Gold-nanorod contrast-enhanced photoacoustic micro-imaging of focused-ultrasound induced blood-brain-barrier opening in a rat model.

Authors: Wang PH, Liu HL, Hsu PH, Lin CY, Wang CR, Chen PY, Wei KC, Yen TC, Li ML

In this study, we develop a novel photoacoustic imaging technique based on gold nanorods (AuNRs) for quantitatively monitoring focused-ultrasound (FUS) induced blood-brain barrier (BBB) opening in a rat model in vivo. This study takes advantage of the strong near-infrared absorption (peak at ≈ 800 nm) of AuNRs and the extravasation tendency from BBB opening foci due to their nano-scale size to passively label the BBB disruption area. Experimental results show that AuNR contrast-enhanced photoacoustic microscopy (PAM) successfully reveals the spatial distribution and temporal response of BBB disruption area in the rat brains. The quantitative measurement of contrast enhancement has potential to estimate the local concentration of AuNRs and even the dosage of therapeutic molecules when AuNRs are further used as nano-carrier for drug delivery or photothermal therapy. The photoacoustic results also provide complementary information to MRI, being helpful to discover more details about FUS induced BBB opening in small animal models.

Introduction

Purpose Drug delivery with BBB opening

Study Objective To evaluate gold-nanorod contrast-enhanced photoacoustic micro-imaging for detecting and monitoring focused-ultrasound-induced blood-brain barrier opening in a rat model.

Animal model / Human subject Rat (strain not specified; age not specified; sex male)

Disease model Healthy

Cargo name and characteristics Gold nanorods (rod-shaped gold nanoparticles used as contrast agent for photoacoustic imaging)

Route of administration Intravenous

Outcomes and Safety

Summary of Outcomes FUS opened the BBB in rats, enabling local accumulation of gold nanorods. Photoacoustic micro-imgaging successfully visualized and quatified the spatial distribution and temporal response of BBB disruption.

Safety-related matter No obvious hemorrhage or overt tissue damage under BBBO parameter used.

Brain Region

Visualization unavailable

Ultrasound Parameters

Ultrasound instrument High-intensity FUS transducer (diameter: 60 mm, radius of curvature: 80 mm)

FUS Frequency 1.5 MHz

FUS Pressure 0.48 Mpa

FUS Mode pulsed

Pulse duration 10 ms

Duration of a single FUS session 30 s

Focal Characteristics Focal depth: 3 mm; Focal length: 80 mm; Aperture size: 60 mm

Treatment frequency single session

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