基于双波长光声显微成像的可视化血脑屏障损伤评估

血脑屏障是中枢神经系统中的一种特殊结构，起到严格调节血管网络与中枢神经系统之间的物质交换、维持正常的脑稳态的关键作用。血脑屏障的损伤常伴有脑部疾病的出现，如癫痫、中风和阿兹海默症等。这些疾病可能进一步发展成为严重的神经炎症甚至导致神经变性。因此，我们迫切需要一种精确监测血脑屏障损伤的方法，以了解其发病机制并更好地指导其治疗策略。然而，目前市面上仍然缺乏一种高分辨率成像技术，用于可视化大规模血脑屏障破坏，并在临床前和临床上对其做出评估。
在本文中，提出了一种基于光声成像的检测方法，这种方法使用了一种双波长光声显微镜，并结合双模态纳米粒子作为外源性造影剂，用于同步揭示大脑皮层内的微血管系统异常和血脑屏障损伤情况。在活体动物研究方面，建立了小鼠和大鼠两种模型，其血脑屏障损伤造模方式分别使用了局部热水滴注方法和高渗甘露醇的单侧颈动脉灌注方法。随后，通过尾静脉将纳米粒子溶液注入实验动物的血液循环系统中，通过双波长光声显微镜同步获得模型动物的大脑皮层内微血管系统和纳米粒子泄露的光声图像。光声图像的结果显示，在小鼠的局部损伤区域以及大鼠的半脑损伤区域，均可检测出明显的纳米粒子信号。同时，本文使用
了荧光成像和伊文思蓝染色两种方法作为评估血脑屏障损伤的验证手段，用于评估该方法的真实性与优越性。
此外，本文进一步统计分析了纳米粒子在病灶区域的泄露范围和泄露浓度，评估了血脑屏障损伤的严重程度，定量揭示了血脑屏障通透率的动态变化。实验结果显示，血脑屏障损伤的严重程度呈现出随时间逐渐恶化，但恶化程度逐渐减缓的趋势。最后，本文利用这种方法研究了血脑屏障损伤在两种不同模型中的可逆性，其中小鼠模型不具有可逆性，而大鼠模型造成的损伤在24 小时后具有逐渐恢复的趋势。基于实验结果，本文提出的方法在微血管系统和纳米粒子泄露的可视化检测方面表现出优异的性能，在评估脑血管疾病引起的微血管系统异常和血脑屏障损伤方面具有巨大潜力。

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