Use of topical methylene blue to image nuclear morphometry with a low-cost scanning darkfield microendoscope.

Significance: Fiber-optic microendoscopy is a promising approach to noninvasively visualize epithelial nuclear morphometry for early cancer and precancer detection. However, the broader clinical application of this approach is limited by a lack of topical contrast agents available for in vivo use. Aim: The aim of this study was to evaluate the ability to image nuclear morphometry in vivo with a novel fiber-optic microendoscope used together with topical application of methylene blue (MB), a dye with FDA approval for use in chromoendoscopy in the gastrointestinal tract. Approach: The low-cost, high-resolution microendoscope implements scanning darkfield imaging without complex optomechanical components by leveraging programmable illumination and the rolling shutter of the image sensor. We validate the integration of our system and MB staining for visualizing epithelial cell nuclei by performing ex vivo imaging on fresh animal specimens and in vivo imaging on healthy volunteers. Results: The results indicate that scanning darkfield imaging significantly reduces specular reflection and resolves epithelial nuclei with enhanced image contrast and spatial resolution compared to non-scanning widefield imaging. The image quality of darkfield images with MB staining is comparable to that of fluorescence images with proflavine staining. Conclusions: Our approach enables real-time microscopic evaluation of nuclear patterns and has the potential to be a powerful noninvasive tool for early cancer detection.

Deep-learning-based image super-resolution of an end-expandable optical fiber probe for application in esophageal cancer diagnostics.

Significance: Endoscopic screening for esophageal cancer (EC) may enable early cancer diagnosis and treatment. While optical microendoscopic technology has shown promise in improving specificity, the limited field of view (<1 mm) significantly reduces the ability to survey large areas efficiently in EC screening. Aim: To improve the efficiency of endoscopic screening, we propose a novel concept of end-expandable endoscopic optical fiber probe for larger field of visualization and for the first time evaluate a deep-learning-based image super-resolution (DL-SR) method to overcome the issue of limited sampling capability. Approach: To demonstrate feasibility of the end-expandable optical fiber probe, DL-SR was applied on simulated low-resolution microendoscopic images to generate super-resolved (SR) ones. Varying the degradation model of image data acquisition, we identified the optimal parameters for optical fiber probe prototyping. The proposed screening method was validated with a human pathology reading study. Results: For various degradation parameters considered, the DL-SR method demonstrated different levels of improvement of traditional measures of image quality. The endoscopists' interpretations of the SR images were comparable to those performed on the high-resolution ones. Conclusions: This work suggests avenues for development of DL-SR-enabled sparse image reconstruction to improve high-yield EC screening and similar clinical applications.

Utility of a Low-Cost 3-D Printed Microscope for Evaluating Esophageal Biopsies.

In this manuscript we assessed the utility of a low-cost 3D printed microscope to evaluate esophageal biopsies. We conducted a comparative analysis between the traditional microscope and our 3-D printed microscope, utilizing a set of esophageal biopsy samples obtained from patients undergoing screening endoscopy. Two pathologists independently examined 30 esophageal biopsies by light microscopy and digital images obtained using a low-cost 3D printed microscope (Observer 1 and 2). The glass slide consensus diagnosis was compared to the findings of 2 additional pathologist who independently just reviewed the digital images (Observer 3 and 4). The intra-observer agreement was substantial to almost perfect for observer 1 (k:0.64) and 2 (k:0.84). All four observers had 100% sensitivity and negative predictive value, whereas specificity ranged from 59% to 100% and positive predictive value ranged from 21% to 100%. The PPV and specificity were lower for the two Observers (3 and 4) who just examined the digital images. Overall, our results suggest that telepathology may be used with high sensitivity and specificity, utilizing the pictures produced by our 3D-printed microscope.

Deployment and assessment of a deep learning model for real-time detection of anal precancer with high frame rate high-resolution microendoscopy.

