Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 22, Pages 8943-8948Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1014501108
Keywords
near-infrared imaging; photoluminescence; principal component analysis imaging; dynamic contrast imaging; deep-tissue imaging
Categories
Funding
- National Institutes of Health-National Cancer Institute [5R01CA135109-02]
- Stanford University Center for Cancer Nanotechnology Excellence Focused on Therapy Response
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Fluorescent imaging in the second near-infrared window (NIR II, 1-1.4 mu m) 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 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.
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