title: Label-free delineation of brain tumors by coherent anti-Stokes Raman scattering microscopy in an orthotopic mouse model and human glioblastoma.
abstract: BACKGROUND
  Coherent anti-Stokes Raman scattering (CARS) microscopy provides fine resolution imaging and displays morphochemical properties of unstained tissue. Here, we evaluated this technique to delineate and identify brain tumors.
  
  
  METHODS
  Different human tumors (glioblastoma, brain metastases of melanoma and breast cancer) were induced in an orthotopic mouse model. Cryosections were investigated by CARS imaging tuned to probe C-H molecular vibrations, thereby addressing the lipid content of the sample. Raman microspectroscopy was used as reference. Histopathology provided information about the tumor's localization, cell proliferation and vascularization.
  
  
  RESULTS
  The morphochemical contrast of CARS images enabled identifying brain tumors irrespective of the tumor type and properties: All tumors were characterized by a lower CARS signal intensity than the normal parenchyma. On this basis, tumor borders and infiltrations could be identified with cellular resolution. Quantitative analysis revealed that the tumor-related reduction of CARS signal intensity was more pronounced in glioblastoma than in metastases. Raman spectroscopy enabled relating the CARS intensity variation to the decline of total lipid content in the tumors. The analysis of the immunohistochemical stainings revealed no correlation between tumor-induced cytological changes and the extent of CARS signal intensity reductions. The results were confirmed on samples of human glioblastoma.
  
  
  CONCLUSIONS
  CARS imaging enables label-free, rapid and objective identification of primary and secondary brain tumors. Therefore, it is a potential tool for diagnostic neuropathology as well as for intraoperative tumor delineation.
authors.affiliation: Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Ortrud
authors.initials: O
authors.lastname: Uckermann
authors.affiliation: Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Roberta
authors.initials: R
authors.lastname: Galli
authors.affiliation: Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Tamosaityte
authors.affiliation: Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Leipnitz
authors.affiliation: Neuropathology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Kathrin D
authors.initials: KD
authors.lastname: Geiger
authors.affiliation: Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schackert
authors.affiliation: Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Edmund
authors.initials: E
authors.lastname: Koch
authors.affiliation: Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Steiner
authors.affiliation: Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kirsch
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D012815:Signal Processing, Computer-Assisted; D013059:Spectrum Analysis, Raman / Q000379:methods*