False-Positive Measurement at 2-Hydroxyglutarate MR Spectroscopy in Isocitrate Dehydrogenase Wild-Type Glioblastoma: A Multifactorial Analysis

Abstract

Background Isocitrate dehydrogenase (IDH) mutation has become one of the most important prognostic biomarkers in glioma management. Measurement of 2-hydroxyglutarate (2HG) with MR spectroscopy has shown high pooled sensitivity, although false-positive results with MR spectroscopy have been reported. Purpose To investigate factors associated with false-positive 2HG measurements at MR spectroscopy in patients with IDH wild-type glioblastoma. Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. Consecutive patients with histopathologically confirmed pre- and posttreatment glioblastoma were evaluated between December 2017 and August 2018. Spectroscopy parameters, including 2HG measurements, were obtained with single-voxel point-resolved spectroscopy, and apparent diffusion coefficient (ADC) values were calculated. Necrosis was graded according to the proportion of necrosis within a volume of interest. Poisson regression analyses were performed to determine factors related to false-positive 2HG measurements. Results A total of 82 patients were included (mean age, 55 years ± 12 [standard deviation]; 40 men). The 2HG measurement showed a false-positive rate of 21% (17 of 82; 95% CI: 13%, 31%) in patients with IDH wild-type glioblastoma. Multivariable analysis revealed that necrosis (prevalence ratio [PR], 3.9; 95% CI: 1.6, 9.4; P = .01) and ADC value (PR, 0.1 × 10^-3 mm²/sec; 95% CI: [0.0, 0.7] × 10^-3 mm²/sec; P = .02) were associated with a greater false-positive rate for the 2HG measurement. Necrosis of more than 20% was associated with a higher rate of false-positive 2HG measurements (50%) than was necrosis of 20% or less (15%, P = .01). The 2HG false-positive rate was higher in patients with pretreatment glioblastoma (46%) than in those with posttreatment glioblastoma (14%, P < .01). Among 17 patients with false-positive findings, 15 (88%; 95% CI: 64%, 99%) had a lactate concentration of 2.0 mmol/L or higher, and 14 (82%, 95% CI: 57%, 96%) had a lactate concentration of 3.0 mmol/L or higher. Conclusion Necrosis and apparent diffusion coefficient were associated with false-positive measurements of 2-hydroxyglutarate at MR spectroscopy in patients with isocitrate dehydrogenase wild-type glioblastoma. © RSNA, 2019 Online supplemental material is available for this article.