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1g-Ultrasound System for the Brain Stimulation of a Freely-moving Mouse
A KAIST research team developed a light-weight capacitive micromachined ultrasonic transducer (CMUT) and succeeded in the ultrasound brain stimulation of a freely-moving mouse. With this lightweight and compact system, researchers can conduct a versatile set of in vivo experiments. Conventional methods for stimulating a specific brain region, such as deep brain stimulation (DBS) and optogenetics technology, are highly invasive because they have to insert probes into a target brain, which makes them difficult to use for clinical application. While transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) are noninvasive, they have a wide range of stimulation and problems with in-depth stimulation, which makes them problematic for target-specific treatment. Therefore, noninvasive and focused ultrasound stimulation technology is gaining a great deal of attention as a next-generation brain stimulation alternative. Since it is delivered noninvasively, it can be applied safely in humans as well as animal experiments. Focused ultrasound stimulation is more advantageous than conventional methods in terms of providing both local and deep stimulation. Animal behavior experiments are essential for brain stimulation research; however, ultrasonic brain stimulation technology is currently in the early stages of development. So far, only research outcomes with fixed anesthetized mice have been studied because of the heavy ultrasonic device. Professor Hyunjoo J. Lee from the School of Electrical Engineering and her team reported a technology that can provide ultrasound stimulation to the brain of a freely-moving mouse through a microminiaturized ultrasound device. The team studied miniaturization and ultra-lightweight CMUTs through microelectromechanical systems (MEMS) technology and designed a device suitable for behavior experiments. The device weighing less than 1g (around 0.05% of the mouse’s weight) has the center frequency, size, focal length, and ultrasonic intensity to fit a mouse’s dimensions. To evaluate the performance of the ultrasonic device, the team stimulated the motor cortex of the mouse brain and observed the movement reaction of its forefoot. They also measured the electromyography (EMG) of the trapezius. As a result, the team confirmed that their ultrasonic device can deliver ultrasound to a depth of 3-4mm in the mouse brain and stimulate an area of the mouse brain that represents 25% of its total size. Based on this research, the team is investigating the effects of ultrasound on sleep by stimulating the brain of sleeping mice. Professor Lee said, “Going beyond experimenting on fixed anesthetized mice, this research succeeded in the brain stimulation of a freely-moving mouse. We are planning to study mice with diseases, such as Parkinson’s disease, dementia, depression, and epilepsy. I believe that this basic research can contribute to treating human brain-related diseases through ultrasound brain stimulation. This research, led by Masters candidates Hyunggug Kim and Seongyeon Kim, was published in Brain Stimulation (10.1016/j.brs.2018.11.007) on November 17, 2018. Figure 1. The miniature transducer for the transcranial ultrasound of a freely-moving mouse Figure 2. Its structure and simulated 2D beam profile in the axial ad radial directions
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