title: Endogenous optical biomarkers of ovarian cancer evaluated with multiphoton microscopy.
abstract: OBJECTIVE
  Among gynecologic cancers, ovarian cancer is the second most common and has the highest mortality. Currently, there is no accurate early diagnostic technique for ovarian cancer. Furthermore, little is understood regarding the early progression of this disease. We have imaged multiphoton interactions of endogenous tissue constituents from normal and abnormal ovarian biopsies that were kept viable during transport from the operating room and microscopy.
  
  
  METHODS
  The ovarian surface and underlying stroma were assessed with two-photon excited fluorescence (2PEF) and second harmonic generation (SHG). High-resolution, optically sectioned images were analyzed for epithelial morphology based on 2PEF and collagen density and structural integrity based on SHG. Additionally, multiwavelength 2PEF provided an estimation of the cellular redox ratio of epithelial cells.
  
  
  RESULTS
  Normal tissue exhibited a uniform epithelial layer with highly structured collagen in the stroma, whereas abnormal tissue exhibited varied epithelium with large cells and substantial quantitative changes to the collagen structure. Samples from patients at high risk for developing ovarian cancer (based on their personal/family history of cancer) exhibited highly variable cellular redox ratios and changes in collagen structure that trended toward cancer samples.
  
  
  CONCLUSIONS
  This study highlights differences in endogenous signals in viable ovarian biopsies based on quantitative collagen structural changes and redox ratio estimates that may lead to improved detection and further insights in ovarian cancer, particularly in the early stages of the disease.
authors.affiliation: Biomedical Engineering Program, University of Arizona, Arizona, USA. nkirk@email.arizona.edu
authors.forename: Nathaniel D
authors.initials: ND
authors.lastname: Kirkpatrick
authors.forename: Molly A
authors.initials: MA
authors.lastname: Brewer
authors.forename: Urs
authors.initials: U
authors.lastname: Utzinger
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D003094:Collagen / Q000032:analysis; D004848:Epithelium / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D036641:Microscopy, Fluorescence, Multiphoton / Q000295:instrumentation*; D009243:NAD / Q000032:analysis; D009249:NADP / Q000032:analysis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D010053:Ovary / Q000473:pathology; D010084:Oxidation-Reduction; D012016:Reference Values; D012307:Risk Factors; D017154:Stromal Cells / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D009243:NAD; D009249:NADP; D003094:Collagen