Raman spectroscopy for glioblastoma

Recently, newer techniques have emerged and are being translated into the operating room, promising delineation of glioblastoma tissue using targeted approaches or identification on a microscopic level, for instance using Raman spectroscopy or confocal microscopy 1).


Detailed analysis of breast ductal carcinoma in situ, and astrocytoma brain tissues as well as cells of glioblastoma U87 MG showed that Raman scattering generates images as accurately as histology hematoxylin and eosin stain used in clinical practice with additional advantage of biochemical information. Combination of AFM maps and Raman images allows to correlate mechanical properties with biochemical composition of cells 2).

3: Wei M, Shi L, Shen Y, Zhao Z, Guzman A, Kaufman LJ, Wei L, Min W. Volumetric chemical imaging by clearing-enhanced stimulated Raman scattering microscopy. Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):6608-6617. doi: 10.1073/pnas.1813044116. Epub 2019 Mar 14. PubMed PMID: 30872474; PubMed Central PMCID: PMC6452712.

4: Szczepaniak J, Strojny B, Chwalibog ES, Jaworski S, Jagiello J, Winkowska M, Szmidt M, Wierzbicki M, Sosnowska M, Balaban J, Winnicka A, Lipinska L, Pilaszewicz OW, Grodzik M. Effects of Reduced Graphene Oxides on Apoptosis and Cell Cycle of Glioblastoma Multiforme. Int J Mol Sci. 2018 Dec 7;19(12). pii: E3939. doi: 10.3390/ijms19123939. PubMed PMID: 30544611; PubMed Central PMCID: PMC6320889.

5: Uskoković V, Graziani V, Wu VM, Fadeeva IV, Fomin AS, Presniakov IA, Fosca M, Ortenzi M, Caminiti R, Rau JV. Gold is for the mistress, silver for the maid: Enhanced mechanical properties, osteoinduction and antibacterial activity due to iron doping of tricalcium phosphate bone cements. Mater Sci Eng C Mater Biol Appl. 2019 Jan 1;94:798-810. doi: 10.1016/j.msec.2018.10.028. Epub 2018 Oct 5. PubMed PMID: 30423766; PubMed Central PMCID: PMC6366449.

6: Kumar S, Visvanathan A, Arivazhagan A, Santhosh V, Somasundaram K, Umapathy S. Assessment of Radiation Resistance and Therapeutic Targeting of Cancer Stem Cells: A Raman Spectroscopic Study of Glioblastoma. Anal Chem. 2018 Oct 16;90(20):12067-12074. doi: 10.1021/acs.analchem.8b02879. Epub 2018 Sep 28. PubMed PMID: 30216048.

7: Bae K, Zheng W, Lin K, Lim SW, Chong YK, Tang C, King NK, Ti Ang CB, Huang Z. Epi-Detected Hyperspectral Stimulated Raman Scattering Microscopy for Label-Free Molecular Subtyping of Glioblastomas. Anal Chem. 2018 Sep 4;90(17):10249-10255. doi: 10.1021/acs.analchem.8b01677. Epub 2018 Aug 17. PubMed PMID: 30070837.

8: Huang LC, Chang YC, Wu YS, Sun WL, Liu CC, Sze CI, Chen SY. Glioblastoma cells labeled by robust Raman tags for enhancing imaging contrast. Biomed Opt Express. 2018 Apr 9;9(5):2142-2153. doi: 10.1364/BOE.9.002142. eCollection 2018 May 1. PubMed PMID: 29760976; PubMed Central PMCID: PMC5946777.

9: Neuschmelting V, Harmsen S, Beziere N, Lockau H, Hsu HT, Huang R, Razansky D, Ntziachristos V, Kircher MF. Dual-Modality Surface-Enhanced Resonance Raman Scattering and Multispectral Optoacoustic Tomography Nanoparticle Approach for Brain Tumor Delineation. Small. 2018 Jun;14(23):e1800740. doi: 10.1002/smll.201800740. Epub 2018 May 4. PubMed PMID: 29726109; PubMed Central PMCID: PMC6541212.

10: Vasimalai N, Vilas-Boas V, Gallo J, Cerqueira MF, Menéndez-Miranda M, Costa-Fernández JM, Diéguez L, Espiña B, Fernández-Argüelles MT. Green synthesis of fluorescent carbon dots from spices for in vitro imaging and tumour cell growth inhibition. Beilstein J Nanotechnol. 2018 Feb 13;9:530-544. doi: 10.3762/bjnano.9.51. eCollection 2018. PubMed PMID: 29527430; PubMed Central PMCID: PMC5827765.

