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Monitoring Blood-Brain Barrier Opening in Rats with a Preclinical Focused Ultrasound System.

Authors: Kim K, Gallus M, Xiao T, Parchure AS, Shah BR, Okada H, Diederich C, Ozhinsky E, Narsinh K

The brain has a highly selective semipermeable blood barrier, termed the blood-brain barrier (BBB), which prevents the delivery of therapeutic macromolecular agents to the brain. The integration of MR-guided low-intensity pulsed focused ultrasound (FUS) with microbubble pre-injection is a promising technique for non-invasive and non-toxic BBB modulation. MRI can offer superior soft-tissue contrast and various quantitative assessments, such as vascular permeability, perfusion, and the spatial-temporal distribution of MRI contrast agents. Notably, contrast-enhanced MRI techniques with gadolinium-based MR contrast agents have been shown to be the gold standard for detecting BBB openings. This study outlines a comprehensive methodology involving MRI protocols and animal procedures for monitoring BBB opening in a rat model. The rat model provides the added benefit of jugular vein catheter utilization, which facilitates rapid medication administration. A stereotactic-guided preclinical FUS transducer facilitates the refinement and streamlining of animal procedures and MRI protocols. The resulting methods are characterized by reproducibility and simplicity, eliminating the need for specialized surgical expertise. This research endeavors to contribute to the optimization of preclinical procedures with rat models and encourage further investigation into the modulation of the BBB to enhance therapeutic interventions in neurological disorders.

Introduction

Purpose Drug delivery with BBB opening
Study Objective To monitor blood–brain barrier opening in rats using a preclinical focused ultrasound system.
Animal model / Human subject Rat; strain not specified; age not specified; sex not specified
Disease model Healthy

Outcomes and Safety

Summary of Outcomes The paper demonstrates that a preclinical focused ultrasound system can open the blood–brain barrier in rats and that the BBB opening can be monitored; the supplied text does not report specific ultrasound parameters or which parameter sets were successful.
Safety-related matter No safety or adverse effects are mentioned 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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