Intestinal Barrier Healing Is Superior to Endoscopic and Histologic Remission for Predicting Major Adverse Outcomes in Inflammatory Bowel Disease: The Prospective ERIca Trial.

BACKGROUND & AIMS: Endoscopic and histologic remission have emerged as key therapeutic goals in the management of inflammatory bowel diseases (IBD) that are associated with favorable long-term disease outcomes. Here, we prospectively compared the predictive value of barrier healing with endoscopic and histologic remission for predicting long-term disease behavior in a large cohort of patients with IBD in clinical remission. METHODS: At baseline, patients with IBD in clinical remission underwent ileocolonoscopy with assessment of intestinal barrier function by confocal endomicroscopy. Endoscopic and histologic disease activity, as well as barrier healing, was prospectively assessed along established scores. During subsequent follow-up, patients were closely monitored for clinical disease activity and the occurrence of major adverse outcomes (MAOs): disease flares, IBD-related hospitalization or surgery, and initiation or dose escalation of systemic steroids, immunosuppressants, small molecules, or biological therapy. RESULTS: The final analysis included 181 patients, 100 with Crohn's disease [CD] and 81 with ulcerative colitis (UC). During a mean follow-up of 35 (CD) and 25 (UC) months, 73% of patients with CD and 69% of patients with UC experienced at least 1 MAO. The probability of MAO-free survival was significantly higher in patients with IBD with endoscopic remission compared with endoscopically active disease. In addition, histologic remission predicted MAO-free survival in patients with UC but not CD. Barrier healing on endomicroscopy was superior to endoscopic and histologic remission for predicting MAO-free survival in both UC and CD. CONCLUSIONS: Barrier healing is associated with decreased risk of disease progression in patients with clinically remittent IBD, with superior predictive performance compared with endoscopic and histologic remission. Analysis of barrier function might be considered as a future treatment target in clinical trials. CLINICALTRIALS: gov number, NCT05157750.

Grading urothelial carcinoma with probe-based confocal laser endomicroscopy during flexible cystoscopy.

PURPOSE: Urothelial bladder cancer (UCB) care requires frequent follow-up cystoscopy and surgery. Confocal laser endomicroscopy (CLE) is a probe-based optical technique that can provide real-time microscopic evaluation with the potential for outpatient grading of UCB. This study aims to investigate the diagnostic accuracy and interobserver variability for the grading of UCB with CLE during flexible cystoscopy (fCLE). METHODS: Participants scheduled for transurethral resection of papillary bladder tumors were prospectively included for intra-operative fCLE. Exclusion criteria were flat lesions, fluorescein allergy or pregnancy. Two independent observers evaluated fCLE, classifying tumors as low- or high-grade urothelial carcinoma (LGUC/HGUC) or benign. Interobserver agreement was calculated with Cohens kappa (κ) and diagnostic accuracy with 2 × 2 tables. Histopathology was the reference test. RESULTS: Histopathology of 34 lesions revealed 14 HGUC, 14 LGUC and 6 benign tumors. Diagnostic yield for fCLE was 80-85% with a κ of 0.75. Respectively, sensitivity, specificity, NPV and PPV were: for benign tumors 0-20%, 96-100%, unmeasureable-50% and 87%, for LGUC 57-64%, 41-58%, 44-53% and 54-69% and for HGUC 38-57%, 56-68%, 38-57% and 56-68%, with an interobserver agreement of κ 0.61. CONCLUSION: fCLE is currently insufficient to grade UCB.

Disruption of the gastric epithelial barrier in Correa's cascade: Clinical evidence via confocal endomicroscopy.

