Invited Article: Molecular biomarkers characterization for human brain glioma grading using visible resonance Raman spectroscopy

Abstract

The accurate identification of the human brain tumor boundary and the complete resection of the tumor are two essential factors for the removal of the glioma tumor in brain surgery. We present a visible resonance Raman (VRR) spectroscopy technique for differentiating the brain tumor margin and glioma grading. Eighty-seven VRR spectra from twenty-one human brain specimens of four types of brain tissues, including the control, glioma grade II, III, and IV tissues, were observed. This study focuses on observing the characteristics of new biomarkers and their changes in the four types of brain tissue. We found that two new RR peaks at 1129 cm−1 and 1338 cm−1 associated with molecular vibrational bonds in four types of brain tissues are significantly different in peak intensities of VRR spectra. These two resonance enhanced peaks may arise from lactic acid/phosphatidic acid and adenosine triphosphate (ATP)/nicotinamide adenine dinucleotide, respectively. We found that lactic acid and ATP concentrations vary with glioma gratings. The higher the grade of malignancy, the more the increase in lactic acid and ATP concentrations. These two RR peaks may be considered as new molecular biomarkers and used to evaluate glioma grades and identify the margin of gliomas from the control tissues. The metabolic process of lactic acid and ATP in glioma cells based on the VRR spectral changes may reveal the Warburg hypothesis.

Optical biopsy identification and grading of gliomas using label-free visible resonance Raman spectroscopy

“…In addition to tryptophan, we consider that the Raman mode of 1588 cm −1 may be contributed by mitochondria, hemeproteins, and DNA bases (Supplemental Table S1). [71][72][73] Based on our previous experimental data using VRR method and autofluorescence method (to be published) on human glioma tumors 23,26,42,43,74 and the experimental and theoretical studies reported in the literature, 47,[67][68][69][70]75 we propose tryptophan as the main contributor to the Raman mode of 1588 cm −1 . One possible form of the tryptophan contribution to 1588 cm −1 mode may be tryptophan radicals because of the microenvironment in the malignant tumor tissues.…”

“…41 It is also a new progress in molecular histopathological diagnosis and grade classification of human brain glioma tissues. 34,42 The VRR technique has been used to study human brain, breast, GYN, GI, and skin and has been used to detect vulnerable atherosclerotic plaques and to study atherosclerotic abdominal aortic tissues, cerebrospinal fluids, and breast cells since 2011. 23,26,34,42,43 The objective of this study is to use VRR as a new Raman technique to evaluate the biomarkers for glioma margins and the correlation between the levels of biomarkers and tumor grades.…”

Combined spatial frequency spectroscopy analysis with visible resonance Raman for optical biopsy of human brain metastases of lung cancers

“…VRR provides an e®ective way to enhance Raman signal from particular chemical bonds associated with key molecules and detect their changes at a molecular level, such as carotenoids, tryptophan, amides, lipids and protein in breast, skin, heart, gynecologic and brain lesions. 14,15,17 These advantages of VRR have led to a rapid progress in its applications in brain and other human cancer diagnosis 14,[17][18][19][20][21] that are di±cult to achieve by conventional nonresonance Raman method. [22][23][24][25][26][27] Recently, another new optical spatial frequency spectroscopy analysis (SFSA) method was introduced based on Fourier spatial frequency spectrum analysis of the underlying structure pattern of tissues.…”

Mammalian cell and tissue imaging using Raman and coherent Raman microscopy

“…Analysis of the fingerprint and high‐wavenumber regions (FP/HW) in the GA‐PLS‐LDA algorithm had an accuracy, sensitivity, and specificity of 96.76, 87.78, and 100%, respectively—higher than the analogous blood test which may be attributable to the simultaneous unique advantages of both FP and HW Raman tissue spectra (Žuvela et al, 2019). Recent work successfully used resonance Raman techniques (RRS) for brain tumor biopsies (Zhou et al, 2018, 2019), skin cancer detections (Liu et al, 2019), and breast cancer subtype separation (Bendau et al, 2020). Using spontaneous RS to scan colon cells from patients, a k‐means clustered image‐trained support vector machine was able to diagnose the samples as having Ulcerative Colitis, Crohn's disease, or no irritable bowel disease (IBD).…”