Low-Intensity MR-Guided Focused Ultrasound Mediated Disruption of the Blood-Brain Barrier for Intracranial Metastatic Diseases.

Authors: Meng Y, Suppiah S, Surendrakumar S, Bigioni L, Lipsman N

Low-intensity MR-guided focused ultrasound in combination with intravenously injected microbubbles is a promising platform for drug delivery to the central nervous system past the blood-brain barrier. The blood-brain barrier is a key bottleneck for cancer therapeutics via limited inter- and intracellular transport. Further, drugs that cross the blood-brain barrier when delivered in a spatially nonspecific way, result in adverse effects on normal brain tissue, or at high concentrations, result in increasing risks to peripheral organs. As such, various anti-cancer drugs that have been developed or to be developed in the future would benefit from a noninvasive, temporary, and repeatable method of targeted opening of the blood-brain barrier to treat metastatic brain diseases. MR-guided focused ultrasound is a potential solution to these design requirements. The safety, feasibility and preliminary efficacy of MRgFUS aided delivery have been demonstrated in various animal models. In this review, we discuss this preclinical evidence, mechanisms of focused ultrasound mediated blood-brain barrier opening, and translational efforts to neuro-oncology patients.

Introduction

Purpose Drug delivery with BBB opening

Study Objective To review preclinical evidence, mechanisms, and translational efforts of low-intensity MR-guided focused ultrasound with microbubbles for targeted, temporary blood–brain barrier opening to improve drug delivery in neuro-oncology.

Disease model Metastatic brain cancer (brain metastases)

MRI or image guidance method MR-guided focused ultrasound (MRgFUS)

Outcomes and Safety

Summary of Outcomes Low-intensity MR-guided focused ultrasound (MRgFUS) combined with intravenously injected microbubbles safely, temporarily, and repeatedly opens the blood-brain barrier in preclinical animal models to enable targeted delivery of anti-cancer therapeutics with preliminary feasibility and efficacy; the successful parameter tested was low-intensity MRgFUS together with IV microbubbles.

Safety-related matter The authors state that MR-guided focused ultrasound (MRgFUS) aided delivery has demonstrated safety, feasibility, and preliminary efficacy in various animal models. They also note that spatially nonspecific BBB-crossing drugs can cause adverse effects on normal brain tissue and, at high concentrations, increased risk to peripheral organs.

Brain Region

Visualization unavailable

Ultrasound Parameters

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

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