Confocal Laser Endomicroscopy Assessment of Pituitary Tumor Microstructure: A Feasibility Study

This is the first study to assess confocal laser endomicroscopy (CLE) use within the transsphenoidal approach and show the feasibility of obtaining digital diagnostic biopsies of pituitary tumor tissue after intravenous fluorescein injection. We confirmed that the CLE probe reaches the tuberculum sellae through the transnasal transsphenoidal corridor in cadaveric heads. Next, we confirmed that CLE provides images with identifiable histological features of pituitary adenoma. Biopsies from nine patients who underwent pituitary adenoma surgery were imaged ex vivo at various times after fluorescein injection and were assessed by a blinded board-certified neuropathologist. With frozen sections used as the standard, pituitary adenoma was diagnosed as “definitively” for 13 and as “favoring” in 3 of 16 specimens. CLE digital biopsies were diagnostic for pituitary adenoma in 10 of 16 specimens. The reasons for nondiagnostic CLE images were biopsy acquisition <1 min or >10 min after fluorescein injection (n = 5) and blood artifacts (n = 1). In conclusion, fluorescein provided sufficient contrast for CLE at a dose of 2 mg/kg, optimally 1–10 min after injection. These results provide a basis for further in vivo studies using CLE in transsphenoidal surgery.

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Prospective evaluation of the utility of intraoperative confocal laser endomicroscopy in patients with brain neoplasms using fluorescein sodium: experience with 74 cases

Neurosurgical FOCUS ◽

10.3171/2016.1.focus15559 ◽

2016 ◽

Vol 40 (3) ◽

pp. E11 ◽

Cited By ~ 39

Author(s):

Nikolay L. Martirosyan ◽

Jennifer M. Eschbacher ◽

M. Yashar S. Kalani ◽

Jay D. Turner ◽

Evgenii Belykh ◽

...

Keyword(s):

Brain Tumors ◽

Ex Vivo ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Fluorescein Sodium ◽

Frozen Sections ◽

Diagnostic Image ◽

Tissue Samples ◽

Specificity And Sensitivity

OBJECTIVE This study evaluated the utility, specificity, and sensitivity of intraoperative confocal laser endomicroscopy (CLE) to provide diagnostic information during resection of human brain tumors. METHODS CLE imaging was used in the resection of intracranial neoplasms in 74 consecutive patients (31 male; mean age 47.5 years; sequential 10-month study period). Intraoperative in vivo and ex vivo CLE was performed after intravenous injection of fluorescein sodium (FNa). Tissue samples from CLE imaging–matched areas were acquired for comparison with routine histological analysis (frozen and permanent sections). CLE images were classified as diagnostic or nondiagnostic. The specificities and sensitivities of CLE and frozen sections for gliomas and meningiomas were calculated using permanent histological sections as the standard. RESULTS CLE images were obtained for each patient. The mean duration of intraoperative CLE system use was 15.7 minutes (range 3–73 minutes). A total of 20,734 CLE images were correlated with 267 biopsy specimens (mean number of images/biopsy location, in vivo 84, ex vivo 70). CLE images were diagnostic for 45.98% in vivo and 52.97% ex vivo specimens. After initiation of CLE, an average of 14 in vivo images and 7 ex vivo images were acquired before identification of a first diagnostic image. CLE specificity and sensitivity were, respectively, 94% and 91% for gliomas and 93% and 97% for meningiomas. CONCLUSIONS CLE with FNa provided intraoperative histological information during brain tumor removal. Specificities and sensitivities of CLE for gliomas and meningiomas were comparable to those for frozen sections. These data suggest that CLE could allow the interactive identification of tumor areas, substantially improving intraoperative decisions during the resection of brain tumors.

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Cystic Pancreatic Neuroendocrine Tumors: Validation of In Vivo Needle-Based Confocal Laser Endomicroscopy Findings by Ex Vivo Analysis

The American Journal of Gastroenterology ◽

10.14309/00000434-201610001-01585 ◽

2016 ◽

Vol 111 ◽

pp. S739-S740

Author(s):

Amrit K. Kamboj ◽

Rohan M. Modi ◽

Benjamin J. Swanson ◽

Mary E. Dillhoff ◽

Darwin L. Conwell ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Ex Vivo ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Pancreatic Neuroendocrine Tumors

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A comprehensive examination of the novel techniques used for in vivo and ex vivo confocal laser endomicroscopy of pancreatic cystic lesions

VideoGIE ◽

10.1016/j.vgie.2016.07.002 ◽

2016 ◽

Vol 1 (1) ◽

pp. 6-7 ◽

Cited By ~ 4

Author(s):