BACKGROUND: Gastric epithelial barrier disruption constitutes a crucial step in gastric cancer (GC). We investigated these disruptions during the Correa's cascade timeline to correlate epithelial barrier dysfunction. MATERIALS AND METHODS: This study was conducted as a single-center, non-randomized clinical trial in China from May 2019 to October 2022. Patients with chronic atrophic gastritis (CAG), gastric intestinal metaplasia (GIM), low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and intramucosal carcinoma underwent probe-based confocal laser endomicroscopy (pCLE). The pCLE scoring system was used to assess gastric epithelial barrier disruption semi-quantitatively. RESULTS: We enrolled 95 patients who underwent a pCLE examination. The control group consisted of 15 individuals, and the experimental group included 17 patients with CAG, 27 patients with GIM, 20 patients with LGIN, and 16 patients with early gastric cancer (EGC). Apart from CAG, which showed no significant difference compared to the control group, a significantly higher incidence of gastric epithelial barrier damage was found in the GIM, LGIN, and EGC groups compared to the control group (Kruskal-Wallis H test = 69.295, p < 0.001). There is no difference in LGIN patients between GIM and LGIN areas, and there is no difference between the two groups compared with the EGC group. The intestinal metaplasia area in LGIN patients causes more severe gastric epithelial damage compared to that in non-LGIN patients. Additionally, compared to control group, a significant difference (p < 0.001) was noted between individuals with Helicobacter pylori-positive atrophic gastritis and those with IM, whereas no significant difference (p > 0.05) was observed among individuals with H. pylori-negative atrophic gastritis. CONCLUSIONS: The gastric epithelial barrier remains dysfunctional from the initiation of H. pylori infection to GC progression. Beyond the "point of no return," subsequent carcinogenesis processes may be attributed to other mechanisms.

Optical Biopsies Using Probe-Based Confocal Laser Endomicroscopy for Autoimmune Pulmonary Alveolar Proteinosis.

INTRODUCTION: Increasing numbers of cases of mild asymptomatic pulmonary alveolar proteinosis (PAP) are being reported with the recent increase in chest computed tomography (CT). Bronchoscopic diagnosis of mild PAP is challenging because of the patchy distribution of lesions, which makes it difficult to obtain sufficient biopsy samples. Additionally, the pathological findings of mild PAP, particularly those that differ from severe PAP, have not been fully elucidated. This study aimed to clarify the pathological findings of mild PAP and the usefulness of optical biopsy using probe-based confocal laser endomicroscopy (pCLE). METHODS: We performed bronchoscopic optical biopsy using pCLE and tissue biopsy in 5 consecutive patients with PAP (three with mild PAP and two with severe PAP). We compared the pCLE images of mild PAP with those of severe PAP by integrating clinical findings, tissue pathology, and chest CT images. RESULTS: pCLE images of PAP showed giant cells with strong fluorescence, amorphous substances, and thin alveolar walls. Images of affected lesions in mild PAP were equivalent to those obtained in arbitrary lung lesions in severe cases. All 3 patients with mild PAP spontaneously improved or remained stable after ≥3 years of follow-up. Serum autoantibodies to granulocyte-macrophage colony-stimulating factor were detected in all 5 cases. CONCLUSION: Optical biopsy using pCLE can yield specific diagnostic findings, even in patients with mild PAP. pCLE images of affected areas in mild and severe PAP showed similar findings, indicating that the dysfunction level of pathogenic alveolar macrophages in affected areas is similar between both disease intensities.

Brain Tumor Anatomy with Tractography Fluorescence and Confocal Endoscopy.

Tractography fluorescence and confocal endomicroscopy are complementary technologies to targeted tumor resection, and it is certain that as our technology for fluorescent probes continues to evolve, the confocal microscope will continue to be refined. Recent work suggests that intraoperative high-resolution augmented reality endomicroscopy, a real-time alternative to invasive biopsy and histopathology, has the potential to better quantify tumor burden at the final stages of surgery and ultimately to improve patient outcomes when combined with wide-field imaging approaches. Additional studies are needed to further elucidate the clinical benefits of these new technologies for brain tumor patients.

Confocal laser endomicroscopy in glial tumors-a histomorphological analysis.

