In Vivo Quantitative Microvasculature Phenotype Imaging of Healthy and Malignant Tissues Using a Fiber-Optic Confocal Laser Microprobe

In Vivo Quantitative Microvasculature Phenotype Imaging of Healthy and Malignant Tissues Using a Fiber-Optic Confocal Laser Microprobe
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DOI:
10.1593/tlo.08118
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发表时间:
2008-06-01
影响因子:
5
通讯作者:
Mahmood, Umar
Mahmood, Umar
中科院分区:
医学3区
文献类型:
--
作者:
Lin, Ken Young;Maricevich, Marco;Mahmood, Umar

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微血管的实时体内成像可能有助于疾病的早期临床检测和对肿瘤-宿主在不同进展阶段的相互作用的理解。体内共焦和多光子显微镜通常受到笨重的光学装置的阻碍,并且对内部器官的访问有限。光纤设置避免了这些限制,并提供了很大的用户可操作性。我们在这里报告的光纤共聚焦荧光微探针成像系统的体内验证。此外,我们开发了一种基于分形的自动图像分析,根据实时数据中的血管直径分布、密度、体积分数和分形维数来表征微血管形态。该系统针对远红外和近红外区域的使用进行了优化。直径为1.5 mm的柔性光纤束和微探针使用户具有很好的可操作性,视野为423 x 423 μ m,组织穿透力高达15 μ m。横向和轴向分辨率分别为3.5和15 μ m。我们表明,它是可能的,以获得高的时间和空间分辨率的图像,几乎任何腹部内脏原位使用远红血池成像探头。使用原位模型的胰腺导管腺癌,我们的特点是肿瘤表面毛细血管,并证明了成像系统和分析可以定量区分正常和肿瘤表面毛细血管。这种临床批准的光纤系统,连同基于分形的图像分析,可以潜在地应用于表征其他肿瘤在体内,并可能是一个有价值的工具,以促进其临床评价。
Real-time in vivo imaging of the microvasculature may help both earlier clinical detection of disease and the understanding of tumor-host interaction at various stages of progression. In vivo confocal and multiphoton microscopy is often hampered by bulky optics setup and has limited access to internal organs. A fiber-optic setup avoids these limitations and offers great user maneuverability. We report here the in vivo validation of a fiber-optic confocal fluorescence microprobe imaging system. In addition, we developed an automated fractal-based image analysis to characterize microvascular morphology based on vessel diameter distribution, density, volume fraction, and fractal dimension from real-time data. The system is optimized for use in the far-red and near-infrared region. The flexible 1.5-mm-diameter fiber-optic bundle and microprobe enable great user maneuverability, with a field of view of 423 x 423 mu m and a tissue penetration of up to 15 mu m. Lateral and axial resolutions are 3.5 and 15 mu m. We show that it is possible to obtain high temporal and spatial resolution images of virtually any abdominal viscera in situ using a far-red blood pool imaging probe. Using an orthotopic model of pancreatic ductal adenocarcinoma, we characterized the tumor surface capillary and demonstrated that the imaging system and analysis can quantitatively differentiate between the normal and tumor surface capillary. This clinically approved fiber-optic system, together with the fractal-based image analysis, can potentially be applied to characterize other tumors in vivo and may be a valuable tool to facilitate their clinical evaluation.