Two-photon excited fluorescence imaging of endogenous contrast in a mouse model of ovarian cancer

Jennifer M. Watson, Samuel L. Marion, Photini F. Rice, Urs Utzinger, Molly A. Brewer, Patricia B Hoyer, Jennifer K Barton

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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. Results 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. Conclusions 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.

Original languageEnglish (US)
Pages (from-to)155-166
Number of pages12
JournalLasers in Surgery and Medicine
Volume45
Issue number3
DOIs
StatePublished - Mar 2013

Fingerprint

Optical Imaging
Photons
Ovarian Neoplasms
Fluorescence
Lipofuscin
NAD
Ovary
Collagen
Ovarian Diseases
Elastin
Age Distribution
Menopause
Carcinogens
Disease Progression
Adipose Tissue
Coloring Agents
Observation
Apoptosis
Mortality

Keywords

  • aging
  • carcinoma
  • lipofuscin
  • lipoprotein
  • microscopy
  • multiphoton
  • NADH

ASJC Scopus subject areas

  • Surgery
  • Dermatology

Cite this

Two-photon excited fluorescence imaging of endogenous contrast in a mouse model of ovarian cancer. / Watson, Jennifer M.; Marion, Samuel L.; Rice, Photini F.; Utzinger, Urs; Brewer, Molly A.; Hoyer, Patricia B; Barton, Jennifer K.

In: Lasers in Surgery and Medicine, Vol. 45, No. 3, 03.2013, p. 155-166.

Research output: Contribution to journalArticle

Watson, Jennifer M. ; Marion, Samuel L. ; Rice, Photini F. ; Utzinger, Urs ; Brewer, Molly A. ; Hoyer, Patricia B ; Barton, Jennifer K. / Two-photon excited fluorescence imaging of endogenous contrast in a mouse model of ovarian cancer. In: Lasers in Surgery and Medicine. 2013 ; Vol. 45, No. 3. pp. 155-166.
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AB - 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. Results 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. Conclusions 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.

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