Real-time calibrating polarization-sensitive diffuse reflectance handheld probe characterizes clinically relevant anatomical locations of oral tissue in vivo

We report on the development of a unique real-time calibrating polarization-sensitive diffuse reflectance (rcPS-DR) handheld probe, and demonstrate its diagnostic potential through in-depth characterization and differentiation of clinically relevant anatomical locations of the oral cavity (i.e., alveolar process, lateral tongue and floor of mouth that account for 80% of all cases of oral squamous cell carcinoma) in vivo. With an embedded calibrating polytetrafluoroethylene (PTFE) optical diffuser, the PS-DR spectra bias arising from instrument response, time-dependent intensity fluctuation and fiber bending is calibrated through real-time measurement of the PS-DR system response function. A total of 554 in vivo rcPS-DR spectra were acquired from different oral tissue sites (alveolar process, n = 226, lateral tongue, n = 150 and floor of mouth, n = 178) of 14 normal subjects. Significantly (P<0.05, unpaired 2-sided Student’s t-test) different spectral ratio (I₅₄₀/I₅₇₅) representing oxygenated hemoglobin contents were found among the alveolar process, lateral tongue and floor of mouth. Further partial least squares discriminant analysis (PLS-DA) and leave-one-out, cross validation (LOOCV) show that, synergizing the complementary information of the two real-time calibrated orthogonal-polarized PS-DR spectra, the rcPS-DR technique is found to better differentiate alveolar process, lateral tongue, and the floor of mouth (accuracies of 88.2%, 83.9%, 84.4%, sensitivities of 80.5%, 75.8%, 78% and specificities of 93.5%, 87.7%, 86.8%) than standard DR (accuracies of 80.8%, 72.9%, 68.5%, sensitivities of 63.2%, 41.5%, 81.3% and specificities of 92.9%, 87.7%, 63.8%) without PS detection. This work showed the feasibility of the rcPS-DR probe as a tool for studying oral cavity lesions in real clinical applications.