11: Kumar Yadav S, Kumar Srivastava A, Dev A, Kaundal B, Roy Choudhury S, Karmakar S. Nanomelatonin triggers superior anticancer functionality in a human malignant glioblastoma cell line. Nanotechnology. 2017 Aug 18;28(36):365102. doi: 10.1088/1361-6528/aa7c76. [Epub ahead of print] PubMed PMID: 28820142.

12: Gao X, Yue Q, Liu Z, Ke M, Zhou X, Li S, Zhang J, Zhang R, Chen L, Mao Y, Li C. Guiding Brain-Tumor Surgery via Blood-Brain-Barrier-Permeable Gold Nanoprobes with Acid-Triggered MRI/SERRS Signals. Adv Mater. 2017 Jun;29(21). doi: 10.1002/adma.201603917. Epub 2017 Mar 15. PubMed PMID: 28295679.

13: Bhamidipati M, Fabris L. Multiparametric Assessment of Gold Nanoparticle Cytotoxicity in Cancerous and Healthy Cells: The Role of Size, Shape, and Surface Chemistry. Bioconjug Chem. 2017 Feb 15;28(2):449-460. doi: 10.1021/acs.bioconjchem.6b00605. Epub 2017 Jan 6. PubMed PMID: 27992181.

14: Keisham B, Cole A, Nguyen P, Mehta A, Berry V. Cancer Cell Hyperactivity and Membrane Dipolarity Monitoring via Raman Mapping of Interfaced Graphene: Toward Non-Invasive Cancer Diagnostics. ACS Appl Mater Interfaces. 2016 Dec 7;8(48):32717-32722. Epub 2016 Nov 22. PubMed PMID: 27934135.

15: Galli R, Uckermann O, Temme A, Leipnitz E, Meinhardt M, Koch E, Schackert G, Steiner G, Kirsch M. Assessing the efficacy of coherent anti-Stokes Raman scattering microscopy for the detection of infiltrating glioblastoma in fresh brain samples. J Biophotonics. 2017 Mar;10(3):404-414. doi: 10.1002/jbio.201500323. Epub 2016 Mar 11. PubMed PMID: 27854107.

16: Stables R, Clemens G, Butler HJ, Ashton KM, Brodbelt A, Dawson TP, Fullwood LM, Jenkinson MD, Baker MJ. Feature driven classification of Raman spectra for real-time spectral brain tumour diagnosis using sound. Analyst. 2016 Dec 19;142(1):98-109. PubMed PMID: 27757448.

17: Huang R, Harmsen S, Samii JM, Karabeber H, Pitter KL, Holland EC, Kircher MF. High Precision Imaging of Microscopic Spread of Glioblastoma with a Targeted Ultrasensitive SERRS Molecular Imaging Probe. Theranostics. 2016 May 7;6(8):1075-84. doi: 10.7150/thno.13842. eCollection 2016. PubMed PMID: 27279902; PubMed Central PMCID: PMC4893636.

18: Kaur E, Sahu A, Hole AR, Rajendra J, Chaubal R, Gardi N, Dutt A, Moiyadi A, Krishna CM, Dutt S. Unique spectral markers discern recurrent Glioblastoma cells from heterogeneous parent population. Sci Rep. 2016 May 25;6:26538. doi: 10.1038/srep26538. PubMed PMID: 27221528; PubMed Central PMCID: PMC4879554.

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20: Kast R, Auner G, Yurgelevic S, Broadbent B, Raghunathan A, Poisson LM, Mikkelsen T, Rosenblum ML, Kalkanis SN. Identification of regions of normal grey matter and white matter from pathologic glioblastoma and necrosis in frozen sections using Raman imaging. J Neurooncol. 2015 Nov;125(2):287-95. doi: 10.1007/s11060-015-1929-4. Epub 2015 Sep 10. PubMed PMID: 26359131.

21: Banerjee HN, Banerji A, Banerjee AN, Riddick E, Petis J, Evans S, Patel M, Parson C, Smith V, Gwebu E, Voisin S. Deciphering the Finger Prints of Brain Cancer Glioblastoma Multiforme from Four Different Patients by Using Near Infrared Raman Spectroscopy. J Cancer Sci Ther. 2015 Feb 3;7(2):44-47. PubMed PMID: 25937869; PubMed Central PMCID: PMC4415986.

