Intraoperative Probe-Based Confocal Laser Endomicroscopy in Surgery and Stereotactic Biopsy of Low-Grade and High-Grade Gliomas

Neurosurgery ◽  
2016 ◽  
Vol 79 (4) ◽  
pp. 604-612 ◽  
Author(s):  
Vladislav Pavlov ◽  
David Meyronet ◽  
Vincent Meyer-Bisch ◽  
Xavier Armoiry ◽  
Brian Pikul ◽  
...  
Keyword(s):  
Open Surgery ◽  
Stereotactic Biopsy ◽  
Aminolevulinic Acid ◽  
Intraoperative Imaging ◽  
Intraoperative Complications ◽  
Tumor Resection ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Low Grade ◽  
Histologic Diagnosis

Abstract BACKGROUND: The management of gliomas is based on precise histologic diagnosis. The tumor tissue can be obtained during open surgery or via stereotactic biopsy. Intraoperative tissue imaging could substantially improve biopsy precision and, ultimately, the extent of resection. OBJECTIVE: To show the feasibility of intraoperative in vivo probe-based confocal laser endomicroscopy (pCLE) in surgery and biopsy of gliomas. METHODS: In our prospective observational study, 9 adult patients were enrolled between September 2014 and January 2015. Two contrast agents were used: 5-aminolevulinic acid (3 cases) or intravenous fluorescein (6 cases). Intraoperative imaging was performed with the Cellvizio system (Mauna Kea Technologies, Paris). A 0.85-mm probe was used for stereotactic procedures, with the biopsy needle modified to have a distal opening. During open brain surgery, a 2.36-mm probe was used. Each series corresponds to a separate histologic fragment. RESULTS: The diagnoses of the lesions were glioblastoma (4 cases), low-grade glioma (2), grade III oligoastrocytoma (2), and lymphoma (1). Autofluorescence of neurons in cortex was observed. Cellvizio images enabled differentiation of healthy “normal” tissue from pathological tissue in open surgery and stereotactic biopsy using fluorescein. 5-Aminolevulinic acid confocal patterns were difficult to establish. No intraoperative complications related to pCLE or to use of either contrast agent were observed. CONCLUSION: We report the initial feasibility and safety of intraoperative pCLE during primary brain tumor resection and stereotactic biopsy procedures. Pending further investigation, pCLE of brain tissue could be utilized for intraoperative surgical guidance, improvement in brain biopsy yield, and optimization of glioma resection via analysis of tumor margins.

scholarly journals Confocal-Assisted Fluorescence Resection of Low-Grade Gliomas

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Cleopatra Charalampaki ◽  
Juergen Schlegel
Keyword(s):  
Normal Tissue ◽  
Imaging Modality ◽  
Brain Structures ◽  
Cellular Level ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Low Grade ◽  
Normal Brain ◽  
Low Grade Gliomas ◽  
Tumor Identification

Abstract INTRODUCTION Low-grade gliomas (LGG) are the most common intra-axial brain tumors. Intraoperatively it's not possible to distinguish optically between the tumor and the normal tissue. Furthermore, it can not be detected with fluorescent agents like 5-aminolevulinacid (5-ALA). Those reasons often lead to inaccurate resection of the tumor. Confocal laser endomicroscopy (CLE) is a cellular imaging modality used for optical biopsies. The aim of this study was to use intraoperative CLE to differentiate tumor from normal tissue and to define borders during resection of LGG on a cellular level. METHODS We investigated the use of intraoperative CLE on 6 patients with LGG. We used a confocal system that is able to detect fluorescence on the infrared spectrum and we applied indocyanine green as a detecting fluorescent agent. We analyzed the accuracy of the intraoperative cellular CLE optical biopsies in comparison with the hematoxylin and eosin stains of the biopsies taken from the tumor and normal tissue borders area. RESULTS With CLE we were able intraoperatively to diagnose the tumor entity, normal brain structures, and vascularization modalities and to control the resection zone on a cellular level. Furthermore, CLE pictures showed exactly the cellular borders between tumor and normal tissue. The correlation of the CLE pictures with the H&E staining was 100%. CONCLUSION CLE, on one hand, allows intraoperative detection and differentiation of single tumor cells, while, on the other hand, it allows defining borders between tumor and normal tissue on a cellular level, dramatically improving the accuracy of surgical resection of LGG. The application and implementation of CLE-assisted surgery increases not only the options for real-tumor identification but also the therapeutic options by extending the resection borders of LGG on a cellular level and, more importantly, by protecting the functionality of normal tissue on the adjacent areas of the human brain.

