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Rapid intraoperative molecular genetic classification of gliomas using Raman spectroscopy.
Neurooncol Adv 2019 May-Dec; 1(1):vdz008NA

Abstract

Background

The molecular genetic classification of gliomas, particularly the identification of isocitrate dehydrogenase (IDH) mutations, is critical for clinical and surgical decision-making. Raman spectroscopy probes the unique molecular vibrations of a sample to accurately characterize its molecular composition. No sample processing is required allowing for rapid analysis of tissue. The aim of this study was to evaluate the ability of Raman spectroscopy to rapidly identify the common molecular genetic subtypes of diffuse glioma in the neurosurgical setting using fresh biopsy tissue. In addition, classification models were built using cryosections, formalin-fixed paraffin-embedded (FFPE) sections and LN-18 (IDH-mutated and wild-type parental cell) glioma cell lines.

Methods

Fresh tissue, straight from neurosurgical theatres, underwent Raman analysis and classification into astrocytoma, IDH-wild-type; astrocytoma, IDH-mutant; or oligodendroglioma. The genetic subtype was confirmed on a parallel section using immunohistochemistry and targeted genetic sequencing.

Results

Fresh tissue samples from 62 patients were collected (36 astrocytoma, IDH-wild-type; 21 astrocytoma, IDH-mutated; 5 oligodendroglioma). A principal component analysis fed linear discriminant analysis classification model demonstrated 79%-94% sensitivity and 90%-100% specificity for predicting the 3 glioma genetic subtypes. For the prediction of IDH mutation alone, the model gave 91% sensitivity and 95% specificity. Seventy-nine cryosections, 120 FFPE samples, and LN18 cells were also successfully classified. Meantime for Raman data collection was 9.5 min in the fresh tissue samples, with the process from intraoperative biopsy to genetic classification taking under 15 min.

Conclusion

These data demonstrate that Raman spectroscopy can be used for the rapid, intraoperative, classification of gliomas into common genetic subtypes.

Authors+Show Affiliations

Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, UK.Renishaw plc., Spectroscopy Products Division, UK.Renishaw plc., Spectroscopy Products Division, UK.Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, UK.Department of Chemistry, University of Oxford, UK.Department of Chemistry, University of Oxford, UK.Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, UK.Department of Chemistry, University of Oxford, UK.Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31608327

Citation

Livermore, Laurent James, et al. "Rapid Intraoperative Molecular Genetic Classification of Gliomas Using Raman Spectroscopy." Neuro-oncology Advances, vol. 1, no. 1, 2019, pp. vdz008.
Livermore LJ, Isabelle M, Bell IM, et al. Rapid intraoperative molecular genetic classification of gliomas using Raman spectroscopy. Neurooncol Adv. 2019;1(1):vdz008.
Livermore, L. J., Isabelle, M., Bell, I. M., Scott, C., Walsby-Tickle, J., Gannon, J., ... Ansorge, O. (2019). Rapid intraoperative molecular genetic classification of gliomas using Raman spectroscopy. Neuro-oncology Advances, 1(1), pp. vdz008. doi:10.1093/noajnl/vdz008.
Livermore LJ, et al. Rapid Intraoperative Molecular Genetic Classification of Gliomas Using Raman Spectroscopy. Neurooncol Adv. 2019;1(1):vdz008. PubMed PMID: 31608327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid intraoperative molecular genetic classification of gliomas using Raman spectroscopy. AU - Livermore,Laurent James, AU - Isabelle,Martin, AU - Bell,Ian Mac, AU - Scott,Connor, AU - Walsby-Tickle,John, AU - Gannon,Joan, AU - Plaha,Puneet, AU - Vallance,Claire, AU - Ansorge,Olaf, Y1 - 2019/05/28/ PY - 2019/10/15/entrez PY - 2019/10/15/pubmed PY - 2019/10/15/medline KW - Raman spectroscopy KW - brain tumor KW - intraoperative KW - isocitrate hydrogenase KW - personalized medicine SP - vdz008 EP - vdz008 JF - Neuro-oncology advances JO - Neurooncol Adv VL - 1 IS - 1 N2 - Background: The molecular genetic classification of gliomas, particularly the identification of isocitrate dehydrogenase (IDH) mutations, is critical for clinical and surgical decision-making. Raman spectroscopy probes the unique molecular vibrations of a sample to accurately characterize its molecular composition. No sample processing is required allowing for rapid analysis of tissue. The aim of this study was to evaluate the ability of Raman spectroscopy to rapidly identify the common molecular genetic subtypes of diffuse glioma in the neurosurgical setting using fresh biopsy tissue. In addition, classification models were built using cryosections, formalin-fixed paraffin-embedded (FFPE) sections and LN-18 (IDH-mutated and wild-type parental cell) glioma cell lines. Methods: Fresh tissue, straight from neurosurgical theatres, underwent Raman analysis and classification into astrocytoma, IDH-wild-type; astrocytoma, IDH-mutant; or oligodendroglioma. The genetic subtype was confirmed on a parallel section using immunohistochemistry and targeted genetic sequencing. Results: Fresh tissue samples from 62 patients were collected (36 astrocytoma, IDH-wild-type; 21 astrocytoma, IDH-mutated; 5 oligodendroglioma). A principal component analysis fed linear discriminant analysis classification model demonstrated 79%-94% sensitivity and 90%-100% specificity for predicting the 3 glioma genetic subtypes. For the prediction of IDH mutation alone, the model gave 91% sensitivity and 95% specificity. Seventy-nine cryosections, 120 FFPE samples, and LN18 cells were also successfully classified. Meantime for Raman data collection was 9.5 min in the fresh tissue samples, with the process from intraoperative biopsy to genetic classification taking under 15 min. Conclusion: These data demonstrate that Raman spectroscopy can be used for the rapid, intraoperative, classification of gliomas into common genetic subtypes. SN - 2632-2498 UR - https://www.unboundmedicine.com/medline/citation/31608327/Rapid_intraoperative_molecular_genetic_classification_of_gliomas_using_Raman_spectroscopy L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31608327/ DB - PRIME DP - Unbound Medicine ER -