title: Vital-dye-enhanced multimodal imaging of neoplastic progression in a mouse model of oral carcinogenesis.
abstract: In this longitudinal study, a mouse model of 4-nitroquinoline 1-oxide chemically induced tongue carcinogenesis was used to assess the ability of optical imaging with exogenous and endogenous contrast to detect neoplastic lesions in a heterogeneous mucosal surface. Widefield autofluorescence and fluorescence images of intact 2-NBDG-stained and proflavine-stained tissues were acquired at multiple time points in the carcinogenesis process. Confocal fluorescence images of transverse fresh tissue slices from the same specimens were acquired to investigate how changes in tissue microarchitecture affect widefield fluorescence images of intact tissue. Widefield images were analyzed to develop and evaluate an algorithm to delineate areas of dysplasia and cancer. A classification algorithm for the presence of neoplasia based on the mean fluorescence intensity of 2-NBDG staining and the standard deviation of the fluorescence intensity of proflavine staining was found to separate moderate dysplasia, severe dysplasia, and cancer from non-neoplastic regions of interest with 91% sensitivity and specificity. Results suggest this combination of noninvasive optical imaging modalities can be used in vivo to discriminate non-neoplastic from neoplastic tissue in this model with the potential to translate this technology to the clinic.
authors.affiliation: Rice University, Department of Bioengineering, 6100 Main Street, Houston, MS-142, Texas 77005.
authors.forename: Anne
authors.initials: A
authors.lastname: Hellebust
authors.affiliation: Rice University, Department of Bioengineering, 6100 Main Street, Houston, MS-142, Texas 77005.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Rosbach
authors.affiliation: University of Texas Dental Branch at Houston, Department of Diagnostic and Biomedical Sciences, 7500 Cambridge Street, Houston, Texas 77054.
authors.forename: Jessica Keren
authors.initials: JK
authors.lastname: Wu
authors.affiliation: University of Texas Dental Branch at Houston, Department of Diagnostic and Biomedical Sciences, 7500 Cambridge Street, Houston, Texas 77054.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nguyen
authors.affiliation: University of Texas, M.D. Anderson Cancer Center, Department of Head and Neck Surgery, 1515 Holcombe Boulevard, Unit 441, Houston, Texas 77030.
authors.forename: Ann
authors.initials: A
authors.lastname: Gillenwater
authors.affiliation: University of Texas Dental Branch at Houston, Department of Diagnostic and Biomedical Sciences, 7500 Cambridge Street, Houston, Texas 77054.
authors.forename: Nadarajah
authors.initials: N
authors.lastname: Vigneswaran
authors.affiliation: Rice University, Department of Bioengineering, 6100 Main Street, Houston, MS-142, Texas 77005.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Richards-Kortum
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry; D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000465:Algorithms; D000818:Animals; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry; D016002:Discriminant Analysis; D018450:Disease Progression; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis / Q000737:chemistry; D006651:Histocytochemistry; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008137:Longitudinal Studies; D051379:Mice; D008808:Mice, Inbred CBA; D018613:Microscopy, Confocal; D064847:Multimodal Imaging / Q000379:methods*; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000737:chemistry / Q000145:classification* / Q000473:pathology*
chemical_list: D005456:Fluorescent Dyes; D015112:4-Nitroquinoline-1-oxide; D003847:Deoxyglucose; D009327:4-Chloro-7-nitrobenzofurazan; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose