血腦屏障阻擋了大部分治療腦部疾病的藥物進入腦內，使得現有醫學在治療腦部疾病的效果不彰。聚焦式超音波能局部且可逆地開啟血腦屏障，使藥物得以進入腦內。本研究開發了可應用於在聚焦式超音波血腦屏障開啟監控之雙模態–超音波及光聲–對比增強造影技術，有助於影像分析及判斷。我們使用金奈米桿做為此雙模態影像增強的對比劑，其奈米等級的大小使其容易從血腦屏障開啟處的血管滲入周圍腦組織，在腦組織中堆積造成超音波的強散射，且其具有特殊的光學特性，可調整光吸收波段於血液光吸收較弱的近紅外光波段內，使其為一良好的光聲和超音波對比劑。本研究使用聚焦式超音波搭配微氣泡在小動物模型上開啟血腦屏障，並注射對比劑金奈米桿增強超音波、光聲影像對比，在活體實驗驗證結果顯示本系統在超音波、光聲和聚焦式超音波共焦下，可用來做血腦屏障開啟位置的定位，以及監控對比劑金奈米桿造成的超音波和光聲對比增強影像。未來可進一步做血腦屏障開啟程度及超音波、光聲的時間強度曲線做定量分析，並且將應用此整合平台於腫瘤光熱治療及監控藥物輸送上。

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.

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