Ultrasound Microsystems for Minimally-Invasive Neuromodulation via Low-Intensity Focused Ultrasound

Minimally-invasive neuromodulation using low-intensity focused ultrasound (LIFU) holds great promise for treating various neurological disorders. It has been demonstrated to modulate neural activity, promoting both excitatory and inhibitory effects. This capability allows for restoring aberrant neural circuitry or suppressing hyperactive regions, thereby alleviating symptoms associated with conditions such as Parkinson's disease, epilepsy, chronic pain, and depression.<br/>One of the key advantages of LIFU neuromodulation is its combination of high spatial resolution, minimal invasiveness, and extensive coverage of the nervous system. Unlike traditional electrical, magnetic, or optical neuromodulation techniques, which can achieve high-spatial resolution at the expense of high invasiveness and reduced brain coverage, ultrasound waves benefit from low wavelengths, scattering, and absorption in brain tissue and hence, can be focused virtually anywhere in the brain, with high-spatial-resolution and without requiring brain surgery. This reduces the risk of infection, tissue damage, and other complications associated with invasive procedures, making it a safer option for patients, and also allows for accessing a broader range of neural circuits with high precision.<br/>Despite the abovementioned promise, there is still a knowledge and technological gap in LIFU neuromodulation to maximize its potential. LIFU neuromodulation is achieved by means of an ultrasound transducer. These transducers generate low-intensity focused ultrasound waves that can penetrate deep into tissues while maintaining spatial specificity. By adjusting the parameters of the ultrasound waves, specific regions of the brain or peripheral nerves can be targeted with precision. However, similar to their use in medical diagnostic imaging, conventional ultrasound transducers used in LIFU neuromodulation have hand-held form factors and require off-the-shelf equipment. These bulky setups lead to two severe limitations: in pre-clinical research, the mismatch of size between bulky transducers and in-vitro/in vivo models (mice, rats) impose severe limitations in understanding the effects of ultrasound on the nervous system and how to better apply LIFU neuromodulation for different disease models; secondly, in clinical applications, the use of LIFU neuromodulation can only be applied in a bed-side scenario, where the patient either would visit the clinic once or twice per week to receive a treatment or would operate a LIFU neuromodulation system at home.<br/>This talk will describe the recent research in the field of ultrasound microsystems towards developing the next generation of LIFU neuromodulation systems that can be seamlessly integrated into in vitro/in vivo experimental setups in pre-clinical settings and used as wearable and minimally-invasive devices for clinical treatments. This description will answer two questions: how to massively integrate all the necessary LIFU neuromodulation functionality into a single-miniaturized and battery-powered microsystem? How can ultrasound microsystems be designed to be mechanically flexible to better adjust to the body's natural curvature?<br/>To answer these questions, the talk will focus on novel ultrasound microfabrication and microsystem integration methods and next-generation ultrasound electronics. Furthermore, the talk will also show a few examples of ongoing projects featuring <i>in vitro</i> and <i>in vivo</i> validation, showcasing the potential of LIFU microsystems for minimally invasive and precise neuromodulation for treating neurological diseases.