Anal cancer incidence is significantly higher in people living with HIV as HIV increases the oncogenic potential of human papillomavirus. The incidence of anal cancer in the United States has recently increased, with diagnosis and treatment hampered by high loss-to-follow-up rates. Novel methods for the automated, real-time diagnosis of AIN 2+ could enable "see and treat" strategies, reducing loss-to-follow-up rates. A previous retrospective study demonstrated that the accuracy of a high-resolution microendoscope (HRME) coupled with a deep learning model was comparable to expert clinical impression for diagnosis of AIN 2+ (sensitivity 0.92 [P = 0.68] and specificity 0.60 [P = 0.48]). However, motion artifacts and noise led to many images failing quality control (17%). Here, we present a high frame rate HRME (HF-HRME) with improved image quality, deployed in the clinic alongside a deep learning model and evaluated prospectively for detection of AIN 2+ in real-time. The HF-HRME reduced the fraction of images failing quality control to 4.6% by employing a high frame rate camera that enhances contrast and limits motion artifacts. The HF-HRME outperformed the previous HRME (P < 0.001) and clinical impression (P < 0.0001) in the detection of histopathologically confirmed AIN 2+ with a sensitivity of 0.91 and specificity of 0.87.

Automated In Vivo High-Resolution Imaging to Detect Human Papillomavirus-Associated Anal Precancer in Persons Living With HIV.

INTRODUCTION: In the United States, the effectiveness of anal cancer screening programs has been limited by a lack of trained professionals proficient in high-resolution anoscopy (HRA) and a high patient lost-to-follow-up rate between diagnosis and treatment. Simplifying anal intraepithelial neoplasia grade 2 or more severe (AIN 2+) detection could radically improve the access and efficiency of anal cancer prevention. Novel optical imaging providing point-of-care diagnoses could substantially improve existing HRA and histology-based diagnosis. This work aims to demonstrate the potential of high-resolution microendoscopy (HRME) coupled with a novel machine learning algorithm for the automated, in vivo diagnosis of anal precancer. METHODS: The HRME, a fiber-optic fluorescence microscope, was used to capture real-time images of anal squamous epithelial nuclei. Nuclear staining is achieved using 0.01% wt/vol proflavine, a topical contrast agent. HRME images were analyzed by a multitask deep learning network (MTN) that computed the probability of AIN 2+ for each HRME image. RESULTS: The study accrued data from 77 people living with HIV. The MTN achieved an area under the receiver operating curve of 0.84 for detection of AIN 2+. At the AIN 2+ probability cutoff of 0.212, the MTN achieved comparable performance to expert HRA impression with a sensitivity of 0.92 ( P = 0.68) and specificity of 0.60 ( P = 0.48) when using histopathology as the gold standard. DISCUSSION: When used in combination with HRA, this system could facilitate more selective biopsies and promote same-day AIN2+ treatment options by enabling real-time diagnosis.

Outcomes of endoscopic submucosal dissection (ESD) plus radiofrequency ablation (RFA) for nodular Barrett's esophagus.

BACKGROUND: Although Endoscopic Submucosal Dissection (ESD) was proven superior to Endoscopic Mucosal Resection (EMR) in achieving higher complete remission rates for neoplastic Barrett's Esophagus (BE), its safety with Radiofrequency Ablation (RFA) remains unstudied. We share our experience with ESD + RFA for nodular BE eradication. METHODS: A retrospective study of all patients ≥18-years with nodular BE who underwent ESD + RFA between September 2015 and December 2020 at our tertiary center. Patients with advanced adenocarcinoma requiring esophagectomy were excluded. Primary outcomes included adverse events (AE) rates and complete eradication rates for adenocarcinoma (CE-EAC), dysplasia (CE-D), and intestinal metaplasia (CE-IM). Secondary outcomes included local recurrence rates following eradication. RESULTS: Eighteen patients were included with a total of 22 ESDs performed and a median of 2 RFA sessions-per-patient [IQR: 1.25, 3]. Sixteen patients were males and/or white (88.9%) with a median BMI of 29.75 kg/m2 [IQR: 26.9, 31.5]. Fourteen patients had long-segment BE (77.7%) while 16 had hiatal hernias (88.9%). Median resection size was 12.1 cm2 [IQR: 5.6, 20.2]. AEs included one intraprocedural micro-perforation (4.5%) and 4 strictures (22.2%), only one of which developed post-RFA. All AEs were successfully treated endoscopically. Over a median of 42.5 months [IQR: 28, 59.25], CE-EAC was achieved in 13 patients (100%), CE-D in 15 patients (100%), and CE-IM in 14 patients (77.8%). Following eradication, 2 patients had recurrent dysplasia (2/15, 13.3%) and one had recurrent intestinal metaplasia (1/14, 7.1%). CONCLUSION: In high-risk patients with long-segment neoplastic BE requiring extensive endoscopic resection, ESD + RFA offers excellent complete eradication rates with rare additional adverse events by RFA. Standard endoscopic surveillance following eradication remains important.

