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

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Brammerloh,  Malte
Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society;
International Max Planck Research School on Neuroscience of Communication, Leipzig, Germany;
Felix Bloch Institute for Solid State Physics, University of Leipzig, Germany;

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Morawski,  Markus
Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Paul Flechsig Institute for Brain Research, University of Leipzig, Germany;

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Reinert,  Tilo
Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Felix Bloch Institute for Solid State Physics, University of Leipzig, Germany;

Lange,  Charlotte
Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Felix Bloch Institute for Solid State Physics, University of Leipzig, Germany;

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Jäger,  Carsten
Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Paul Flechsig Institute for Brain Research, University of Leipzig, Germany;

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Pine,  Kerrin
Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Gavriilidis,  Filippos
Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Trampel,  Robert
Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Reimer,  Enrico
Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Weiskopf,  Nikolaus
Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Felix Bloch Institute for Solid State Physics, University of Leipzig, Germany;

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Kirilina,  Evgeniya
Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Center for Cognitive Neuroscience Berlin (CCNB), FU Berlin, Germany;

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Brammerloh_2021.pdf
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Citation

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.


Cite as: https://hdl.handle.net/21.11116/0000-0008-DBB3-7
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.