22: Galli R, Uckermann O, Andresen EF, Geiger KD, Koch E, Schackert G, Steiner G, Kirsch M. Intrinsic indicator of photodamage during label-free multiphoton microscopy of cells and tissues. PLoS One. 2014 Oct 24;9(10):e110295. doi: 10.1371/journal.pone.0110295. eCollection 2014. PubMed PMID: 25343251; PubMed Central PMCID: PMC4208781.

23: Uckermann O, Galli R, Tamosaityte S, Leipnitz E, Geiger KD, Schackert G, Koch E, Steiner G, Kirsch M. Label-free delineation of brain tumors by coherent anti-Stokes Raman scattering microscopy in an orthotopic mouse model and human glioblastoma. PLoS One. 2014 Sep 8;9(9):e107115. doi: 10.1371/journal.pone.0107115. eCollection 2014. PubMed PMID: 25198698; PubMed Central PMCID: PMC4159970.

24: Karabeber H, Huang R, Iacono P, Samii JM, Pitter K, Holland EC, Kircher MF. Guiding brain tumor resection using surface-enhanced Raman scattering nanoparticles and a hand-held Raman scanner. ACS Nano. 2014 Oct 28;8(10):9755-66. doi: 10.1021/nn503948b. Epub 2014 Aug 22. PubMed PMID: 25093240; PubMed Central PMCID: PMC4212801.

25: Kast RE, Auner GW, Rosenblum ML, Mikkelsen T, Yurgelevic SM, Raghunathan A, Poisson LM, Kalkanis SN. Raman molecular imaging of brain frozen tissue sections. J Neurooncol. 2014 Oct;120(1):55-62. doi: 10.1007/s11060-014-1536-9. Epub 2014 Jul 20. PubMed PMID: 25038847.

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Vital and necrotic glioblastoma tissues were studied by Raman microspectroscopy to identify possibilities for the development of an in vivo Raman method for real-time intraoperative brain biopsy guidance. The histologic malignancy grade of gliomas depends on the presence of parameters such as endothelial proliferation and necrosis, which are often not evenly distributed within the tumor. Because tissue samples obtained by stereotactic surgery are relatively small, sampling errors may easily occur by missing these crucial features. Although necrosis is important for grading, specimens containing only necrosis are diagnostically useless. Raman microspectroscopic mapping experiments were performed on unfixed cryosections of glioblastoma, obtained from 20 patients. After spectral acquisition, a clustering analysis was performed, resulting in groups of similar spectra. Each cluster was assigned a color, and pseudo-color Raman maps of the tissue sections were constructed. After the Raman experiments, the tissue sections were stained for histopathologic analysis, enabling identification of the histologic origin of the Raman spectra and assignment of the Raman spectral clusters to either vital or necrotic tissue. A classification model for discrimination between vital and necrotic tumor tissue based on linear discriminant analysis was developed. The classification model was evaluated using independent Raman data obtained from nine other tissue sections and yielded 100% accuracy. Information about the biochemical differences between necrosis and vital tumor was obtained by the analysis of difference spectra. Necrotic tissue was found to consistently contain higher levels of cholesterol (-esters). This in vitro result indicates that Raman spectra contain the information to distinguish vital glioblastoma from necrosis and makes Raman spectroscopy a powerful candidate for guidance of stereotactic brain biopsy. 3)


1)
Schipmann S, Schwake M, Molina ES, Stummer W. Markers for Identifying and Targeting Glioblastoma Cells during Surgery. J Neurol Surg A Cent Eur Neurosurg. 2019 Aug 29. doi: 10.1055/s-0039-1692976. [Epub ahead of print] PubMed PMID: 31466109.
2)
Abramczyk H, Imiela A, Brozek-Pluska B, Kopec M. Advances in Raman imaging combined with AFM and fluorescence microscopy are beneficial for oncology and cancer research. Nanomedicine (Lond). 2019 Jul;14(14):1873-1888. doi: 10.2217/nnm-2018-0335. Epub 2019 Jul 15. PubMed PMID: 31305216.
3)
Koljenović S, Choo-Smith LP, Bakker Schut TC, Kros JM, van den Berge HJ, Puppels GJ. Discriminating vital tumor from necrotic tissue in human glioblastoma tissue samples by Raman spectroscopy. Lab Invest. 2002 Oct;82(10):1265-77. PubMed PMID: 12379761.
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