Optical detection of oral carcinoma via structured illumination fluorescence lifetime imaging

In this work, we compare standard wide-field fluorescence lifetime imaging microscopy (FLIM) and structured illumination FLIM (SI-FLIM) as methods for the early detection of oral squamous cell carcinoma (OSCC). Our technique, SI-FLIM, provides depth dependent fluorescence lifetime information of the oral epithelium, isolating the endogenous fluorophore of interest, NADH, from interfering fluorescence generated mainly by collagen in the lamina propria. Male golden Syrian hamsters (Cricetus auratus) were used as the animal model for OSCC. They were treated with a carcinogen, 7,12-Dimethylbenz[a]anthracene (DMBA), for a twelve-week period by applying the DMBA suspended in mineral oil to their cheek pouches 3 times per week. The progression of OSCC was monitored over a 12-week period with imaging beginning at the 6th week. The cheek pouch with lesions was imaged in a 3x4 grid (twelve total images), with each section of the grid being correlated with histopathological analysis. The NADH fluorescence channel, as a diagnostic indicator, was compared for both SI-FLIM and widefield FLIM. ROC analysis, in the task of distinguishing between mild dysplasia and normal tissue, showed that SI-FLIM (AUC=0.83, se=0.07) may be a better indicator for early cases of mild dysplasia when compared to widefield FLIM (AUC=0.63, se=0.07) with statistical significance.