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Automated evaluation of probe-based confocal laser endomicroscopy in the lung
摘要： Probe-based confocal endomicroscopy provides real time videos of autoflourescent elastin structures within the alveoli. With it, multiple changes in the elastin structure due to different diffuse parenchymal lung diseases have previously been described. However, these evaluations have mainly relied on qualitative evaluation by the examiner and manually selected parts post-examination. Objectives To develop a fully automatic method for quantifying structural properties of the imaged alveoli elastin and to perform a preliminary assessment of their diagnostic potential. Methods 46 patients underwent probe-based confocal endomicroscopy, of which 38 were divided into 4 groups categorizing different diffuse parenchymal lung diseases. 8 patients were imaged in representative healthy lung areas and used as control group. Alveolar elastin structures were automatically segmented with a trained machine learning algorithm and subsequently evaluated with two methods developed for quantifying the local thickness and structural connectivity. Measurements and main results The automatic segmentation algorithm performed generally well and all 4 patient groups showed statistically significant differences with median elastin thickness, standard deviation of thickness and connectivity compared to the control group. Conclusion Alveoli elastin structures can be quantified based on their structural connectivity and thickness statistics with a fully-automated algorithm and initial results highlight its potential for distinguishing parenchymal lung diseases from normal alveoli.
关键词： diffuse parenchymal lung diseases,automated evaluation,elastin structures,probe-based confocal laser endomicroscopy,lung
更新于2025-09-23 15:21:01
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D30Angiogenesis evaluation in locally advanced colo-rectal and gastric cancers by probe-based Confocal Laser Endomicroscopy (pCLE)
摘要： Probe-based Confocal Laser Endomicroscopy ( pCLE) is an innovative endoscopic technique that allows taking high resolution images of the mucosa, facilitating the identification of cellular and subcellular microstructures permitting an evaluation of the microvasculature during endoscopic examination. Angiogenesis is a hallmark of cancer development inducing the formation of new vasculature to support its growth. The aim of our study was to evaluate tumor neoangiogenesis through pCLE imaging in locally advanced gastric and rectal cancer patients, before and after neoadjuvant radio-chemotherapy (RT/CT). Methods: 74 consecutive patients affected by Rectal Cancer (RC, 19F, 55 M mean age: 65 years) and 28 consecutive patients with Gastric Cancer (GC, 7F, 21 M mean age: 64 years) underwent endoscopy with pCLE-GastroFlex UHD probe (Mauna Kea Technologies) and i.v. fluorescein infusion in order to evaluate intratumoral vascularization and to evaluate the efficiency of blood flow. After RT/CT treatment, 33 RC (27M, 6F) and 7 GC (2F, 5M) patients were revaluated using pCLE; neoangiogenesis was evaluated according to Cannizzaro-Spessotto (CS) scale, assigning one point to each of the following features: tortuous vessels, large vessels, leakage and defective flux. Results: 22 out of 35 (62.8%) RC and 4 out of 9 (44,4%) GC patients showed an improvement of angiogenesis index, while in the remaining 13 RC (39.4%) and 5 GC (71.4%) there were no changes of the vascular architecture following the treatment. There was a significant difference ( p < 0.05) in neoangiogenesis CS scores between RC pre- (median CS score: 2.7) and post-RT/CT (median CS score: 1.6), while there’s no difference ( p > 0.05) between GC patients pre- (median CS score: 2.6) and post-therapy (median CS score: 2.0). Our data show a better reactivation of vessels’ morphology and functions in RC patients, with an improvement of angiogenesis index. In GC patients median angiogenesis index remained unmodified, without positive changes in vascular morphology, probably due to the presence of fibrosis. Conclusions: The results of our work demonstrate that pCLE technique is suitable to evaluate the alterations of the intratumoral microvasculature and reveal a functional improvement of vasculature in post-therapy RC patients. It may constitute a innovative approach in order to identify subjects that respond to the therapy, improving the outcome of the patients.
