Confocal Laser Endomicroscopy for Real-time Histomorphological Diagnosis

Charalampaki, Patra; Javed, Mehreen; Daali, Samira; Heiroth, Hi-Jae; Igressa, Alhadi; Weber, Friedrich

doi:10.1227/neu.0000000000000805

Cited by 42 publications

(35 citation statements)

References 21 publications

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“…Investigation continues into the use of CLE, particularly in intraoperative diagnosis of gliomas and meningiomas. Although not yet in common clinical use, the effectiveness and reliability of CLE in the patients with brain tumors has been consistently validated, warranting further investigation and refinement of its usage 2,11…”

Section: Introductionmentioning

confidence: 99%

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

Belykh¹,

Patel²,

Miller³

et al. 2018

CMAR

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BackgroundConfocal laser endomicroscopy (CLE) is used during fluorescence-guided brain tumor surgery for intraoperative microscopy of tumor tissue with cellular resolution. CLE could augment and expedite intraoperative decision-making and potentially aid in diagnosis and removal of tumor tissue.ObjectiveTo describe an extension of CLE imaging modality that produces Z-stack images and three-dimensional (3D) pseudocolored volumetric images.Materials and methodsHand-held probe-based CLE was used to collect images from GL261-luc2 gliomas in C57BL/6 mice and from human brain tumor biopsies. The mice were injected with fluorescein sodium (FNa) before imaging. Patients received FNa intraoperatively, and biopsies were imaged immediately in the operating room. Some specimens were counterstained with acridine orange, acriflavine, or Hoechst and imaged on a benchtop confocal microscope. CLE images at various depths were acquired automatically, compiled, rendered into 3D volumes using Fiji software and reviewed by a neuropathologist and neurosurgeons.ResultsCLE imaging, Z-stack acquisition, and 3D image rendering were performed using 19 mouse gliomas and 31 human tumors, including meningiomas, gliomas, and pituitary adenomas. Volumetric images and Z-stacks provided additional information about fluorescence signal distribution, cytoarchitecture, and the course of abnormal vasculature.Conclusion3D and Z-stack CLE imaging is a unique new option for live intraoperative endomicroscopy of brain tumors. The 3D images afford an increased spatial understanding of tumor cellular architecture and visualization of related structures compared with two-dimensional images. Future application of specific fluorescent probes could benefit from this rapid in vivo imaging technology for interrogation of brain tumor tissue.

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Section: Introductionmentioning

confidence: 99%

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

Belykh¹,

Patel²,

Miller³

et al. 2018

CMAR

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“…Needle-based confocal devices have also been developed, providing access to solid organ imaging. [116][117][118][119][120]…”

Section: Optical Imaging Modalitiesmentioning

confidence: 99%

In Vivo and Ex Vivo Microscopy: Moving Toward the Integration of Optical Imaging Technologies Into Pathology Practice

Wells

Thrall

Sorokina

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

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The traditional surgical pathology assessment requires tissue to be removed from the patient, then processed, sectioned, stained, and interpreted by a pathologist using a light microscope. Today, an array of alternate optical imaging technologies allow tissue to be viewed at high resolution, in real time, without the need for processing, fixation, freezing, or staining. Optical imaging can be done in living patients without tissue removal, termed in vivo microscopy, or also in freshly excised tissue, termed ex vivo microscopy. Both in vivo and ex vivo microscopy have tremendous potential for clinical impact in a wide variety of applications. However, in order for these technologies to enter mainstream clinical care, an expert will be required to assess and interpret the imaging data. The optical images generated from these imaging techniques are often similar to the light microscopic images that pathologists already have expertise in interpreting. Other clinical specialists do not have this same expertise in microscopy, therefore, pathologists are a logical choice to step into the developing role of microscopic imaging expert. Here, we review the emerging technologies of in vivo and ex vivo microscopy in terms of the technical aspects and potential clinical applications. We also discuss why pathologists are essential to the successful clinical adoption of such technologies and the educational resources available to help them step into this emerging role.

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“…It can provide cross-sectional images of intact tissue (i.e., optical sectioning) as a non-invasive real-time alternative to slide-mounted histology for guiding glioma resections. Several commercial intraoperative confocal microscope devices have been implemented in previous studies ( 22 , 23 ). In 2011, Sanai et al ( 24 ) reported the first in vivo human study demonstrating the feasibility of this technology for guiding brain tumor resections.…”

Section: Introductionmentioning

confidence: 99%

Video-Mosaicked Handheld Dual-Axis Confocal Microscopy of Gliomas: An ex vivo Feasibility Study in Humans

et al. 2020

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Background Intraoperative confocal microscopy can enable high-resolution cross-sectional imaging of intact tissues as a non-invasive real-time alternative to gold-standard histology. However, all current means of intraoperative confocal microscopy are hindered by a limited field of view (FOV), presenting a challenge for evaluating gliomas, which are highly heterogeneous. Objective This study explored the use of image mosaicking with handheld dual-axis confocal (DAC) microscopy of fresh human glioma specimens. Methods In this preliminary technical feasibility study, fresh human glioma specimens from 6 patients were labeled with a fast-acting topical stain (acridine orange) and imaged using a newly developed DAC microscope prototype. Results In comparison to individual image frames with small fields of view, mosaicked images from a DAC microscope correlate better with gold-standard H&E-stained histology images, including the ability to visualize gradual transitions from areas of dense cellularity to sparse cellularity within the tumor. Conclusion LS-DAC microscopy provides high-resolution, high-contrast images of glioma tissues that agree with corresponding H&E histology. Compared with individual image frames, mosaicked images provide more accurate representations of the overall cytoarchitecture of heterogeneous glioma tissues. Further investigation is needed to evaluate the ability of high-resolution mosaicked microscopy to improve the extent of glioma resection and patient outcomes.

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Confocal Laser Endomicroscopy for Real-time Histomorphological Diagnosis

Cited by 42 publications

References 21 publications

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

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

In Vivo and Ex Vivo Microscopy: Moving Toward the Integration of Optical Imaging Technologies Into Pathology Practice

Video-Mosaicked Handheld Dual-Axis Confocal Microscopy of Gliomas: An ex vivo Feasibility Study in Humans

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