In Vivo Diagnostic Accuracy of High-Resolution Microendoscopy in Differentiating Neoplastic from Non-Neoplastic Colorectal Polyps: A Prospective Study

Abstract

High-resolution microendoscopy (HRME) is a low-cost, “optical biopsy” technology that allows for subcellular imaging. The purpose of this study was to determine the in vivo diagnostic accuracy of the HRME for the differentiation of neoplastic from non-neoplastic colorectal polyps and compare it to that of high-definition white-light endoscopy (WLE) with histopathology as the gold standard. Three endoscopists prospectively detected a total of 171 polyps from 94 patients that were then imaged by HRME and classified in real-time as neoplastic (adenomatous, cancer) or non-neoplastic (normal, hyperplastic, inflammatory). HRME had a significantly higher accuracy (94%), specificity (95%), and positive predictive value (87%) for the determination of neoplastic colorectal polyps compared to WLE (65%, 39%, and 55%, respectively). When looking at small colorectal polyps (less than 10 mm), HRME continued to significantly outperform WLE in terms of accuracy (95% vs. 64%), specificity (98% vs. 40%) and positive predictive value (92% vs. 55%). These trends continued when evaluating diminutive polyps (less than 5 mm) as HRME's accuracy (95%), specificity (98%), and positive predictive value (93%) were all significantly greater than their WLE counterparts (62%, 41%, and 53%, respectively). In conclusion, this in vivo study demonstrates that HRME can be a very effective modality in the differentiation of neoplastic and non-neoplastic colorectal polyps. A combination of standard white-light colonoscopy for polyp detection and HRME for polyp classification has the potential to truly allow the endoscopist to selectively determine which lesions can be left in situ, which lesions can simply be discarded, and which lesions need formal histopathologic analysis.

Quantitative analysis ofex vivocolorectal epithelium using an automated feature extraction algorithm for microendoscopy image data

“…Recent studies examining manual inspection of microendoscopy images of known diagnoses have demonstrated strong interobserver agreement, indicating that well-trained clinicians should be able to effectively incorporate these methods into clinical practice. 20 Qualitative assessment of these images by a highly trained observer is likely to continue to yield clinically relevant data, but widespread adoption of high-resolution, in vivo, microendoscopy methods for improved detection of occult dysplasia remains a challenge. A user-independent method of image analysis could provide additional data to make an informed decision and reduce the burden of training required for the clinician at the point-of-care.…”

“…17 These systems offer real-time, histology-level information to be displayed to the clinician at the time of endoscopy, potentially greatly improving biopsy targeting to locations most likely to show evidence of dysplasia. 18,19 Nonscanning, wide-field fiber bundle microendoscopy methods have also been demonstrated to yield high-resolution image data from the superficial epithelium with promising diagnostic accuracy despite the limited field of view, 20 restricted by the biopsy port (∼2 mm) through which these devices are deployed in vivo. While certain technical challenges that remain before microendoscopy methods may be widely disseminated in clinical applications, the combination of improved wide-field endoscopic methods and high-resolution microendoscopy methods may greatly improve upon currently achieved accuracy.…”

“…While certain technical challenges that remain before microendoscopy methods may be widely disseminated in clinical applications, the combination of improved wide-field endoscopic methods and high-resolution microendoscopy methods may greatly improve upon currently achieved accuracy. 20,21 Furthermore, although several clinical trials of a high-resolution fiber bundle microendoscopy device have demonstrated excellent interobserver agreement in interpretation and classification of fiber bundle microendoscopy images of colorectal polyps, 20 there is currently no widely accepted, quantitative image analysis criteria that can be used to objectively classify fluorescence image data of colorectal polyps without human intervention. Previously demonstrated interobserver agreement of microendoscopic image interpretation is dependent on highly trained staff and physicians.…”

Multimodal Imaging and Spectroscopy Fiber-bundle Microendoscopy Platform for Non-invasive, <em>In Vivo</em> Tissue Analysis

“…[1][2][3] One such imaging technique, high-resolution fluorescence microendoscopy, can image apical tissue micro-architecture with sub-cellular resolution in a small, microscale field-of-view, using a topical contrast agent such as proflavine, fluorescein, or pyranine ink. 1,[3][4][5][6][7][8][9][10][11] This imaging modality has shown promising clinical performance in qualitatively differentiating diseased and healthy epithelial tissue in realtime with low inter-observer variability. 8 Occasionally, investigators will use high-resolution fluorescence microscopy data to extract quantitative features such as cell and nuclear size or gland area, but this remains a primarily qualitative technique targeted towards visualizing tissue morphology.…”

Differential structured illumination microendoscopy for in vivo imaging of molecular contrast agents

“…When used in conjunction with contrast agents, high resolution microendoscopy (HRME) has shown promise to improve early detection of precancerous lesions based on changes in nuclear size, shape, and density (9)(10)(11)(12)(13)(14)(15). However, the coherent fiber optic bundles used in microendoscopes lack inherent optical sectioning capabilities (8); out-of-focus light generated in highly scattering tissues can result in poor image contrast that obscures cellular detail (16,17), which is particularly problematic in tissues with glandular epithelium, such as the breast, where microendoscopic images do not show sufficient contrast to differentiate between normal and neoplastic tissue (18).…”