gms | German Medical Science

Objective: Molecular markers in glioma are essential for diagnosis, treatment and prognosis. Isocitrate-dehydrogenase 1/2 (IDH1/2) is one of the major diagnostic classifiers which plays a significant role in tumor metabolism. So far it is a postoperative immuno-histological or molecular diagnosis. Novel MRI-sequences like blood-oxygen-level-dependent (BOLD) and quantitive-imaging-of-extraction-of-oxygen-and-tissue (QUIXOTIC) seem to be useful to study tumor-metabolism and may have the potential as a preoperative tool to predict the mutational status of IDH in glioma. Here we present a method to distinguish between IDH wildtype and mutational status in glioma in native MRI and relate this to molecular-metabolic markers.

Methods: Fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted (DWI) images were used to locate the tumor and the solid tumor regions. The QUIXOTIC and qBOLD sequences were used for further metabolic imaging. ROIs were transferred to QUIXOTIC and qBOLD images after co-registering them with FLAIR and DWI. PCR was performed from tumor samples for HIF-1a, hexokinase 2 and carbonic anhydrase 9. Tumors were grouped for IDH mutation status. Data analysis were performed using MATLAB, SPSS and GraphPad Prism.

Results: 3TMR imaging was performed on 29 patients with preoperative suspicion of glioma. Final histological diagnosis consisted of glioblastoma (n=13), anaplastic astrocytoma (n=4), oligodendroglioma (n=7), anaplastic oligodendroglioma (n=3) and diffuse astrocytoma (n=2). 16 tumors contained IDH mutations whereas 13 were identified as wildtype. Hexokinase 2 was significantly elevated in IDH wildtype tumors (2.52±0.52 vs 15.63±5.18, p=0.0014). ADC mapping displayed significant differences between IDH mutated and wildtype tumors (p=0.047). Furthermore, significant differences could be detected in contralateral-cortex/tumor comparison for IDH mutated glioma in qBOLD-R2ex (p<0.001), GESSE R2* (p<0.001) and QUIXOTIC-T2prepR2 (p<0.001), which was not found in IDH wildtype glioma.

Conclusion: This study demonstrates that native metabolic MRI imaging and ADC mapping has the potential to preoperatively distinguish between wildtype and mutated IDH status in glioma. Metabolic differences between IDH wildtype and mutant were confirmed by PCR analysis of hexokinase 2. Further studies are necessary to establishment of cut-off values for the specific MRI sequences.