2-Hydroxyglutarate magnetic resonance spectroscopy for preoperative IDH molecular profiling – A review of the literature and real-world clinical translation in a busy neurosurgical neuro-oncology unit

Abstract

2-hydroxyglutarate (2HG), a metabolic by-product that accumulates in IDH-mutated (IDHmut) glioma cells, can be quantified through magnetic resonance spectroscopy (MRS) offering a non-invasive method to determine molecular subtype. Incorporation of 2HG MRS into standard pre-operative MR protocol offers an adjunct to surgical decision making but limitations in post-processing and barriers exist to its integration into routine clinical practice. Our study explored the real-world translation of 2HG MRS into a busy neuro-oncology surgical unit at the Royal North Shore Hospital campus.

69 Spectra were acquired and reported prospectively between March 2018 and March 2024 in patients with suspected glioma using a 3 T Siemens Vida MRI, in addition to standard clinical magnetic resonance imaging and assessment. SV PRESS MRS was acquired with optimised parameters and the spectroscopic waveform analysed externally by a single center. The MRS voxel was localised on 3D FLAIR sequencing. Immunohistochemistry and genomic analysis were available for 30 patients to validate 2HG outcomes against standard ex vivo methods.

Utilising 1.2 mM as threshold calculated sensitivity was 80.9 %, specificity 77.8 %. Positive predictive value was 89.5 % and negative predictive value was 63.6 %. Utilising 3 mM as threshold calculated specificity 100 % given the absence of false negatives but sensitivity was significantly reduced <10 %.

2HG/Cr ratio with a cutoff of 0.085 for positivity yielded sensitivity 94.7%, specificity 66.67% and accuracy 85.7%

Our experience re-demonstrates the potential of 2HG MRS in preoperative imaging in suspected IDHmut gliomas in a busy neuro-oncology unit but highlights the limitations of real-world clinical translation, technical complexities and difficulty in standardization.