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  4. Awake Blood-Brain Barrier Opening in Mice with a Wearable Focused Ultrasound Device

Awake Blood-Brain Barrier Opening in Mice with a Wearable Focused Ultrasound Device

Z Wang1*, L Zhu1,2 , H Chen1,2 , (1) Department of Biomedical Engineering, Washington University in St. Louis(2) Department of Radiation Oncology, Washington University in St. Louis

Presentations

(Sunday, 7/29/2018) 3:00 PM - 6:00 PM

Room: Exhibit Hall

Purpose: Blood-brain barrier (BBB) opening with focused ultrasound and microbubbles (MB) have been demonstrated to be a noninvasive, targeted, safe, and effective technique mostly in anesthetized animal models. However, the requirement of anesthesia limits the future clinical application of this noninvasive technology for the treatment of brain diseases as patient real-time feedback is critical to ensure the safety of the treatment. So far only one study demonstrated the feasibility of BBB opening using FUS in awake non-human primates after training the non-human primates to cooperate during the treatment. No study has evaluated the feasibility of FUS-induced BBB opening in the most commonly used animal model – mice, because of the technical challenges associated with designing a device for FUS sonication in awake mice.

Methods: A wearable helmet was designed for non-invasive, targeted FUS sonication of the mouse brain while the animals were awake. The helmet had a modular design featuring easy removal and installing of the unit for targeting different brain regions. The performance of the helmet in inducing BBB opening at the caudate putamen was assessed in four awake mice and four anesthetized mice in the presence of intravenously injected microbubbles. Evans blue was co-injected with the microbubbles for the evaluation of the BBB permeability using fluorescence imaging of ex vivo brain slices.

Results: The whole helmet with ultrasound transducer and wirings weighted 6.6g. The constraint design of the helmet minimized the effect of mouse movement on targeting. The helmet achieved localized BBB opening at the targeted brain location. The fluorescence intensity of the Evan’s blue in the brains of awake mice was higher than that in anesthetized mice, suggesting that FUS-induced BBB opening was affected by anesthesia.

Conclusion: The helmet design of the FUS device provides an innovative tool to study FUS-induced BBB opening in awake mice.

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