title: In vivo detection of citrate in brain tumors by 1H magnetic resonance spectroscopy at 3T.
abstract: OBJECTIVE
  To test whether citrate is elevated in adult patients with gliomas using (1)H magnetic resonance spectroscopy (MRS) at 3T in vivo.
  
  
  METHODS
  Thirty-four adult patients were enrolled in the study, including six subjects with glioblastomas, eight subjects with astrocytomas (World Health Organization grade 3, n = 5; grade 2, n = 3), and 20 subjects with oligodendrogliomas (grade 3, n = 5; grade 2, n = 15). Five healthy volunteers were studied for baseline citrate data. Single-voxel localized spectra were collected with point-resolved spectroscopy (PRESS) echo times of 35 and 97 ms and were analyzed with LCModel software using numerically calculated basis spectra that included the effects of the PRESS radiofrequency and gradient pulses.
  
  
  RESULTS
  Citrate was not measurable by MRS in healthy brain but was detected in tumor patients at both echo times. The citrate concentration was estimated to be as high as 1.8 mM with reference to water at 42 M, with Cramér-Rao lower bounds (CRLB) as low as 5%. The mean citrate level was 0.7 ± 0.4 mM (mean ± SD, n = 32) with a median CRLB of ∼12%. No correlation was identified between citrate concentration and tumor grade or histological type.
  
  
  CONCLUSIONS
  Citrate was increased in the majority of gliomas in adult patients. The elevated citrate in our data indicates an altered metabolic state of tumor relative to healthy brain.
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Changho
authors.initials: C
authors.lastname: Choi
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Ganji
authors.forename: Akshay
authors.initials: A
authors.lastname: Madan
authors.forename: Keith M
authors.initials: KM
authors.lastname: Hulsey
authors.forename: Zhongxu
authors.initials: Z
authors.lastname: An
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.forename: Marco C
authors.initials: MC
authors.lastname: Pinho
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DeBerardinis
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bachoo
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Maher
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000737:chemistry*; D019343:Citric Acid / Q000032:analysis*; D005260:Female; D005910:Glioma / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019343:Citric Acid
keywords: 1H MRS; 3T; PRESS (point-resolved spectroscopy); adults; citrate; density-matrix simulation; gliomas