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Deep-tissue anatomical imaging of mice using carbon nanotube fluorophores in the second near-infrared window

机译:在第二个近红外窗口中使用碳纳米管荧光团对小鼠进行深层解剖成像

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摘要

Fluorescent imaging in the second near-infrared window (NIR II, 1-1.4 urn) holds much promise due to minimal autofluorescence and tissue scattering. Here, using well-functionalized biocompati-ble 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 postinjection, 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 postinjection. 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) 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.
机译:由于几乎没有自发荧光和组织散射,因此在第二个近红外窗口(NIR II,1-1.4 um)中进行荧光成像很有希望。在这里,我们使用功能完善的生物相容性单壁碳纳米管(SWNT)作为NIR II荧光成像剂,在静脉注射SWNT的过程中对小鼠进行了高帧率视频成像,并研究了SWNT通过小鼠解剖结构的路径。我们在注射后数秒内通过肺和肾脏实时观察SWNT循环,在稍晚的时间点观察到脾脏和肝脏。通过主成分分析(PCA)进行动态对比增强成像,发现随着注射时间的延长,器官的解剖分辨率大大提高。重要的是,PCA能够区分出诸如胰腺之类的器官,而这些器官无法从实时原始图像中分辨出来。进行了组织体模研究,以比较NIR II区域中的成像与传统的NIR I生物透明窗(700-900 nm)。与NIR II区域中的SWNT相比,对普通NIR I染料(吲哚花青绿)的特征尺寸的检查显示,随着特征深度的增加,特征对比度和完整性的丧失更加迅速。蒙特卡罗模拟证实了近红外区与近红外区之间散射的增加。在体内荧光中,NIR II区域中的成像与PCA分析相结合可能代表通过深部组织进行高分辨率光学成像的有力方法,可用于从生物医学研究到疾病诊断的广泛应用。

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