FLAIRectomy in Supramarginal Resection of Glioblastoma Correlates With Clinical Outcome and Survival Analysis: A Prospective, Single Institution, Case Series

2020 ◽  
Author(s):  
Francesco Certo ◽  
Roberto Altieri ◽  
Massimiliano Maione ◽  
Claudio Schonauer ◽  
Giuseppe Sortino ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Dna Methyltransferase ◽  
Aminolevulinic Acid ◽  
Intraoperative Imaging ◽  
Tumor Resection ◽  
Case Series ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Volumetric Analysis ◽  
Mr Images

Abstract Background Extent of tumor resection (EOTR) in glioblastoma surgery plays an important role in improving survival. Objective To analyze the efficacy, safety and reliability of fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) images used to guide glioblastoma resection (FLAIRectomy) and to volumetrically measure postoperative EOTR, which was correlated with clinical outcome and survival. Methods A total of 68 glioblastoma patients (29 males, mean age 65.8) were prospectively enrolled. Hyperintense areas on FLAIR images, surrounding gadolinium-enhancing tissue on T1-weighted MR images, were screened for signal changes suggesting tumor infiltration and evaluated for supramaximal resection. The surgical protocol included 5-aminolevulinic acid (5-ALA) fluorescence, neuromonitoring, and intraoperative imaging tools. 5-ALA fluorescence intensity was analyzed and matched with the different sites on navigated MR, both on postcontrast T1-weighted and FLAIR images. Volumetric evaluation of EOTR on T1-weighted and FLAIR sequences was compared. Results FLAIR MR volumetric evaluation documented larger tumor volume than that assessed on contrast-enhancing T1 MR (72.6 vs 54.9 cc); residual tumor was seen in 43 patients; postcontrast T1 MR volumetric analysis showed complete resection in 64 cases. O6-methylguanine-DNA methyltransferase promoter was methylated in 8/68 (11.7%) cases; wild type Isocytrate Dehydrogenase-1 (IDH-1) was found in 66/68 patients. Progression free survival and overall survival (PFS and OS) were 17.43 and 25.11 mo, respectively. Multiple regression analysis showed a significant correlation between EOTR based on FLAIR, PFS (R2 = 0.46), and OS (R2 = 0.68). Conclusion EOTR based on FLAIR and 5-ALA fluorescence is feasible. Safety of resection relies on the use of neuromonitoring and intraoperative multimodal imaging tools. FLAIR-based EOTR appears to be a stronger survival predictor compared to gadolinium-enhancing, T1-based resection.

scholarly journals Implementation of real-time probe-based confocal laser endomicroscopy (pCLE) for differentiation of colorectal polyps during routine colonoscopy

2017 ◽  
Vol 05 (11) ◽  
pp. E1104-E1110 ◽  
Author(s):  
Tim Belderbos ◽  
Martijn van Oijen ◽  
Leon Moons ◽  
Peter Siersema
Keyword(s):  
Real Time ◽  
Narrow Band Imaging ◽  
Prospective Trial ◽  
Training Session ◽  
Tertiary Hospital ◽  
Colorectal Polyps ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Histologic Diagnosis ◽  
Post Hoc

Abstract Background and aims Probe-based confocal laser endomicroscopy (pCLE) is used to differentiate between neoplastic and non-neoplastic colorectal polyps during colonoscopy. We aimed to assess the accuracy of two endoscopists starting to use real-time pCLE for differentiation of colorectal polyps and to determine the negative predictive value (NPV) for neoplasia in polyps ≤ 5 mm. Methods Patients undergoing colonoscopy in a tertiary hospital were included in this prospective trial. After a training session, two colonoscopists assessed 50 polyps between August 2012 and April 2014. They sequentially used narrow-band imaging (NBI) and real-time pCLE to differentiate non-adenomatous, adenomatous, and carcinomatous polyps during colonoscopy. Histologic diagnosis by a gastrointestinal pathologist was the gold standard. Results were compared to post-hoc pCLE by a panel of gastroenterologists and pathologists. Results The accuracy of real-time pCLE was 76 %, compared to 73 % for NBI, and was not significantly different between the first 50 cases (74 %) and the last 50 cases (78 %, P = 0.64). The accuracy in polyps > 5 mm was 87 % versus 59 % in polyps ≤ 5 mm (P = 0.04) and increased from 45 % (13/29) in poor quality images to 86 % (44/51) in fair quality images and 95 % (19/20) in good quality images (P < 0.01). The post-hoc pCLE accuracy was 62 %. The NPV for polyps ≤ 5 mm was 58 % for real-time pCLE and 54 % for post-hoc pCLE. Conclusion Although a fair accuracy of real-time pCLE for differentiation of colorectal polyps can be achieved within 50 cases, low NPV and difficulty in obtaining high-quality pCLE images hamper implementation in routine clinical practice.

