Unraveling the contributions to the neuromelanin-MRI contrast

Nikos Priovoulos*, Stan C.J. van Boxel, Heidi I.L. Jacobs, Benedikt A. Poser, Kamil Uludag, Frans R.J. Verhey, Dimo Ivanov

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)

Abstract

The Locus Coeruleus (LC) and the Substantia Nigra (SN) are small brainstem nuclei that change with aging and may be involved in the development of various neurodegenerative and psychiatric diseases. Magnetization Transfer (MT) MRI has been shown to facilitate LC and the SN visualization, and the observed contrast is assumed to be related to neuromelanin accumulation. Imaging these nuclei may have predictive value for the progression of various diseases, but interpretation of previous studies is hindered by the fact that the precise biological source of the contrast remains unclear, though several hypotheses have been put forward. To inform clinical studies on the possible biological interpretation of the LC- and SN contrast, we examined an agar-based phantom containing samples of natural Sepia melanin and synthetic Cys-Dopa-Melanin and compared this to the in vivo human LC and SN. T1 and T2* maps, MT spectra and relaxation times of the phantom, the LC and the SN were measured, and a two-pool MT model was fitted. Additionally, Bloch simulations and a transient MT experiment were conducted to confirm the findings. Overall, our results indicate that Neuromelanin-MRI contrast in the LC likely results from a lower macromolecular fraction, thus facilitating interpretation of results in clinical populations. We further demonstrate that in older individuals T1 lengthening occurs in the LC.

Original languageEnglish
Pages (from-to)2757-2774
Number of pages18
JournalBrain Structure & Function
Volume225
Issue number9
Early online date22 Oct 2020
DOIs
Publication statusPublished - Dec 2020

Keywords

  • Neuromelanin
  • Neuromelanin-MRI
  • Locus coeruleus
  • Substantia nigra
  • Magnetization transfer
  • HUMAN LOCUS-COERULEUS
  • SUBSTANTIA-NIGRA
  • HUMAN BRAIN
  • RELAXATION
  • DISEASE
  • IRON
  • T-ASTERISK(2)
  • RELEVANCE
  • BIOMARKER
  • CERULEUS

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