Amrit K. Kamboj ◽

Rohan M. Modi ◽

Benjamin Swanson ◽

Darwin L. Conwell ◽

Somashekar G. Krishna

Keyword(s):

Ex Vivo ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Cystic Lesions ◽

The Novel ◽

Comprehensive Examination

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VHM12 Confocal Laser Endomicroscopy (CLE): Evaluation of Pancreatic Cystic Lesions In Vivo and Ex Vivo

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2011.03.1208 ◽

2011 ◽

Vol 73 (4) ◽

pp. AB111 ◽

Cited By ~ 1

Author(s):

Victoria Gomez ◽

Muhammad Waseem Shahid ◽

Murli Krishna ◽

Horacio J. Asbun ◽

Michael B. Wallace

Keyword(s):

Ex Vivo ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Cystic Lesions

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Novel techniques for diagnosis of serous cystadenoma: fern pattern of vascularity confirmed by in vivo and ex vivo confocal laser endomicroscopy

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2016.07.015 ◽

2017 ◽

Vol 85 (1) ◽

pp. 258-259 ◽

Cited By ~ 8

Author(s):

Rohan M. Modi ◽

Benjamin Swanson ◽

Peter Muscarella ◽

Darwin L. Conwell ◽

Somashekar G. Krishna

Keyword(s):

Ex Vivo ◽

Serous Cystadenoma ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser

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Deep Neural Network for Differentiation of Brain Tumor Tissue Displayed by Confocal Laser Endomicroscopy

Frontiers in Oncology ◽

10.3389/fonc.2021.668273 ◽

2021 ◽

Vol 11 ◽

Author(s):

Andreas Ziebart ◽

Denis Stadniczuk ◽

Veronika Roos ◽

Miriam Ratliff ◽

Andreas von Deimling ◽

...

Keyword(s):

Brain Tumor ◽

Tumor Tissue ◽

Ex Vivo ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Site Classification ◽

Histopathological Analysis ◽

Test Accuracy ◽

Tumor Type ◽

Resected Tumor

BackgroundReliable on site classification of resected tumor specimens remains a challenge. Implementation of high-resolution confocal laser endoscopic techniques (CLEs) during fluorescence-guided brain tumor surgery is a new tool for intraoperative tumor tissue visualization. To overcome observer dependent errors, we aimed to predict tumor type by applying a deep learning model to image data obtained by CLE.MethodsHuman brain tumor specimens from 25 patients with brain metastasis, glioblastoma, and meningioma were evaluated within this study. In addition to routine histopathological analysis, tissue samples were stained with fluorescein ex vivo and analyzed with CLE. We trained two convolutional neural networks and built a predictive level for the outputs.ResultsMultiple CLE images were obtained from each specimen with a total number of 13,972 fluorescein based images. Test accuracy of 90.9% was achieved after applying a two-class prediction for glioblastomas and brain metastases with an area under the curve (AUC) value of 0.92. For three class predictions, our model achieved a ratio of correct predicted label of 85.8% in the test set, which was confirmed with five-fold cross validation, without definition of confidence. Applying a confidence rate of 0.999 increased the prediction accuracy to 98.6% when images with substantial artifacts were excluded before the analysis. 36.3% of total images met the output criteria.ConclusionsWe trained a residual network model that allows automated, on site analysis of resected tumor specimens based on CLE image datasets. Further in vivo studies are required to assess the clinical benefit CLE can have.

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P397 Response to biologics in IBD patients assessed by Computerized image analysis of Probe Based Confocal Laser Endomicroscopy with molecular labeling

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.521 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S406-S407

Author(s):

M Iacucci ◽

E Grisan ◽

N Labarile ◽

O Nardone ◽

S C Smith ◽

...

Keyword(s):

Predictive Value ◽

Ex Vivo ◽

Binding Activity ◽

Biological Agent ◽

Confocal Imaging ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Tertiary Referral Centre ◽

