Slowed diffusion in tumors revealed by microfiberoptic epifluorescence photobleaching

Jay R. Thiagarajah, Jung Kyung Kim, Mazin Magzoub, A. S. Verkman

    Research output: Contribution to journalArticle

    Abstract

    It has not been possible to measure diffusion deep in solid tissues such as tumors because of the limited light penetration of conventional optical techniques. Here we report a microfiberoptic epifluorescence photobleaching (MFEP) method in which photobleaching is done by laser epi-illumination through a multimode fiberoptic whose micron-sized tip can be introduced deep into tissues. We applied MFEP to measure the diffusion of fluorescent macromolecules in tumors in living mice, at depths well beyond those accessible by surface optical measurements. Macromolecule diffusion was slowed about twofold within 200 μm of the surface of a solid tumor, but was slowed greater than tenfold beyond 500 μm. Our results reveal a remarkable and previously unrecognized slowing of diffusion deep in tumors, which correlated with the differing tissue architectures of tumor periphery versus core, and with altered tumor vasculature produced by aquaporin-1 deletion. MFEP should have wide applications for measuring diffusion in organs, solid tumors and other light-inaccessible tissue masses.

    Original languageEnglish (US)
    Pages (from-to)275-280
    Number of pages6
    JournalNature Methods
    Volume3
    Issue number4
    DOIs
    StatePublished - Apr 1 2006

    Fingerprint

    Photobleaching
    Tumors
    Neoplasms
    Tissue
    Macromolecules
    Aquaporin 1
    Light
    Lighting
    Lasers

    ASJC Scopus subject areas

    • Biotechnology
    • Molecular Biology
    • Cell Biology

    Cite this

    Thiagarajah, J. R., Kim, J. K., Magzoub, M., & Verkman, A. S. (2006). Slowed diffusion in tumors revealed by microfiberoptic epifluorescence photobleaching. Nature Methods, 3(4), 275-280. https://doi.org/10.1038/nmeth863

    Slowed diffusion in tumors revealed by microfiberoptic epifluorescence photobleaching. / Thiagarajah, Jay R.; Kim, Jung Kyung; Magzoub, Mazin; Verkman, A. S.

    In: Nature Methods, Vol. 3, No. 4, 01.04.2006, p. 275-280.

    Research output: Contribution to journalArticle

    Thiagarajah, JR, Kim, JK, Magzoub, M & Verkman, AS 2006, 'Slowed diffusion in tumors revealed by microfiberoptic epifluorescence photobleaching', Nature Methods, vol. 3, no. 4, pp. 275-280. https://doi.org/10.1038/nmeth863
    Thiagarajah, Jay R. ; Kim, Jung Kyung ; Magzoub, Mazin ; Verkman, A. S. / Slowed diffusion in tumors revealed by microfiberoptic epifluorescence photobleaching. In: Nature Methods. 2006 ; Vol. 3, No. 4. pp. 275-280.
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