Magnetic Resonance Spectroscopic Assessment of Isocitrate Dehydrogenase Status in Gliomas: The New Frontiers of Spectrobiopsy in Neurodiagnostics

Abstract

In the era of integrated genomic-histologic analysis of brain tumors, new biomarkers have been introduced as diagnostic, prognostic, and therapeutic indicators. The analysis of the mutation in the isocitrate dehydrogenase (IDH) genes IDH1 and IDH2 has provided important diagnostic and prognostic information for patients affected by diffuse glioma (i.e., the presence of the mutation has been related to an increased survival rate). The reference standard of IDH mutation detection has been its assessment in surgical specimens, immunohistochemistry, and/or genetic sequencing. Knowing the IDH status information preoperatively would be of great importance, because it has been related to tumor progression and the response to treatment. The oncometabolite 2-hydroxyglutarate (2HG), accumulated in gliomas with IDH mutation status, can be detected invivo using magnetic resonance spectroscopy (MRS). The 2HG-MRS technique remains technically challenging. We have summarized the results of the first pilot study in Australia, which included 10 patients affected by glioma. The data recorded from May 2017 to November 2018 were analyzed. In our exploratory study, we reached a sensitivity and specificity of 100%, confirming the strong predictive role of 2HG, as detected using MRS, in the diagnosis of glioma. In the present study, we have focused on methodological tips and future perspectives of the technique in the neuroimaging and neuro-oncological scenario. We would advocate the integration of 2HG-MRS into standard clinical practice.