Laser-Generated Focused Ultrasound for Brain Stimulation Using Carbon Nanotube Composite Transducer

Abstract

Focused Ultrasound (FUS) can non-invasively and precisely intervene in key circuits that control common and challenging brain disorders. Neurons can be activated or inhibited by adjusting the parameters of FUS. However precise targeting at the microscopic level requires a spatial accuracy of several millimeters. Therefore, the development of high precision neurostimulation is essential to stimulate specific brain regions effectively. Laser-generated focused ultrasound (LGFUS) has shown potential for precision therapeutic ultrasound applications due to its ability to generate high-pressure, broadband shock waves with a narrow focal spot. However, there has been little research on neurostimulation using shock waves with pulse durations of sub microseconds. Our study thoroughly explores the potential of neurostimulation by LGFUS using carbon nanotube (CNT) composite transducers and presents LGFUS as an excellent precision tool for brain stimulation. In this study, we explore the structural properties of CNT composite transducers as LGFUS tools to achieve high-precision neuromodulation. To comprehensively investigate the LGFUS properties, CNT composite transducers with different diameters and support structures were fabricated. The peak positive and negative sound pressure generated by the CNT composite transducer are 32 to 52 MPa and -9 to -24 MPa for 2 to 8 cm diameters, respectively. Our experiments confirmed a correlation between increasing transducer diameter and increasing peak pressure in LGFUS. We investigated responses to rat brain stimulation with LGFUS generated from the explored CNT composite transducers. Electroencephalographic (EEG) signals recorded from rat brains before and after LGFUS stimulation show distinct differences in time and frequency domains. After stimulation, the EEG signal has increased, indicating increased neural activity and distinct changes in the 1-30 Hz band. These changes in the EEG signal highlight the ability to accurately stimulate the brain with LGFUS generated by CNT composite transducers. Finally, as a preliminary experiment to confirm the possibility of human brain stimulation, the possibility of LGFUS penetration into the human cadaver skull was investigated. The peak positive sound pressures before and after skull penetration were 14.6 MPa and 1.1 MPa, respectively, and the central frequency was changed from 1 MHz and 464 kHz, respectively. These results of LGFUS have important implications for future neurostimulation research and transcranial applications, suggesting potential use for high-precision brain stimulation.