Ultrasound has been used extensively in medicine and industry for more than 70 years (Fry 1958; Rezayat 2016; Darrow 2019) by delivering mechanical energy (sound waves) to tissue. Ultrasound as a technique for neuromodulation is essentially characterized into two main categories segregated by the intensity (spatial peak temporal average intensity [SPTA]) of the acoustic wave. High-intensity focused ultrasound (HIFU) with intensity typically >1 W/cm2 produces reliable and permanent brain lesions through thermal ablation, whereas low-intensity focused ultrasound (LIFU) does not produce lesions but can excite or suppress neural activity with very rare occurrence of adverse effects (Pasquinelli 2019). Although HIFU secured the United States Food and Drug Administration (FDA)’s approval for essential tremor in 2016 and approval for other conditions is apparently on the horizon, systematic efforts aimed at determining clinical utility for LIFU have only recently begun (Truong 2021). Transcranial focused ultrasound (tFUS) is a LIFU technique that is characterized by long trains (several hundred milliseconds) and has been shown to both potentiate and suppress neural activity (Bystritsky 2011; Bystritsky 2015) as well as alter behavior in mammalian brains (Fomenko 2018). The low energy of tFUS falls below the threshold for inducing any tissue damage and is often used with intensities that are near or below those used in diagnostic ultrasound.

The BrainSonix system comprises the ultrasound console (stimulator), transducer with ground-breaking “clipping” mechanism, transducer holder, and coupling pads. The system is fully integrated (i.e. enclosure and monitor) allowing portability and tabletop operation. The stimulator includes an all-in-one computer with an ultrasonic drive generator. The ultrasonic drive voltage is provided through a BNC port on the front panel. Upon entering the desired exposure parameters (pressure, average intensity, pulse length, pulse repetition frequency, sonication duration, intersonication time, and number of sonications), the system automatically calculates the voltage required to meet those settings (Schafer 2021).

Three different circular, single-element, spherically focused transducers are available with an aperture of 61 mm. Nominal focal lengths of 55, 65, and 80 mm are provided for targeting different regions of the brain. The transducers include a slightly convex front layer for optimal impedance matching.

The transducer holder attaches the transducer firmly to the head above the temporal window. It allows both angular and linear displacement to accurately target intended structures.

MR synchronization is provided via a fiber optic input line and optically isolated digital signal line (TTL). EEG synchronization is also provided either via TTL or optical signal.

The main goal of the calibration process is to ensure that the intended ultrasound exposure is provided on a repeatable and consistent basis. The BrainSonix system includes a state-of-the-art calibration technique to ensure that the experimenter can focus on the clinical study and not on replicability (Schafer 2021). Specifically, the process is conducted for every stimulator, in combination with any specific transducers, cables, RF filters that are supplied with the system. The calibration settings are stored in a file and made available for post-hoc stimulation verification.

When setting up for a stimulation session, calibration data is first retrieved. The user is first asked to confirm the transducer serial number and cable configuration. The system then obtains the acoustic output characteristics from the calibration file data. Next, the user is asked to enter desired stimulation parameters. Based on acoustic output limits established for the study protocol, the system automatically determines whether the entered treatment parameters exceed limits. The system will not allow proceeding to the stimulation initiation step, if parameters are not adjusted to be in compliance with output limits.

The BrainSonix device has been rigorously validated in several clinical trials. The system has secured multiple Investigational Device Exemption (IDE) and Non-significant Risk (NSR) letters from the United States FDA. The system is IEC electrical safety and EMC certified. Contact Soterix Medical team for any support related to trial approvals (IRB / IDE in the United States and ITA in Canada).