scholarly journals Fluorescent Imaging and Multifusion Segmentation for Enhanced Visualization and Delineation of Glioblastomas Margins

Signals ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 304-335
Author(s):  
Aditi Deshpande ◽  
Thomas Cambria ◽  
Charles Barnes ◽  
Alexandros Kerwick ◽  
George Livanos ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Fluorescent Protein ◽  
Image Acquisition ◽  
Tumor Resection ◽  
Fluorescent Imaging ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Test Bed ◽  
Tumor Margins ◽  
Green Fluorescent

This study investigates the potential of fluorescence imaging in conjunction with an original, fused segmentation framework for enhanced detection and delineation of brain tumor margins. By means of a test bed optical microscopy system, autofluorescence is utilized to capture gray level images of brain tumor specimens through slices, obtained at various depths from the surface, each of 10 µm thickness. The samples used in this study originate from tumor cell lines characterized as Gli36ϑEGRF cells expressing a green fluorescent protein. An innovative three-step biomedical image analysis framework is presented aimed at enhancing the contrast and dissimilarity between the malignant and the remaining tissue regions to allow for enhanced visualization and accurate extraction of tumor boundaries. The fluorescence image acquisition system implemented with an appropriate unsupervised pipeline of image processing and fusion algorithms indicates clear differentiation of tumor margins and increased image contrast. Establishing protocols for the safe administration of fluorescent protein molecules, these would be introduced into glioma tissues or cells either at a pre-surgery stage or applied to the malignant tissue intraoperatively; typical applications encompass areas of fluorescence-guided surgery (FGS) and confocal laser endomicroscopy (CLE). As a result, this image acquisition scheme could significantly improve decision-making during brain tumor resection procedures and significantly facilitate brain surgery neuropathology during operation.

Su1997 - Generation and Validation of New Confocal Laser Endomicroscopy Criteria for the Diagnosis of Low-Grade Dysplasia in Barrett's Esophagus

2018 ◽  
Vol 154 (6) ◽  
pp. S-660
Author(s):  
Massimiliano Di Pietro ◽  
Helga Bertani ◽  
Maria O'Donovan ◽  
Patricia Santos ◽  
Jacobo Ortiz Fernández-Sordo ◽  
...  
Keyword(s):  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Low Grade ◽  
Low Grade Dysplasia

scholarly journals Comparison of intraoperative MR imaging and 3D-navigated ultrasonography in the detection and resection control of lesions

2001 ◽  
Vol 10 (2) ◽  
pp. 1-5 ◽  
Author(s):  
Volker M. Tronnier ◽  
Matteo M. Bonsanto ◽  
Andreas Staubert ◽  
Michael Knauth ◽  
Stefan Kunze ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Intraoperative Imaging ◽  
Tumor Resection ◽  
Lesion Detection ◽  
Imaging Modalities ◽  
Attractive Alternative ◽  
Low Grade ◽  
Resection Control ◽  
Low Field ◽  
Supratentorial Gliomas

Object The authors undertook a study to compare two intraoperative imaging modalities, low-field magnetic resonance (MR) imaging and a prototype of a three-dimensional (3D)–navigated ultrasonography in terms of imaging quality in lesion detection and intraoperative resection control. Methods Low-field MR imaging was used for intraoperative resection control and update of navigational data in 101 patients with supratentorial gliomas. Thirty-five patients with different lesions underwent surgery in which the prototype of a 3D-navigated ultrasonography system was used. A prospective comparative study of both intraoperative imaging modalities was initiated with the first seven cases presented here. In 35 patients (70%) in whom ultrasonography was performed, accurate tumor delineation was demonstrated prior to tumor resection. In the remaining 30% comparison of preoperative MR imaging data and ultrasonography data allowed sufficient anatomical localization to be achieved. Detection of metastases and high-grade gliomas and intra-operative delineation of tumor remnants were comparable between both imaging modalities. In one case of a low-grade glioma better visibility was achieved with ultrasonography. However, intraoperative findings after resection were still difficult to interpret with ultrasonography alone most likely due to the beginning of a learning curve. Conclusions Based on these preliminary results, intraoperative MR imaging remains superior to intraoperative ultrasonography in terms of resection control in glioma surgery. Nevertheless, the different features (different planes of slices, any-plane slicing, and creation of a 3D volume and matching of images) of this new ultrasonography system make this tool a very attractive alternative. The intended study of both imaging modalities will hopefully allow a comparison regarding sensitivity and specificity of intraoperative tumor remnant detection, as well as cost effectiveness.

