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Increased metabolic activity, a hallmark of epithelial cell malignant transformation, induces subtle changes in the oral tissue autofluorescence. The optical “redox-ratio”, defined as the autofluorescence intensity of NADH divided by that of FAD, is sensitive to changes in the cellular metabolic rate. A decrease in the redox-ratio indicates increased cellular metabolic activity, as is typically observed in malignant cells. Specific changes in the fluorescence lifetime of both NADH and FAD have also been associated with increased metabolic activity in malignant oral epithelial cells. 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. 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 statistical 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.
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