Visualization of brain microvasculature and blood flow in vivo: Feasibility study using confocal laser endomicroscopy

Belykh, Evgenii; Zhao, Xiaochun; Ngo, Brandon; Farhadi, Dara S.; Kindelin, Adam; Ahmad, Saif; Martirosyan, Nikolay L.; Lawton, Michael T.; Preul, Mark C.

doi:10.1111/micc.12678

Cited by 10 publications

(10 citation statements)

References 35 publications

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“…Belykh and colleagues investigated the feasibility of CLE to qualitatively and quantitatively analyze real-time blood flow patterns in brain under normal conditions, after injury and in pathologic brain and spinal cord microvasculature in a large animal model and patient samples ( 27 ). In the swine model, SF concentrations ranged from 1 - 5 mg/kg and 0.1% - 0.005%/5 ml.…”

Section: Resultsmentioning

confidence: 99%

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Confocal laser imaging in neurosurgery: A comprehensive review of sodium fluorescein-based CONVIVO preclinical and clinical applications

et al. 2022

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Given the established direct correlation that exists among extent of resection and postoperative survival in brain tumors, obtaining complete resections is of primary importance. Apart from the various technological advancements that have been introduced in current clinical practice, histopathological study still remains the gold-standard for definitive diagnosis. Frozen section analysis still represents the most rapid and used intraoperative histopathological method that allows for an intraoperative differential diagnosis. Nevertheless, such technique owes some intrinsic limitations that limit its overall potential in obtaining real-time diagnosis during surgery. In this context, confocal laser technology has been suggested as a promising method to have near real-time intraoperative histological images in neurosurgery, thanks to the results of various studies performed in other non-neurosurgical fields. Still far to be routinely implemented in current neurosurgical practice, pertinent literature is growing quickly, and various reports have recently demonstrated the utility of this technology in both preclinical and clinical settings in identifying brain tumors, microvasculature, and tumor margins, when coupled to the intravenous administration of sodium fluorescein. Specifically in neurosurgery, among different available devices, the ZEISS CONVIVO system probably boasts the most recent and largest number of experimental studies assessing its usefulness, which has been confirmed for identifying brain tumors, offering a diagnosis and distinguishing between healthy and pathologic tissue, and studying brain vessels. The main objective of this systematic review is to present a state-of-the-art summary on sodium fluorescein-based preclinical and clinical applications of the ZEISS CONVIVO in neurosurgery.

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Section: Resultsmentioning

confidence: 99%

“…Looking at the only available CONVIVO vascular experience by Belykh and colleagues from 2021, patients received 5 ml of 10% SF i.v. 5 minutes prior to CLE imaging ( 27 ). The earliest visualization of the vessel wall was 8 minutes after SF injection, with visualization being more common at approximately 30 minutes after injection.…”

Section: Discussionmentioning

confidence: 99%

Confocal laser imaging in neurosurgery: A comprehensive review of sodium fluorescein-based CONVIVO preclinical and clinical applications

et al. 2022

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“…Belykh et al examined the presence of thrombosis, flow velocity changes, and agglutination in gliomas during neurosurgery, demonstrating the feasibility and potential of examining capillaries by CLE. It was demonstrated that lymphatic channels could also be differentiated from blood vessels [23]. Further research is needed to evaluate the transferability of these results in the head and neck region.…”

Section: Discussionmentioning

confidence: 98%

Impact of intraepithelial capillary loops and atypical vessels in confocal laser endomicroscopy for the diagnosis of laryngeal and hypopharyngeal squamous cell carcinoma

Sievert

Eckstein

Mantsopoulos

et al. 2021

Eur Arch Otorhinolaryngol

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Purpose Confocal laser endomicroscopy (CLE) allows surface imaging of the laryngeal and pharyngeal mucosa in vivo at a thousand-fold magnification. This study aims to compare irregular blood vessels and intraepithelial capillary loops in healthy mucosa and squamous cell carcinoma (SCC) via CLE. Materials and methods We included ten patients with confirmed SCC and planned total laryngectomy in this study between March 2020 and February 2021. CLE images of these patients were collected and compared with the corresponding histology in hematoxylin and eosin staining. We analyzed the characteristic endomicroscopic patterns of blood vessels and intraepithelial capillary loops for the diagnosis of SCC. Results In a total of 54 sequences, we identified 243 blood vessels which were analyzed regarding structure, diameter, and Fluorescein leakage, confirming that irregular, corkscrew-like vessels (24.4% vs. 1.3%; P < .001), dilated intraepithelial capillary loops (90.8% vs. 28.7%; P < .001), and increased capillary leakage (40.7% vs. 2.5%; P < .001), are significantly more frequently detected in SCC compared to the healthy epithelium. We defined a vessel diameter of 30 μm in capillary loops as a cut-off value, obtaining a sensitivity, specificity, PPV, and NPV and accuracy of 90.6%, 71.3%, 57.4%, 94.7%, and 77.1%, respectively, for the detection of malignancy based solely on capillary architecture. Conclusion Capillaries within malignant lesions are fundamentally different from those in healthy mucosa regions. The capillary architecture is a significant feature aiding the identification of malignant mucosa areas during in-vivo, real-time CLE examination.

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“…Future analysis will include an assessment of tumor microvasculature in addition to tumor cell morphology and architecture. Interpretation of erythrocyte flow, thrombosis, and velocity changes may help to classify glioma subtypes, normal and injured brain tissues (33). Due to the lack of blood flow in ex vivo samples, these features were not included during the CNN training process in this study.…”

Section: Discussionmentioning

confidence: 99%

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

Ziebart

Stadniczuk²,

Roos

et al. 2021

Front. Oncol.

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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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Visualization of brain microvasculature and blood flow in vivo: Feasibility study using confocal laser endomicroscopy

Cited by 10 publications

References 35 publications

Confocal laser imaging in neurosurgery: A comprehensive review of sodium fluorescein-based CONVIVO preclinical and clinical applications

Confocal laser imaging in neurosurgery: A comprehensive review of sodium fluorescein-based CONVIVO preclinical and clinical applications

Impact of intraepithelial capillary loops and atypical vessels in confocal laser endomicroscopy for the diagnosis of laryngeal and hypopharyngeal squamous cell carcinoma

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

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