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PMID: 12756303 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 12 ·2003-06-10 ·Pages 7075-80

Zipfel WR, Williams RM, Christie R, Nikitin AY, Hyman BT, Webb WW

Abstract

Multicolor nonlinear microscopy of living tissue using two- and three-photon-excited intrinsic fluorescence combined with second harmonic generation by supermolecular structures produces images with the resolution and detail of standard histology without the use of exogenous stains. Imaging of intrinsic indicators within tissue, such as nicotinamide adenine dinucleotide, retinol, indoleamines, and collagen provides crucial information for physiology and pathology. The efficient application of multiphoton microscopy to intrinsic imaging requires knowledge of the nonlinear optical properties of specific cell and tissue components. Here we compile and demonstrate applications involving a range of intrinsic molecules and molecular assemblies that enable direct visualization of tissue morphology, cell metabolism, and disease states such as Alzheimer's disease and cancer.

MeSH Terms
Alzheimer Disease/metabolism,pathology Animals Biophysical Phenomena Biophysics Collagen/metabolism Female Fluorescent Dyes Humans Indoles/metabolism Mammary Neoplasms, Experimental/metabolism,pathology Mice Microscopy, Fluorescence/methods NAD/metabolism Neurofibrillary Tangles/metabolism,pathology Photons Vitamin A/metabolism
Chemicals
Fluorescent Dyes Indoles NAD Vitamin A Collagen
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Zipfel Warren R
Department of Applied and Engineering Physics, Cornell University, Ithaca, NY 14853, USA.
Williams Rebecca M
Christie Richard
Nikitin Alexander Yu
Hyman Bradley T
Webb Watt W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0832308100
Published
2003-06-10
Epub
2003-00-19
Pages
7075-80
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC165832
Subset
IM
Grants
NCI NIH HHS · CA96823-01 · United States
NCI NIH HHS · BC991016 · United States
NIA NIH HHS · R01 AG008487 · United States
NCI NIH HHS · R56 CA096823 · United States
NCI NIH HHS · PC010342 · United States
NCI NIH HHS · R01 CA096823 · United States
PHS HHS · R33-645644 · United States
NIA NIH HHS · AG08487 · United States
NIBIB NIH HHS · 9-P41-EB0011976-16 · United States
External Links
PubMed source DOI: 10.1073/pnas.0832308100 PMC Full Text View journal details
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