Miniaturized Handheld Confocal Microscopy for Neurosurgery

Sankar, Tejas; Delaney, Peter; Ryan, Robert W.; Eschbacher, Jennifer; Abdelwahab, Mohammed; Nakaji, Peter; Coons, Stephen W.; Scheck, Adrienne C.; Smith, Kris A.; Spetzler, Robert F.; Preul, Mark C.

doi:10.1227/01.neu.0000365772.66324.6f

Cited by 75 publications

(85 citation statements)

References 29 publications

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“…5,[15][16][17][18] We have investigated the feasibility of CLE in a murine malignant glioma model to distinguish normal brain, microvasculature, and tumor margins. 4,8,9,14 Furthermore, we have demonstrated its potential application as an intraoperative tool in human brain tumor surgery. 3,13 In the current study, we sought to evaluate the utility, specificity, and sensitivity of CLE using fluorescein sodium (FNa) as a fluorophore to detect brain tumor tissue.…”

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confidence: 94%

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

Martirosyan¹,

Eschbacher

Kalani³

et al. 2016

FOC

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164

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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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confidence: 94%

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

Martirosyan¹,

Eschbacher

Kalani³

et al. 2016

FOC

Self Cite

164

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“…13,39,[44][45][46] A miniaturized confocal laser endomicroscope integrated into the distal tip of a conventional video-endoscope now allows confocal fluorescent imaging of brain tissue in vivo. 12,25,[35][36][37] We recently investigated the feasibility of two handheld portable fiberoptic confocal endomicroscopes for acquiring in vivo images of experimental gliomas using fluorescent dyes. A 488-nm (Optiscan 5.1) visible-wavelength confocal endomicroscope (VWCE) system using fluorescein sodium (FNa) and acriflavine hydrochloride (AF) and a 780-nm near-infrared confocal endomicroscope (NIRCE) system (both from Optiscan Pty., Ltd.) using indocyanine green (ICG) were used in a murine malignant glioma model to distinguish among normal brain, microvasculature, and tumor margins.…”

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confidence: 99%

“…A 488-nm (Optiscan 5.1) visible-wavelength confocal endomicroscope (VWCE) system using fluorescein sodium (FNa) and acriflavine hydrochloride (AF) and a 780-nm near-infrared confocal endomicroscope (NIRCE) system (both from Optiscan Pty., Ltd.) using indocyanine green (ICG) were used in a murine malignant glioma model to distinguish among normal brain, microvasculature, and tumor margins. 25,37 We have also assessed the feasibility of using the VWCE with FNa in human brain tumor surgery and explored its use with 5-aminolevulinic acid (5-ALA) in gliomas. Currently, 5-ALA is not approved for intracranial applications in the US, although it is approved to aid malignant glioma resection in Europe and Asia.…”

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confidence: 99%

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Potential application of a handheld confocal endomicroscope imaging system using a variety of fluorophores in experimental gliomas and normal brain

Martirosyan

Georges

Eschbacher

et al. 2014

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Object The authors sought to assess the feasibility of a handheld visible-wavelength confocal endomicroscope imaging system (Optiscan 5.1, Optiscan Pty., Ltd.) using a variety of rapid-acting fluorophores to provide histological information on gliomas, tumor margins, and normal brain in animal models. Methods Mice (n = 25) implanted with GL261 cells were used to image fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA), acridine orange (AO), acriflavine (AF), and cresyl violet (CV). A U251 glioma xenograft model in rats (n = 5) was used to image sulforhodamine 101 (SR101). A swine (n = 3) model with AO was used to identify confocal features of normal brain. Images of normal brain, obvious tumor, and peritumoral zones were collected using the handheld confocal endomicroscope. Histological samples were acquired through biopsies from matched imaging areas. Samples were visualized with a benchtop confocal microscope. Histopathological features in corresponding confocal images and photomicrographs of H & E–stained tissues were reviewed. Results Fluorescence induced by FNa, 5-ALA, AO, AF, CV, and SR101 and detected with the confocal endomicroscope allowed interpretation of histological features. Confocal endomicroscopy revealed satellite tumor cells within peritumoral tissue, a definitive tumor border, and striking fluorescent cellular and subcellular structures. Fluorescence in various tumor regions correlated with standard histology and known tissue architecture. Characteristic features of different areas of normal brain were identified as well. Conclusions Confocal endomicroscopy provided rapid histological information precisely related to the site of microscopic imaging with imaging characteristics of cells related to the unique labeling features of the fluorophores. Although experimental with further clinical trial validation required, these data suggest that intraoperative confocal imaging can help to distinguish normal brain from tumor and tumor margin and may have application in improving intraoperative decisions during resection of brain tumors.

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“…Here the integration of NLM into a conventional microscope system is advanced including the option of navigation and matching image-guidance data. A hand-held device has been designed and used in animal research (Sankar et al, 2010) and in humans (Schlosser, H.G., Bojarski, C. 2011 (Epub)). For the reusable system used in endoscopy in the last years a setrilizablility has not been achieved.…”

Section: Further Developmentsmentioning

confidence: 99%

Confocal Neurolasermicroscopy - Modern Perspectives for Glioma Resection on a Cellular Level

Schlosser¹,

Bojarski²

2011

Advances in the Biology, Imaging and Therapies for Glioblastoma

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Miniaturized Handheld Confocal Microscopy for Neurosurgery

Cited by 75 publications

References 29 publications

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

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

Potential application of a handheld confocal endomicroscope imaging system using a variety of fluorophores in experimental gliomas and normal brain

Confocal Neurolasermicroscopy - Modern Perspectives for Glioma Resection on a Cellular Level

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