关键词： Cannizzaro-Spessotto (CS) scale,angiogenesis,probe-based Confocal Laser Endomicroscopy ( pCLE),neoadjuvant radio-chemotherapy (RT/CT),gastrointestinal (colorectal) cancers
更新于2025-09-23 15:19:57
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Probe-based confocal laser endomicroscopy versus biopsies in the diagnostics of oesophageal and gastric lesions: A prospective, pathologist-blinded study
摘要： Background and aim: Probe-based confocal laser endomicroscopy (pCLE) provides real-time microscopic visualisation. Our aim was to compare the diagnostic accuracy of pCLE with standard biopsies in patients with visible oesophageal or gastric lesions. Methods: This was a single-centre, prospective, pathologist-blinded study. Patients underwent high-resolution endoscopy, and lesions were examined by pCLE followed by standard biopsies. A definitive diagnosis was determined from resection specimen. Main outcomes were overall diagnostic accuracy, sensitivity, specificity and positive and negative predictive values. Results: We examined 74 lesions in 67 patients. Definitive diagnoses revealed 34 malignant and 40 non-malignant lesions. pCLE diagnosis was correct in 89.2% (66/74), while diagnosis based on biopsy was correct in 85% (57/67; p ? 0.6). The overall diagnostic accuracy of biopsies was 85% (76–94%) and that of pCLE was 89% (79–96%). pCLE correctly diagnosed malignant lesions, comprising oesophageal adenocarcinoma, oesophageal squamous-cell cancer or gastric adenocarcinoma, in 88.2% (30/34) of cases, while biopsy was correctly diagnosed in 75.9% (22/29; p ? 0.3). Sensitivity and specificity to diagnose a malignant lesion were 75.9% (95% confidence interval (CI) 56–89%) and 100% (95% CI 90–100%) for biopsies and 88.2% (95% CI 72–97%) and 92% (95% CI 79–98%) for pCLE. No differences between biopsies and pCLE were found with regard to sensitivity, specificity to diagnose dysplastic and benign lesions (p > 0.2). Conclusion: pCLE provides satisfactory diagnostic accuracy comparable with standard biopsies in patients with oesophageal or gastric lesions. ClinicalTrials.gov identifier: NCT0292049)
关键词： Confocal laser endomicroscopy,oesophageal and gastric cancer
更新于2025-09-23 15:19:57
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Quantitative Diagnosis of Atrophic Gastritis by Probe-Based Confocal Laser Endomicroscopy
摘要： Aims. The aims of this study were to characterize nonatrophic and atrophic gastric mucosa under conventional endoscopy and probe-based confocal laser endomicroscopy (pCLE) modes and to de?ne quantitative diagnostic parameters for these lesions under pCLE. Method. In phase I, 64 patients with gastric mucosal lesions diagnosed by gastrointestinal endoscopy were enrolled in the study. Normal mucosa and suspicious lesions were evaluated under normal white light imaging (WLI) and pCLE mode. Descriptive characteristic of gastric mucosal in?ammation and atrophy under pCLE were de?ned according to the histology. In phase II, the criteria for nonatrophic gastritis (NAG) and chronic atrophic gastritis (CAG) under pCLE were used to diagnose the mucosal lesions in 431 patients. Diagnostic accuracy of each endoscopy modes was evaluated by measuring the concordance with histology. Result. A total of 64 patients with 187 positions were enrolled in the ?rst part of this study. According to the histological diagnosis, the vessel diameter was increased in the NAG (11.18 ± 0.1 μm) and CAG (13.21 ± 0.29 μm) groups compared to the normal group (10.58 ± 0.13 μm); meanwhile, the distance between glands was 17.75 ± 0.51 μm in the normal group, 22.38 ± 0.45 μm in the NAG group, and 34.66 ± 0.82 μm in the CAG group, which increased signi?cantly compared to nonatrophic mucosa. In order to di?erentiate atrophic mucosa from nonatrophic mucosa in real time, the cuto? value between these two kinds of lesions was >30 μm in distance between glands. In phase II, 431 patients with 431 positions were evaluated under pCLE by using the criteria above. The sensitivity, speci?city, PPV, and NPV for the diagnostic parameter were 90.3%, 78.8%, 85.1%, and 85.8%. The consistency of pCLE (Kappa value ? 0.698) with histology was much better than WLI (Kappa value ? 0.393). Conclusion. pCLE shows high potential for the diagnosis of gastric in?ammation and atrophy based on quantitative criteria and has the ability to be a substitute for histology in the diagnosis of di?use lesions in the stomach.
