Neuropathological Applications of Microscopy with Ultraviolet Surface Excitation (MUSE): A Concordance Study of Human Primary and Metastatic Brain Tumors

Author:

Lechpammer Mirna123,Todd Austin1,Tang Vivian1ORCID,Morningstar Taryn1,Borowsky Alexander1,Shahlaie Kiarash4,Kintner John A.1,McPherson John D.5,Bishop John W.1,Fereidouni Farzad1,Harmany Zachary T.1ORCID,Coley Nicholas1,Zagzag David6ORCID,Wong Jason W. H.7,Tao Jiang89,Hesson Luke B.81011,Burnett Leslie89,Levenson Richard1

Affiliation:

1. Department of Pathology and Laboratory Medicine, University of California Davis Health, Sacramento, CA 95817, USA

2. Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York, NY 10016, USA

3. Pathology and Laboratory Operations, Foundation Medicine, Inc., Cambridge, MA 02141, USA

4. Department of Neurosurgery, University of California Davis Health, Sacramento, CA 95817, USA

5. Department of Biochemistry and Molecular Medicine, University of California Davis Health, Sacramento, CA 95817, USA

6. Departments of Pathology and Neurosurgery, New York University Langone Medical Center, New York, NY 10016, USA

7. School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China

8. Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia

9. School of Clinical Medicine, University of New South Wales Sydney, St Vincent’s Healthcare Clinical Campus, Darlinghurst NSW 2010, Australia

10. Department of Molecular Genetics, Douglass Hanly Moir Pathology, Macquarie Park NSW 2113, Australia

11. School of Clinical Medicine, University of New South Wales Sydney, Randwick NSW 2052, Australia

Abstract

Whereas traditional histology and light microscopy require multiple steps of formalin fixation, paraffin embedding, and sectioning to generate images for pathologic diagnosis, Microscopy using Ultraviolet Surface Excitation (MUSE) operates through UV excitation on the cut surface of tissue, generating images of high resolution without the need to fix or section tissue and allowing for potential use for downstream molecular tests. Here, we present the first study of the use and suitability of MUSE microscopy for neuropathological samples. MUSE images were generated from surgical biopsy samples of primary and metastatic brain tumor biopsy samples (n = 27), and blinded assessments of diagnoses, tumor grades, and cellular features were compared to corresponding hematoxylin and eosin (H&E) images. A set of MUSE-treated samples subsequently underwent exome and targeted sequencing, and quality metrics were compared to those from fresh frozen specimens. Diagnostic accuracy was relatively high, and DNA and RNA integrity appeared to be preserved for this cohort. This suggests that MUSE may be a reliable method of generating high-quality diagnostic-grade histologic images for neuropathology on a rapid and sample-sparing basis and for subsequent molecular analysis of DNA and RNA.

Funder

NCI IMAT

Publisher

MDPI AG

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