Applications of focused ultrasound in the brain: from thermoablation to drug delivery

Focused ultrasound (FUS) is a disruptive medical technology, and its implementation in the clinic represents the culmination of decades of research. Lying at the convergence of physics, engineering, imaging, biology and neuroscience, FUS offers the ability to non-invasively and precisely intervene in key circuits that drive common and challenging brain conditions. The actions of FUS in the brain take many forms, ranging from transient blood–brain barrier opening and neuromodulation to permanent thermoablation. Over the past 5 years, we have seen a dramatic expansion of indications for and experience with FUS in humans, with a resultant exponential increase in academic and public interest in the technology. Applications now span the clinical spectrum in neurological and psychiatric diseases, with insights still emerging from preclinical models and human trials. In this Review, we provide a comprehensive overview of therapeutic ultrasound and its current and emerging indications in the brain. We examine the potential impact of FUS on the landscape of brain therapies as well as the challenges facing further advancement and broader adoption of this promising minimally invasive therapeutic alternative.

Key points

• Recent advances have led to a surge of interest in focused ultrasound (FUS) as a non-invasive, potentially disruptive tool for the most intractable neurological conditions.
• Magnetic resonance-guided FUS thermoablation has been approved for the treatment of essential tremor and tremor-dominant Parkinson disease and is being investigated in psychiatric applications as well as in chronic pain and epilepsy.
• Transient opening of the blood–brain barrier for drug delivery is a burgeoning field, with early human studies demonstrating a favourable safety profile as well as versatility across and scalability within a range of clinical indications.
• Future studies will investigate the delivery of established pharmaceuticals and novel therapies in combination with FUS blood–brain barrier opening.
• Emerging applications are also harnessing the myriad of ways in which FUS can interact with the CNS, including immune modulation and neuromodulation.

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Acknowledgements

We acknowledge Hang Yu Lin for her artistic contribution to the figures in this article. N. L. acknowledges and is grateful for the generous philanthropic gifts to the Sunnybrook Foundation, Sunnybrook Research Institute and the Harquail Centre for Neuromodulation as well as the support of the Focused Ultrasound Foundation.