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Sci Transl Med. 2015 Oct 14;7(309):309ra163. doi: 10.1126/scitranslmed.aab0195.

Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy.

Author information

1
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
2
Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.
3
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
4
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.
5
Department of Pathology, New York University, New York, NY 10016, USA. Department of Neurology, New York University, New York, NY 10016, USA.
6
Barrow Brain Tumor Research Center, Division of Neurosurgical Oncology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
7
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
8
Invenio Imaging Inc., Menlo Park, CA 94025, USA.
9
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. dorringe@med.umich.edu xie@chemistry.harvard.edu.
10
Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA. dorringe@med.umich.edu xie@chemistry.harvard.edu.

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.

PMID:
26468325
PMCID:
PMC4900155
DOI:
10.1126/scitranslmed.aab0195
[Indexed for MEDLINE]
Free PMC Article

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