Bladder cancer is the 6th most common cancer in the United States. While cystoscopy is routinely performed for patients under surveillance, there is a critical need to improve its ability to accurately characterize bladder lesions with high specificity. Previously we developed a real-time and low-cost (<$5,000) confocal high-resolution microendoscope (confocal HRME) and demonstrated that it can resolve subcellular and clinically relevant features in highly scattering tissue samples. In this study, we evaluate the utility of the confocal HRME in conjunction with conventional cystoscopy to characterize bladder precancer and cancer lesions at different scales. Patients scheduled for cystoscopy at Lyndon B. Johnson Hospital in Houston, Texas were first examined with a standard cystoscope, followed by intravesical instillation of proflavine (0.01% w/v in sterile PBS) for fluorescence imaging. In vivo HRME images of normal and suspicious lesions were then acquired and compared to histopathology as the gold standard. Our preliminary results showed that confocal HRME images of normal bladder epithelium was characterized by an intact lining of umbrella cells. As disease progressed in urothelial carcinoma, the regular layered structure became disrupted, accompanied with nuclear crowding and enlargement of urothelial cells. We also compared the imaging performance of the confocal HRME with the non-confocal mode, and confocal images revealed improved imaging contrast of nuclear morphology, especially in lesions with crowded nuclei. In summary, the confocal HRME, when combined with widefield cystoscopy, can resolve disease associated features at the subcellular level and has the potential to improve early detection of bladder cancer.
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