Resonance Raman imaging for detecting and monitoring molecular pathological changes in human brain tumors related to Warburg effect

摘要

The goal of the research is to determine the prognostic molecular pathological changes in components and composition, for human brain glioma gradings in comparison with normal tissues using three-dimensional Raman imaging profiles by visible Resonance Raman (VRR) imaging. VRR images from twenty-five specimens including three healthy tissues, one normal control, and twenty-one glioma tissues of grades Ⅱ, Ⅱ-Ⅲ and Ⅲ-Ⅳ were measured and investigated using WITec300R confocal micro Raman imaging system with laser excitation of 532nm. Two-dimensional RR spectral mappings performed in 20μm × 20μm generated 400 images which integrated the intensity of the specific biochemical bonds as the third dimension. The three-dimension (3D) map demonstrated the spatial distributions of three selected sets of RR spectra of molecular biomarkers, and revealed significant differences in the spectra between normal and glioma tissues of different grades due to the composition changes in key molecules. These RR molecular spectral fingerprints have displayed: a clear enhancement of RR vibrational modes at 1129-113 1cm~(-1) and 2934cm~(-1) which are supposed to be arising from phosphatidic acid/lipoproteins; evident decreased RR vibrational modes at 1442cm~(-1) and 2854/2885cm~(-1) which are from saturated fatty acids bonds in all-grades of glioma brain tissues compared with normal tissues; and enhanced RR spectral modes of 1129 cm~(-1) and 2938cm~(-1) which suggest contribution from lactate. These findings may provide a novel proof for anaerobic glycolysis metabolic process in brain glioma cancer tissues that has been explained by Warburg effects.