关键词： quantitative diagnosis,probe-based confocal laser endomicroscopy,atrophic gastritis,gastric mucosa,histology
更新于2025-09-23 15:19:57
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Peroral cholangioscopya??guided probe-based confocal laser endomicroscopy for preoperative diagnosis of pancreatic cancer in a patient with surgically altered anatomy
摘要： A 79-year-old man was referred to our hospital because of jaundice. He had previously undergone Billroth-II gastrectomy for gastric cancer. Contrast CT showed a mass lesion in the pancreatic head with contrast effects and invasion of the distal bile ducts. Additionally, ERCP was performed to obtain more detail. Because of the patient’s prior gastrectomy, ERCP was performed with a short-type single-balloon enteroscope, SIF-H290S (Olympus Medical Systems, Tokyo, Japan) with a working length of 152 cm and channel diameter of 3.2 mm. Cholangiography showed a defect in the distal bile duct. The procedure was then completed with fluoroscopy-guided biopsy of the bile duct. However, the size of the biopsy sample was insufficient to enable a conclusive diagnosis. ERCP was performed again 2 weeks later. With the aim of improving diagnostic ability, a CF-H260AI colonoscope (Olympus Medical Systems Corporation, Tokyo, Japan) with a working length of 133 cm and channel diameter of 3.7 mm was used to perform peroral cholangioscopy (POCS) guided by SpyGlass DS (Boston Scientific Corp, Marlborough, Mass, USA) fluorescein-dripping laser endomicroscopy (pCLE) probe-based confocal (CholangioFlex, Cellvizio; Mauna Kea Technologies, Inc, Paris, France) and POCS-guided biopsy. When the papilla was reached, it was possible to insert the cholangioscope inside the bile duct. Both findings suggested cancer, with POCS showing an irregular, hemorrhagic, papillary protrusion lesion, and pCLE showing a dark ductal structure with irregular margins. POCS confirmed that the bile ducts at nonlesion sites had normal mucosa, and pCLE showed a reticular network of thin, dark, branching bands, considered to be normal. POCS-guided biopsies were performed at both lesion and nonlesion sites. In contrast to the initial fluoroscopy-guided biopsy performed with ERCP, a sample of sufficient size was collected by the POCS-guided biopsy. The biopsy samples contained atypical cells with hyperchromatic nuclei and eosinophilic cytoplasm. Similarly to the pCLE findings, these formed a ductal structure with irregular margins. The nuclei showed marked variations in size, irregular morphology, and irregular arrangement, indicating adenocarcinoma. Biopsy specimens from normal bile ducts showed no malignancy. Therefore, a preoperative diagnosis of pancreatic cancer was made, and pancreatoduodenectomy was performed. The histopathologic findings from the surgical samples were similar to those from the POCS biopsy tissue samples, and irregular, invasive proliferation by atypical bile ducts with eosinophilic cytoplasm was found, confirming pancreatic cancer.
关键词： pancreatic cancer,probe-based confocal laser endomicroscopy,surgically altered anatomy,peroral cholangioscopy
更新于2025-09-23 15:19:57
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EUS-guided confocal laser endomicroscopy: Can we use thick and wide for diagnosis of early cancer?
摘要： In this issue of Gastrointestinal Endoscopy, Krishna et al1 report their investigation of the use of EUS–needle-based confocal laser endomicroscopy (EUS-nCLE) for differentiating intraductal papillary mucinous neoplasms (IPMNs) with high-grade dysplasia or adenocarcinoma (HGD-Ca) from those with low- to intermediate-grade dysplasia. They performed a post hoc analysis of a series of consecutive IPMNs with a de?nitive diagnosis. In their study, the authors performed 3 phases of evaluation of IPMNs for determining the EUS-nCLE criteria. The authors report that quanti?cation of “papillary epithelial width” and “darkness” identi?ed high-grade dysplasia and adenocarcinoma in IPMNs with high accuracy.1
关键词： EUS-nCLE,IPMNs,high-grade dysplasia,EUS-guided confocal laser endomicroscopy,adenocarcinoma
更新于2025-09-23 15:19:57
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Cresyl violet as a new contrast agent in probe‐based confocal laser endomicroscopy for in vivo diagnosis of gastric intestinal metaplasia
摘要： Background and Aim: Cresyl violet (CV) is a topical dye that allows simultaneous chromoendoscopy and in vivo confocal laser endomicroscopy (CLE) in identification of neoplastic changes of the lower GI tract without intravenous injection of fluorescein, but as yet no investigation has reported its application in the diagnosis of gastric intestinal metaplasia (GIM). This study aims to assess the feasibility as well as diagnosis accuracy of topical CV for in vivo diagnosis of GIM by using probe-based confocal laser endomicroscopy (pCLE). Methods: In this prospective, open-label, feasibility study, 129 confocal videos from 22 patients with known GIM were analyzed and compared with corresponding histological images to establish the CV staining characteristics. In addition, 47 patients with known or suspected GIM were prospectively enrolled to evaluate the accuracy of this topical CV endomicroscopic imaging. Results: PCLE with topical CV enabled clear visualization of the goblet cells, absorptive cells and intestinal villi of GIM. The accuracy, sensitivity, specificity, positive and negative predictive value of pCLE diagnosis of GIM on a per-location analysis was 93.01%, 91.95%, 93.51%, 86.96%, and 96.11%, respectively. The ICC for inter-observer agreement and mean kappa value for intra-observer agreement for the diagnosis of GIM was 0.82 and 0.87, respectively. Conclusions: Topical CV enables real-time chromoendoscopy in conjunction with pCLE examination of the stomach and warrants accurate diagnosis of GIM. It may be an acceptable and potentially alternative dye for confocal imaging in the future.
