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Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging

机译:对比度增强光学相干性断层扫描,具有皮摩尔敏感性,用于体内成像功能

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Optical Coherence Tomography (OCT) enables real-time imaging of living tissues at cell-scale resolution over millimeters in three dimensions. Despite these advantages, functional biological studies with OCT have been limited by a lack of exogenous contrast agents that can be distinguished from tissue. Here we report an approach to functional OCT imaging that implements custom algorithms to spectrally identify unique contrast agents: large gold nanorods (LGNRs). LGNRs exhibit 110-fold greater spectral signal per particle than conventional GNRs, which enables detection of individual LGNRs in water and concentrations as low as 250?pM in the circulation of living mice. This translates to ~40 particles per imaging voxel in vivo. Unlike previous implementations of OCT spectral detection, the methods described herein adaptively compensate for depth and processing artifacts on a per sample basis. Collectively, these methods enable high-quality noninvasive contrast-enhanced imaging of OCT in living subjects, including detection of tumor microvasculature at twice the depth achievable with conventional OCT. Additionally, multiplexed detection of spectrally-distinct LGNRs was demonstrated to observe discrete patterns of lymphatic drainage and identify individual lymphangions and lymphatic valve functional states. These capabilities provide a powerful platform for molecular imaging and characterization of tissue noninvasively at cellular resolution, called MOZART.
机译:光学相干断层扫描(OCT)使得在三维毫米上的细胞尺度分辨率下的活组织实时成像。尽管有这些优势,但八月的功能性生物学研究受到可以与组织区分开的外源性造影剂的限制。在这里,我们报告了一种方法来实现了用于谱谱识别唯一对比剂的定制算法的功能OCT成像的方法:大金纳径(LGNR)。 LGNRS每粒子比常规GNR表示110倍,可以在水和浓度下检测水中的单个LGNR,浓度为250μm,在生物小鼠的循环中。这在体内每次成像体素〜40颗粒转化为〜40颗粒。与先前的OCT光谱检测的实现不同,本文描述的方法适自适应地补偿每个样本的深度和处理伪影。总的来说,这些方法使得高质量的非侵入性对比增强的活性受试者的成像,包括用常规OCT可实现的深度的两倍检测肿瘤微血管。另外,证明了光谱不同的LGNR的多路复用检测观察淋巴引流的离散模式,并识别单个淋巴管和淋巴阀功能状态。这些能力提供了一种强大的平台,用于在蜂窝分辨率下非侵入地进行组织的分子成像和表征,称为莫扎特。

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