Abstract
Blood-brain barrier (BBB) blocks most drugs for the treatment of brain diseases, resulting in poor performance of current medical treatments of brain diseases. Focused ultrasound (FUS) along with micro-bubble administration can induce BBB disruption locally and reversibly, allowing drugs penetrating into the brain. In this study, we developed a dual modal - ultrasound and photoacoustic - contrast-enhanced imaging technique to monitor FUS induced BBB disruption. This technique provides the complementary characteristics of two different images, helping us to perform image analysis and recognition. Gold nanorods (AuNR) were used as the contrast agent-, whose nanometer-scale size provides the intrinsic extravasation tendency from BBB opening foci. The accumulation of AuNRs in brain tissue results in strong scattering of ultrasound. In addition, AuNRs used own typical optical tunability, having absorption peak at near-infrared spectral range. Based on the above properties, AuNRs can serve as a good contrast agent for both PA and US imaging in BBB disruption study. This study used focused ultrasound with microbubbles to induce BBB disruption on a small animal models and injected contrast agent - AuNRs to enhance contrast of ultrasound and photoacoustic images. The in vivo experimental results showed that our developed US/PA/FUS confocal system can be used for targeting the position of BBB disruption, and monitoring the ultrasound and photoacoustic contrast-enhanced images caused by AuNRs. In further research, our system can be used for quantitative analysis on BBB disruption as well as time intensity curve of ultrasound and photoacoustic signal, also can be applied to photothermal therapy on tumor and monitoring drug delivery.