Choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios together with age assemble a significant Cox's proportional-hazards regression model for prediction of survival in high-grade gliomas

Br J Radiol. 2016 Nov;89(1067):20150502. doi: 10.1259/bjr.20150502. Epub 2016 Sep 14.


Objective: A long-lasting concern has prevailed for the identification of predictive biomarkers for high-grade gliomas (HGGs) using MRI. However, a consensus of which imaging parameters assemble a significant survival model is still missing in the literature; we investigated the significant positive or negative contribution of several MR biomarkers in this tumour prognosis.

Methods: A retrospective cohort of supratentorial HGGs [11 glioblastoma multiforme (GBM) and 17 anaplastic astrocytomas] included 28 patients (9 females and 19 males, respectively, with a mean age of 50.4 years, standard deviation: 16.28 years; range: 13-85 years). Oedema and viable tumour measurements were acquired using regions of interest in T1 weighted, T2 weighted, fluid-attenuated inversion recovery, apparent diffusion coefficient (ADC) and MR spectroscopy (MRS). We calculated Kaplan-Meier curves and obtained Cox's proportional hazards.

Results: During the follow-up period (3-98 months), 17 deaths were recorded. The median survival time was 1.73 years (range, 0.287-8.947 years). Only 3 out of 20 covariates (choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios and age) showed significance in explaining the variability in the survival hazards model; score test: χ2 (3) = 9.098, p = 0.028.

Conclusion: MRS metabolites overcome volumetric parameters of peritumoral oedema and viable tumour, as well as tumour region ADC measurements. Specific MRS ratios (Cho/Naa, L-L/Cr) might be considered in a regular follow-up for these tumours. Advances in knowledge: Cho/Naa ratio is the strongest survival predictor with a log-hazard function of 2.672 in GBM. Low levels of lipids-lactate/Cr ratio represent up to a 41.6% reduction in the risk of death in GBM.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / analysis
  • Biomarkers / analysis*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology*
  • Choline / analysis
  • Creatine / analysis
  • Female
  • Glioma / mortality
  • Glioma / pathology*
  • Humans
  • Lactic Acid / analysis
  • Lipids / analysis
  • Magnetic Resonance Spectroscopy*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Retrospective Studies
  • Survival Rate


  • Biomarkers
  • Lipids
  • Aspartic Acid
  • Lactic Acid
  • N-acetylaspartate
  • Creatine
  • Choline