FEASIBILITY STUDY OF A CLINICAL BLOOD-BRAIN BARRIER OPENING ULTRASOUND SYSTEM.

In this paper, we investigate the focalization properties of single-element transducers at intermediate frequencies (500 kHz) through primate and human skulls. The study addresses the transcranial targeting involved in ultrasound-induced blood brain barrier (BBB) opening with clinically relevant targets such as the hippocampus and the basal ganglia, which are typically affected by early Alzheimer's and Parkinson's disease, respectively. The targeted brain structures were extracted from three-dimensional (3D) brain atlases registered with the skulls and used to virtually position and orient the transducers. The frequency dependence is first investigated and the capability of targeting of different structures is explored. Preliminary in vivo feasibility is investigated in mice at this frequency. A simple, affordable and convenient system is found to be feasible for BBB opening in primates and humans capable of successfully targeting the hippocampus, putamen and substantia nigra and could thus allow for its broader impact and applications.