New Technologies in Endourology Comparison of 2.6- and 1.4-mm Imaging Probes for Confocal Laser Endomicroscopy of the Urinary Tract Winifred Adams, M.D., 1 Katherine Wu, B.S., 2 Jen-Jane Liu, M.D., 1 Shelly Teng Teng Hsiao, B.A., 2 Kristin C. Jensen, M.D., 2,3 and Joseph C. Liao, M.D. 1,2 Abstract Introduction: Probe-based confocal laser endomicroscopy (pCLE) is an emerging technology for dynamic, in vivo imaging of the urinary tract with micron-scale resolution. We conducted a comparative analysis of pCLE with a 2.6-mm probe and a 1.4-mm probe that is compatible with flexible endoscopes. Materials and Methods: Sixty-seven patients scheduled for bladder tumor resection were recruited. pCLE imaging was performed using 2.6- and 1.4-mm probes. Image quality with the different probes was examined and further compared with standard histopathology. Results: Images with the 2.6-mm probe have better resolution of cell morphology. The 1.4-mm probe has a wider field of view and better view of microarchitecture. While image quality with the 2.6-mm probe is superior, the 1.4-mm probe is compatible with flexible cystoscopy and maneuverability is maintained, enabling imaging of areas of the bladder that were previously challenging to access with the larger probe. Conclusions: The optical specifications of the 2.6-mm probe are more suitable for distinguishing urinary tract histopathology. Further design optimization to improve resolution and additional validation of the diagnostic accuracy of the smaller probe are needed to help extend application of pCLE for optical biopsy of the upper and lower urinary tract. Introduction P robe-based confocal laser endomicroscopy (pCLE) is an emerging technology that complements standard white-light endoscopy to provide dynamic imaging of en- doluminal tracts with micron-scale resolution. 1 On the basis of the well-established principles of confocal microscopy and fiberoptics, pCLE enables real-time optical biopsy of mucosal lesions with images comparable to standard histopathological analysis. To date, pCLE has been principally applied in the gastrointestinal and respiratory tracts, and is able to distin- guish Barrett’s esophagus and colonic neoplasia from benign tissue. 2–9 The urinary tract, with good accessibility and di- verse pathology that can be managed endoscopically, is well suited for pCLE, particularly in settings where in vivo mi- croscopy may improve diagnostic accuracy and impact treatment. Recently, we reported the first ex vivo and in vivo feasibility studies of pCLE in the urinary tract with a 2.6-mm imaging probe. 10,11 Using fluorescein as a contrast agent, we devel- oped a pCLE imaging protocol and investigated its potential application for bladder cancer diagnosis. As the fifth most common cancer, bladder cancer has a high recurrence rate and requires lifelong surveillance. 12,13 White-light cystoscopy, the standard modality for the diagnosis, treatment, and surveil- lance of bladder cancer, has numerous well-recognized shortcomings, including operator dependency and challenges in differentiation of nonpapillary lesions, such as carcinoma in situ (CIS) from inflammation. 14,15 In this study, we examine the clinical feasibility of a re- cently available 1.4-mm probe 8 and performed a comparative analysis with the 2.6-mm probe. The smaller probe is com- patible with flexible cystoscopes and could expand the po- tential applications of pCLE in the urinary tract. Materials and Methods With local institutional review board approval, patients scheduled to undergo cystoscopy under anesthesia or transurethral resection of bladder tumors were recruited from November 2009 to June 2010. White-light cystoscopy was first performed, followed by administration of fluores- cein contrast and pCLE through a 26F resectoscope and/or a 15F flexible cystoscope (Karl Storz, Culver City, CA). As previously described, 400 mL 0.1% intravesical or 0.5 mL 10% intravenous fluorescein sodium (Alcon Laboratories, 1 Department of Urology and Bio-X Program, Stanford University School of Medicine, Stanford, California. 2 Veterans Affairs Palo Alto Health Care System, Palo Alto, California. 3 Department of Pathology, Stanford University School of Medicine, Stanford, California. JOURNAL OF ENDOUROLOGY Volume 25, Number 6, June 2011 ª Mary Ann Liebert, Inc. Pp. ---–--- DOI: 10.1089/end.2010.0686 1