The long-term goal of the proposed research is to develop a novel multimodal approach for optical staging of epithelial precancerous lesions and early neoplasms using the nonlinear optical imaging techniques of multiphoton microscopy (MPM) and second harmonic generation microscopy (SHGM). The research will combine the ability to detect and map endogenous tissue autofluorescence in the epithelium and stroma assessed by MPM with second harmonic generation originating specifically from stromal structural proteins, primarily collagen. Significant optical and microstructural alterations have been documented with neoplastic transformation. However, while a number of previous optical methods have been associated with high sensitivity to neoplastic change, they generally lacked specificity in detection and staging. It is anticipated that the ability to assess both microarchitectural and optical changes in-depth by MPM-SHGM, resulting in image representations on a level similar to histology, will result in higher specificity than previous techniques. The MPM-SHGM technique will be developed and refined in a model of oral squamous cell carcinoma (which occurs in a site suited for the development of optical assessment techniques) and will be applicable to other epithelial neoplasms at various tissue sites in the future. In brief, the project will involve the a) the spatiotemporal study of epithelial neoplastic transformation in vivo in order to better understand alterations in endogenous optical signals revealed by MPM-SHGM and to identify significant image-based parameters which may serve as markers of neoplastic progression, b) the development and refinement of a noninvasive staging methodology by MPM-SHGM which may assist in guiding surgical resection and in surveillance of patients at risk for recurrence, and c) evaluation of the combination of exogenous contrast agents with MPM-SHGM to reveal molecular-specific signal alterations indicative of neoplastic potential. This research addresses a significant problem in staging of epithelial neoplasms. There is a need for highly specific noninvasive detection methods to assist in the early staging of epithelial neoplasms in general because the chances of patient survival are directly correlated to the stage at which epithelial cancers are detected and treated. Oral cancer, the 6th most common cancer in the world and one which is associated with a five-year survival rate of only 50-55%, is associated with a significant local recurrence rate for which early detection and staging is of primary importance to patient survival. Despite occurring in a highly accessible tissue for inspection high mortality and morbidity rates, particularly following recurrence, indicate the need for improved detection and staging of oral neoplasia.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Baker, Houston
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Medical Br Galveston
Schools of Medicine
United States
Zip Code
Pal, Rahul; Edward, Kert; Ma, Liang et al. (2017) Spectroscopic characterization of oral epithelial dysplasia and squamous cell carcinoma using multiphoton autofluorescence micro-spectroscopy. Lasers Surg Med 49:866-873
Pal, Rahul; Shilagard, Tuya; Yang, Jinping et al. (2016) Remodeling of the Epithelial-Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging. Cancer Res 76:4637-47
Pal, Rahul; Yang, Jinping; Ortiz, Daniel et al. (2015) In-vivo nonlinear optical microscopy (NLOM) of epithelial-connective tissue interface (ECTI) reveals quantitative measures of neoplasia in hamster oral mucosa. PLoS One 10:e0116754
Szaniszlo, Peter; Fennewald, Susan M; Qiu, Suimin et al. (2014) Temporal characterization of lymphatic metastasis in an orthotopic mouse model of oral cancer. Head Neck 36:1638-47
Edward, Kert; Qiu, Suimin; Resto, Vicente et al. (2012) In vivo layer-resolved characterization of oral dysplasia via nonlinear optical micro-spectroscopy. Biomed Opt Express 3:1579-93
Chitchian, Shahab; Vincent, Kathleen L; Vargas, Gracie et al. (2012) Automated segmentation algorithm for detection of changes in vaginal epithelial morphology using optical coherence tomography. J Biomed Opt 17:116004
Vargas, Gracie; Patrikeev, Igor; Wei, Jingna et al. (2012) Quantitative assessment of microbicide-induced injury in the ovine vaginal epithelium using confocal microendoscopy. BMC Infect Dis 12:48
Motamedi, Saam; Shilagard, Tuya; Edward, Kert et al. (2011) Gold nanorods for intravital vascular imaging of preneoplastic oral mucosa. Biomed Opt Express 2:1194-203
Vargas, Gracie; Shilagard, Tuya; Ho, Ki-Hong et al. (2009) Multiphoton autofluorescence microscopy and second harmonic generation microscopy of oral epithelial neoplasms. Conf Proc IEEE Eng Med Biol Soc 2009:6311-3