title: Accuracy of 2-hydroxyglutarate quantification by short-echo proton-MRS at 3 T: a phantom study.
abstract: OBJECTIVE
  We set out to investigate the potential confounding effect of variable concentration of N-acetyl-l-aspartate (NAA) and Glutamate (Glu) on measurement of the brain oncometabolite 2-hydroxyglutarate (2HG) using a standard MRS protocol. This issue may arise due to spectral overlap at clinical magnetic field strengths and thus complicate the usage of 2HG as a putative biomarker of gliomas bearing mutations of the isocitrate dehydrogenase (IDH) 1 and 2 genes.
  
  
  METHODS
  Spectra from 25 phantoms (50 mL falcon test tubes) containing a range of known concentrations of 2HG, NAA and Glu were acquired using a clinical 3 T scanner with a quadrature head coil, single-voxel point-resolved spectroscopy sequence with TE = 30 ms. Metabolite concentrations were estimated by linear combination analysis and a simulated basis set.
  
  
  RESULTS
  NAA and Glu concentrations can have a significant confounding effect on 2HG measurements, whereby the negative changes in concentration of these metabolites typically observed in (peri)lesional areas can lead to under-estimation of 2HG concentration with respect to spectra acquired in presence of physiological levels of NAA and Glu.
  
  
  CONCLUSIONS
  The confounding effect of NAA and Glu concentration changes needs to be considered: in patients, it may mask the presence of 2HG at low concentrations, however it is not expected to lead to false positives. 2HG data acquired using standard short echo-time MRS protocols should be considered with caution.
authors.affiliation: Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Bertolino
authors.affiliation: B.U. Oncology, Nerviano Medical Sciences srl, Nerviano, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Marchionni
authors.affiliation: Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ghielmetti
authors.affiliation: Department of Bioengineering, UCLA, Los Angeles CA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Burns
authors.affiliation: Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Finocchiaro
authors.affiliation: Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Anghileri
authors.affiliation: Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bruzzone
authors.affiliation: Scientific Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy. Electronic address: lminati@ieee.org.
authors.forename: Ludovico
authors.initials: L
authors.lastname: Minati
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D005910:Glioma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005977:Glutarates / Q000378:metabolism*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D009154:Mutation; D019047:Phantoms, Imaging; D066244:Proton Magnetic Resonance Spectroscopy / Q000295:instrumentation*
chemical_list: D005977:Glutarates; C019417:alpha-hydroxyglutarate; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D007521:Isocitrate Dehydrogenase
keywords: 2-Hydroxyglutarate (2HG); Accuracy; Brain; Glioma; Magnetic resonance spectroscopy (MRS)