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

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 r...

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Autores principales: Brammerloh, Malte, Morawski, Markus, Friedrich, Isabel, Reinert, Tilo, Lange, Charlotte, Pelicon, Primož, Vavpetič, Primož, Jankuhn, Steffen, Jäger, Carsten, Alkemade, Anneke, Balesar, Rawien, Pine, Kerrin, Gavriilidis, Filippos, Trampel, Robert, Reimer, Enrico, Arendt, Thomas, Weiskopf, Nikolaus, Kirilina, Evgeniya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Academic Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363938/
https://www.ncbi.nlm.nih.gov/pubmed/34119638
http://dx.doi.org/10.1016/j.neuroimage.2021.118255
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author Brammerloh, Malte
Morawski, Markus
Friedrich, Isabel
Reinert, Tilo
Lange, Charlotte
Pelicon, Primož
Vavpetič, Primož
Jankuhn, Steffen
Jäger, Carsten
Alkemade, Anneke
Balesar, Rawien
Pine, Kerrin
Gavriilidis, Filippos
Trampel, Robert
Reimer, Enrico
Arendt, Thomas
Weiskopf, Nikolaus
Kirilina, Evgeniya
author_facet Brammerloh, Malte
Morawski, Markus
Friedrich, Isabel
Reinert, Tilo
Lange, Charlotte
Pelicon, Primož
Vavpetič, Primož
Jankuhn, Steffen
Jäger, Carsten
Alkemade, Anneke
Balesar, Rawien
Pine, Kerrin
Gavriilidis, Filippos
Trampel, Robert
Reimer, Enrico
Arendt, Thomas
Weiskopf, Nikolaus
Kirilina, Evgeniya
author_sort Brammerloh, Malte
collection PubMed
description 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 ([Formula: see text]) 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 [Formula: see text] 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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spelling pubmed-83639382021-10-01 Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry Brammerloh, Malte Morawski, Markus Friedrich, Isabel Reinert, Tilo Lange, Charlotte Pelicon, Primož Vavpetič, Primož Jankuhn, Steffen Jäger, Carsten Alkemade, Anneke Balesar, Rawien Pine, Kerrin Gavriilidis, Filippos Trampel, Robert Reimer, Enrico Arendt, Thomas Weiskopf, Nikolaus Kirilina, Evgeniya Neuroimage Article 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 ([Formula: see text]) 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 [Formula: see text] 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. Academic Press 2021-10-01 /pmc/articles/PMC8363938/ /pubmed/34119638 http://dx.doi.org/10.1016/j.neuroimage.2021.118255 Text en © 2021 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brammerloh, Malte
Morawski, Markus
Friedrich, Isabel
Reinert, Tilo
Lange, Charlotte
Pelicon, Primož
Vavpetič, Primož
Jankuhn, Steffen
Jäger, Carsten
Alkemade, Anneke
Balesar, Rawien
Pine, Kerrin
Gavriilidis, Filippos
Trampel, Robert
Reimer, Enrico
Arendt, Thomas
Weiskopf, Nikolaus
Kirilina, Evgeniya
Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry
title Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry
title_full Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry
title_fullStr Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry
title_full_unstemmed Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry
title_short Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry
title_sort measuring the iron content of dopaminergic neurons in substantia nigra with mri relaxometry
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363938/
https://www.ncbi.nlm.nih.gov/pubmed/34119638
http://dx.doi.org/10.1016/j.neuroimage.2021.118255
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