Emerging endoscopic imaging technologies for bladder cancer detection

Abstract

Modern urologic endoscopy is the result of continuous innovations since the early nineteenth century. White-light cystoscopy is the primary strategy for identification, resection, and local staging of bladder cancer. While highly effective, white light cystoscopy has several well-recognized shortcomings. Recent advances in optical imaging technologies and device miniaturization hold the potential to improve bladder cancer diagnosis and resection. Photodynamic diagnosis and narrow band imaging are the first to enter the clinical arena. Confocal laser endomicroscopy, optical coherence tomography, Raman spectroscopy, UV autofluorescence, and others have shown promising clinical and pre-clinical feasibility. We review their mechanisms of action, highlight their respective advantages, and propose future directions.

Figure 1. New bladder imaging technologies with corresponding white light cystoscopy (WLC)

(A) Bladder tumors appeared pink under blue fluorescence of photodynamic diagnosis (PDD); (B) Narrow band imaging (NBI) enhances visualization of aberrant tumor vasculature; (C) Confocal laser endomicroscopy (CLE) enables in vivo microscopy of a papillary urothelial carcinoma; (D) Subsurface imaging of a papillary urothelial cancer using optical coherence tomography (OCT) showing loss of normal urothelial layers. Image reproduced with permission from Elsevier.

Figure 2. Multimodal imaging using narrow band imaging and confocal laser endomicroscopy

(A) Endoscopic view of the confocal imaging probe adjacent to a papillary tumor at the bladder dome. Yellow tinge corresponds with intravesical fluorescein as contrast agent for CLE. (B) Narrow band imaging highlights tissue and tumor vasculature. (C) Concomitant endomicroscopy image shows well-organized papillary border and monomorphic urothelial cells consistent with a low grade papillary urothelial carcinoma.

Figure 3. Tumor autofluorescence with an ultraviolet (UV) imaging probe

(A) Cystoscopic view of the imaging probe adjacent to normal urothelium and tumor; (B) Color-coding is integrated in real-time and facilitates interpretation of autofluorescence measurements and differentiation of normal (green) and malignant (red) tissue; (C) Histogram of the autofluorescent measurements showing the calculated mean diagnostic ratios of healthy tissue (0.91) and the papillary tumor (0.26). Image reproduced with permission from Elsevier.

Figure 4. Scanning fiber endoscopy (SFE) of a bladder phantom and excised pig bladder to generate surface mosaics of the urothelium

(A) A bladder phantom with painted on vessels was imaged using a conventional endoscope from which a (B) 3D mosaic was constructed. (C) A multi-modal mosaic was generated by SFE imaging of the same phantom with green fluorescent microspheres to mimic hotspots (arrows). Using the SFE, a mosaic (D/E) was constructed from roughly a thousand frames taken within an excised pig bladder. Image courtesy of Eric Seibel, University of Washington.

Figure 5. A prototype telerobotic system for the bladder

(A) Schematic of the dexterous bladder telerobotic system. The central rigid stem contains an optical scope and irrigation apparatus. (B) The dexterous end effector has multiple channels including its own optics and channels for laser and other tools such as tissue optical interrogation catheters. (C) The dexterous instrumentation manipulated to various areas of an ex vivo bovine bladder. Courtesy of Nabil Simaan and Duke Herrell, Vanderbilt University.