Photoacoustic imaging of gold nanorods in the brain delivered via microbubble-assisted focused ultrasound: a tool for <i>in vivo</i> molecular neuroimaging.
Authors: Hartman RK, Hallam KA, Donnelly EM, Emelianov SY
The protective barriers of the CNS present challenges during the treatment and monitoring of diseases. In particular, the blood brain barrier is a major hindrance to the delivery of imaging contrast agents and therapeutics to the brain. In this work, we use gas microbubble-assisted focused ultrasound to transiently open the blood brain barrier and locally deliver silica coated gold nanorods across the barrier. This particular nanoagent possesses a strong optical absorption which enables <i>in vivo</i> and <i>ex vivo</i> visualization of the delivered particles using ultrasound-guided photoacoustic imaging. The results of these studies demonstrate the potential of ultrasound-guided photoacoustics to image contrast agents delivered via microbubble-assisted focused ultrasound for longitudinal diagnostic imaging and for therapeutic monitoring of neurological diseases.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To demonstrate that gas microbubble-assisted focused ultrasound can transiently open the blood–brain barrier to deliver silica-coated gold nanorods and enable their visualization using ultrasound-guided photoacoustic imaging.
Animal model / Human subject
Mouse, C57BL/6
MRI or image guidance method
Ultrasound-guided (photoacoustic imaging)
Cargo name and characteristics
Silica-coated gold nanorods (nanoparticle): gold nanorod core with silica shell, strong optical absorption enabling in vivo and ex vivo ultrasound-guided photoacoustic imaging; used as an imaging contrast agent delivered across the blood–brain barrier.
Route of administration
Retro-orbitally
Outcomes and Safety
Summary of Outcomes
Gas microbubble-assisted focused ultrasound transiently opened the blood–brain barrier to deliver silica-coated gold nanorods which were successfully visualized in vivo and ex vivo using ultrasound-guided photoacoustic imaging.
Safety-related matter
No adverse effects, histological analysis indicated no RBC extravasation or gross tissue damage following BBB opening with nanoparticle introduced
Brain Region
Ultrasound Parameters
Ultrasound instrument
single-element focused ultrasound transducer
FUS Frequency
2 MHz
FUS Mode
pulsed
Pulse duration
10 ms
Duration of a single FUS session
60 seconds
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
single session
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