Purpose
Proton magnetic resonance spectroscopy (MRS) of the brain can detect
2-hydroxyglutarate (2HG), the oncometabolite produced in
neoplasms harboring a mutation in the gene coding for
isocitrate dehydrogenase ( IDH). We conducted a prospective longitudinal imaging study to determine whether quantitative assessment of 2HG by MRS could serve as a noninvasive clinical imaging
biomarker for IDH-mutated
gliomas. Patients and Methods 2HG MRS was performed in 136 patients using point-resolved spectroscopy at 3 T in parallel with standard clinical magnetic resonance imaging and assessment. Data were analyzed in patient cohorts representing the major phases of the
glioma clinical course and were further subgrouped by histology and treatment type to evaluate 2HG. Histologic correlations were performed. Results Quantitative 2HG MRS was technically and biologically reproducible. 2HG concentration > 1 mM could be reliably detected with high confidence. During the period of indolent disease, 2HG concentration varied by less than ± 1 mM, and it increased sharply with
tumor progression. 2HG concentration was positively correlated with
tumor cellularity and significantly differed between high- and lower-grade
gliomas. In response to cytotoxic
therapy, 2HG concentration decreased rapidly in 1p/19q codeleted
oligodendrogliomas and with a slower time course in
astrocytomas and
mixed gliomas. The magnitude and time course of the decrease in 2HG concentration and magnitude of the decrease in
tumor volume did not differ between
oligodendrogliomas treated with
temozolomide or
carmustine. Criteria for 2HG MRS were established to make a presumptive molecular diagnosis of an IDH mutation in
gliomas technically unable to undergo a
surgical procedure. Conclusion 2HG concentration as measured by MRS was reproducible and reliably reflected the disease state. These data provide a basis for incorporating 2HG MRS into clinical management of IDH-mutated
gliomas.