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In vivo wide-area cellular imaging by side-view endomicroscopy

Nature Methods volume 7, pages 303–305 (2010)Cite this article

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Abstract

In vivo imaging of small animals offers several possibilities for studying normal and disease biology, but visualizing organs with single-cell resolution is challenging. We describe rotational side-view confocal endomicroscopy, which enables cellular imaging of gastrointestinal and respiratory tracts in mice and may be extensible to imaging organ parenchyma such as cerebral cortex. We monitored cell infiltration, vascular changes and tumor progression during inflammation and tumorigenesis in colon over several months.

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Figure 1: In vivo side-view endomicroscopy.
Figure 2: Visualization of FoxP3+ GFP+ Treg cells in a DSS-induced colitis model.
Figure 3: Longitudinal imaging of colorectal tumorigenesis.

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Acknowledgements

This work was supported by the Wellman Center for Photomedicine, Human Frontier Science Program (cross-disciplinary fellowship 2006), Tosteson Fellowship, National Research Foundation of Korea (R31-2008-000-10071-0) and the US National Institutes of Health (R21AI081010, RC1DK086242, RC2DK088661, U54CA143837, U01CA084301, R01CA85140, P01CA08124, R01CA96915 and R01CA126642).

Author information

Authors and Affiliations

  1. Department of Dermatology, Wellman Center for Photomedicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA

    Pilhan Kim & Seok H Yun

  2. Department of Radiation Oncology, Edwin L. Steele Lab for Tumor Biology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA

    Euiheon Chung, Hiroshi Yamashita, Dai Fukumura & Rakesh K Jain

  3. Division of Gastroenterology, Tufts Medical Center, Boston, Massachusetts, USA

    Kenneth E Hung

  4. Department of Pathology, Center for the Study of Inflammatory Bowel Disease, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA

    Atsushi Mizoguchi

  5. Department of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Raju Kucherlapati

  6. Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Yuseong-gu, Daejeon, Korea.,

    Seok H Yun

  7. The Harvard–Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Massachusetts, USA

    Seok H Yun

Authors
  1. Pilhan Kim
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Contributions

P.K. developed endomicroscopy, performed experiments and wrote the manuscript. E.C. and H.Y. performed the conditional-knockout procedure and helped with angiogenesis imaging. K.E.H. developed the conditional-knockout procedure. A.M. designed the colitis model. R.K., D.F. and R.K.J. designed the tumor model and angiogenesis study. S.H.Y. directed the overall project, developed endomicroscopy and wrote the manuscript with input from other authors.

Corresponding author

Correspondence to Seok H Yun.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–9 (PDF 1601 kb)

Supplementary Video 1

Virtual cellular colonoscopy visualizing the microvasculature of normal colonic mucosa. (MOV 4039 kb)

Supplementary Video 2

Real-time endoscopic view of the blood vessels in the normal colon. (MOV 2730 kb)

Supplementary Video 3

Fly-through movie showing the blood vessels of esophageal mucosa. (MOV 2246 kb)

Supplementary Video 4

Time-lapse movie showing the interaction of dendritic cells (green) and Ovalbumin (OVA) allergen (red) at 12 h after OVA challenge. (MOV 735 kb)

Supplementary Video 5

Real-time movie showing the angiogenic blood vessels near the tumor at week 16 after conditional Apc knockout. (MOV 1912 kb)

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Kim, P., Chung, E., Yamashita, H. et al. In vivo wide-area cellular imaging by side-view endomicroscopy. Nat Methods 7, 303–305 (2010). https://doi.org/10.1038/nmeth.1440

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