OBJECTIVE: The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to examine tissue without the need for fixation or staining. This study aims to analyze gliomas in confocal laser endomicroscopy and identify reliable diagnostic criteria for glial matter and glial tumors. MATERIAL AND METHODS: One-hundred-and-five glioma specimens were analyzed using a 670-nm confocal laser endomicroscope and then processed into hematoxylin-eosin-stained frozen sections. All confocal images and frozen sections were evaluated for the following criteria: presence of tumor, cellularity, nuclear pleomorphism, changes of the extracellular glial matrix, microvascular proliferation, necrosis, and mitotic activity. Recurring characteristics were identified. Accuracy, sensitivity, specificity, and positive and negative predictive values were assessed for each feature. RESULTS: All 125 specimens could be processed and successfully analyzed via confocal laser endomicroscopy. We found diagnostic criteria to identify white and grey matter and analyze cellularity, nuclear pleomorphism, changes in the glial matrix, vascularization, and necrosis in glial tumors. An accuracy of > 90.0 % was reached for grey matter, cellularity, and necrosis, > 80.0 % for white matter and nuclear pleomorphism, and > 70.0 % for microvascular proliferation and changes of the glial matrix. Mitotic activity could not be identified. Astroglial tumors showed significantly less nuclear pleomorphism in confocal laser endomicroscopy than oligodendroglial tumors (p < 0.001). Visualization of necrosis aids in the differentiation of low grade gliomas and high grade gliomas  (p < 0.002). CONCLUSION: Autofluorescence-based confocal laser endomicroscopy proved not only useful in differentiation between tumor and brain tissue but also revealed useful clues to further characterize tissue without processing in a lab. Possible applications include the improvement of extent of resection and the safe harvest of representative tissue for histopathological and molecular genetic diagnostics.

Diagnosis of malignancy in oropharyngeal confocal laser endomicroscopy using GPT 4.0 with vision.

PURPOSE: Confocal Laser Endomicroscopy (CLE) is an imaging tool, that has demonstrated potential for intraoperative, real-time, non-invasive, microscopical assessment of surgical margins of oropharyngeal squamous cell carcinoma (OPSCC). However, interpreting CLE images remains challenging. This study investigates the application of OpenAI's Generative Pretrained Transformer (GPT) 4.0 with Vision capabilities for automated classification of CLE images in OPSCC. METHODS: CLE Images of histological confirmed SCC or healthy mucosa from a database of 12 809 CLE images from 5 patients with OPSCC were retrieved and anonymized. Using a training data set of 16 images, a validation set of 139 images, comprising SCC (83 images, 59.7%) and healthy normal mucosa (56 images, 40.3%) was classified using the application programming interface (API) of GPT4.0. The same set of images was also classified by CLE experts (two surgeons and one pathologist), who were blinded to the histology. Diagnostic metrics, the reliability of GPT and inter-rater reliability were assessed. RESULTS: Overall accuracy of the GPT model was 71.2%, the intra-rater agreement was κ = 0.837, indicating an almost perfect agreement across the three runs of GPT-generated results. Human experts achieved an accuracy of 88.5% with a substantial level of agreement (κ = 0.773). CONCLUSIONS: Though limited to a specific clinical framework, patient and image set, this study sheds light on some previously unexplored diagnostic capabilities of large language models using few-shot prompting. It suggests the model`s ability to extrapolate information and classify CLE images with minimal example data. Whether future versions of the model can achieve clinically relevant diagnostic accuracy, especially in uncurated data sets, remains to be investigated.

Oral mucosa - an examination map for confocal laser endomicroscopy within the oral cavity: an experimental clinical study.

OBJECTIVES: Confocal laser endomicroscopy (CLE) is an optical method that enables microscopic visualization of oral mucosa. Previous studies have shown that it is possible to differentiate between physiological and malignant oral mucosa. However, differences in mucosal architecture were not taken into account. The objective was to map the different oral mucosal morphologies and to establish a "CLE map" of physiological mucosa as baseline for further application of this powerful technology. MATERIALS AND METHODS: The CLE database consisted of 27 patients. The following spots were examined: (1) upper lip (intraoral) (2) alveolar ridge (3) lateral tongue (4) floor of the mouth (5) hard palate (6) intercalary line. All sequences were examined by two CLE experts for morphological differences and video quality. RESULTS: Analysis revealed clear differences in image quality and possibility of depicting tissue morphologies between the various localizations of oral mucosa: imaging of the alveolar ridge and hard palate showed visually most discriminative tissue morphology. Labial mucosa was also visualized well using CLE. Here, typical morphological features such as uniform cells with regular intercellular gaps and vessels could be clearly depicted. Image generation and evaluation was particularly difficult in the area of the buccal mucosa, the lateral tongue and the floor of the mouth. CONCLUSION: A physiological "CLE map" for the entire oral cavity could be created for the first time. CLINICAL RELEVANCE: This will make it possible to take into account the existing physiological morphological features when differentiating between normal mucosa and oral squamous cell carcinoma in future work.

