Development of miniaturized transcranial ultrasound focusing system for small animal neuromodulation

Abstract

Ultrasound brain stimulation is a promising next-generation technology for the treatment of brain disorders because of its high stimulation resolution compared to other non-invasive brain stimulation methods. Evaluating the efficacy of ultrasound brain neuromodulation is a critical, yet challenging step required for clinical trials and commercialization. However, conventional ultrasound devices used for preclinical systems are currently too bulky to target brains of mice, the most commonly used animal model for brain disorders. In this thesis, I developed a miniaturized ultrasound neuromodulation system composed of a capacitive micromachined ultrasound transducer (CMUT) and an acoustic lens designed based on the phase-conjugation mirror principle which compensates for the skull aberration to achieve accurate brain targeting. The advantages of using CMUT include small size of the system and uniform acoustic phase from the transducer. Moreover, focused ultrasound stimulation in a freely-moving mouse was demonstrated for the first time using the developed system. By enabling the evaluation of efficacy and safety of ultrasound neuromodulation in small animals, the developed system can be used in a wide range of applications such as identification of treatable brain disorders, understanding the mechanism of neuromodulation, and investigating the long-term efficacy and side-effects of ultrasound neuromodulation.