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

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.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 wi...

[1]  M. Mikhael,et al.  Supratentorial gliomas: surgical considerations and immediate postoperative results. Gross total resection versus partial resection. , 1987, Neurosurgery.

[2]  Mitchel S Berger,et al.  An extent of resection threshold for newly diagnosed glioblastomas. , 2011, Journal of neurosurgery.

[3]  Rita de Cássia Fernandes Borges,et al.  Detecting alterations of glucose and lipid components in human serum by near-infrared Raman spectroscopy , 2015 .

[4]  C. Kruchko,et al.  CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. , 2012, Neuro-oncology.

[5]  K. Rhee,et al.  Classical Raman spectroscopic studies of NADH and NAD+ bound to liver alcohol dehydrogenase by difference techniques. , 1987, Biochemistry.

[6]  Yan Zhou,et al.  Human brain cancer studied by resonance Raman spectroscopy , 2012, Journal of biomedical optics.

[7]  Laura A. Sordillo,et al.  Vulnerable atherosclerotic plaque detection by resonance Raman spectroscopy , 2016, Journal of biomedical optics.

[8]  Susan M. Chang,et al.  Relationship of MR-derived lactate, mobile lipids, and relative blood volume for gliomas in vivo. , 2005, AJNR. American journal of neuroradiology.

[9]  Oren Sagher,et al.  Extent of resection in patients with glioblastoma: limiting factors, perception of resectability, and effect on survival. , 2012, Journal of neurosurgery.

[10]  M. Mikhael,et al.  Effect of the extent of surgical resection on survival and quality of life in patients with supratentorial glioblastomas and anaplastic astrocytomas. , 1987, Neurosurgery.

[11]  Robert R. Alfano,et al.  Resonant Raman spectra of grades of human brain glioma tumors reveal the content of tryptophan by the 1588 cm-1 mode , 2015, Photonics West - Biomedical Optics.

[12]  A. Chakravarti,et al.  Lipid metabolism emerges as a promising target for malignant glioma therapy. , 2013, CNS oncology.

[13]  R. Alfano,et al.  Resonance Raman and Raman Spectroscopy for Breast Cancer Detection , 2013, Technology in cancer research & treatment.

[14]  Robert R. Alfano,et al.  Resonance Raman of BCC and normal skin , 2017, BiOS.

[15]  Susan M. Chang,et al.  Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Kevin Petrecca,et al.  Failure pattern following complete resection plus radiotherapy and temozolomide is at the resection margin in patients with glioblastoma , 2012, Journal of Neuro-Oncology.

[17]  Yang Pu,et al.  Optical spectroscopic characteristics of lactate and mitochondrion as new biomarkers in cancer diagnosis: understanding Warburg effect , 2012, Other Conferences.

[18]  K. Yue,et al.  A Raman study of the binding of Fe(III) to ATP and AMP. , 1992, The Biochemical journal.

[19]  Francis L Martin,et al.  Diagnostic segregation of human brain tumours using Fourier-transform infrared and/or Raman spectroscopy coupled with discriminant analysis. , 2013, Analytical methods : advancing methods and applications.

[20]  Michel Vert,et al.  Effects of morphology, conformation and configuration on the IR and Raman spectra of various poly(lactic acid)s , 1998 .

[21]  Joshua D. Rabinowitz,et al.  Glucose feeds the TCA cycle via circulating lactate , 2017, Nature.

[22]  Laura A. Sordillo,et al.  The Kynurenine Pathway: A Primary Resistance Mechanism in Patients with Glioblastoma. , 2017, Anticancer research.

[23]  A Leviton,et al.  Limitations of the World Health Organization classification of childhood supratentorial astrocytic tumors , 2000, Cancer.

[24]  V. L. Doyle,et al.  Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy , 2003, Magnetic resonance in medicine.

[25]  R. Alfano,et al.  Laser induced fluorescence spectroscopy from native cancerous and normal tissue , 1984 .

[26]  G. Maksimov,et al.  Study of the Peripheral Nerve Fibers Myelin Structure Changes during Activation of Schwann Cell Acetylcholine Receptors , 2016, PloS one.