PT  - JOURNAL ARTICLE
AU  - Malte Brammerloh
AU  - Markus Morawski
AU  - Isabel Weigelt
AU  - Tilo Reinert
AU  - Charlotte Lange
AU  - Primož Pelicon
AU  - Primož Vavpetič
AU  - Steffen Jankuhn
AU  - Carsten Jäger
AU  - Anneke Alkemade
AU  - Rawien Balesar
AU  - Kerrin Pine
AU  - Filippos Gavriilidis
AU  - Robert Trampel
AU  - Enrico Reimer
AU  - Thomas Arendt
AU  - Nikolaus Weiskopf
AU  - Evgeniya Kirilina
TI  - Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry
AID  - 10.1101/2020.07.01.170563
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.01.170563
4099  - http://biorxiv.org/content/early/2020/07/02/2020.07.01.170563.short
4100  - http://biorxiv.org/content/early/2020/07/02/2020.07.01.170563.full
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.