Intraoperative in vivo confocal laser endomicroscopy imaging at glioma margins: can we detect tumor infiltration?

Authors

Yuan Xu, Department of Neurosurgery, The Loyal and Edith Davis Neurosurgical Research Laboratory, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
Andrea M. Mathis, Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Switzerland.
Bianca Pollo, Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
Jürgen Schlegel, Department of Neuropathology, Institute of Pathology, TUM School of Medicine, Technical University Munich, Germany.
Theoni Maragkou, Institute of Tissue Medicine and Pathology, University of Bern, Switzerland.
Kathleen Seidel, Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Switzerland.
Philippe Schucht, Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Switzerland.
Kris A. Smith, Department of Neurosurgery, The Loyal and Edith Davis Neurosurgical Research Laboratory, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
Randall W. Porter, Department of Neurosurgery, The Loyal and Edith Davis Neurosurgical Research Laboratory, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
Andreas Raabe, Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Switzerland.
Andrew S. Little, Department of Neurosurgery, The Loyal and Edith Davis Neurosurgical Research Laboratory, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
Nader Sanai, Department of Neurosurgery, The Loyal and Edith Davis Neurosurgical Research Laboratory, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
Dennis C. Agbanyim, Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Switzerland.
Nikolay L. Martirosyan, Department of Neurosurgery, The Loyal and Edith Davis Neurosurgical Research Laboratory, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.Follow
Jennifer M. Eschbacher, Department of Neuropathology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
Karl Quint, Quint Healthcare, Fürth, Germany; and.
Mark C. Preul, Department of Neurosurgery, The Loyal and Edith Davis Neurosurgical Research Laboratory, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
Ekkehard Hewer, Institute of Pathology, Lausanne University Hospital, University of Lausanne, Switzerland.

Document Type

Article

Abstract

OBJECTIVE: Confocal laser endomicroscopy (CLE) is a US Food and Drug Administration-cleared intraoperative real-time fluorescence-based cellular resolution imaging technology that has been shown to image brain tumor histoarchitecture rapidly in vivo during neuro-oncological surgical procedures. An important goal for successful intraoperative implementation is in vivo use at the margins of infiltrating gliomas. However, CLE use at glioma margins has not been well studied. METHODS: Matching in vivo CLE images and tissue biopsies acquired at glioma margin regions of interest (ROIs) were collected from 2 institutions. All images were reviewed by 4 neuropathologists experienced in CLE. A scoring system based on the pathological features was implemented to score CLE and H&E images from each ROI on a scale from 0 to 5. Based on the H&E scores, all ROIs were divided into a low tumor probability (LTP) group (scores 0-2) and a high tumor probability (HTP) group (scores 3-5). The concordance between CLE and H&E scores regarding tumor probability was determined. The intraclass correlation coefficient (ICC) and diagnostic performance were calculated. RESULTS: Fifty-six glioma margin ROIs were included for analysis. Interrater reliability of the scoring system was excellent when used for H&E images (ICC [95% CI] 0.91 [0.86-0.94]) and moderate when used for CLE images (ICC [95% CI] 0.69 [0.40-0.83]). The ICCs (95% CIs) of the LTP group (0.68 [0.40-0.83]) and HTP group (0.68 [0.39-0.83]) did not differ significantly. The concordance between CLE and H&E scores was 61.6%. The sensitivity and specificity values of the scoring system were 79% and 37%. The positive predictive value (PPV) and negative predictive value were 65% and 53%, respectively. Concordance, sensitivity, and PPV were greater in the HTP group than in the LTP group. Specificity was higher in the newly diagnosed group than in the recurrent group. CONCLUSIONS: CLE may detect tumor infiltration at glioma margins. However, it is not currently dependable, especially in scenarios where low probability of tumor infiltration is expected. The proposed scoring system has excellent intrinsic interrater reliability, but its interrater reliability is only moderate when used with CLE images. These results suggest that this technology requires further exploration as a method for consistent actionable intraoperative guidance with high dependability across the range of tumor margin scenarios. Specific-binding and/or tumor-specific fluorophores, a CLE image atlas, and a consensus guideline for image interpretation may help with the translational utility of CLE.

Publication Date

8-4-2023

Publication Title

Journal of neurosurgery

E-ISSN

1933-0693

First Page

1

Last Page

10

PubMed ID

37542440

Digital Object Identifier (DOI)

10.3171/2023.5.JNS23546

Recommended Citation

Xu, Yuan; Mathis, Andrea M.; Pollo, Bianca; Schlegel, Jürgen; Maragkou, Theoni; Seidel, Kathleen; Schucht, Philippe; Smith, Kris A.; Porter, Randall W.; Raabe, Andreas; Little, Andrew S.; Sanai, Nader; Agbanyim, Dennis C.; Martirosyan, Nikolay L.; Eschbacher, Jennifer M.; Quint, Karl; Preul, Mark C.; and Hewer, Ekkehard, "Intraoperative in vivo confocal laser endomicroscopy imaging at glioma margins: can we detect tumor infiltration?" (2023). Neurosurgery. 1973.
https://scholar.barrowneuro.org/neurosurgery/1973