Present and future of endoscopy precision for inflammatory bowel disease.

Several advanced imaging techniques are now available for endoscopists managing inflammatory bowel disease (IBD) patients. These tools, including dye-based and virtual chromoendoscopy, probe-based confocal laser endomicroscopy and endocytoscopy, are increasingly innovative applications in clinical practice. They allow for a more in-depth and refined evaluation of the mucosal and vascular bowel surface, getting closer to histology. They have demonstrated a remarkable ability in assessing intestinal inflammation, histologic remission, and predicting relapse and favorable long-term outcomes. In addition, the future application of molecular endoscopy to predict biological drug responses has yielded preliminary but encouraging results. Furthermore, these techniques are crucial in detecting and characterizing IBD-related dysplasia, assisting endoscopic mucosal resection and submucosal dissection towards a surgery-sparing approach. Artificial intelligence (AI) holds great potential in this promising landscape, as it can provide an objective and reproducible assessment of inflammation and dysplasia. Moreover, it can improve the prediction of outcomes and aid in subsequent therapeutic decision-making. This review aims to summarize the promising role of state-of-the-art advanced endoscopic techniques and related AI-enabled models for managing IBD, paving the way for precision medicine.

Role of ultra-high definition endoscopy (endomicroscopy and endocytoscopy) and real-time histologic examination in inflammatory bowel disease: Scoping review.

OBJECTIVES: Confocal laser endomicroscopy (CLE) and endocytoscopy (EC) are ultra-high definition (HD) imaging modalities that enable real-time histological assessment. Although existent for nearly two decades, their role in current clinical decision making in inflammatory bowel disease management is not well defined. METHODS: We searched PubMed using keywords ("confocal" OR "CLE" OR "endocytoscopy") AND ("IBD" OR "inflammatory bowel" OR "Crohn*" OR "Crohn's" OR "colitis ulcerosa" OR "ulcerative colitis") between 2005 and March 2023. We identified 52 studies for detailed review. RESULTS: Confocal laser endomicroscopy was useful in real-time assessment of histologic inflammation and dysplasia characterization in both ulcerative colitis (UC) and Crohn's disease. Although CLE was associated with higher per-biopsy yield for UC-associated neoplasia (UCAN), the benefit was offset by higher procedure time, frequent equipment failure, and conflicting results on incremental yield over chromoendoscopy. Assessment of barrier dysfunction by CLE did not correlate with disease/endoscopic activity but could predict major adverse outcomes. The implications of residual CLE abnormalities in endoscopic remission remain uncertain. Ex vivo binding of labeled biologics can help in predicting biologic response in UC. EC can discriminate mucosal inflammatory cells by morphology and allows assessment of histologic activity. EC combined with pit pattern was better than pit pattern alone for UCAN. Artificial intelligence-assisted EC in UCAN needs further study. CONCLUSION: Ultra-HD imaging in inflammatory bowel disease can be useful in assessment of UCAN, barrier dysfunction, predicting histologic remission, and biologic response. Future controlled studies are warranted to define the role of these novel technologies in clinical decision making.

Self-Supervised Joint Learning for pCLE Image Denoising.

Probe-based confocal laser endoscopy (pCLE) has emerged as a powerful tool for disease diagnosis, yet it faces challenges such as the formation of hexagonal patterns in images due to the inherent characteristics of fiber bundles. Recent advancements in deep learning offer promise in image denoising, but the acquisition of clean-noisy image pairs for training networks across all potential scenarios can be prohibitively costly. Few studies have explored training denoising networks on such pairs. Here, we propose an innovative self-supervised denoising method. Our approach integrates noise prediction networks, image quality assessment networks, and denoising networks in a collaborative, jointly trained manner. Compared to prior self-supervised denoising methods, our approach yields superior results on pCLE images and fluorescence microscopy images. In summary, our novel self-supervised denoising technique enhances image quality in pCLE diagnosis by leveraging the synergy of noise prediction, image quality assessment, and denoising networks, surpassing previous methods on both pCLE and fluorescence microscopy images.

