Modular video endoscopy for in vivo cross-polarized and vital-dye fluorescence imaging of Barrett's-associated neoplasia

A modular video endoscope is developed and tested to allow imaging in different modalities. This system incorporates white light imaging (WLI), cross-polarized imaging (CPI), and vital-dye fluorescence imaging (VFI), using interchangeable filter modules. CPI and VFI are novel endoscopic modalities that probe mucosal features associated with Barrett's neoplasia. CPI enhances vasculature, while VFI enhances glandular architecture. In this pilot study, we demonstrate the integration of these modalities by imaging areas of Barrett's metaplasia and neoplasia in an esophagectomy specimen. We verify that those key image features are also observed during an in vivo surveillance procedure. CPI images demonstrate improved visualization of branching blood vessels associated with neoplasia. VFI images show glandular architecture with increased glandular effacement associated with neoplasia. Results suggests that important pathologic features seen in CPI and VFI are not visible during standard endoscopic white light imaging, and thus the modalities may be useful in future in vivo studies for discriminating neoplasia from Barrett's metaplasia. We further demonstrate that the integrated WLI/CPI/VFI endoscope is compatible with complementary high-resolution endomicroscopy techniques such as the high-resolution microendoscope, potentially enabling two-step (“red-flag” widefield plus confirmatory high-resolution imaging) protocols to be enhanced

Quantitative analysis of high-resolution microendoscopic images for diagnosis of neoplasia in patients with Barrett’s esophagus

Background and Aims: Previous studies show that microendoscopic images can be interpreted visually to identify the presence of neoplasia in patients with Barrett’s esophagus (BE), but this approach is subjective and requires clinical expertise. This study describes an approach for quantitative image analysis of microendoscopic images to identify neoplastic lesions in patients with BE. Methods: Images were acquired from 230 sites from 58 patients by using a fiberoptic high-resolution microendoscope during standard endoscopic procedures. Images were analyzed by a fully automated image processing algorithm, which automatically selected a region of interest and calculated quantitative image features. Image features were used to develop an algorithm to identify the presence of neoplasia; results were compared with a histopathology diagnosis. Results: A sequential classification algorithm that used image features related to glandular and cellular morphology resulted in a sensitivity of 84% and a specificity of 85%. Applying the algorithm to an independent validation set resulted in a sensitivity of 88% and a specificity of 85%. Conclusions: This pilot study demonstrates that automated analysis of microendoscopic images can provide an objective, quantitative framework to assist clinicians in evaluating esophageal lesions from patients with BE. (Clinical trial registration number: NCT01384227 and NCT02018367.

Diagnosis of Neoplasia in Barrett’s Esophagus using Vital-dye Enhanced Fluorescence Imaging

The ability to differentiate benign metaplasia in Barrett’s Esophagus (BE) from neoplasia in vivo remains difficult as both tissue types can be flat and indistinguishable with white light imaging alone. As a result, a modality that highlights glandular architecture would be useful to discriminate neoplasia from benign epithelium in the distal esophagus. VFI is a novel technique that uses an exogenous topical fluorescent contrast agent to delineate high grade dysplasia and cancer from benign epithelium. Specifically, the fluorescent images provide spatial resolution of 50 to 100 μm and a field of view up to 2.5 cm, allowing endoscopists to visualize glandular morphology. Upon excitation, classic Barrett’s metaplasia appears as continuous, evenly-spaced glands and an overall homogenous morphology; in contrast, neoplastic tissue appears crowded with complete obliteration of the glandular framework. Here we provide an overview of the instrumentation and enumerate the protocol of this new technique. While VFI affords a gastroenterologist with the glandular architecture of suspicious tissue, cellular dysplasia cannot be resolved with this modality. As such, one cannot morphologically distinguish Barrett’s metaplasia from BE with Low-Grade Dysplasia via this imaging modality. By trading off a decrease in resolution with a greater field of view, this imaging system can be used at the very least as a red-flag imaging device to target and biopsy suspicious lesions; yet, if the accuracy measures are promising, VFI may become the standard imaging technique for the diagnosis of neoplasia (defined as either high grade dysplasia or cancer) in the distal esophagus

Quantitative Analysis of High-Resolution Microendoscopic Images for Diagnosis of Esophageal Squamous Cell Carcinomaﾠ

