Sonothermogenetics: A New Frontier for Focused Ultrasound?
Mark V. Kingsley
In previous articles, I’ve written about ultrasound used to stimulate the brain to wake up coma patients, as a promising treatment for chronic pain, and even as a tool for neuroscientists to accurately predict human behavior. Every month, without fail, there has been a new story about how functional ultrasound and its use for neuromodulation is making exciting progress in both research and treatment. This month is no exception, with a lot of buzz around a new kind of deep brain stimulation and a new technique with a convoluted name: sonothermogenetics.
Some definitions are necessary to fully understand what this technique is and what it accomplishes. First, functional ultrasound refers to medical ultrasound imaging that measures neural activity in the brain, a natural extension of Doppler imaging. Neuromodulation refers to the alteration of nerve activity through the targeted delivery of stimulus. Sonothermogenetics, then, is an example of neuromodulation that utilizes functional ultrasound as the tool to stimulate (and modulate) neurons in the brain. The sono– root of the word refers to ultrasound waves while the thermo- part is what is novel about this treatment. Sonothermogenetics involves TRPV1 (transient receptor potential cation channel subfamily V member 1), a genetic protein that functions as a thermosensitive ion channel.
In plain English, sonothermogenetics combines functional ultrasound and this viral construct (TRPV1) to target specific types of neurons and turn them “on and off.” This new technique comes courtesy of a team at the Washington University of St. Louis trying to come up with a way to achieve deep brain stimulation without resorting to invasive surgery. While not the first solution using function ultrasound for this purpose, the introduction of genetics into this area of exploration is new and exciting.
The study that demonstrated the application of this technique used live mice, a common first step in scientific experimentation before gradually advancing toward human trials. For the study, the mice wore an ultrasound device around the head, providing tiny blasts of heat barely warmer than body temperature through low-intensity functional ultrasound. The combined effect works like a switch that can turn neurons off and on, and therefore trigger specific behaviors in the mice. Yes, that is correct: this technique was shown to precisely control the motor activity, while this technique was applied in vivo on mice.
The study is a fascinating proof of concept for sonothermogenetics with implications for the future of how we study the brain and treat neurological disorders. Today, there are an estimated 700 million cases of mental and neurological disorders. The team behind this study is hopeful that since this technique is non-invasive, it may soon scale to larger animals including humans. Advances in the investigation of brain functions and treatment of neurological disorders in humans have been slow since we could not previously target specific neurons through non-invasive procedures.