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A fluorescence-image-guided spectral domain OCT (FG-SDOCT) system is described. With the recent development of spectral domain OCT, the new system is able to visualize morphological details of urinary bladder with high image fidelity (e.g., 10um/12um axial/lateral resolutions, >110dB dynamic range) at 4~8-fold improved frame rate. Ex vivo study based on an AY-27 rat cancer model was performed to evaluate its ability to enhance the sensitivity and specificity. Total 82 specimens were examined by hyperisin-induced fluorescence imaging, OCT and histological microscopy sequentially. The preliminary results demonstrate the sensitivity and specificity of FG-SDOCT is 100% and 90% respectively, compared to 85% and 49% for fluorescence imaging. This significant improvement indicates that FG-OCT is a very promising technique for effective early bladder cancer diagnosis in combination of endoscopic OCT.