Background & Aims: High-resolution microendoscopy is an optical imaging technique with the potential to improve the accuracy of endoscopic screening for esophageal squamous neoplasia. Although these microscopic images can be interpreted readily by trained personnel, quantitative image analysis software could facilitate the use of this technology in low-resource settings. In this study, we developed and evaluated quantitative image analysis criteria for the evaluation of neoplastic and non-neoplastic squamous esophageal mucosa. Methods: We performed an image analysis of 177 patients undergoing standard upper endoscopy for screening or surveillance of esophageal squamous neoplasia, using high-resolution microendoscopy, at 2 hospitals in China and at 1 hospital in the United States from May 2010 to October 2012. Biopsy specimens were collected from imaged sites (n = 375), and a consensus diagnosis was provided by 2 expert gastrointestinal pathologists and used as the standard. Results: Quantitative information from the high-resolution images was used to develop an algorithm to identify high-grade squamous dysplasia or invasive squamous cell cancer, based on histopathology findings. Optimal performance was obtained using the mean nuclear area as the basis for classification, resulting in sensitivities and specificities of 93% and 92% in the training set, 87% and 97% in the test set, and 84% and 95% in an independent validation set, respectively. Conclusions: High-resolution microendoscopy with quantitative image analysis can aid in the identification of esophageal squamous neoplasia. Use of software-based image guides may overcome issues of training and expertise in low-resource settings, allowing for widespread use of these optical biopsy technologies

Low-Cost High-Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial

Background & Aims: Esophageal squamous cell neoplasia has a high mortality rate as a result of late detection. In high-risk regions such as China, screening is performed by Lugol’s chromoendoscopy (LCE). LCE has low specificity, resulting in unnecessary tissue biopsy with a subsequent increase in procedure cost and risk. The purpose of this study was to evaluate the accuracy of a novel, low-cost, high-resolution microendoscope (HRME) as an adjunct to LCE. Methods: In this prospective trial, 147 consecutive high-risk patients were enrolled from 2 US and 2 Chinese tertiary centers. Three expert and 4 novice endoscopists performed white-light endoscopy followed by LCE and HRME. All optical images were compared with the gold standard of histopathology. Results: By using a per-biopsy analysis, the sensitivity of LCE vs LCE + HRME was 96% vs 91% (P = .0832), specificity was 48% vs 88% (P < .001), positive predictive value was 22% vs 45% (P < .0001), negative predictive value was 98% vs 98% (P = .3551), and overall accuracy was 57% vs 90% (P < .001), respectively. By using a per-patient analysis, the sensitivity of LCE vs LCE + HRME was 100% vs 95% (P = .16), specificity was 29% vs 79% (P < .001), positive predictive value was 32% vs 60%, 100% vs 98%, and accuracy was 47% vs 83% (P < .001). With the use of HRME, 136 biopsies (60%; 95% confidence interval, 53%–66%) could have been spared, and 55 patients (48%; 95% confidence interval, 38%–57%) could have been spared any biopsy. Conclusions: In this trial, HRME improved the accuracy of LCE for esophageal squamous cell neoplasia screening and surveillance. HRME may be a cost-effective optical biopsy adjunct to LCE, potentially reducing unnecessary biopsies and facilitating real-time decision making in globally underserved regions. ClinicalTrials.gov, NCT 01384708

Quantitative analysis of in vivo high-resolution microendoscopic images for the detection of neoplastic colorectal polyps

Colonoscopy is routinely performed for colorectal cancer screening but lacks the capability to accurately characterize precursor lesions and early cancers. High-resolution microendoscopy (HRME) is a low-cost imaging tool to visualize colorectal polyps with subcellular resolution. We present a computer-aided algorithm to evaluate HRME images of colorectal polyps and classify neoplastic from benign lesions. Using histopathology as the gold standard, clinically relevant features based on luminal morphology and texture are quantified to build the classification algorithm. We demonstrate that adenomatous polyps can be identified with a sensitivity and specificity of 100% and 80% using a two-feature linear discriminant model in a pilot test set. The classification algorithm presented here offers an objective framework to detect adenomatous lesions in the colon with high accuracy and can potentially improve real-time assessment of colorectal polyps