title: Rapid, label-free detection of brain tumors with stimulated Raman scattering microscopy.
abstract: Surgery is an essential component in the treatment of brain tumors. However, delineating tumor from normal brain remains a major challenge. We describe the use of stimulated Raman scattering (SRS) microscopy for differentiating healthy human and mouse brain tissue from tumor-infiltrated brain based on histoarchitectural and biochemical differences. Unlike traditional histopathology, SRS is a label-free technique that can be rapidly performed in situ. SRS microscopy was able to differentiate tumor from nonneoplastic tissue in an infiltrative human glioblastoma xenograft mouse model based on their different Raman spectra. We further demonstrated a correlation between SRS and hematoxylin and eosin microscopy for detection of glioma infiltration (κ = 0.98). Finally, we applied SRS microscopy in vivo in mice during surgery to reveal tumor margins that were undetectable under standard operative conditions. By providing rapid intraoperative assessment of brain tissue, SRS microscopy may ultimately improve the safety and accuracy of surgeries where tumor boundaries are visually indistinct.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Minbiao
authors.initials: M
authors.lastname: Ji
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Orringer
authors.forename: Christian W
authors.initials: CW
authors.lastname: Freudiger
authors.forename: Shakti
authors.initials: S
authors.lastname: Ramkissoon
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.forename: Darryl
authors.initials: D
authors.lastname: Lau
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Golby
authors.forename: Isaiah
authors.initials: I
authors.lastname: Norton
authors.forename: Marika
authors.initials: M
authors.lastname: Hayashi
authors.forename: Nathalie Y R
authors.initials: NY
authors.lastname: Agar
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Young
authors.forename: Cathie
authors.initials: C
authors.lastname: Spino
authors.forename: Sandro
authors.initials: S
authors.lastname: Santagata
authors.forename: Sandra
authors.initials: S
authors.lastname: Camelo-Piragua
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.forename: Oren
authors.initials: O
authors.lastname: Sagher
authors.forename: X Sunney
authors.initials: XS
authors.lastname: Xie
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D003116:Color; D004801:Eosine Yellowish-(YS) / Q000737:chemistry; D005909:Glioblastoma / Q000175:diagnosis* / Q000473:pathology; D005910:Glioma; D006416:Hematoxylin / Q000737:chemistry; D006801:Humans; D051379:Mice; D008853:Microscopy / Q000379:methods*; D009368:Neoplasm Transplantation; D015588:Observer Variation; D015203:Reproducibility of Results; D013059:Spectrum Analysis, Raman / Q000379:methods*
chemical_list: D004801:Eosine Yellowish-(YS); D006416:Hematoxylin