Applications of focused ultrasound-mediated blood-brain barrier opening.

Authors: Gorick CM, Breza VR, Nowak KM, Cheng VWT, Fisher DG, Debski AC, Hoch MR, Demir ZEF, Tran NM, Schwartz MR, Sheybani ND, Price RJ

The blood brain barrier (BBB) plays a critically important role in the regulation of central nervous system (CNS) homeostasis, but also represents a major limitation to treatments of brain pathologies. In recent years, focused ultrasound (FUS) in conjunction with gas-filled microbubble contrast agents has emerged as a powerful tool for transiently and non-invasively disrupting the BBB in a targeted and image-guided manner, allowing for localized delivery of drugs, genes, or other therapeutic agents. Beyond the delivery of known therapeutics, FUS-mediated BBB opening also demonstrates the potential for use in neuromodulation and the stimulation of a range of cell- and tissue-level physiological responses that may prove beneficial in disease contexts. Clinical trials investigating the safety and efficacy of FUS-mediated BBB opening are well underway, and offer promising non-surgical approaches to treatment of devastating pathologies. This article reviews a range of pre-clinical and clinical studies demonstrating the tremendous potential of FUS to fundamentally change the paradigm of treatment for CNS diseases.

Introduction

Purpose Drug delivery with BBB opening

Study Objective To review preclinical and clinical studies on focused ultrasound-mediated blood–brain barrier opening and its potential for targeted, noninvasive delivery and modulation in central nervous system diseases.

Outcomes and Safety

Summary of Outcomes Focused ultrasound (FUS) combined with gas-filled microbubbles transiently and noninvasively opens the blood–brain barrier to enable localized delivery of drugs, genes and other therapeutics and can induce neuromodulation and beneficial cell- and tissue-level physiological responses; clinical studies indicate promising safety and efficacy. The review does not report specific FUS parameter sets tested or identify particular successful sonication parameters.

Safety-related matter The paper states that clinical trials investigating the safety and efficacy of focused ultrasound–mediated BBB opening are well underway. No specific adverse effects or safety concerns are reported in the provided text.

Brain Region

Visualization unavailable

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None

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