Ventral posterior substantia nigra iron increases over 3 years in Parkinson's disease

Mov Disord. 2019 Jul;34(7):1006-1013. doi: 10.1002/mds.27730. Epub 2019 Jun 10.


Background: Parkinson's disease (PD) is characterized in part by the progressive accumulation of iron within the substantia nigra (SN); however, its spatial and temporal dynamics remain relatively poorly understood.

Objectives: The objective of this study was to investigate spatial patterns and temporal evolution of SN iron accumulation in PD.

Methods: A total of 18 PD patients (mean disease duration = 6.2 years) receiving dopaminergic therapy and 16 healthy controls were scanned with 3T MRI at baseline and 3 years later using quantitative susceptibility mapping, an indirect marker of iron content. Iron was assessed separately in the posterior SN and anterior SN at the ventral and dorsal levels of the SN. The results were corrected for the false discovery rate.

Results: A significant group effect was found for the ventral posterior SN (P < .001) and anterior SN (P = .042) quantitative susceptibility mapping as well as significant group x time interaction effects (P = .02 and P = .043, respectively). In addition, a significant intragroup change during 3 years of follow-up was found only in the ventral posterior SN of PD (P = .012), but not healthy controls. No significant effects were detected for any dorsal SN measures. No associations were identified with clinical measures.

Conclusions: We found both cross-sectional and longitudinal SN iron changes to be confined to its more ventral location in PD. Because pathology studies also show the ventral SN to degenerate early and to the greatest extent in PD, the assessment of iron levels by quantitative susceptibility mapping in this area may potentially represent a disease progression biomarker in PD. © 2019 International Parkinson and Movement Disorder Society.

Keywords: MRI; Parkinson's disease; iron; longitudinal; quantitative susceptibility mapping; substantia nigra.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / metabolism*
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Iron / metabolism*
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Substantia Nigra / metabolism*
  • Substantia Nigra / pathology


  • Biomarkers
  • Iron