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Two-Photon and Second Harmonic Microscopy in Clinical and Translational Cancer Research

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Abstract

Application of two-photon microscopy (TPM) to translational and clinical cancer research has burgeoned over the last several years, as several avenues of pre-clinical research have come to fruition. In this review, we focus on two forms of TPM—two-photon excitation fluorescence microscopy, and second harmonic generation microscopy—as they have been used for investigating cancer pathology in ex vivo and in vivo human tissue. We begin with discussion of two-photon theory and instrumentation particularly as applicable to cancer research, followed by an overview of some of the relevant cancer research literature in areas that include two-photon imaging of human tissue biopsies, human skin in vivo, and the rapidly developing technology of two-photon microendoscopy. We believe these and other evolving two-photon methodologies will continue to help translate cancer research from the bench to the bedside, and ultimately bring minimally invasive methods for cancer diagnosis and treatment to therapeutic reality.

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Acknowledgments

The authors thank the reviewers for their helpful suggestions on this manuscript, and sincerely apologize to all colleagues whose work we could not cite in this review due to space constraints. This work was supported by National Institute of Health grants R21DA030256 to SWP, and 1DP2OD006501-01 to EBB, and Department of Defense grant W81XWH-09-1-0405 to EBB. This paper is subject to the NIH Public Access Policy.

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Associate Editor Daniel Elson oversaw the review of this article.

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Perry, S.W., Burke, R.M. & Brown, E.B. Two-Photon and Second Harmonic Microscopy in Clinical and Translational Cancer Research. Ann Biomed Eng 40, 277–291 (2012). https://doi.org/10.1007/s10439-012-0512-9

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