A Community-Based Management of COVID-19 in a Mobile Container Unit.

Vaccine uptake is a multifactor measure of successful immunization outcomes that includes access to healthcare and vaccine hesitancy for both healthcare workers and communities. The present coronavirus disease (COVID-19) pandemic has highlighted the need for novel strategies to expand vaccine coverage in underserved regions. Mobile clinics hold the promise of ameliorating such inequities, although there is a paucity of studies that validate environmental infection in such facilities. Here, we describe community-based management of COVID-19 through a Smart Pod mobile clinic deployed in an underserved community area in the United States (Aldine, Harris County, TX, USA). In particular, we validate infection control and biological decontamination of the Smart Pod by testing surfaces and the air-filtration system for the COVID-19 virus and bacterial pathogens. We show the Smart Pod to be efficacious in providing a safe clinical environment for vaccine delivery. Moreover, in the Smart Pod, up-to-date education of community healthcare workers was provided to reduce vaccine hesitancy and improve COVID-19 vaccine uptake. The proposed solution has the potential to augment existing hospital capacity and combat the COVID-19 pandemic locally and globally.

Lifestyle Risk Factors, Quality of Life, and Intervention Preferences of Barrett's Esophagus Patients: A Prospective Cohort Study.

BACKGROUND AND AIMS: Lifestyle counseling to achieve a healthy weight, quit smoking, and reduce alcohol is a cornerstone in the management of Barrett's Esophagus (BE). However, little is known about whether patients make these recommended lifestyle changes or the impact of non-adherence on their quality of life (QOL). This study characterized the lifestyle risk factors, QOL, and intervention preferences of BE patients as a first step toward developing lifestyle change interventions for this population. METHODS: Patients with a confirmed BE diagnosis (N = 106) completed surveys at a surveillance endoscopy visit (baseline) and at 3- and 6-month follow-ups. Patients reported on lifestyle risk factors, adherence determinants (e.g., perceived benefits/barriers, risk, intentions), QOL, and intervention preferences. RESULTS: Most patients (56%) had uncontrolled reflux, were overweight/obese (65.1%), and had low dietary fiber intake (91%). Many (45%) reported poor QOL. Patients' perceived risk of developing esophageal cancer was high, but their behavior change intentions were low. Despite receiving lifestyle counseling from physicians, there were no significant changes in patients' QOL or lifestyle risk factors over time. Nonetheless, patients indicated strong interest in internet (62.6%) and multimedia programs (57.9%) addressing acid reflux and weight control. CONCLUSION: BE patients reported uncontrolled reflux, poor QOL, and multiple lifestyle risk factors that did not change over time. Despite low levels of intention for making lifestyle changes, patients were interested receiving more information about controlling acid reflux, suggesting a potential teachable moment and opportunity for web-based and multimedia multiple behavior interventions that seek to control acid reflux symptoms through weight loss and a high fiber diet.

Gender-Specific Factors Influencing Gastroenterologists to Pursue Careers in Advanced Endoscopy: Perceptions vs Reality.

INTRODUCTION: In 2020, only 19% of 63 matched advanced endoscopy (AE) fellows were women. This study evaluates the gender-specific factors that influence gastroenterologists to pursue careers in AE. METHODS: An anonymous survey was distributed to gastroenterology fellows and attendings through various gastroenterology society online forums. Data were collected on demographics, training, mentorship, current practice, family planning, and career satisfaction. RESULTS: Women comprised 71.1% of the 332 respondents. 24.7% of female fellows plan to pursue an AE career compared with 37.5% of male fellows (P = 0.195). The main motivating factor for both genders was interest in the subject area. Interest in another subspecialty was the main deterring factor for both genders. Women were more deterred by absence of same-sex mentors (P < 0.001), perception of gender-based bias in the workplace (P = 0.009), family planning (P = 0.018), fertility/pregnancy risks from radiation (P < 0.001), and lack of ergonomic equipment (P = 0.003). AE gastroenterologists of both genders were satisfied with their career decision and would recommend the field to any fellow. Most respondents (64%) believed that more female role models/mentors would improve representation of women in AE. DISCUSSION: There are multiple gender-specific factors that deter women from pursuing AE. Increasing the number of female role models is strongly perceived to improve representation of women in AE. Most AE attendings are satisfied with their career and would recommend it to fellows of any gender. Thus, early targeted mentorship of female trainees has potential to improve recruitment of women to the field.

