Browsing by Author "Gillenwater, Ann"

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    Development of a multimodal foveated endomicroscope for the detection of oral cancer
    (The Optical Society, 2017) Shadfan, Adam; Darwiche, Hawraa; Blanco, Jesus; Gillenwater, Ann; Richards-Kortum, Rebecca; Tkaczyk, Tomasz S.
    A multimodal endomicroscope was developed for cancer detection that combines hyperspectral and confocal imaging through a single foveated objective and a vibrating optical fiber bundle. Standard clinical examination has a limited ability to identify early stage oral cancer. Optical detection methods are typically restricted by either achievable resolution or a small field-of-view. By combining high resolution and widefield spectral imaging into a single probe, a device was developed that provides spectral and spatial information over a 5 mm field to locate suspicious lesions that can then be inspected in high resolution mode. The device was evaluated on ex vivo biopsies of human oral tumors.
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    Optical Contrast Agents to Distinguish Benign Inflammation from Neoplasia in Epithelial Tissues
    (2016-01-29) Hellebust, Anne E; Richards-Kortum, Rebecca Rae; Farach-Carson, Mary; Gillenwater, Ann; Sikora, Andrew; Tkaczyk, Tomasz
    A minimally-invasive, optical strategy to detect and discriminate between inflammation and neoplasia could improve early cancer detection by reducing the number of false positive exams due to benign inflammation. This thesis describes research to optimize optical molecular contrast agents to observe architectural, metabolic, and biomolecular changes from inflammation and cancer in the gastrointestinal tract. My goal was to: 1) understand the limitations of autofluorescence imaging for cancer detection, 2) image exogenous fluorescent contrast agents specific to inflammation and neoplasia in rodent models, and 3) topically deliver a contrast agent cocktail in vivo in a mouse model. Wide field autofluorescence imaging of oral tissue utilizes endogenous tissue contrast to discriminate neoplastic from normal tissue; clinical studies of this technique show good sensitivity but poor specificity. I conducted a confocal microscopy study of 47 biopsies from 20 patients; results showed a similar decrease in autofluorescence in the stroma of inflamed and neoplastic tissue. This finding helps explain the low specificity of wide field autofluorescence imaging. Topically applied exogenous contrast agents could be used to improve discrimination between neoplasia and inflammation. I tested individual fluorescent contrast agents and contrast agent cocktails in chemically induced rodent models of inflammation and neoplasia. The first model used autofluorescence imaging with fluorescence imaging of proflavine to highlight cell nuclei and 2-NBDG to assess metabolic activity for oral cancer detection. A classification algorithm based on proflavine and 2-NBDG staining separated neoplastic from non-neoplastic areas on the tongue with 91% sensitivity and specificity. In the second model, a contrast agent cocktail composed of proflavine, a fluorescently labelled CD45-targeted antibody to identify inflammatory cells, and permeation enhancers was evaluated for topical in vivo delivery to image ulcerative colitis. The antibody identified the presence of inflammation and established topical delivery of antibody sized agents in vivo. These results provide evidence that topically applied contrast agent cocktails could improve discrimination between inflammation and neoplasia when endogenous contrast is insufficient. An optical-based strategy utilizing contrast agent cocktails to observe architectural, metabolic, and biomolecular changes associated with inflammation and cancer could improve early cancer detection by reducing the number of false positives from inflammation.
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    Programmable bio-nanochip-based cytologic testing of oral potentially malignant disorders in Fanconi anemia
    (Wiley, 2015) Floriano, Pierre; Abram, Tim; Taylor, Leander; Le, Cathy; Talavera, Humberto; Nguyen, Michael; Raja, Rameez; Gillenwater, Ann; McDevitt, John; Vigneswaran, Nadarajah
    Fanconi anemia (FA) is caused by mutations of DNA repair genes. The risk of oral squamous cell carcinoma (OSCC) among FA patients is 800-folds higher than in the general population. Early detection of OSCC, preferably at it precursor stage, is critical in FA patients to improve their survival. In an ongoing clinical trial, we are evaluating the effectiveness of the programmable bio-nanochip (p-BNC)-based oral cytology test in diagnosing oral potentially malignant disorders (OPMD) in non-FA patients. We used this test to compare cytomorphometric and molecular biomarkers in OSCC cell lines derived from FA and non-FA patients to brush biopsy samples of a FA patient with OPMD and normal mucosa of healthy volunteers. Our data showed that expression patterns of molecular biomarkers were not notably different between sporadic and FA-OSCC cell lines. The p-BNC assay revealed significant differences in cytometric parameters and biomarker MCM2 expression between cytobrush samples of the FA patient and cytobrush samples of normal oral mucosa obtained from healthy volunteers. Microscopic examination of the FA patient's OPMD confirmed the presence of dysplasia. Our pilot data suggests that the p-BNC brush biopsy test recognized dysplastic oral epithelial cells in a brush biopsy sample of a FA patient.
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    Vital-dye-enhanced multimodal imaging of neoplastic progression in a mouse model of oral carcinogenesis
    (SPIE, 2013) Hellebust, Anne; Rosbach, Kelsey; Wu, Jessica Keren; Nguyen, Jennifer; Gillenwater, Ann; Vigneswaran, Nadarajah; Richards-Kortum, Rebecca
    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.