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

Belykh, Evgenii; Zhao, Xiaochun; Ngo, Brandon; Farhadi, Dara S.; Byvaltsev, Vadim A.; Eschbacher, Jennifer; Nakaji, Peter; Preul, Mark C.

doi:10.3389/fonc.2020.599250

Cited by 26 publications

(64 citation statements)

References 34 publications

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“…Alternatively, fluorescein could be combined with Raman spectroscopy, which has been shown to accurately delineate tumor versus normal brain at the margins of resection, with superior performance compared to 5-ALA (55). Confocal laser endomicroscopy has also been combined with fluorescein and recently investigated as a means of increasing extent of resection by providing real-time intraoperative verification of pathologic tumor tissue (56)(57)(58). Several studies have also mentioned the potential benefit of quantitatively measuring fluorescence intensity and integrating this technology with the operative microscope, which could increase both the safety and the sensitivity of fluorescein as an adjunct for glioma resection (9,17,29).…”

Section: Future Directionsmentioning

confidence: 99%

Rationale and Clinical Implications of Fluorescein-Guided Supramarginal Resection in Newly Diagnosed High-Grade Glioma

et al. 2021

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Current standard of care for glioblastoma is surgical resection followed by temozolomide chemotherapy and radiation. Recent studies have demonstrated that >95% extent of resection is associated with better outcomes, including prolonged progression-free and overall survival. The diffusely infiltrative pattern of growth in gliomas results in microscopic extension of tumor cells into surrounding brain parenchyma that makes complete resection unattainable. The historical goal of surgical management has therefore been maximal safe resection, traditionally guided by MRI and defined as removal of all contrast-enhancing tumor. Optimization of surgical resection has led to the concept of supramarginal resection, or removal beyond the contrast-enhancing region on MRI. This strategy of extending the cytoreductive goal targets a tumor region thought to be important in the recurrence or progression of disease as well as resistance to systemic and local treatment. This approach must be balanced against the risk of impacting eloquent regions of brain and causing permanent neurologic deficit, an important factor affecting overall survival. Over the years, fluorescent agents such as fluorescein sodium have been explored as a means of more reliably delineating the boundary between tumor core, tumor-infiltrated brain, and surrounding cortex. Here we examine the rationale behind extending resection into the infiltrative tumor margins, review the current literature surrounding the use of fluorescein in supramarginal resection of gliomas, discuss the experience of our own institution in utilizing fluorescein to maximize glioma extent of resection, and assess the clinical implications of this treatment strategy.

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Section: Future Directionsmentioning

confidence: 99%

Rationale and Clinical Implications of Fluorescein-Guided Supramarginal Resection in Newly Diagnosed High-Grade Glioma

et al. 2021

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“…In this work the authors provided 3D images of different kind of brain tumors, suggesting that this technology may afford an increased spatial understanding of tumor cellular architecture and visualization of related structures compared with two-dimensional images. In 2020, the same group tested for the first time the feasibility of positioning the Convivo probe in a trans-sphenoidal corridor in cadaver heads and obtained 19 biopsies from nine patients who underwent pituitary adenoma surgery for ex vivo imaging at various times after fluorescein injection [ 41 ]. A blinded board-certified neuropathologist analyzed the images, resulting in a 8/13 pituitary adenomas correctly identified through CLE analysis using frozen sections as the standard.…”

Section: Resultsmentioning

confidence: 99%

“…In a recent works by Belykh and colleagues, the dye was studied for ex-vivo pituitary tumors analysis, identifying the correct timing for SF administration in respect to biopsy procedure [ 45 ]. In 2020 the authors reported for the first time the increasing diagnostic power that a second intravenous injection of such dye may confer in the analysis of intracranial lesions [ 41 ]. Thanks to its proven effect in increasing EOR and ability to enhance CLE images, highlighting tumor cells in fluorescent areas, to date this dye appears to be one of the best contrast enhancers that can be coupled to confocal imaging.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, the great majority of available studies is biased by: (1) low number of biopsies per case (the recent availability of probes that can be used directly in vivo in OR hopefully will improve such aspect); (2) low number of biopsies performed at tumor border; (3) unspecified or “low controlled” blindness of the study from the pathologist point of view. Hence, considering ex vivo experiences, many studies have demonstrated different sensibility/specificity for HGGs, often over 80/85% and also higher for extra-axial tumors [ 28 , 32 , 41 ]. In particular, Snuderl and colleagues in 2012 analyzed ten preselected images from tumor cases, blinding pathologists to histological results, simulating a frozen section analysis, founding that identification of grade and tumor type by trained neuropathologists resulted to have a sensibility of 88% and specificity of 100% [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

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Confocal Laser Microscopy in Neurosurgery: State of the Art of Actual Clinical Applications

Restelli

Pollo

Vetrano

et al. 2021

JCM

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Achievement of complete resections is of utmost importance in brain tumor surgery, due to the established correlation among extent of resection and postoperative survival. Various tools have recently been included in current clinical practice aiming to more complete resections, such as neuronavigation and fluorescent-aided techniques, histopathological analysis still remains the gold-standard for diagnosis, with frozen section as the most used, rapid and precise intraoperative histopathological method that permits an intraoperative differential diagnosis. Unfortunately, due to the various limitations linked to this technique, it is still unsatisfactorily for obtaining real-time intraoperative diagnosis. Confocal laser technology has been recently suggested as a promising method to obtain near real-time intraoperative histological data in neurosurgery, due to its established use in other non-neurosurgical fields. Still far to be widely implemented in current neurosurgical clinical practice, this technology was initially studied in preclinical experiences confirming its utility in identifying brain tumors, microvasculature and tumor margins. Hence, ex vivo and in vivo clinical studies evaluated the possibility with this technology of identifying and classifying brain neoplasms, discerning between normal and pathologic tissue, showing very promising results. This systematic review has the main objective of presenting a state-of-the-art summary on actual clinical applications of confocal laser imaging in neurosurgical practice.

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“…In contrast, e x vivo imaging after topical staining is significantly less affected by the timing of fluorescein administration. Insufficient contrast can be avoided by readministration of fluorescein and thus increase image quality ( 32 ). Future analysis will include an assessment of tumor microvasculature in addition to tumor cell morphology and architecture.…”

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

Cited by 26 publications

References 34 publications

Rationale and Clinical Implications of Fluorescein-Guided Supramarginal Resection in Newly Diagnosed High-Grade Glioma

Rationale and Clinical Implications of Fluorescein-Guided Supramarginal Resection in Newly Diagnosed High-Grade Glioma

Confocal Laser Microscopy in Neurosurgery: State of the Art of Actual Clinical Applications

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

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