scholarly journals Socio-Organizational Impact of Confocal Laser Endomicroscopy in Neurosurgery and Neuropathology: Results from a Process Analysis and Expert Survey

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2128
Author(s):  
Marina L. Fotteler ◽  
Friederike Liesche-Starnecker ◽  
Maria C. Brielmaier ◽  
Johannes Schobel ◽  
Jens Gempt ◽  
...  
Keyword(s):  
Tissue Sample ◽  
Process Analysis ◽  
Tumor Resection ◽  
Routine Care ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Organizational Impact ◽  
Expert Survey ◽  
Current Process ◽  
Use Of Resources

During brain tumor resection surgery, it is essential to determine the tumor borders as the extent of resection is important for post-operative patient survival. The current process of removing a tissue sample for frozen section analysis has several shortcomings that might be overcome by confocal laser endomicroscopy (CLE). CLE is a promising new technology enabling the digital in vivo visualization of tissue structures in near real-time. Research on the socio-organizational impact of introducing this new methodology to routine care in neurosurgery and neuropathology is scarce. We analyzed a potential clinical workflow employing CLE by comparing it to the current process. Additionally, a small expert survey was conducted to collect data on the opinion of clinical staff working with CLE. While CLE can contribute to a workload reduction for neuropathologists and enable a shorter process and a more efficient use of resources, the effort for neurosurgeons and surgery assistants might increase. Experts agree that CLE offers huge potential for better diagnosis and therapy but also see challenges, especially due to the current state of experimental use, including a risk for misinterpretations and the need for special training. Future studies will show whether CLE can become part of routine care.

scholarly journals Curriculum review: colorectal cancer surveillance and management of dysplasia in IBD

2018 ◽  
Vol 9 (4) ◽  
pp. 271-277 ◽  
Author(s):  
Hajir Ibraheim ◽  
Angad Singh Dhillon ◽  
Ioannis Koumoutsos ◽  
Shraddha Gulati ◽  
Bu’Hussain Hayee
Keyword(s):  
Colorectal Cancer ◽  
Cancer Surveillance ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Colonic Disease ◽  
Low Grade ◽  
High Definition ◽  
Management Options ◽  
Detection Rates ◽  
Increased Risk

The significantly increased risk of colorectal cancer (CRC) in longstanding colonic inflammatory bowel disease (IBD) justifies the need for endoscopic surveillance. Unlike sporadic CRC, IBD-related CRC does not always follow the predictable sequence of low-grade to high-grade dysplasia and finally to invasive carcinoma, probably because the genetic events shared by both diseases occur in different sequences and frequencies. Surveillance is recommended for patients who have had colonic disease for at least 8-10 years either annually, every 3 years or every 5 years with the interval dependant on the presence of additional risk factors. Currently, the recommended endoscopic strategy is high-definition chromoendoscopy with targeted biopsies, although the associated lengthier procedure time and need for experienced endoscopists has limited its uniform uptake in daily practice. There is no clear consensus on the management of dysplasia, which continues to be a challenging area particularly when endoscopically invisible. Management options include complete resection (and/or referral to a tertiary centre), close surveillance or proctocolectomy. Technical advances in endoscopic imaging such as confocal laser endomicroscopy, show exciting potential in increasing dysplasia detection rates but are still far from being routinely used in clinical practice.

scholarly journals Intraoperative free margins assessment of oropharyngeal squamous cell carcinoma with confocal laser endomicroscopy: a pilot study

2021 ◽  
Author(s):  
Matti Sievert ◽  
Florian Stelzle ◽  
Marc Aubreville ◽  
Sarina K. Mueller ◽  
Markus Eckstein ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Pilot Study ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Resection ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Optical Biopsy ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Uniform Size

Abstract Purpose This pilot study aimed to assess the feasibility of intraoperative assessment of safe margins with confocal laser endomicroscopy (CLE) during oropharyngeal squamous cell carcinoma (OPSCC) surgery. Methods We included five consecutive patients confirmed OPSCC and planned tumor resection in September and October 2020. Healthy appearing mucosa in the marginal zone, and the tumor margin, were examined with CLE and biopsy during tumor resection. A total of 12,809 CLE frames were correlated with the gold standard of hematoxylin and eosin staining. Three head and neck surgeons and one pathologist were asked to identify carcinoma in a sample of 169 representative images, blinded to the histological results. Results Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE optical biopsy of OPSCC demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 86%, 90%, 79%, 88%, and 82%, respectively, with inter-rater reliability and κ-value of 0.60. Conclusion CLE can be easily integrated into the intraoperative setting, generate real-time, in-vivo microscopic images of the oropharynx for evaluation and demarcation of cancer. It can eventually contribute to a less radical approach by enabling a more precise evaluation of the cancer margin.

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