Assessment of Tumor Cells in a Mouse Model of Diffuse Infiltrative Glioma by Raman Spectroscopy

Glioma of infiltrative nature is challenging for surgeons to achieve tumor-specific and maximal resection. Raman spectroscopy provides structural information on the targeted materials as vibrational shifts. We utilized Raman spectroscopy to distinguish invasive tumors from normal tissues. Spectra obtained from replication-competent avian sarcoma-(RCAS-) based infiltrative glioma cells and glioma tissues (resembling low-grade human glioma) were compared with those obtained from normal mouse astrocytes and normal tissues. In cell analysis, the spectra at 950–1000, 1030, 1050–1100, 1120–1130, 1120–1200, 1200–1300, 1300–1350, and 1450 cm−1 were significantly higher in infiltrative glioma cells than in normal astrocytes. In brain tissue analysis, the spectra at 1030, 1050–1100, and 1200–1300 cm−1 were significantly higher in infiltrative glioma tissues than in normal brain tissues. These spectra reflect the structures of proteins, lipids, and DNA content. The sensitivity and specificity to predict glioma cells by distinguishing normal cells were 98.3% and 75.0%, respectively. Principal component analysis elucidated the significance of spectral difference between tumor tissues and normal tissues. It is possible to distinguish invasive tumors from normal tissues by using Raman spectroscopy.

[1]  Sanjiv S Gambhir,et al.  Raman's “Effect” on Molecular Imaging , 2011, The Journal of Nuclear Medicine.

[2]  Matthias Kirsch,et al.  Raman spectroscopic grading of astrocytoma tissues: using soft reference information , 2011, Analytical and bioanalytical chemistry.

[3]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[4]  X. Xie,et al.  Rapid, Label-Free Detection of Brain Tumors with Stimulated Raman Scattering Microscopy , 2013, Science Translational Medicine.

[5]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[6]  R. Barnard,et al.  The classification of tumours of the central nervous system. , 1982, Neuropathology and applied neurobiology.

[7]  C. Brennan,et al.  A Brain Tumor Molecular Imaging Strategy Using A New Triple-Modality MRI-Photoacoustic-Raman Nanoparticle , 2011, Nature Medicine.

[8]  Ji-Xin Cheng,et al.  Ex vivo and in vivo imaging of myelin fibers in mouse brain by coherent anti-Stokes Raman scattering microscopy. , 2008, Optics express.

[9]  D. Silbergeld,et al.  Isolation and characterization of human malignant glioma cells from histologically normal brain. , 1997, Journal of neurosurgery.

[10]  Abdelilah Beljebbar,et al.  Raman spectral imaging of single living cancer cells: a preliminary study. , 2009, The Analyst.

[11]  F. Martin,et al.  Discrimination of zone-specific spectral signatures in normal human prostate using Raman spectroscopy. , 2010, The Analyst.

[12]  C. Krishna,et al.  Discrimination of normal, benign, and malignant breast tissues by Raman spectroscopy. , 2006, Biopolymers.

[13]  B. Scheithauer,et al.  The 2007 WHO classification of tumours of the central nervous system , 2007, Acta Neuropathologica.

[14]  Oliver A. C. Stevens,et al.  Endoscopic Raman spectroscopy enables objective diagnosis of dysplasia in Barrett's esophagus. , 2014, Gastrointestinal endoscopy.

[15]  S. Lam,et al.  Near‐infrared Raman spectroscopy for optical diagnosis of lung cancer , 2003, International journal of cancer.

[16]  G. Maira,et al.  Assessment of angiogenesis by CD105 and nestin expression in peritumor tissue of glioblastoma. , 2010, International journal of oncology.

[17]  E. Holland,et al.  Mouse models of CNS embryonal tumors , 2009, Brain Tumor Pathology.

[18]  R. Dasari,et al.  Prospects for in vivo Raman spectroscopy , 2000 .

[19]  Carmelo Anile,et al.  Gene Expression Profile of Glioblastoma Peritumoral Tissue: An Ex Vivo Study , 2013, PloS one.

[20]  C. Kendall,et al.  Vibrational spectroscopy: a clinical tool for cancer diagnostics. , 2009, The Analyst.

[21]  Christoph Krafft,et al.  Characterization of lipid extracts from brain tissue and tumors using Raman spectroscopy and mass spectrometry , 2009, Analytical and bioanalytical chemistry.

[22]  D. Silberberg,et al.  MHC antigen expression on bulk isolated macrophage-microglia from newborn mouse brain: induction of Ia antigen expression by γ-interferon , 1987, Journal of Neuroimmunology.

[23]  M. Rosenblum,et al.  Dose-Dependent Effects of Platelet-Derived Growth Factor-B on Glial Tumorigenesis , 2004, Cancer Research.

[24]  Jürgen Popp,et al.  Raman spectroscopy--a prospective tool in the life sciences. , 2003, Chemphyschem : a European journal of chemical physics and physical chemistry.

[25]  Mads S. Bergholt,et al.  In vivo diagnosis of gastric cancer using Raman endoscopy and ant colony optimization techniques , 2011, International journal of cancer.

[26]  W. Marsden I and J , 2012 .

[27]  M. Manfait,et al.  Ex vivo and in vivo diagnosis of C6 glioblastoma development by Raman spectroscopy coupled to a microprobe , 2010, Analytical and bioanalytical chemistry.

[28]  Gregory W. Auner,et al.  Identification of Pediatric Brain Neoplasms Using Raman Spectroscopy , 2012, Pediatric Neurosurgery.

[29]  Abhilash Pandya,et al.  Raman spectroscopy detects and distinguishes neuroblastoma and related tissues in fresh and (banked) frozen specimens. , 2009, Journal of pediatric surgery.

[30]  J. Choo,et al.  Highly sensitive immunoassay of lung cancer marker carcinoembryonic antigen using surface-enhanced Raman scattering of hollow gold nanospheres. , 2009, Analytical chemistry.

[31]  R. Mirimanoff,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[32]  M. Goodman,et al.  Near-Infrared Micro-Raman Spectroscopy for in Vitro Detection of Cervical Cancer , 2010, Applied spectroscopy.

[33]  G. Maira,et al.  Stem Cell Marker Nestin and c-Jun NH2-Terminal Kinases in Tumor and Peritumor Areas of Glioblastoma Multiforme: Possible Prognostic Implications , 2007, Clinical Cancer Research.

[34]  A. Koloydenko,et al.  Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy , 2013, Proceedings of the National Academy of Sciences.

[35]  Q. Tu,et al.  Diagnostic applications of Raman spectroscopy. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[36]  R. Dasari,et al.  Diagnosing breast cancer by using Raman spectroscopy. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Marc D Porter,et al.  Detection of the potential pancreatic cancer marker MUC4 in serum using surface-enhanced Raman scattering. , 2011, Analytical chemistry.

[38]  G. Maira,et al.  Activated ERK1/2 expression in glioblastoma multiforme and in peritumor tissue. , 2007, International journal of oncology.