Pitt Shield

Targeted delivery of therapeutic agents to the mouse brain using a stereotactic-guided focused ultrasound device.

Authors: Hu Z, Yang Y, Ye D, Chen S, Gong Y, Chukwu C, Chen H

Existing protocols of focused ultrasound (FUS) combined with microbubble-mediated blood-brain barrier (BBB) opening (FUS-BBBO) in preclinical research require expensive ultrasound equipment and complex operating procedures. We developed a low-cost, easy-to-use, and precise FUS device for small animal models in preclinical research. Here, we provide a detailed protocol for building the FUS transducer, attaching the transducer to a stereotactic frame for precise brain targeting, applying the integrated FUS device to perform FUS-BBBO in mice, and evaluating the FUS-BBBO outcome. For complete details on the use and execution of this protocol, please refer to Hu et al. (2022).<sup>1</sup>.

Introduction

Purpose Drug delivery with BBB opening
Study Objective To develop and provide a detailed protocol for a low-cost, easy-to-use, and precise focused ultrasound device for microbubble-mediated blood–brain barrier opening in mice.
Animal model / Human subject Mouse (Mus musculus); strain: None; age: None; sex: None
Disease model Blood-brain barrier opening (FUS-BBBO) in mice for brain drug delivery (preclinical model)
MRI or image guidance method Stereotactic frame guidance (transducer attached to a stereotactic frame for precise brain targeting)
Targeted brain region(s) Thalamus
Target coordinates AP: +2.26 mm, ML: -1.50 mm, DV: -3.30 mm

Outcomes and Safety

Summary of Outcomes A low-cost, easy-to-use focused ultrasound device enables highly precise stereotactic targeting to open the blood–brain barrier and facilitate brain drug delivery in mice.
Safety-related matter The paper states that undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Brain Region

Ultrasound Parameters

FUS Frequency 1.5, 3, 6
FUS Mode pulsed
Pulse duration 10 ms
Duration of a single FUS session 120 s
Treatment frequency single

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