Multifocal skull-compensated transcranial focused ultrasound system for neuromodulation applications based on acoustic holography

Abstract

Transcranial focused ultrasound stimulation is a promising therapeutic modality for human brain disorders because of its noninvasiveness, long penetration depth, and versatile spatial control capability through beamforming and beam steering. However, the skull presents a major hurdle for successful applications of ultrasound stimulation. Specifically, skull-induced focal aberration limits the capability for accurate and versatile targeting of brain subregions. In addition, there lacks a fully functional preclinical neuromodulation system suitable to conduct behavioral studies. Here, we report a miniature ultrasound system for neuromodulation applications that is capable of highly accurate multiregion targeting based on acoustic holography. Our work includes the design and implementation of an acoustic lens for targeting brain regions with compensation for skull aberration through time-reversal recording and a phase conjugation mirror. Moreover, we utilize MEMS and 3D-printing technology to implement a 0.75-g lightweight neuromodulation system and present in vivo characterization of the packaged system in freely moving mice. This preclinical system is capable of accurately targeting the desired individual or multitude of brain regions, which will enable versatile and explorative behavior studies using ultrasound neuromodulation to facilitate widespread clinical adoption.

Airy-beam holographic sonogenetics for advancing neuromodulation precision and flexibility

“…Future research is needed to develop innovative strategies for arbitrary dynamic focusing using the Airy-beam holographic metasurface. Second, acoustic holograms designed using the time-reversal approach were used in ultrasound neuromodulation without genetic engineering ( 44 , 45 ). However, these devices used acoustic lenses with thicknesses much greater than the wavelength; therefore, they tend to be bulky.…”

A review: flexible devices for nerve stimulation

“…Researchers have extensively studied miniaturized ultrasound neurostimulation devices based on an initial understanding of the principle mechanisms of ultrasound neuromodulation. Our group reported the specifications of a small, focused ultrasound transducer, as depicted in Figure 11A, which had a center frequency of 650 kHz, a diameter of 12 mm, a focal point of 9 mm, and a peak acoustic pressure of up to 0.47 MPa in the focal area [113] . Kook et al developed a lightweight miniature ultrasound neuromodulation system, weighing just 0.75 g, through the integration of a 3D-printed acoustic lens and a MEMS ultrasound transducer [Figure 11B] [114] .…”

“…Ultrasound neurostimulators. (A) Miniatured focused ultrasound transducer to stimulate PAG for analgesia[113]…”