Transcranial focused ultrasound in the human brain

Many patients suffering with neurological and psychiatric disorders remain disabled despite modern medical and surgical approaches. Novel, safe, minimally invasive, and widely deployable therapies are urgently needed. Recent advances in focused ultrasound technology are opening a number of new therapeutic frontiers. Here, we review the emergence of transcranial focused ultrasound as a possible therapeutic tool for human brain disorders in the framework of 3 distinct applications: (1) high-intensity focused ultrasound (HIFU) to create therapeutic lesions in dysfunctional brain targets, (2) low-intensity focused ultrasound (LIFU) to open the blood-brain barrier (BBB), and (3) LIFU to stimulate neural elements to modulate the activity in neural circuits. These applications are discussed in the context of the historical evolution of transcranial focused ultrasound and the possible mechanism of action through which the various applications of ultrasound exert their effects, and we provide an overview of their clinical therapeutic potential.