Confocal endomicroscopy diagnostic criteria for early signet-ring cell carcinoma in hereditary diffuse gastric cancer.

BACKGROUND: Recognition of early signet-ring cell carcinoma (SRCC) in patients with hereditary diffuse gastric cancer (HDGC) undergoing endoscopic surveillance is challenging. We hypothesized that probe-based confocal laser endomicroscopy (pCLE) might help diagnose early cancerous lesions in the context of HDGC. The aim of this study was to identify pCLE diagnostic criteria for early SRCC. METHODS: Patients with HDGC syndrome were prospectively recruited and pCLE assessment was performed on areas suspicious for early SRCC and control regions during an endoscopic surveillance procedure. Targeted biopsies were taken for gold standard histologic assessment. In Phase I two investigators assessed video sequences off-line to identify pCLE features related to SRCC. In Phase II pCLE diagnostic criteria were evaluated in an independent video set by the investigators blinded to the histologic diagnosis. Sensitivity, specificity, accuracy, and interobserver agreement were calculated. RESULTS: Forty-two video sequences from 16 HDGC patients were included in Phase I. Four pCLE patterns associated to SRCC histologic features were identified: (A) glands with attenuated margins, (B) glands with spiculated or irregular shape, (C) heterogenous granular stroma with sparse glands, (D) enlarged vessels with tortuous shape. In Phase II, 38 video sequences from 15 patients were assessed. Criteria A and B and C had the highest diagnostic accuracy, with a κ for interobserver agreement ranging from 0.153 to 0.565. A panel comprising these 3 criteria with a cut-off of at least one positive criterion had a sensitivity of 80.9% (95%CI:58.1-94.5%) and a specificity of 70.6% (95%CI:44.0-89.7%) for a diagnosis of SRCC. CONCLUSIONS: We have generated and validated off-line pCLE criteria for early SRCC. Future real-time validation of these criteria is required.

The Application of Probe-Based Confocal Laser Endomicroscopy as a Diagnostic Tool in Choledochoscopic Gallbladder-Preserving Surgery.

BACKGROUND AND AIMS: Choledochoscopic gallbladder-preserving surgery (CGPS) has the advantage of treating benign gallbladder diseases on the premise of gallbladder preservation. However, it has no reliable preoperative diagnosis if the gallbladder is benign. Probe-based confocal laser endomicroscopy (pCLE) can obtain real-time and clear endoscopic images at the cell level in vivo. It is widely used in the diagnosis of digestive system diseases, but not in gallbladder diseases yet. We applied these two technologies in a complementary way into the diagnosis of gallbladder diseases and thereby lifted the reliability of CGPS. METHODS: We retrospectively analyzed the total 28 patients with the indication of CGPS with intraoperative pCLE scan referred to the Second Affiliated Hospital of Baotou Medical College between October 2019 and July 2020. The intraoperative pCLE results were compared with the postoperative pathology in various gallbladder diseases. RESULTS: We compared the intraoperative pCLE diagnosis with the postoperative pathological diagnosis and found a complete match without exception in both sensitivity and specificity. CONCLUSIONS: Based on our investigation, pCLE can provide the same accuracy as the traditional pathology in the diagnosis of gallbladder diseases with the additional advantages like noninvasive, real time, and instancy. This study serves to validate the correlation between CLE and histology. It holds a broad prospect in the application of pCLE as an intraoperative diagnosis in CGPS.

Dynamic real-time optical microscopy of oral mucosal lesions using confocal laser endomicroscopy.

