Probe-based three-dimensional confocal laser endomicroscopy of brain tumors: technical note

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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Confocal Laser Endomicroscopy for Brain Tumors

Case Medical Research ◽

10.31525/ct1-nct04280952 ◽

2020 ◽

Author(s):

Keyword(s):

Brain Tumors ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser

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Confocal Laser Endomicroscopy (CLE) for Diagnosis and Histomorphologic Imaging of Brain Tumors in Vivo

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0032-1312097 ◽

2012 ◽

Vol 73 (S 01) ◽

Author(s):

Cleopatra Charalampaki ◽

Sebastian Foersch ◽

Axel Heimann ◽

Konstantin Mpoukouvalas ◽

Oliver Kempski

Keyword(s):

Brain Tumors ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser

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Confocal Laser Endomicroscopy for Diagnosis and Histomorphologic Imaging of Brain Tumors In Vivo

PLoS ONE ◽

10.1371/journal.pone.0041760 ◽

2012 ◽

Vol 7 (7) ◽

pp. e41760 ◽

Cited By ~ 51

Author(s):

Sebastian Foersch ◽

Axel Heimann ◽

Ali Ayyad ◽

Gilles A. Spoden ◽

Luise Florin ◽

...

Keyword(s):

Brain Tumors ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser

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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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INNV-08. THE UTILIZATION OF INTRAOPERATIVE CONFOCAL LASER ENDOMICROSCOPY DURING THE FLUORESCENCE GUIDED SURGERY FOR BRAIN TUMORS

Neuro-Oncology ◽

10.1093/neuonc/noy148.582 ◽

2018 ◽

Vol 20 (suppl_6) ◽

pp. vi139-vi139

Author(s):

Evgenii Belykh ◽

Claudio Cavallo ◽

Xiaochun Zhao ◽

Eric Miller ◽

Arpan A Patel ◽

...

Keyword(s):

Brain Tumors ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Guided Surgery ◽

Fluorescence Guided Surgery

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Technical Note: First Use of Endonasal Confocal Laser Endomicroscopy – Feasibility and Proof of Concept

International Archives of Otorhinolaryngology ◽

10.1055/s-0041-1724091 ◽

2021 ◽

Author(s):

Nina Wenda ◽

Ralf Kiesslich ◽

Jan Gosepath

Keyword(s):

Real Time ◽

Head And Neck Carcinoma ◽

Cellular Level ◽

Technical Note ◽

Sinus Surgery ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Real Time Analysis ◽

Morphological Criteria

Abstract Introduction Probe-based confocal laser endomicroscopy (p-CLE) is a method for real-time in vivo visualization of mucosal changes on a cellular level. Due to the size of the endoscopes, it was mainly used in the gastrointestinal tract so far. First investigations on head and neck carcinoma described the oropharyngeal application. The further miniaturization of the laser probe now allows endonasal application and, thus, first experiences with the investigation of endonasal neoplasms. Objectives The aim of the present investigation is to elucidate, based on the morphological criteria validated in the oropharynx, whether these criteria be transferred in a similar way to the endonasal mucosa. Methods We conducted p-CLE (Cellvizio, Paris, France) with intravenous fluorescein staining in endoscopic sinus surgery in a patient with sinonasal inverted papilloma and a histologically confirmed squamous cell carcinoma. We compared the cellular visualization of pathological changes with those of healthy mucosa in the same specimen, and also with our former findings in the oropharynx. Results Endonasal p-CLE proved to be quite feasible in the surgical setting, and the transfer of malignancy criteria in analogy to histological examination could be optically retraced. Furthermore, additional criteria for tissue dignity assessment were obtained. Conclusion Our results suggest that endonasal application of p-CLE represents a valuable extension of the diagnostic repertoire available to date by an additional real-time analysis of the nasal mucosa. This is of particular value in surgically challenging anatomical areas such as the paranasal sinuses.Further investigation and validation will be necessary.

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Confocal laser microscopy of impregnated central nervous system tissue

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100102559 ◽

1988 ◽

Vol 46 ◽

pp. 94-95

Author(s):

J.N. Turner ◽

M. Siemens ◽

D. Szarowski ◽

D.N. Collins

Keyword(s):

Electron Microscopy ◽

Central Nervous System ◽

Nervous System ◽

Three Dimensional ◽

Dimensional Structure ◽

Confocal Laser ◽

High Contrast ◽

Central Nervous System Tissue ◽

Tissue Samples ◽

Reflected Light

A classic preparation of central nervous system tissue (CNS) is the Golgi procedure popularized by Cajal. The method is partially specific as only a few cells are impregnated with silver chromate usualy after osmium post fixation. Samples are observable by light (LM) or electron microscopy (EM). However, the impregnation is often so dense that structures are masked in EM, and the osmium background may be undesirable in LM. Gold toning is used for a subtle but high contrast EM preparation, and osmium can be omitted for LM. We are investigating these preparations as part of a study to develop correlative LM and EM (particularly HVEM) methodologies in neurobiology. Confocal light microscopy is particularly useful as the impregnated cells have extensive three-dimensional structure in tissue samples from one to several hundred micrometers thick. Boyde has observed similar preparations in the tandem scanning reflected light microscope (TSRLM).

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Some quantitative applications of vascular corrosion casting

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100124094 ◽

1992 ◽

Vol 50 (1) ◽

pp. 738-739

Author(s):

Fred E. Hossler

Keyword(s):

Blood Vessels ◽

Nuclear Orientation ◽

Three Dimensional ◽

Surrounding Tissue ◽

Confocal Laser ◽

Corrosion Casting ◽

Venous Valve ◽

Casting Technique ◽

Low Viscosity ◽

Quantitative Measurements

Preparation of replicas of the complex arrangement of blood vessels in various organs and tissues has been accomplished by infusing low viscosity resins into the vasculature. Subsequent removal of the surrounding tissue by maceration leaves a model of the intricate three-dimensional anatomy of the blood vessels of the tissue not obtainable by any other procedure. When applied with care, the vascular corrosion casting technique can reveal fine details of the microvasculature including endothelial nuclear orientation and distribution (Fig. 1), locations of arteriolar sphincters (Fig. 2), venous valve anatomy (Fig. 3), and vessel size, density, and branching patterns. Because casts faithfully replicate tissue vasculature, they can be used for quantitative measurements of that vasculature. The purpose of this report is to summarize and highlight some quantitative applications of vascular corrosion casting. In each example, casts were prepared by infusing Mercox, a methyl-methacrylate resin, and macerating the tissue with 20% KOH. Casts were either mounted for conventional scanning electron microscopy, or sliced for viewing with a confocal laser microscope.

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