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  Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry

Brammerloh, M., Morawski, M., Friedrich, I., Reinert, T., Lange, C., Pelicon, P., et al. (2021). Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry. NeuroImage, 239: 118255. doi:10.1016/j.neuroimage.2021.118255.

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 Creators:
Brammerloh, Malte1, 2, 3, Author              
Morawski, Markus1, 4, Author              
Friedrich, Isabel4, Author
Reinert, Tilo1, 3, Author              
Lange, Charlotte1, 3, Author
Pelicon, Primož5, Author
Vavpetič, Primož5, Author
Jankuhn, Steffen3, Author
Jäger, Carsten1, 4, Author              
Alkemade, Anneke6, Author
Balesar, Rawien6, 7, Author
Pine, Kerrin1, Author              
Gavriilidis, Filippos1, Author              
Trampel, Robert1, Author              
Reimer, Enrico1, Author              
Arendt, Thomas4, Author
Weiskopf, Nikolaus1, 3, Author              
Kirilina, Evgeniya1, 8, Author              
Affiliations:
1Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_2205649              
2International Max Planck Research School on Neuroscience of Communication, Leipzig, Germany, ou_persistent22              
3Felix Bloch Institute for Solid State Physics, University of Leipzig, Germany, ou_persistent22              
4Paul Flechsig Institute for Brain Research, University of Leipzig, Germany, ou_persistent22              
5Jožef Stefan Institute, Ljubljana, Slovenia, ou_persistent22              
6Integrative Model-Based Cognitive Neuroscience Research Unit (IMCN), University of Amsterdam, the Netherlands, ou_persistent22              
7The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands, ou_persistent22              
8Center for Cognitive Neuroscience Berlin (CCNB), FU Berlin, Germany, ou_persistent22              

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Free keywords: Substantia nigra; Nigrosome; Quantitative MRI; Neuromelanin; Ion-beam microscopy; Iron-induced contrast
 Abstract: In Parkinson’s disease, the depletion of iron-rich dopaminergic neurons in nigrosome 1 of the substantia nigra precedes motor symptoms by two decades. Methods capable of monitoring this neuronal depletion, at an early disease stage, are needed for early diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is particularly suitable for this task due to its sensitivity to tissue microstructure and in particular, to iron. However, the exact mechanisms of MRI contrast in the substantia nigra are not well understood, hindering the development of powerful biomarkers. In the present report, we illuminate the contrast mechanisms in gradient and spin echo MR images in human nigrosome 1 by combining quantitative 3D iron histology and biophysical modeling with quantitative MRI on post mortem human brain tissue. We show that the dominant contribution to the effective transverse relaxation rate () in nigrosome 1 originates from iron accumulated in the neuromelanin of dopaminergic neurons. This contribution is appropriately described by a static dephasing approximation of the MRI signal. We demonstrate that the contribution from dopaminergic neurons reflects the product of cell density and cellular iron concentration. These results demonstrate that the in vivo monitoring of neuronal density and iron in nigrosome 1 may be feasible with MRI and provide directions for the development of biomarkers for an early detection of dopaminergic neuron depletion in Parkinson’s disease.

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Language(s): eng - English
 Dates: 2021-06-022021-03-212021-06-072021-06-112021-10-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.neuroimage.2021.118255
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Project name : -
Grant ID : 616905
Funding program : European Union’s Seventh Framework Programme
Funding organization : European Research Council
Project name : -
Grant ID : 681094
Funding program : Horizon 2020
Funding organization : European Union
Project name : -
Grant ID : P1-0112, I0-0005, J7-9398, N1-0090
Funding program : -
Funding organization : Slovenian research agency

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Title: NeuroImage
Source Genre: Journal
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Publ. Info: Orlando, FL : Academic Press
Pages: - Volume / Issue: 239 Sequence Number: 118255 Start / End Page: - Identifier: ISSN: 1053-8119
CoNE: https://pure.mpg.de/cone/journals/resource/954922650166