Intraoperative detection of isocitrate dehydrogenase mutations in human gliomas using a miniature mass spectrometer

Hannah Marie Brown, Fan Pu, Mahua Dey, James Miller, Mitesh V. Shah, Scott A. Shapiro, Zheng Ouyang, Aaron A. Cohen-Gadol, R. Graham Cooks

Research output: Contribution to journalArticle

Abstract

Knowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement. [Figure not available: see fulltext.]

Original languageEnglish (US)
JournalAnalytical and Bioanalytical Chemistry
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Isocitrate Dehydrogenase
Mass spectrometers
Glioma
Mutation
Operating rooms
Biopsy
Pathology
Operating Rooms
Metabolites
Surgery
Noise
Glutamic Acid
Brain
Decision Making
Electric power utilization
Decision making
Ions
Tissue
Costs and Cost Analysis
Costs

Keywords

  • Ambient ionization mass spectrometry
  • Isocitrate dehydrogenase mutation
  • Miniature mass spectrometry
  • Molecular cancer diagnostics
  • Point-of-care diagnostics

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

Cite this

Intraoperative detection of isocitrate dehydrogenase mutations in human gliomas using a miniature mass spectrometer. / Brown, Hannah Marie; Pu, Fan; Dey, Mahua; Miller, James; Shah, Mitesh V.; Shapiro, Scott A.; Ouyang, Zheng; Cohen-Gadol, Aaron A.; Cooks, R. Graham.

In: Analytical and Bioanalytical Chemistry, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Shapiro, Scott A.

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AU - Cohen-Gadol, Aaron A.

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AB - Knowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement. [Figure not available: see fulltext.]

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