OBJECTIVES: Confocal laser endomicroscopy (CLE) is a novel non-invasive point-of-care optical biopsy technology that enables real-time in vivo microscopic visualisation of cellular and tissue architecture. In this study, we assessed the diagnostic accuracy of a hand-held fluorescence single-fibre distal-scanning CLE (fsdCLE) platform for diagnosing oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Forty-seven patients presenting with 63 distinct oral mucosal lesions were subjected to optical biopsy using a miniaturised fsdCLE system (ViewnVivo®, Optiscan Imaging Ltd) and topical exogenous acriflavine hydrochloride contrast agent before undergoing tissue biopsy and histopathological consensus review by four pathologists. CLE images were captured in vivo in real-time during clinical examination and assessed on-the-fly for the presence of cellular and architectural features of OED/OSCC offering an instantaneous diagnosis. Predicted optical diagnoses were compared to definitive consensus tissue histopathology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for the presence/absence of dysplasia/malignancy on optical biopsy. Percentage agreement, Fleiss' kappa, and intraclass correlation coefficient (ICC) were calculated for each assessment stage during the consensus histopathology process. RESULTS: Diagnostic accuracy was extremely high at 88.9%. Other metrics were sensitivity 86.8%, specificity 92%, PPV 94.3% and NPV 82.1%. One hundred percent of carcinoma cases were detected accurately using CLE in the clinic. CONCLUSION: fsdCLE is a highly accurate, easy-to-use, rapid and slide-free point-of-care in vivo optical technology for diagnosing OED/OSCC and discriminating between dysplastic and non-dysplastic pathology. It demonstrates near-perfect agreement with traditional consensus histopathology without the need for physical tissue biopsy.

Robotic bronchoscopic needle-based confocal laser endomicroscopy to diagnose peripheral lung nodules.

BACKGROUND AND OBJECTIVE: Robotic bronchoscopy has demonstrated high navigational success in small peripheral lung nodules but the diagnostic yield is discrepantly lower. Needle based confocal laser endomicroscopy (nCLE) enables real-time microscopic imaging at the needle tip. We aim to assess feasibility, safety and needle repositioning based on real-time nCLE-guidance during robotic bronchoscopy in small peripheral lung nodules. METHODS: Patients with suspected peripheral lung cancer underwent fluoroscopy and radial EBUS assisted robotic bronchoscopy. After radial EBUS nodule identification, nCLE-imaging of the target area was performed. nCLE-malignancy and airway/lung parenchyma criteria were used to identify the optimal sampling location. In case airway was visualized, repositioning of the biopsy needle was performed. After nCLE tool-in-nodule confirmation, needle passes and biopsies were performed at the same location. MEASUREMENTS AND MAIN RESULTS: Twenty patients were included (final diagnosis n = 17 (lung) cancer) with a median lung nodule size of 14.5 mm (range 8-28 mm). No complications occurred. In 19/20 patients, good quality nCLE-videos were obtained. In 9 patients (45%), real-time nCLE-imaging revealed inadequate positioning of the needle and repositioning was performed. After repositioning, nCLE-imaging provided tool-in-nodule-confirmation in 19/20 patients. Subsequent ROSE demonstrated representative material in 9/20 patients (45%) and overall diagnostic yield was 80% (16/20). Of the three patients with malignant nCLE-imaging but inadequate pathology, two were diagnosed with malignancy during follow-up. CONCLUSION: Robotic bronchoscopic nCLE-imaging is feasible and safe. nCLE-imaging in small, difficult-to-access lung nodules provided additional real-time feedback on the correct needle positioning with the potential to optimize the sampling location and diagnostic yield.

Needle-based confocal laser endomicroscopy for real-time granuloma detection.

BACKGROUND AND OBJECTIVE: Needle-based confocal laser endomicroscopy (nCLE) allows real-time microscopic imaging at the needle tip. nCLE malignancy criteria are used for tool-in-lesion confirmation during bronchoscopic lung nodule analysis. However, to date, nCLE criteria for granulomas are lacking. The aim was to identify and validate nCLE granuloma criteria and assess if blinded raters can distinguish malignant from granulomatous nCLE videos. METHODS: In patients with suspected sarcoidosis, nCLE-imaging of mediastinal lymph nodes was performed during endoscopic ultrasound procedures, followed by needle aspiration. nCLE granuloma criteria were identified by comparison with pathology and final diagnoses. Additionally, nCLE-videos of granulomatous lung nodules part of prospective trials and clinical care were compared to the proposed nCLE granuloma criteria. Blinded raters validated nCLE videos of sarcoid and reactive mediastinal lymph nodes and malignant and granulomatous lung nodules twice. RESULTS: Granuloma criteria were identified (brighter-toned, homogeneous and well-demarcated lesions) based on nCLE-imaging in 14 sarcoidosis patients. Raters evaluated 26 nCLE-videos obtained in lymph nodes (n = 15 sarcoidosis; n = 11 reactive and total of 260 ratings). Granuloma criteria were recognized with 88% accuracy. The inter-observer (κ = 0.63, 95% CI 0.54-0.72) and intra-observer reliability (κ = 0.70 ± 0.06) were substantial. Based on 12 nCLE-videos obtained in lung nodules (n = 4 granulomas, n = 6 malignancy, n = 2 malignancy + granulomas and total of 120 ratings) granuloma and malignancy criteria were recognized with 92% and 75% accuracy. CONCLUSION: nCLE imaging facilitates real-time granuloma visualization. Blinded raters accurately and consistently recognized granulomas on nCLE-imaging and distinguished nCLE granuloma criteria from malignancy. Our data show the potential of nCLE as a real-time bronchoscopic guidance tool for lung nodule analysis.

