Focus Ultrasound Based Microbubble Mediated Blood-Brain Barrier Opening: A Technique to Create Localized Transient Openings in Blood-Brain Barrier of Mouse by Sonoporation

Abstract

Source: Haumann, R. et al. A High-Throughput Image-Guided Stereotactic Neuronavigation and Focused Ultrasound System for Blood-Brain Barrier Opening in Rodents. J. Vis. Exp. (2020)

This video describes a method of temporarily disrupting the blood-brain barrier (BBB) by creating transient openings using microbubble-mediated focused ultrasound (FUS). These transient local BBB openings can eventually be used to deliver larger-sized drug molecules directly into the brain parenchyma.

Protocol

All procedures involving human participants have been performed in compliance with the institutional, national and international guidelines for human welfare and have been reviewed by the local institutional review board. 1. Focused Ultrasound System NOTE: The described setup is an in-house built BBB disruption system based on commercially available components and includes a 3D-printed custom-made cone and deta…

Representative Results

Figure 1: Focused ultrasound setup. (A) Schematic representation of the focused ultrasound setup. (B) Picture of the focused ultrasound setup. The system consists of a top-down mounted transducer on a 1D linear stage over a second 2D stage for automatic 3D positioning. The transducer is built in a water-filled beam-cone, closed at the bottom with an acoustically …

Materials

1 mL luer-lock syringe	Becton Dickinson	309628	Plastipak
19 G needle	Terumo Agani	8AN1938R1
23 G needle	Terumo Agani	8AN2316R1
3M Transpore surgical tape	Science applied to life	7000032707	Or similar
Arbitrary waveform generator	Siglent		SDG1025, 25 mHz, 125 MSa/s
Automated stereotact	In-house built		Stereotact with all elements were in-house built
Bruker In-Vivo Xtreme	Bruker		Includes software
Buffered NaCl solution	B. Braun Melsungen AG	220/12257974/110
Buprenorfine hydrochloride	Indivior UK limitd		0.324 mg
Cage enrichment: paper-pulp smart home	Bio services
Carbon filter	Bickford	NC0111395	Omnicon f/air
Ceramic spoon
Cotton swabs
D-luciferin, potassium salt	Gold Biotechnology	LUCK-1
Ethanol	VUmc pharmacy		70%
Evans Blue	Sigma Aldrich	E2129
Fresenius NaCl 0.9%	Fresenius Kabi		Nacl 0.9 %, 1000 mL
Histoacryl	Braun Surgical		Histoacryl 0.5 mL
Hydrophone	Precision Acoustics
Insulin syringe	Becton Dickinson	324825/324826	0.5 mL and 0.3 mL
Isoflurane	TEVA Pharmachemie BV	8711218013196	250 mL
Ketamine	Alfasan		10 %, 10 mL
Mouse food: Teklad global 18% protein rodent diet	Envigo	2918-11416M
Neoflon catheter	Becton Dickinson	391349	26 GA 0.6 x 19 mm
Oscilloscope	Keysight technologies		Infiniivision DSOX024A
Plastic tubes	Greiner bio-one	210261	50 mL
Power amplifier	Electronics & Innovation Ltd	210L	Model 210L
Preamplifier DC Coupler	Precision Acoustics		Serial number: DCPS94
Scissors	Sigma Aldrich	S3146-1EA	Or similar
Sedazine	AST Farma		2%
SonoVue microbubbles	Bracco		8 µl/mL
Sterile water	Fresenius Kabi		1000 mL
Syringe			Various syringes can be used
Temgesic	Indivior UK limitd		0.3 mg/mL
Transducer	Precision Acoustics		1 mhz
Tweezers	Sigma Aldrich	F4142-1EA	Or similar
Ultrasound gel	Parker Laboratories Inc.	01-02	Aquasonic 100
Vidisic gel	Bausch + Lomb		10 g