The STEMRI trial: magnetic resonance spectroscopy imaging can define tumor areas enriched in glioblastoma-stem-like cells

Despite maximally-safe resection of the MRI-defined contrast-enhanced (CE) central tumor area and chemo-radiotherapy, most glioblastoma patients relapse within one year in peritumor FLAIR regions. Spectroscopic MRI (MRSI) can discriminate metabolic tumor areas with higher recurrence potential as CNI+ regions (Choline/N-acetyl-aspartate Index>2) can predict relapse sites. As relapses are mainly imputed to glioblastoma stem-like cells (GSC), CNI+ areas might be GSC-enriched. We conducted a prospective trial in 16 GBM patients subjected to preoperative MRSI/MRI and surgery/chemo-radiotherapy to investigate GSC content in CNI+ versus CNI- biopsies from CE/FLAIR. Biopsy characterization by RNAseq revealed that FLAIR/CNI+ areas were enriched in stem-related gene signature, but also in pathways related to DNA repair, adhesion/migration and mitochondrial bioenergetics. 51 biopsy samples obtained from 16 patients in 4 different tumor regions defined by MRI/MRSI ((1) FLAIR/CNI-; (2) FLAIR/CNI+; (3) CE/CNI-; (4)CE/CNI+). No technical replicates and no reference samples