This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jbio.201800396 Development and first in-human use of a Raman spectroscopy guidance system integrated with a brain biopsy needle Joannie Desroches 1,2** , Émile Lemoine 1,2** , Michael Pinto 1 , Eric Marple 6 , Kirk Urmey 6 , Roberto Diaz 3 , Marie-Christine Guiot 4 , Brian C. Wilson 5 , Kevin Petrecca 3* and Frederic Leblond 1,2* *Corresponding Authors: Kevin Petrecca (email: Kevin.petrecca@mcgill.ca) and Frédéric Leblond (email: Frederic.leblond@polymtl.ca) **Joannie Desroches and Émile Lemoine should be considered joint first authors 1 Department of Engineering Physics, Polytechnique Montreal, CP 6079, Succ. Centre-Ville, Montreal, QC, H3C 3A7, Canada 2 Centre de Recherche du Centre Hospitalier de l’Université de Montréal, 900 rue, Saint-Denis, H2X 0A9, QC, Canada. 3 Brain Tumour Research Centre, Montreal Neurological Institute and Hospital, Dept. of Neurology and Neurosurgery, McGill University, 3801 University St., Montreal, QC, H3A 2B4, Canada. 4 Division of Neuropathology, Department of Pathology, Montreal Neurological Institute and Hospital, McGill University, 3801 University St, Montreal, QC, H3A 2B4, Canada. 5 Princess Margaret Cancer Centre-University Health Network/University of Toronto, 15-314, 101 College St., Toronto, ON, M5G 1L7, Canada. 6 EMVision LLC, 1471 F Road, Loxahatchee, Florida, 33470, United States. Keywords: cancer, neurosurgery, biopsy, optical systems, medical imaging, Raman spectroscopy Short title: J. Desroches et al.: Raman spectroscopy system for brain needle biopsy guidance Abstract Navigation-guided brain biopsies are the standard of care for diagnosis of several brain pathologies. However, imprecise targeting and tissue heterogeneity often hinder obtaining high-quality tissue samples, resulting in poor diagnostic yield. We report the development and first clinical testing of a navigation-guided fiberoptic Raman probe that allows surgeons to interrogate brain tissue in situ at the tip of the biopsy needle, prior to tissue removal. The This article is protected by copyright. All rights reserved.