127 Clinical translation of advanced MR spectroscopy as an imaging biomarker for IDH-mutations in lower-grade gliomas

Abstract Introduction Diffuse gliomas, the most common adult primary brain tumour, are classified by their histological, genetic, and molecular characteristics. Isocitrate dehydrogenase (IDH) mutations correlate with longer mean survival and progression-free survival time. IDH mutations lead to tumour metabolic changes and the production of oncometabolite 2-hydroxyglutarate (2HG). 2HG can be measured with MR spectroscopy (MRS) non-invasively and is one of the first specific imaging biomarkers. In this study, we validate advanced MRS methods as IDH-mutation imaging biomarkers and address the necessary steps to translate them into clinical standard of care. Methods MRS techniques were evaluated and validated using simulations, novel phantoms, and healthy volunteers. PRESS, sLASER, and MEGA-PRESS sequences were tested after being optimised for 2HG measurement (2.25 ppm peaks for PRESS and sLASER and a 4.02 ppm peak for MEGA-PRESS). Preliminary data from a clinical study is presented to validate the optimised sequences; 4 patients with suspected gliomas have participated thus far. Results Simulations of MRS sequences provided optimised acquisition parameters for the measurement of 2HG, while purpose-built tumour-mimicking phantom experiments determined sensitivity, specificity, and reproducibility of the different methods. Further synthetic MRS measurements using combinations of tumour simulations/phantoms determined the optimal noise and SNR ranges. In the early stages of the clinical study, MEGA-PRESS successfully predicted IDH mutation status in all 4 patients. Other important genetic markers were also successfully predicted in all four patients. Conclusions MEGA-PRESS proved to be the most robust MRS method and demonstrated accurate and precise measurement of phantom and synthetic 2HG with acceptable SNR. MEGA-PRESS, in a small study of glioma patients, accurately predicted their important genetic markers for tumour classification.