Cancer development in oral epithelial tissue induces subtle changes in tissue autofluorescence that are associated with increased metabolic activity in malignant oral epithelial cells. These autofluorescence biomarkers of oral cancer progression include a decrease in the optical “redox ratio”, defined as the autofluorescence intensity of NADH divided by that of FAD, and specific changes in the fluorescence lifetime of both NADH and FAD. We therefore hypothesized that more specific biomarkers of oral cancer and dysplasia can more accurately be quantified by endogenous fluorescence lifetime imaging (FLIM). In this work, FLIM images of benign, dysplastic and early stage cancerous oral lesions from 52 patients were acquired at three emission channels (390±20nm, 452±22.5nm and >500nm) using a handheld multispectral FLIM endoscope. For each pixel, the fluorescence decays collected at the three emission bands were analyzed using a biexponential decay model, resulting on 16 FLIM-derived parameters per pixel, which generated multiparametric FLIM images of each oral lesion. Statistical analysis was performed on each of the computed FLIM parameters (Wilcoxon test: Normal vs. Benign, Normal vs. Dysplasia/Cancer; Mann-Whitney test: Benign vs. Dysplasia/Cancer). Results from this analysis revealed that FLIM-derived parameters associated with collagen lifetime, NADH lifetime, FAD autofluorescence, and the optical redox ratio were statistically different between dysplastic/cancerous vs. benign oral lesions. This study provides the first demonstration for the clinical imaging of autofluorescence biochemical and metabolic biomarkers of oral epithelial cancer and dysplasia, which could potentially enable early detection of oral cancer.
Elvis Duran, DaeYon Hwang, Shuna Cheng, Rodrigo Cuenca, Bilal Malik, Kristen C. Maitland, John Wright, Y.S. Lisa Cheng, Beena Ahmed, and Javier A. Jo, "In vivo metabolic imaging of early stage oral cancer and dysplasia based on autofluorescence lifetime endoscopy (Conference Presentation)," Proc. SPIE 10578, Medical Imaging 2018: Biomedical Applications in Molecular, Structural, and Functional Imaging, 105780S (Presented at SPIE Medical Imaging: February 12, 2018; Published: 14 March 2018); https://doi.org/10.1117/12.2293794.5751396627001.
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