Mounzer Rawad, Shkarin Pavel, Papademetris Xenophon, Constable Todd, Ruddle Nancy H, Fahmy Tarek M
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Lymphat Res Biol. 2007;5(3):151-8. doi: 10.1089/lrb.2007.5302.
Evaluation of lymphedema and lymph node metastasis in humans has relied primarily on invasive or radioactive modalities. While noninvasive technologies such as magnetic resonance imaging (MRI) offer the potential for true three-dimensional imaging of lymphatic structures, invasive modalities, such as optical fluorescence microscopy, provide higher resolution and clearer delineation of both lymph nodes and lymphatic vessels. Thus, contrast agents that image lymphatic vessels and lymph nodes by both fluorescence and MRI may further enhance our understanding of the structure and function of the lymphatic system. Recent applications of bimodal (fluorescence and MR) contrast agents in mice have not achieved clear visualization of lymphatic vessels and nodes. Here the authors describe the development of a nanoparticulate contrast agent that is taken up by lymphatic vessels to draining lymph nodes and detected by both modalities.
A unique nanoparticulate contrast agent composed of a polyamidoamine dendrimer core conjugated to paramagnetic contrast agents and fluorescent probes was synthesized. Anesthetized mice were injected with the nanoparticulates in the hind footpads and imaged by MR and fluorescence microscopy. High resolution MR and fluorescence images were obtained and compared to traditional techniques for lymphatic visualization using Evans blue dye.
Lymph nodes and lymphatic vessels were clearly observed by both MRI and fluorescence microscopy using the bimodal nanoparticulate contrast agent. Characteristic tail-lymphatics were also visualized by both modalities. Contrast imaging yielded a higher resolution than the traditional method employing Evans blue dye. MR data correlated with fluorescence and Evans blue dye imaging.
A bimodal nanoparticulate contrast agent facilitates the visualization of lymphatic vessels and lymph nodes by both fluorescence microscopy and MRI with strong correlation between the two modalities. This agent may translate to applications such as the assessment of malignancy and lymphedema in humans and the evaluation of lymphatic vessel function and morphology in animal models.
对人类淋巴水肿和淋巴结转移的评估主要依赖于侵入性或放射性方法。虽然诸如磁共振成像（MRI）等非侵入性技术为淋巴结构的真正三维成像提供了可能，但侵入性方法，如光学荧光显微镜，能提供更高分辨率以及对淋巴结和淋巴管更清晰的描绘。因此，能通过荧光和MRI对淋巴管和淋巴结成像的造影剂可能会进一步增进我们对淋巴系统结构和功能的理解。双模态（荧光和磁共振）造影剂在小鼠中的近期应用尚未实现对淋巴管和淋巴结的清晰可视化。在此，作者描述了一种纳米颗粒造影剂的研发，该造影剂被淋巴管摄取至引流淋巴结，并能通过两种方式检测到。
合成了一种独特的纳米颗粒造影剂，其由与顺磁性造影剂和荧光探针共轭的聚酰胺胺树枝状大分子核心组成。对麻醉的小鼠后足垫注射纳米颗粒，并通过磁共振和荧光显微镜成像。获得了高分辨率的磁共振和荧光图像，并与使用伊文思蓝染料的传统淋巴可视化技术进行比较。
使用双模态纳米颗粒造影剂通过磁共振成像和荧光显微镜均清晰观察到了淋巴结和淋巴管。两种方式也都可视化了特征性的尾部淋巴管。造影成像比采用伊文思蓝染料的传统方法具有更高的分辨率。磁共振数据与荧光和伊文思蓝染料成像相关。
一种双模态纳米颗粒造影剂有助于通过荧光显微镜和磁共振成像对淋巴管和淋巴结进行可视化，且两种方式之间具有很强的相关性。这种造影剂可能会转化应用于诸如人类恶性肿瘤和淋巴水肿的评估以及动物模型中淋巴管功能和形态的评估等领域。
