gms | German Medical Science

Objective: Mutations in the isocytrate dehydrogenase 1 (IDH1) gene are early events in glioma pathogenesis and cause profound metabolic changes. Because this genotype is found in virtually every tumor cell, therapies targeting mutant IDH1 protein are being developed. As neurosurgery provides direct access to brain tumors, methods for intraoperative determination of IDH1 genotype are needed and would allow direct administration of innovative therapies. We recently showed that optical Fourier-transform infrared (FT-IR) spectroscopy allows the assessment of IDH1 in in vitro systems and cryosections of brain tumors. Here, we evaluated if the technology can be likewise applied for the analysis of fresh samples of human glioma.

Methods: Infrared spectra were obtained from fresh, unprocessed biopsies of 64 glioma patients using a small, portable infrared spectrometer (Alpha-P ATR, Bruker Optic GmbH). The measurements were performed within minutes after tissue removal (median 6.5 min; range 1 to 20 min).

Results: IDH1 mutation was linked to changes in spectral bands assigned to molecular groups of lipids and proteins. The spectra of brain tumor samples showed high inter-patient variability; however, supervised classification recognized relevant spectral regions at 1103, 1362, 1406, 1446, 1457, 1558 cm-1 and assigned 86% of tumors to the correct group.

Conclusion: Here, we show that vibrational spectroscopy reveals the IDH1 genotype of fresh glioma biopsies. Because it can provide information in seconds and no tissue processing is needed, an implementation into the intraoperative workflow might allow online diagnosis of the IDH1 genotype. The intraoperative confirmation of the IDH1 mutation status might guide the decision to pursue definitive neurosurgical resection and allow the application of future in situ therapies.