Clinical Application of Confocal Laser Endomircoscopy Combined with Cryobiopsy in the Diagnosis of Interstitial Lung Disease.

INTRODUCTION: Confocal laser endomicroscopy (CLE) has the characteristics of high resolution, real-time imaging, and no radiation, which is helpful for the precise and effective implementation of transbronchial cryobiopsy (TBCB). The study aimed to compare the efficacy and safety of TBCB combined with CLE (CLE group) or fluoroscopy (fluoroscopy group) in the diagnosis of interstitial lung disease (ILD). METHODS: From a prospective randomized controlled trial, 80 patients with undiagnosed ILD or ILD requiring biopsy between January 2022 and November 2022 were randomly assigned to CLE group and fluoroscopy group. The rate to reach an etiological diagnosis of ILD, maximum cross-sectional area of specimens, operation time, and complications were compared between the two groups. RESULTS: The rate to reach an etiological diagnosis in the CLE group was significantly higher than that in the fluoroscopy group (95.0% vs. 80.0%, p < 0.05), but there was no difference in the maximum cross-sectional area of the specimens (42.1 ± 10.1 mm2 vs. 41.5 ± 10.3 mm2, p > 0.05). In terms of operation time, the CLE group was significantly shorter than the fluoroscopy group (37.6 ± 10.6 min vs. 54.8 ± 24.9 min, p < 0.05). The bleeding volume in the CLE group was significantly lower than that in the fluoroscopy group (4.9 ± 3.6 mL/case vs. 9.0 ± 9.2 mL/case, p < 0.05). Further analysis showed that the incidence of moderate bleeding was also lower in the CLE group (20.0% vs. 75.0%, p < 0.001). In addition, the incidence of pneumothorax in the CLE group was significantly lower than that in the fluoroscopy group (0 vs. 25.0%, p < 0.001). CONCLUSIONS: Compared with simple fluoroscopy, the combination of CLE significantly improves the rate of etiological diagnosis, shortens the operation time, and reduces complications such as bleeding and pneumothorax.

Fiber Bundle Image Reconstruction Using Convolutional Neural Networks and Bundle Rotation in Endomicroscopy.

Fiber-bundle endomicroscopy has several recognized drawbacks, the most prominent being the honeycomb effect. We developed a multi-frame super-resolution algorithm exploiting bundle rotation to extract features and reconstruct underlying tissue. Simulated data was used with rotated fiber-bundle masks to create multi-frame stacks to train the model. Super-resolved images are numerically analyzed, which demonstrates that the algorithm can restore images with high quality. The mean structural similarity index measurement (SSIM) improved by a factor of 1.97 compared with linear interpolation. The model was trained using images taken from a single prostate slide, 1343 images were used for training, 336 for validation, and 420 for testing. The model had no prior information about the test images, adding to the robustness of the system. Image reconstruction was completed in 0.03 s for 256 × 256 images indicating future real-time performance is within reach. The combination of fiber bundle rotation and multi-frame image enhancement through machine learning has not been utilized before in an experimental setting but could provide a much-needed improvement to image resolution in practice.

[Experience in the use of confocal laser endomicroscopy for the diagnosis of bladder papillary tumors].

