Abstract
A long-standing goal of translational neuroscience is the ability to noninvasively deliver therapeutic agents to specific brain regions with high spatiotemporal resolution. Focused ultrasound (FUS) is an emerging technology that can noninvasively deliver energy up the order of 1 kW/cm2 with millimeter and millisecond resolution to any point in the human brain with Food and Drug Administration-approved hardware. Although FUS is clinically utilized primarily for focal ablation in conditions such as essential tremor, recent breakthroughs have enabled the use of FUS for drug delivery at lower intensities (i.e., tens of watts per square centimeter) without ablation of the tissue. In this review, we present strategies for image-guided FUS-mediated pharmacologic neurointerventions. First, we discuss blood–brain barrier opening to deliver therapeutic agents of a variety of sizes to the central nervous system. We then describe the use of ultrasound-sensitive nanoparticles to noninvasively deliver small molecules to millimeter-sized structures including superficial cortical regions and deep gray matter regions within the brain without the need for blood–brain barrier opening. We also consider the safety and potential complications of these techniques, with attention to temporal acuity. Finally, we close with a discussion of different methods for mapping the ultrasound field within the brain and describe future avenues of research in ultrasound-targeted drug therapies.
Highlights
Focused Ultrasound as a Potential Modality for Noninvasive NeurointerventionNeuropsychiatric diseases have emerged as one of the largest public health threats today, contributing to an estimated 57% of years lived with disability in the United States from 1990 to 2016 (Mokdad et al, 2018)
Clinical Applications of Blood–Brain Barrier Opening Currently, the majority of Focused ultrasound (FUS)-mediated blood–brain barrier opening (BBBO) trials being conducted in humans are for delivering chemotherapeutic agents to treat brain tumors (Table 1)
Focal Noninvasive Drug Delivery With Ultrasonic Drug Uncaging As discussed earlier, most work regarding drug delivery in the brain using FUS is centered around BBBO for the delivery of agents that do not normally cross the intact BBB
Summary
Focused Ultrasound as a Potential Modality for Noninvasive NeurointerventionNeuropsychiatric diseases have emerged as one of the largest public health threats today, contributing to an estimated 57% of years lived with disability in the United States from 1990 to 2016 (Mokdad et al, 2018). We will first introduce a number of methods for drug delivery to the brain and discuss applications of FUS to achieve targeted delivery, namely by temporarily opening the BBB or by directly releasing pharmacologic agents from carrier particles within millimeter-sized structures. Clinical Applications of Blood–Brain Barrier Opening Currently, the majority of FUS-mediated BBBO trials being conducted in humans are for delivering chemotherapeutic agents to treat brain tumors (Table 1).
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