关键词： gastric intestinal metaplasia,probe-based confocal laser endomicroscopy,Cresyl violet
更新于2025-09-19 17:13:59
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Optical biopsy in gastroenterology: Focus on confocal laser endomicroscopy
摘要： The quality of endoscopy images has improved remarkably over the last several decades. Current generation endoscopes provide high-definition images with superior resolution and are capable of magnification as well. This means that subtle lesions are less likely to be missed on routine endoscopy. However, high definition alone may not be superior to standard white light endoscopy for in vivo characterization of polyps [1]. Differentiation of the lesions as neoplastic vs. non-neoplastic is essential as it bears implication on subsequent management and surveillance strategies. For example, hyperplastic polyps bear no malignant potential. On the other hand, adenomatous polyps harbor a definite risk of malignant transformation and need to be resected. The integration of image enhancement techniques like narrow band imaging (NBI) in the endoscopes have largely overcome the issue of discriminating neoplastic and non-neoplastic polyps in the gastrointestinal (GI) tract. Novel image enhancement techniques allow better characterization of the lesions as compared with high-definition endoscopy alone [2].
关键词： non-neoplastic polyps,neoplastic polyps,Optical biopsy,gastroenterology,confocal laser endomicroscopy
更新于2025-09-16 10:30:52
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Visualization of the human enteric nervous system by confocal laser endomicroscopy in Hirschsprung's disease: An alternative to intraoperative histopathological diagnosis?
摘要： Background: Hirschsprung's disease is a congenital abnormality of the enteric nervous system (ENS) presenting severe constipation soon after birth due to the lack of ganglion cells in the distal gut. Surgery for Hirschsprung's disease requires an intraoperative histopathological diagnosis to assess the extent of aganglionosis. Confocal laser endomicroscopy (CLE) is a novel endoscopic technique allowing real-time, in vivo analysis of cellular details during ongoing endoscopy. In this study, we evaluated the possibility of a new application of CLE to provide real-time observations of the ENS in patients with Hirschsprung's disease. In this preclinical feasibility study, we assessed the visualization of the ENS by CLE using surgically resected intestines. Methods: The subjects were nine patients who underwent pull-through surgery for Hirschsprung's disease between September 2014 and March 2016. The colon specimens were stained with 0.1% cresyl violet and evaluated using CLE. We compared the CLE findings with those of the histopathological examination. Key Results: The ENS was clearly visualized as a ladder-like structure in the ganglionic segment but was not observed in the aganglionic segment. Of the 69 samples, corresponding positive and negative results for both CLE and the histopathology were obtained in 61 (88%). In addition, CLE was able to visualize unique, wavy structures comprising thick nerve bundles characteristic of the aganglionic/transition zone in Hirschsprung's disease. Conclusions and Inferences: As a novel tool for visualizing the human ENS, CLE has the potential to revolutionize how pediatric surgeons identify the level of ganglionosis during surgery for Hirschsprung's disease and may be a superior alternative to intraoperative histopathological diagnosis.
关键词： Hirschsprung's disease,enteric nervous system,transition zone,intraoperative frozen section,confocal laser endomicroscopy
更新于2025-09-16 10:30:52
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Towards automated in vivo bladder tumor stratifcation using Confocal Laser Endomicroscopy
摘要： Purpose Urothelial carcinoma of the bladder (UCB) is the most common urinary cancer. White-light cystoscopy (WLC) forms the corner stone for the diagnosis of UCB. However, histopathological assessment is required for adjuvant treatment selection. Probe-based confocal laser endomicroscopy (pCLE) enables the visualization of the micro-architecture of bladder lesions during WLC, which allows for real-time tissue differentiation and grading of UCB. To improve the diagnostic process of UCB, computer aided classification of pCLE videos of in vivo bladder lesions were evaluated in this study. Materials and Methods We implemented pre-processing methods to optimize contrast and to reduce striping artifacts in each individual pCLE frame. Subsequently, a semi-automatic frame selection was performed. The selected frames were used to train a feature extractor, based on pre-trained ImageNet networks. A recurrent neural network, in specific long-short term memory (LSTM), was used to predict the grade of the bladder lesions. The differentiation of lesions was performed at two levels, namely (i) healthy and benign versus malignant tissue and (ii) low-grade versus high-grade papillary UCB. A total of 53 patients with 72 lesions were included in this study, resulting in approximately 140.000 pCLE frames. Results The semi-automated frame selection reduced the number of frames to approximately 66.500 informative frames. The accuracy for the differentiation of (i) healthy and benign versus malignant urothelium was 79% and (ii) high-grade and low-grade papillary UCB with 82%. Conclusions A feature extractor in combination with a LSTM results in an proper stratification of pCLE videos of in vivo bladder lesions.
关键词： confocal laser endomicroscopy,deep learning,bladder tumor,long-short term memory,classification
更新于2025-09-12 10:27:22