RT Journal Article
SR Electronic
T1 Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.01.170563
DO 10.1101/2020.07.01.170563
A1 Malte Brammerloh
A1 Markus Morawski
A1 Isabel Weigelt
A1 Tilo Reinert
A1 Charlotte Lange
A1 Primož Pelicon
A1 Primož Vavpetič
A1 Steffen Jankuhn
A1 Carsten Jäger
A1 Anneke Alkemade
A1 Rawien Balesar
A1 Kerrin Pine
A1 Filippos Gavriilidis
A1 Robert Trampel
A1 Enrico Reimer
A1 Thomas Arendt
A1 Nikolaus Weiskopf
A1 Evgeniya Kirilina
YR 2020
UL http://biorxiv.org/content/early/2020/07/02/2020.07.01.170563.abstract
AB In Parkinson’s disease, the depletion of iron-rich dopaminergic neurons in substantia nigra’s nigrosome 1 precedes first motor symptoms by two decades. Monitoring this neuronal depletion at an early disease stage is needed for diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is particularly suitable for this task due to its sensitivity to tissue iron. However, the mechanisms of MRI contrast in substantia nigra are not well understood, hindering the development of specific biomarkers. We showed that the dominant contribution to the effective transverse MRI relaxation rate in nigrosome 1 originates from iron accumulated in the neuromelanin of dopaminergic neurons. We linked quantitatively to the product of cell density and local iron concentration in dopaminergic neurons, combining quantitative 3D iron histology, biophysical modeling, and quantitative MRI on post mortem brain tissue. This knowledge opens an avenue for monitoring neuronal iron and density in vivo and may be applied to detect early neurodegeneration in Parkinson’s disease.Competing Interest StatementThe Max Planck Institute for Human Cognitive and Brain Sciences has an institutional research agreement with Siemens Healthcare. NW was a speaker at an event organized by Siemens Healthcare and was reimbursed for the travel expenses.