Fluorescent Intensity

Abstract Background The increase in therapeutic choices in inflammatory bowel diseases (IBD) imposed the identification of personalized therapeutic strategy. Confocal laser endomicroscopy (CLE) is a new endoscopic tool developed to obtain virtual in vivo histology. This study aimed to identify CLE in vivo and ex vivo features predictive of response for patients starting biologics. Methods We performed a prospective observational study at a single tertiary referral centre. 29 IBD patients (14 ulcerative colitis-UC and 15 Crohn’s Disease-CD) underwent colonoscopy with CLE before and 12-14 weeks after starting anti -TNF or 16 weeks after anti α4β7 integrin. CLE parameters analyzed were: crypt distribution along the mucosal surface, crypt area (CA), eccentricity, diameter, inter-cryptic distance (ICD), vessel tortuosity (VT), fluorescein leakage through the colonic mucosa (FLCM). Ex-vivo binding activity of fluorescein labelled biologics on corresponding biopsies was also assessed. Mosaicism reconstruction of CLE images were analyzed using a dedicated software algorithm (CellvizioViewer, Mauna Kea Technologies, ParisFrance). A dedicated Graphical User Interface was designed to enable a semiautomated analysis. Results After treatment, VT resulted significantly changed in overall IBD population (p<0.05), FLCM were reduced in UC patients (p<0.05), whilst CA, eccentricity and ICD decreased in CD patients (p< 0.05). The univariate regression analysis identified FLCM as the most accurate parameter for predicting responsiveness (AUROC) 83%, accuracy 83%, positive predictive value-PPV 94% and negative predictive value-NPV 57%). FLCM and ICD were the best discriminants in responders Vs non responders in UC patients (AUROC 85%, accuracy 85%, PPV 100% and NPV 71%); whilst VT, CA and ICD in CD patients (AUROC 95%, 86% and 83%; accuracy 90%, 90% and 88%; PPV 100%, 100% and 86%; and NPV 75%, 75% and 100%, respectively). Ex vivo confocal imaging revealed that UC patients, especially those responders, had higher basal fluorescent intensity signals with a significant reduction after biological treatment (p< 0.05), whereas in CD patients no significant change was found. An increased mucosal binding to the fluorescent labelled biological agent was associated to a higher likelihood of response to the treatment; this effect was higher in UC patients (AUROC 81%, accuracy 77%, PPV 100%, NPV 63%) compared to CD patients (AUROC 64%, accuracy 79%, PPV 80%, NPV 50%). Conclusion FLCM and ICD were the best discriminants of response in UC, while VT, CA and ICD in CD. A higher mucosal binding to a biological agent before treatment was observed in responders UC patients but not in CD patients.

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Intraoperative Confocal Laser Endomicroscopy Ex Vivo Examination of Tissue Microstructure During Fluorescence-Guided Brain Tumor Surgery

Frontiers in Oncology ◽

10.3389/fonc.2020.599250 ◽

2020 ◽

Vol 10 ◽

Author(s):

Evgenii Belykh ◽

Xiaochun Zhao ◽

Brandon Ngo ◽

Dara S. Farhadi ◽

Vadim A. Byvaltsev ◽

...

Keyword(s):

Brain Tumors ◽

Positive Predictive Value ◽

Predictive Value ◽

Ex Vivo ◽

High Specificity ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Normal Brain ◽

Wide Field

BackgroundNoninvasive intraoperative optical biopsy that provides real-time imaging of histoarchitectural (cell resolution) features of brain tumors, especially at the margin of invasive tumors, would be of great value. To assess clinical-grade confocal laser endomicroscopy (CLE) and to prepare for its use intraoperatively in vivo, we performed an assessment of CLE ex vivo imaging in brain lesions.MethodsTissue samples from patients who underwent intracranial surgeries with fluorescein sodium (FNa)–based wide-field fluorescence guidance were acquired for immediate intraoperative ex vivo optical biopsies with CLE. Hematoxylin-eosin–stained frozen section analysis of the same specimens served as the gold standard for blinded neuropathology comparison. FNa 2 to 5 mg/kg was administered upon induction of anesthesia, and FNa 5 mg/kg was injected for CLE contrast improvement. Histologic features were identified, and the diagnostic accuracy of CLE was assessed.ResultsOf 77 eligible patients, 47 patients with 122 biopsies were enrolled, including 32 patients with gliomas and 15 patients with other intracranial lesions. The positive predictive value of CLE optical biopsies was 97% for all specimens and 98% for gliomas. The specificity of CLE was 90% for all specimens and 94% for gliomas. The second FNa injection in seven patients, a mean of 2.6 h after the first injection, improved image quality and increased the percentage of accurately diagnosed images from 67% to 93%. Diagnostic CLE features of lesional glioma biopsies and normal brain were identified. Seventeen histologic features were identified.ConclusionsResults demonstrated high specificity and positive predictive value of ex vivo intraoperative CLE optical biopsies and justify an in vivo intraoperative trial. This new portable, noninvasive intraoperative imaging technique provides diagnostic features to discriminate lesional tissue with high specificity and is feasible for incorporation into the fluorescence-guided surgery workflow, particularly for patients with invasive brain tumors.

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