A recently published review “Ultrasonic Neuromodulation” in the Journal of Neural Engineering, discusses the history of the physics, engineering and research of ultrasonic waves and its effects on neural activity.
The use of ultrasonic waves for neuromodulation is a lesser known and applied technique, although research on this topic dates back to 1929. This review includes an array of empirical evidence that
Figure 1: Focused ultrasound to stimulate and suppress neural activity.
(Credit: Focused Ultrasound Foundation, http://www.fusfoundation.org/mechanisms-of-action/neuromodulation)
The use of non-invasive ultrasonic stimulation in excitable tissues of the central nervous system has opened up this field for more neural, clinical and engineering research. The Focused Ultrasound Foundation has already identified various important applications for clinical utility and therapeutic benefit. Some of these include brain and pre-surgical mapping, non-destructive suppression of neural disorders, cancer therapy, retinal prostheses, and non-invasive pain treatment. What’s probably most interesting is the advancement of the current ultrasonic technologies to accurately focus ultrasound through the skull, without the former limitations of the attenuating effects of skull bones, onto millimetre sized target brain structures in animals.
Ultimately, the use of ultrasound in basic research can provide neuroscientists with an important reversible and non-invasive tool to stimulate or suppress certain neural circuit segments. When this is applied in conjunction with imaging techniques, researchers may gain new insights into neural networks. Additionally, ultrasound along with neural dust may further be of use in correcting neural dysfunction or perhaps even enhancing certain functions within the central nervous system. This paves the way for beneficial therapeutic applications in cases with depression, epilepsy and Parkinson’s disease.
High frequency ultrasonic waves as an energy-based focal ablative technique for precision medical applications, such as targeting of cancer cells in vivo
Acoustic retinal prostheses
Combines multifocal acoustic pattern
generation and ultrasonic retinal stimulation
and has been applied efficiently in vivo,
in vitro and in humans
Figure 2: Depiction of retinal stimulation techniques
Ultrasonic waves are transmitted into the eye and produce a projected pattern for stimulating retinal neurons. (Credit: Ghezzi, Front Neurosci 2015)
Ultrasound-responsive drug delivery
Microbubbles (A) enhance cell membrane permeability, but is restricted to cardiovascular targets and tumor endothelium
Nanobubbles or nanodroplets (B) of smaller size (<1μm) can efficiently delivery to all target cells
Polymeric micelles (C) with nanometer size and high loading efficiency enhance intracellular uptake at target cells
Microemulsions (D) as stable liquid solutions can efficiently release drugs inside tumors by means of ultrasound aggregation and ultrasound triggered release
Figure 3: Illustration of various ultrasound-responsive drug delivery systems.
(Credit: Zhao et al., Int J Nanomedicine 2013)
Jagannathan J, Sanghvi NK, Crum LA, Yen C, Medel R, Dumont AS, et al. High intensity focused ultrasound surgery (HIFU) of the brain: A historical perspective, with modern applications. Neurosurgery 2009 Febr;64(2):201-211.
Li G, Zhao H, Zhou H, Yan F, Wang J, Xu C, et al. Improved anatomical specificity of non-invasive neuro-stimulation by high frequency (5MHz) ultrasound. Sci Rep 2016 Apr;6:24738.
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