INTRODUCTION: Visual confirmation of suspicious changes in the urinary tract mucosa is the cornerstone in the diagnosis of urothelial cancer. However, with bladder tumors, it is impossible to obtain histopathological data during cystoscopy both in white light and in photodynamic and narrow-spectrum modes, as well as with computerized chromoendoscopy. Confocal laser endomicroscopy (probe-based confocal laser endomicroscopy - pCLE) is an optical imaging technique that provides high-resolution in vivo imaging and real-time evaluation of urothelial lesions. AIM: To assess the diagnostic capabilities of pCLE in papillary bladder tumors and compare its results with standard pathomorphological study. MATERIALS AND METHODS: A total of 38 patients (27 men, 11 women, aged 41-82 years) with primary bladder tumors diagnosed on the imaging methods were included in the study. For the diagnosis and treatment, all patients underwent transurethral resection (TUR) of the bladder. When a standard white light cystoscopy with assessment of the entire urothelium, 10% sodium fluorescein was administrated intravenously as a contrast dye. pCLE was performed with CystoFlexTMUHD 2.6 mm (7.8 Fr) probe, which was passed through the 26 Fr resectoscope using a telescope bridge to visualize normal and pathological urothelial lesions. A laser with a wavelength of 488 nm and a speed of 8 to 12 frames per second allowed to obtain an endomicroscopic image. These images were compared with standard histopathological analysis using hematoxylin-eosin (H&E) staining of tumor fragments removed during TUR of the bladder. RESULTS: Based on real-time pCLE, 23 patients had a diagnosis of low-grade urothelial carcinoma, while in 12 patients the endomicroscopic picture corresponded to high-grade urothelial carcinoma, 2 patients had typical changes for inflammatory process and 1 case of carcinoma in situ was suspected, which was confirmed by histopathological study. Endomicroscopic images demonstrated clear differences between normal bladder mucosa and high- and low-grade tumors. In the normal urothelium, the larger umbrella cells are located most superficially, followed by smaller intermediate cells, as well as the lamina propria with blood vessels network. In contrast, low-grade urothelial carcinoma is characterized by denser, normal-shaped small cells located superficially than a central fibrovascular core. High-grade urothelial carcinoma exhibits markedly irregular cell architecture and cellular pleomorphism. CONCLUSION: pCLE is a promising new method for in-vivo diagnosing of bladder cancer. Our results show its potential for endoscopic determination of the histological characteristics of bladder tumors and the ability to differentiate between benign and malignant processes, as well as the histological grade of tumor cells.

Feasibility and Safety of Tethered Capsule Endomicroscopy in Patients With Barrett's Esophagus in a Multi-Center Study.

BACKGROUND & AIMS: Tethered capsule endomicroscopy (TCE) involves swallowing a small tethered pill that implements optical coherence tomography (OCT) imaging, procuring high resolution images of the whole esophagus. Here, we demonstrate and evaluate the feasibility and safety of TCE and a portable OCT imaging system in patients with Barrett's esophagus (BE) in a multi-center (5-site) clinical study. METHODS: Untreated patients with BE as per endoscopic biopsy diagnosis were eligible to participate in the study. TCE procedures were performed in unsedated patients by either doctors or nurses. After the capsule was swallowed, the device continuously obtained 10-µm-resolution cross-sectional images as it traversed the esophagus. Following imaging, the device was withdrawn through mouth, and disinfected for subsequent reuse. BE lengths were compared to endoscopy findings when available. OCT-TCE images were compared to volumetric laser endomicroscopy (VLE) images from a patient who had undergone VLE on the same day as TCE. RESULTS: 147 patients with BE were enrolled across all sites. 116 swallowed the capsule (79%), 95/114 (83.3%) men and 21/33 (63.6%) women (P = .01). High-quality OCT images were obtained in 104/111 swallowers (93.7%) who completed the procedure. The average imaging duration was 5.55 ± 1.92 minutes. The mean length of esophagus imaged per patient was 21.69 ± 5.90 cm. A blinded comparison of maximum extent of BE measured by OCT-TCE and EGD showed a strong correlation (r = 0.77-0.79). OCT-TCE images were of similar quality to those obtained by OCT-VLE. CONCLUSIONS: The capabilities of TCE to be used across multiple sites, be administered to unsedated patients by either physicians or nurses who are not expert in OCT-TCE, and to rapidly and safely evaluate the microscopic structure of the esophagus make it an emerging tool for screening and surveillance of BE patients. Clinical trial registry website and trial number: NCT02994693 and NCT03459339.