Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Version of Record online: 29 JAN 2013
Copyright © 2013 Wiley Periodicals, Inc.
Lasers in Surgery and Medicine
Volume 45, Issue 3, pages 155–166, March 2013
How to Cite
Watson, J. M., Marion, S. L., Rice, P. F., Utzinger, U., Brewer, M. A., Hoyer, P. B. and Barton, J. K. (2013), Two-photon excited fluorescence imaging of endogenous contrast in a mouse model of ovarian cancer. Lasers Surg. Med., 45: 155–166. doi: 10.1002/lsm.22115
Samuel L. Marion, Urs Utzinger, Patricia B Hoyer, Jennifer K. Barton, money to institution from NIH; Patricia B. Hoyer, employment by University of Arizona, grants pending, US Patent No. 7,638,678.
- Issue online: 18 MAR 2013
- Version of Record online: 29 JAN 2013
- Manuscript Accepted: 3 JAN 2013
- National Institutes of Health
- National Cancer Institute Research Grant. Grant Number: R01 CA119200
- University of Arizona Cancer Center Support Grant (CCSG). Grant Number: CA023074
Background and Objective
Ovarian cancer has an extremely high mortality rate resulting from poor understanding of the disease. In order to aid understanding of disease etiology and progression, we identify the endogenous fluorophores present in a mouse model of ovarian cancer and describe changes in fluorophore abundance and distribution with age and disease.
Study Design/Materials and Methods
A mouse model of ovarian cancer was created by dosing with 4-vinylcyclohexene diepoxide, which induces follicular apoptosis (simulating menopause), and 7,12-dimethylbenz[a]anthracene, a known carcinogen. Imaging of ovarian tissue was completed ex vivo with a multiphoton microscope using excitation wavelength of 780 nm and emission collection from 405 to 505 nm. Two-photon excited fluorescence images and corresponding histologic sections with selective stains were used to identify endogenous fluorophores.
The majority of collected fluorescence emission was attributed to NADH and lipofuscin, with additional contributions from collagen and elastin. Dim cellular fluorescence from NADH did not show observable changes with age. Changes in ovarian morphology with disease development frequently caused increased fluorescence contributions from collagen and adipose tissue-associated NADH. Lipofuscin fluorescence was much brighter than NADH fluorescence and increased as a function of both age and disease.
Our finding of NADH fluorescence patterns similar to that seen previously in human ovary, combined with the observation of lipofuscin accumulation with age and disease also seen in human organs, suggests that the findings from this model may be relevant to human ovarian disease. Increased lipofuscin fluorescence might be used as an indicator of disease in the ovary and this finding warrants further study. Lasers Surg. Med. 45: 155–166, 2013. © 2013 Wiley Periodicals, Inc.