A cross-polarization method has been used to eliminate the specular reflection and enhance the diffusive backscattering of fluorescence excitation light from tissue-like phantoms and skin tissue. We have demonstrated that the non-uniformity of excitation and collection of a fluorescence imaging system can be corrected by normalizing fluorescence signal to the cross-polarized reflection signal recorded from the same site. The ratio image of fluorescence vs. cross-polarized reflection provides a map of relative fluorescence yield over the tissue surface. This ratio imaging technique may hold the potential to detect early cancer, which usually starts from the superficial layer of tissue, based on the contrast in the fluorescence yield between early lesion and surrounding normal tissue.
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