Brain iron MRI: a biomarker for amyotrophic lateral sclerosis

J Magn Reson Imaging. 2013 Dec;38(6):1472-9. doi: 10.1002/jmri.24121. Epub 2013 Apr 5.


Purpose: To evaluate the usefulness of MRI detection of hypointensity areas (iron deposits) in the brain using a dedicated MRI technique in patients with ALS in establishing this sign as a potential surrogate biomarker that correlates with the severity of disease.

Materials and methods: Forty-six ALS patients and 26 age-matched controls were examined by MRI. The ALS Functional Rating Scale (ALSFRS) score was determined before the first MRI examination. The sub-set of 25 ALS patients was re-examined around 6 months after the first MRI examination. The MRI examination consisted of routine T1W, T2W, and FLAIR sequences with the addition of a thin slice heavily T2* weighted sequence to accentuate magnetic susceptibility artifacts.

Results: T2*W sequence is superior to any other MRI sequence in detecting hypointensities in the brain of ALS patients. Hypointensities were found only in the precentral gyruses gray matter (PGGM) and were detected in 42 patients. The extent of hypointensities was measured and scored (0-3) and correlated with ALSFRS (r = -0.545). Twenty-five patients were re-examined 6 months later, and the majority of them showed the shift toward higher MRI scores. No control subjects had hypointensities in PGGM.

Conclusion: The detection of hypointensities in PGGM appears to be a very promising surrogate MRI biomarker for ALS due to its simplicity, high sensitivity and specificity, suitability for longitudinal studies, and relationship with the pathogenesis of the disease.

Keywords: MRI; amyotrophic lateral sclerosis; biomarkers; brain iron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / pathology*
  • Biomarkers / metabolism
  • Brain / metabolism*
  • Brain / pathology*
  • Female
  • Humans
  • Image Enhancement / methods
  • Image Interpretation, Computer-Assisted / methods*
  • Iron / metabolism*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution


  • Biomarkers
  • Iron