title: Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy.
abstract: Differentiating tumor from normal brain is a major barrier to achieving optimal outcome in brain tumor surgery. New imaging techniques for visualizing tumor margins during surgery are needed to improve surgical results. We recently demonstrated the ability of stimulated Raman scattering (SRS) microscopy, a nondestructive, label-free optical method, to reveal glioma infiltration in animal models. We show that SRS reveals human brain tumor infiltration in fresh, unprocessed surgical specimens from 22 neurosurgical patients. SRS detects tumor infiltration in near-perfect agreement with standard hematoxylin and eosin light microscopy (κ = 0.86). The unique chemical contrast specific to SRS microscopy enables tumor detection by revealing quantifiable alterations in tissue cellularity, axonal density, and protein/lipid ratio in tumor-infiltrated tissues. To ensure that SRS microscopic data can be easily used in brain tumor surgery, without the need for expert interpretation, we created a classifier based on cellularity, axonal density, and protein/lipid ratio in SRS images capable of detecting tumor infiltration with 97.5% sensitivity and 98.5% specificity. Quantitative SRS microscopy detects the spread of tumor cells, even in brain tissue surrounding a tumor that appears grossly normal. By accurately revealing tumor infiltration, quantitative SRS microscopy holds potential for improving the accuracy of brain tumor surgery.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Minbiao
authors.initials: M
authors.lastname: Ji
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Spencer
authors.initials: S
authors.lastname: Lewis
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Camelo-Piragua
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Shakti H
authors.initials: SH
authors.lastname: Ramkissoon
authors.affiliation: Department of Pathology, New York University, New York, NY 10016, USA. Department of Neurology, New York University, New York, NY 10016, USA.
authors.forename: Matija
authors.initials: M
authors.lastname: Snuderl
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Sriram
authors.initials: S
authors.lastname: Venneti
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Fisher-Hubbard
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Mia
authors.initials: M
authors.lastname: Garrard
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Fu
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Heth
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Cormac O
authors.initials: CO
authors.lastname: Maher
authors.affiliation: Barrow Brain Tumor Research Center, Division of Neurosurgical Oncology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
authors.forename: Nader
authors.initials: N
authors.lastname: Sanai
authors.affiliation: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Johnson
authors.affiliation: Invenio Imaging Inc., Menlo Park, CA 94025, USA.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Freudiger
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Oren
authors.initials: O
authors.lastname: Sagher
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. dorringe@med.umich.edu xie@chemistry.harvard.edu.
authors.forename: Xiaoliang Sunney
authors.initials: XS
authors.lastname: Xie
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA. dorringe@med.umich.edu xie@chemistry.harvard.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Orringer
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery*; D005910:Glioma / Q000175:diagnosis / Q000473:pathology / Q000601:surgery; D006801:Humans; D008853:Microscopy / Q000379:methods*; D023421:Models, Animal; D059906:Neuroimaging / Q000379:methods*; D010524:Peripheral Nervous System Neoplasms / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D013059:Spectrum Analysis, Raman / Q000379:methods*