We report the recent technical improvements in our microelectromechanical systems (MEMS)-based spectral-domain endoscopic OCT (SDEOCT) and applications for in vivo bladder imaging diagnosis. With the technical advances in MEMS mirror fabrication and endoscopic light coupling methods, the new SDEOCT system is able to visualize morphological details of the urinary bladder with high image fidelity close to bench-top OCT (e.g., 10 mum12 mum axial/lateral resolutions, >108 dB dynamic range) at a fourfold to eightfold improved frame rate. An in vivo animal study based on a porcine acute inflammation model following protamine sulfate instillation is performed to further evaluate the utility of SDEOCT system to delineate bladder morphology and inflammatory lesions as well as to detect subsurface blood flow. In addition, a preliminary clinical study is performed to identify the morphological features pertinent to bladder cancer diagnosis, including loss of boundary or image contrast between urothelium and the underlying layers, heterogeneous patterns in the cancerous urothelium, and margin between normal and bladder cancers. The results of a human study (91% sensitivity, 80% specificity) suggest that SDEOCT enables a high-resolution cross-sectional image of human bladder structures to detect transitional cell carcinomas (TCC); however, due to reduced imaging depth of SDEOCT in cancerous lesions, staging of bladder cancers may be limited to T1 to T2a (prior to muscle invasion).

Purpose-We examined the utility and potential limitations of MEMS (Microelectro-mechanical systems) based spectral-domain cystoscopic optical coherence tomography (COCT) to improve the diagnosis of early bladder cancer.Materials and Methods-OCT catheter was integrated into the single instrument channel of a 22Fr cystoscope to permit white-light guided COCT over a large field of view of 4.6mm wide and 2.1mm deep per scan at 8 frames/s and 10um resolution. Intraoperative COCT diagnosis was performed in 56 patients, with a total of 110 lesions examined and compared with biopsied histology.Results-The overall sensitivity of COCT (94%) was significantly higher than cystoscopy (75%, p=0.02) and voided cytology (59%, p=0.005); the major enhancement over cystoscopy was for lowgrade pTa-1 cancer and carcinoma in situ (p<0.018). The overall specificity of COCT (81%) was comparable to voided cytology (88.9%, p=0.49), but significantly higher than cystoscopy (62.5%, p=0.02). Conclusions-MEMS-basedCOCT, owing to its high resolution and detection sensitivity and large field of view, offers great potential for 'optical biopsy' to enhance the diagnosis of non-papillary bladder tumors and their recurrences and to guide bladder tumor resection.

Non‐muscle‐invasive bladder cancer is a frequent disease with many recurrences, making it a labour‐intensive and costly disease. In part, these frequent recurrences are due to inadequate diagnosis. Diagnostic reference standards to date are urinary cytology and cysto‐urethroscopy, but both standards have significant limitations. Urinary cytology is specific, but the sensitivity, especially for low‐grade tumours, is very low. Moreover, the reproducibility of cytology is low. However, cysto‐urethroscopy misses many tumours, especially flat carcinoma in situ, causing flaws in the initial diagnosis and treatment, i.e. transurethral resection. Therefore, new techniques are necessary to improve the detection of bladder cancer. Here we review the advantage and disadvantage of conventional white‐light and fluorescence‐based cystoscopy, and discuss novel endoscopic imaging techniques that are in the clinical and preclinical stage of development.

An interpixel-shifted spectral imaging technique is applied to MEMS-based spectraldomain endoscopic optical coherence tomography (SDEOCT) to enhance signal-to-noise ratio and effective imaging depth for in vivo imaging diagnosis of biological tissue. To validate the enhancements of pixel-shifted SDEOCT, experimental comparisons are presented to image animal and human bladder architectures in vivo and to diagnose human transitional cell cancers. Preliminary study shows that interpixel shifted SDEOCT not only increases the depth of field of SDOCT but also eliminates excessive artifacts induced by spectral aliasing effect, thus improving image contrast in areas with large depths (e.g. over 1.5 mm). These results suggest that endoscopic OCT equipped with interpixelshifted spectral camera has the potential to enhance the diagnosis of biological tissue in in vivo settings that require a larger field of view in the axial direction, such as papillary bladder tumors with deep surface irregularities (e.g. asperities or invaginations).