Identification of primary tumors of brain metastases by Raman imaging and support vector machines

Abstract Vibrational spectroscopic imaging techniques are new tools for visualizing chemical components in tissue without staining. The spectroscopic signature can be used as a molecular fingerprint of pathological tissues. Fourier transform infrared imaging which is more common than Raman imaging so far has already been applied to identify the primary tumor of brain metastases. The current study introduces a two level discrimination model for Raman microspectroscopic images to distinguish normal brain, necrosis and tumor tissue, and subsequently to determine the primary tumor. 22 Specimens of normal brain tissue and brain metastasis of bladder carcinoma, lung carcinoma, mamma carcinoma, colon carcinoma, prostate carcinoma and renal cell carcinoma were snap frozen, and thin tissue sections were prepared. Raman microscopic images were collected with 785 nm laser excitation at 10 μm step size. Cluster analysis, vertex component analysis and principal component analysis were applied for data preprocessing. Then, data of 17 specimens were used to train the discrimination model based on support vector machines with radial basis functions kernel. The training data were discriminated with accuracy better than 99%. Finally, the discrimination model correctly predicted independent specimens. The results were superior to discrimination by partial least squares discriminant analysis and support vector machines with linear basis function kernel that were applied for comparison.

[1]  Chih-Jen Lin,et al.  LIBSVM: A library for support vector machines , 2011, TIST.

[2]  Christoph Krafft,et al.  Identification of primary tumors of brain metastases by SIMCA classification of IR spectroscopic images. , 2006, Biochimica et biophysica acta.

[3]  B. Dietzek,et al.  Raman and CARS microspectroscopy of cells and tissues. , 2009, The Analyst.

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

[5]  N. Pavlidis,et al.  Brain metastasis of unknown primary: a diagnostic and therapeutic dilemma. , 2005, Cancer treatment reviews.

[6]  Philip Heraud,et al.  In vivo prediction of the nutrient status of individual microalgal cells using Raman microspectroscopy. , 2007, FEMS microbiology letters.

[7]  Wei Zheng,et al.  Classification of colonic tissues using near-infrared Raman spectroscopy and support vector machines. , 2008, International journal of oncology.

[8]  Christoph Krafft,et al.  Methodology for fiber-optic Raman mapping and FTIR imaging of metastases in mouse brains , 2007, Analytical and bioanalytical chemistry.

[9]  Jürgen Popp,et al.  Identification and differentiation of single cells from peripheral blood by Raman spectroscopic imaging , 2010, Journal of biophotonics.

[10]  J. Popp,et al.  Towards detection and identification of circulating tumour cells using Raman spectroscopy. , 2010, The Analyst.

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

[12]  Frank Winkler,et al.  Therapy and prophylaxis of brain metastases , 2010, Expert review of anticancer therapy.

[13]  J Popp,et al.  Micro-Raman spectroscopic identification of bacterial cells of the genus Staphylococcus and dependence on their cultivation conditions. , 2005, The Analyst.

[14]  J Popp,et al.  Identification of single eukaryotic cells with micro-Raman spectroscopy. , 2006, Biopolymers.

[15]  Yin Zhang,et al.  Imaging with Raman spectroscopy. , 2010, Current pharmaceutical biotechnology.

[16]  J. Fleiss,et al.  Statistical methods for rates and proportions , 1973 .

[17]  Christoph Krafft,et al.  Disease recognition by infrared and Raman spectroscopy , 2009, Journal of biophotonics.

[18]  Benjamin Bird,et al.  Label-free imaging of human cells: algorithms for image reconstruction of Raman hyperspectral datasets. , 2010, The Analyst.

[19]  J. Mo,et al.  Baseline correction by improved iterative polynomial fitting with automatic threshold , 2006 .

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

[21]  Nicholas Stone,et al.  Investigation of support vector machines and Raman spectroscopy for lymph node diagnostics. , 2010, The Analyst.

[22]  Christoph Krafft,et al.  Suitability of infrared spectroscopic imaging as an intraoperative tool in cerebral glioma surgery , 2009, Analytical and bioanalytical chemistry.

[23]  Max Diem,et al.  Spectral unmixing and clustering algorithms for assessment of single cells by Raman microscopic imaging , 2011 .

[24]  B. Wood,et al.  Effects of pre‐processing of Raman spectra on in vivo classification of nutrient status of microalgal cells , 2006 .

[25]  P. Eilers A perfect smoother. , 2003, Analytical chemistry.

[26]  Christoph Krafft,et al.  Identification of Primary Tumors of Brain Metastases by Infrared Spectroscopic Imaging and Linear Discriminant Analysis , 2006, Technology in cancer research & treatment.

[27]  Jürgen Popp,et al.  Discriminating isogenic cancer cells and identifying altered unsaturated fatty acid content as associated with metastasis status, using k-means clustering and partial least squares-discriminant analysis of Raman maps. , 2010, Analytical chemistry.

[28]  Jürgen Popp,et al.  A comprehensive study of classification methods for medical diagnosis , 2009 .