Enhanced photoacoustic neuroimaging with gold nanorods and PEBBLEs

Abstract

Photoacoustic (PA) imaging provides excellent optical contrast with decent penetration and high spatial resolution, making it attractive for a variety of neural applications. We evaluated optical contrast agents with high absorption in the near infrared (NIR) as potential enhancers for PA neuroimaging: optical dyes, gold nanorods (GNRs) and PEBBLEs loaded with indocyanine green. Two PA systems were developed to test these agents in excised neural tissue and in vivo mouse brain. Lobster nerves were stained with the agents for 30 minutes and placed in a hybrid nerve chamber capable of electrical stimulation and recording, optical spectroscopy and PA imaging. Contrast agents boosted the PA signal by at least 30 dB using NIR illumination from a tunable pulsed laser. Photobleaching may be a limiting factor for optical dyes-the PA signal decreased steadily with laser illumination. The second setup enabled in vivo transcranial imaging of the mouse brain. A custom clinical ultrasound scanner and a 10-MHz linear array provided near real-time images during and after an injection of 2 nM gold nanorods into the tail vein. The peak PA signal from the brain vasculature was enhanced by up to 2 dB at 710 nm. Temporal dynamics of the PA signal were also consistent with mixing of the GNRs in the blood. These studies provide a baseline for enhanced PA imaging in neural tissue. The smart contrast agents employed in this study can be further engineered for molecular targeting and controlled drug delivery with potential treatment for a myriad of neural disorders.