Interrogation of IDH1 Status in Gliomas by Fourier Transform Infrared Spectroscopy

Area of Science:

• Biomedical Engineering
• Molecular Spectroscopy
• Oncology

Background:

• Isocitrate dehydrogenase 1 (IDH1) mutations are key biomarkers in diffuse gliomas, impacting diagnosis, prognosis, and treatment.
• Vibrational spectroscopy, particularly Fourier transform infrared (FTIR) spectroscopy, offers label-free analytical capabilities for cancer detection.
• Intraoperative molecular classification of IDH1 status can guide surgical strategies for glioma patients.

Purpose of the Study:

• To evaluate the efficacy of synchrotron-based FTIR microanalysis for distinguishing IDH1-mutated from IDH1-wildtype gliomas.
• To assess the potential of attenuated total reflection (ATR)-FTIR spectroscopy for detecting IDH1 mutation-associated changes in blood serum.
• To explore the application of FTIR spectroscopy for rapid, label-free molecular subtyping of gliomas.

Main Methods:

• Synchrotron-based FTIR microanalysis was performed on tissue microarray sections from 79 glioma patients.
• ATR-FTIR spectroscopy was used to analyze blood serum samples from 72 brain tumour patients, with and without centrifugal filtration.
• Classification models were developed to differentiate between IDH1-mutated and IDH1-wildtype gliomas based on spectral data.

Main Results:

• Synchrotron FTIR microanalysis achieved 82.4% sensitivity and 83.4% specificity in distinguishing IDH1-mutated from IDH1-wildtype gliomas.
• ATR-FTIR spectroscopy, enhanced by centrifugal filtration, achieved balanced accuracies up to approximately 69% in blood serum classification.
• FTIR spectroscopy demonstrated the ability to detect molecular, epigenetic, and metabolic changes associated with IDH1 mutations.

Conclusions:

• FTIR microspectroscopy is a viable tool for rapid, label-free intraoperative assessment of IDH1 mutation status in gliomas.
• Blood serum analysis using ATR-FTIR spectroscopy shows potential for non-invasive pre-biopsy determination of IDH1 molecular status.
• FTIR spectroscopy can contribute to improved diagnostics and personalized treatment strategies for glioma patients.