Automated software-assisted diagnosis of esophageal squamous cell neoplasia using high-resolution microendoscopy.

BACKGROUND AND AIMS: High-resolution microendoscopy (HRME) is an optical biopsy technology that provides subcellular imaging of esophageal mucosa but requires expert interpretation of these histopathology-like images. We compared endoscopists with an automated software algorithm for detection of esophageal squamous cell neoplasia (ESCN) and evaluated the endoscopists' accuracy with and without input from the software algorithm. METHODS: Thirteen endoscopists (6 experts, 7 novices) were trained and tested on 218 post-hoc HRME images from 130 consecutive patients undergoing ESCN screening/surveillance. The automated software algorithm interpreted all images as neoplastic (high-grade dysplasia, ESCN) or non-neoplastic. All endoscopists provided their interpretation (neoplastic or non-neoplastic) and confidence level (high or low) without and with knowledge of the software overlay highlighting abnormal nuclei and software interpretation. The criterion standard was histopathology consensus diagnosis by 2 pathologists. RESULTS: The endoscopists had a higher mean sensitivity (84.3%, standard deviation [SD] 8.0% vs 76.3%, P = .004), lower specificity (75.0%, SD 5.2% vs 85.3%, P < .001) but no significant difference in accuracy (81.1%, SD 5.2% vs 79.4%, P = .26) of ESCN detection compared with the automated software algorithm. With knowledge of the software algorithm, the specificity of the endoscopists increased significantly (75.0% to 80.1%, P = .002) but not the sensitivity (84.3% to 84.8%, P = .75) or accuracy (81.1% to 83.1%, P = .13). The increase in specificity was among novices (P = .008) but not experts (P = .11). CONCLUSIONS: The software algorithm had lower sensitivity but higher specificity for ESCN detection than endoscopists. Using computer-assisted diagnosis, the endoscopists maintained high sensitivity while increasing their specificity and accuracy compared with their initial diagnosis. Automated HRME interpretation would facilitate widespread usage in resource-poor areas where this portable, low-cost technology is needed.

Advances in optical gastrointestinal endoscopy: a technical review.

Optical endoscopy is the primary diagnostic and therapeutic tool for management of gastrointestinal (GI) malignancies. Most GI neoplasms arise from precancerous lesions; thus, technical innovations to improve detection and diagnosis of precancerous lesions and early cancers play a pivotal role in improving outcomes. Over the last few decades, the field of GI endoscopy has witnessed enormous and focused efforts to develop and translate accurate, user-friendly, and minimally invasive optical imaging modalities. From a technical point of view, a wide range of novel optical techniques is now available to probe different aspects of light-tissue interaction at macroscopic and microscopic scales, complementing white light endoscopy. Most of these new modalities have been successfully validated and translated to routine clinical practice. Herein, we provide a technical review of the current status of existing and promising new optical endoscopic imaging technologies for GI cancer screening and surveillance. We summarize the underlying principles of light-tissue interaction, the imaging performance at different scales, and highlight what is known about clinical applicability and effectiveness. Furthermore, we discuss recent discovery and translation of novel molecular probes that have shown promise to augment endoscopists' ability to diagnose GI lesions with high specificity. We also review and discuss the role and potential clinical integration of artificial intelligence-based algorithms to provide decision support in real time. Finally, we provide perspectives on future technology development and its potential to transform endoscopic GI cancer detection and diagnosis.

Simple differential digital confocal aperture to improve axial response of line-scanning confocal microendoscopes.

Line-scanning confocal microendoscopy offers video-rate cellular imaging of scattering tissue with relatively simple hardware, but its axial response is inferior to that of point-scanning systems. Based on Fourier optics theory, we designed differential confocal apertures with a simple subtraction technique to improve the line-scanning sectioning performance. Taking advantage of digital slit apertures on a digital light projector and a CMOS rolling shutter, we demonstrate real-time optical sectioning performance comparable to point scanning in a dual-camera microendoscope (<$6,000). We validate the background rejection capability when imaging porcine columnar epithelium stained with fluorescent contrast agents with different uptake mechanisms and staining properties.