Immediate Label-Free Ex Vivo Evaluation of Human Brain Tumor Biopsies With Confocal Reflectance Microscopy

Jennifer M. Eschbacher, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.Follow
Joseph F. Georges, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.
Evgenii Belykh, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.Follow
Mohammedhassan Izady Yazdanabadi, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.
Nikolay L. Martirosyan, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.Follow
Emily Szeto, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.
Catherine Y. Seiler, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.
Michael A. Mooney, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.
Jessica K. Daniels, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.
Katherine Y. Goehring, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.
Kendall R. Van Keuren-Jensen, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.
Mark C. Preul, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.
Stephen W. Coons, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.Follow
Shwetal Mehta, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.
Peter Nakaji, Department of Neuropathology and Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Department of Neurosurgery, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania; School of Life Sciences, Arizona State University, Tempe, Arizona; Irkutsk State Medical University, Irkutsk, Russia; Department of Neurobiology, Barrow Brain Tumor Research Center and The Biobank Core, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Division of Neurogenomics, Translational Genomics Institute, Phoenix, Arizona.

Document Type

Article

Abstract

Confocal microscopy utilizing fluorescent dyes is widely gaining use in the clinical setting as a diagnostic tool. Reflectance confocal microscopy is a method of visualizing tissue specimens without fluorescent dyes while relying on the natural refractile properties of cellular and subcellular structures. We prospectively evaluated 76 CNS lesions with confocal reflectance microscopy (CRM) to determine cellularity, architecture, and morphological characteristics. A neuropathologist found that all cases showed similar histopathological features when compared to matched hematoxylin and eosin-stained sections. RNA isolated from 7 tissues following CRM imaging retained high RNA integrity, suggesting that CRM does not alter tissue properties for molecular studies. A neuropathologist and surgical pathologist masked to the imaging results independently evaluated a subset of CRM images. In these evaluations, 100% of images reviewed by the neuropathologist and 95.7% of images reviewed by the surgical pathologist were correctly diagnosed as lesional or nonlesional. Furthermore, 97.9% and 91.5% of cases were correctly diagnosed as tumor or not tumor by the neuropathologist and surgical pathologist, respectively, while 95.8% and 85.1% were identified with the correct diagnosis. Our data indicate that CRM is a useful tool for rapidly screening patient biopsies for diagnostic adequacy, molecular studies, and biobanking.

Keywords

Brain biopsy, Confocal reflectance microscopy, Intraoperative tissue analysis, Neoplasms

Medical Subject Headings

Adult; Aged; Aged, 80 and over; Biological Specimen Banks (standards); Biopsy (methods, standards); Brain Neoplasms (pathology); Cryoultramicrotomy (methods, standards); Female; Humans; Male; Microscopy, Confocal (methods, standards); Middle Aged; Molecular Imaging (methods, standards); Retrospective Studies; Single-Blind Method; Young Adult

Publication Date

12-1-2017

Publication Title

Journal of neuropathology and experimental neurology

E-ISSN

1554-6578

Volume

76

Issue

12

First Page

1008

Last Page

1022

PubMed ID

29136454

Digital Object Identifier (DOI)

10.1093/jnen/nlx089

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