False-positive measurement at 2-hydroxyglutarate MR spectroscopy in isocitrate dehydrogenase wild-type glioblastoma: A multifactorial analysis

Chong Hyun Suh, Ho Sung Kim, Wooyul Paik, Changho Choi, Kyeong Hwa Ryu, Donghyun Kim, Dong Cheol Woo, Ji Eun Park, Seung Chai Jung, Choong Gon Choi, Sang Joon Kim

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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 6 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 3 1023 mm2/sec; 95% CI: [0.0, 0.7] 3 1023 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.

Original languageEnglish (US)
Pages (from-to)752-762
Number of pages11
JournalRadiology
Volume291
Issue number3
DOIs
StatePublished - Jan 1 2019

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Isocitrate Dehydrogenase
Glioblastoma
Magnetic Resonance Spectroscopy
Necrosis
Lactic Acid
Spectrum Analysis
alpha-hydroxyglutarate
Research Ethics Committees
Informed Consent
Glioma
Retrospective Studies
Biomarkers
Regression Analysis
Mutation

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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False-positive measurement at 2-hydroxyglutarate MR spectroscopy in isocitrate dehydrogenase wild-type glioblastoma : A multifactorial analysis. / Suh, Chong Hyun; Kim, Ho Sung; Paik, Wooyul; Choi, Changho; Ryu, Kyeong Hwa; Kim, Donghyun; Woo, Dong Cheol; Park, Ji Eun; Jung, Seung Chai; Choi, Choong Gon; Kim, Sang Joon.

In: Radiology, Vol. 291, No. 3, 01.01.2019, p. 752-762.

Research output: Contribution to journalArticle

Suh, CH, Kim, HS, Paik, W, Choi, C, Ryu, KH, Kim, D, Woo, DC, Park, JE, Jung, SC, Choi, CG & Kim, SJ 2019, 'False-positive measurement at 2-hydroxyglutarate MR spectroscopy in isocitrate dehydrogenase wild-type glioblastoma: A multifactorial analysis', Radiology, vol. 291, no. 3, pp. 752-762. https://doi.org/10.1148/radiol.2019182200
Suh, Chong Hyun ; Kim, Ho Sung ; Paik, Wooyul ; Choi, Changho ; Ryu, Kyeong Hwa ; Kim, Donghyun ; Woo, Dong Cheol ; Park, Ji Eun ; Jung, Seung Chai ; Choi, Choong Gon ; Kim, Sang Joon. / False-positive measurement at 2-hydroxyglutarate MR spectroscopy in isocitrate dehydrogenase wild-type glioblastoma : A multifactorial analysis. In: Radiology. 2019 ; Vol. 291, No. 3. pp. 752-762.
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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 6 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 3 1023 mm2/sec; 95{\%} CI: [0.0, 0.7] 3 1023 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.",
author = "Suh, {Chong Hyun} and Kim, {Ho Sung} and Wooyul Paik and Changho Choi and Ryu, {Kyeong Hwa} and Donghyun Kim and Woo, {Dong Cheol} and Park, {Ji Eun} and Jung, {Seung Chai} and Choi, {Choong Gon} and Kim, {Sang Joon}",
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TY - JOUR

T1 - False-positive measurement at 2-hydroxyglutarate MR spectroscopy in isocitrate dehydrogenase wild-type glioblastoma

T2 - A multifactorial analysis

AU - Suh, Chong Hyun

AU - Kim, Ho Sung

AU - Paik, Wooyul

AU - Choi, Changho

AU - Ryu, Kyeong Hwa

AU - Kim, Donghyun

AU - Woo, Dong Cheol

AU - Park, Ji Eun

AU - Jung, Seung Chai

AU - Choi, Choong Gon

AU - Kim, Sang Joon

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 6 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 3 1023 mm2/sec; 95% CI: [0.0, 0.7] 3 1023 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.

AB - 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 6 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 3 1023 mm2/sec; 95% CI: [0.0, 0.7] 3 1023 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.

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