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The dominant mode of neurologic and psychiatric care of patients is pharmacologic, indicating the need for technologies that allow mapping the brain’s response to drugs of interest. Towards this end we have developed ultrasonic drug uncaging for neuropsychiatric applications. In this technique, ultrasound sensitive drug-loaded nanoparticles are administered intravenously to a subject and focused ultrasound is applied to a region of interest of the nervous system, at intensities sufficient to induce drug release from the nanoparticles as they circulate in the tissue blood volume. In doing so, we enable targeted delivery of the drug payload to few millimeters-sized regions of the brain noninvasively. In this session we will discuss our progress to date in developing ultrasonic drug uncaging for pharmacologic brain mapping, with validation in rodent models, as well as our progress towards two planned first-in-human trials to commence in 2024: 1) targeted anesthetic delivery to the brain for reversible pseudolesion studies to map epileptogenic brain regions in patients with treatment resistant epilepsy and 2) targeted ketamine delivery to the anterior cingulate to maximize therapeutic efficacy for the affective component of chronic pain.
