numerical simulations, we demonstrate that this technology can precisely target the therapeutic area and generate the desired effects of cavitation.