Second near infrared (NIR-II) window fluorescence imaging between 1000 and 1700 nm with reduced scattering and autofluorescence and deep tissue light penetration allows early and non-invasive determination of vascular pathologies. Here, we demonstrate in vivo NIR-II imaging techniques for tracking hyperglycaemia-induced Intracerebral Hemorrhage (ICH) and Blood Brain Barrier (BBB) hyperpermeability in Cerebral Cavernous Malformation (CCM) deficient mice (CCM1+/−). We synthesised PEGylated Ag₂S quantum dots (QDs) with a bright fluorescent emission peak centred at 1135 nm under an 808 nm NIR light for dynamic imaging of cerebral vasculature in mice and determined the development of ICH and BBB impairment in hyperglycaemic CCM1+/− mice. In vivo optical imaging was conducted with micro-CT (including k-mean cluster analysis) as well as in vivo permeability assays using FITC-dextran perfusion and IgG staining, respectively. The increased BBB permeability in CCM1+/− mice was further demonstrated to be associated with a high-glucose-caused decrease of CCM1 expressions. This study validates that deep-penetrating NIR-II QDs can be used for the tracking of ICH and BBB hyperpermeability in transgenic mice models of cerebral vascular anomalies.

中文翻译：

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NIR-II 窗口追踪高血糖引起的脑海绵状血管瘤缺陷小鼠脑出血。

1000 至 1700 nm 之间的第二近红外 (NIR-II) 窗口荧光成像减少了散射和自发荧光以及深层组织光穿透，可以对血管病理进行早期和非侵入性测定。在这里，我们展示了体内NIR-II 成像技术，用于跟踪脑海绵状血管畸形 (CCM) 缺陷小鼠 (CCM1+/-) 中高血糖引起的脑出血 (ICH) 和血脑屏障 (BBB) 通透性过高。我们合成了聚乙二醇化 Ag ₂ S 量子点 (QD)，在 808 nm 近红外光下具有以 1135 nm 为中心的明亮荧光发射峰，用于小鼠脑血管系统的动态成像，并确定高血糖 CCM1+/- 小鼠中 ICH 和 BBB 损伤的发展情况。体内通过显微 CT（包括k均值聚类分析）进行光学成像，并分别使用 FITC-葡聚糖灌注和 IgG 染色进行体内渗透性测定。CCM1+/- 小鼠中 BBB 通透性的增加被进一步证明与高葡萄糖引起的 CCM1 表达减少有关。这项研究验证了深穿透性 NIR-II 量子点可用于追踪脑血管异常转基因小鼠模型中的 ICH 和 BBB 通透性过高。