第二近红外窗口碳纳米管荧光团对小鼠深部组织的解剖成像
Deep-Tissue Anatomical Imaging of Mice Using Carbon Nanotube Fluorophores in the Second Near Infrared Window
摘要：
第二近红外窗口（NIR II，1-1.4 μm）中的荧光成像由于最小的自发荧光和组织散射而具有很大的前景。在这里，使用功能良好的生物相容性单壁碳纳米管（SWNTs）作为近红外II荧光成像剂，我们进行了高帧率的视频成像的小鼠在静脉注射的SWNTs和调查的路径SWNTs通过小鼠解剖。我们在注射后几秒钟观察到通过肺和肾的实时SWNT循环，并在稍晚的时间点观察到通过脾和肝的SWNT循环。通过主成分分析（PCA）进行动态对比增强成像，发现随着注射后时间的变化，大大提高了器官的解剖分辨率。重要的是，PCA能够区分无法从实时原始图像中分辨的器官，如胰腺。进行组织体模研究以比较NIR II区域中的成像与传统NIR I生物透明窗口（700- 900 nm）。一种常见的近红外I染料（吲哚菁绿，ICG）的特征尺寸的检查表明，随着特征深度的增加，与近红外II区域中的单壁碳纳米管相比，特征对比度和完整性的损失更快。通过蒙特卡罗模拟证实了NIR I与NIR II区域中散射增加的影响。在近红外II区域结合PCA分析的体内荧光成像可以代表一种强大的方法，通过深层组织的高分辨率光学成像，用于从生物医学研究到疾病诊断的广泛应用。
英文摘要：
Fluorescent imaging in the second near infrared window (NIR II, 1-1.4 μm) holds much promise due to minimal autofluorescence and tissue scattering. Here, using well functionalized biocompatible single-walled carbon nanotubes (SWNTs) as NIR II fluorescent imaging agents, we performed high frame rate video imaging of mice during intravenous injection of SWNTs and investigated the path of SWNTs through the mouse anatomy. We observed in real-time SWNT circulation through the lungs and kidneys several seconds post-injection, and spleen and liver at slightly later time points. Dynamic contrast enhanced imaging through principal component analysis (PCA) was performed and found to greatly increase the anatomical resolution of organs as a function of time post-injection. Importantly, PCA was able to discriminate organs such as the pancreas which could not be resolved from real-time raw images. Tissue phantom studies were performed to compare imaging in the NIR II region to the traditional NIR I biological transparency window (700- 900 nm). Examination of the feature sizes of a common NIR I dye (indocyanine green, ICG) showed a more rapid loss of feature contrast and integrity with increasing feature depth as compared to SWNTs in the NIR II region. The effects of increased scattering in the NIR I versus NIR II region were confirmed by Monte Carlo simulation. In vivo fluorescence imaging in the NIR II region combined with PCA analysis may represent a powerful approach to high resolution optical imaging through deep tissues, useful for a wide range of applications from biomedical research to disease diagnostics.
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