Toward an early diagnostic marker of Parkinson’s: measuring iron in dopaminergic neurons with MR 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. Monitoring this neuronal depletion, at an early disease stage, is needed for early diagnosis. Magnetic resonance imaging (MRI) is particularly suitable for this task due to its sensitivity to iron. However, the exact mechanisms of MRI contrast in nigrosome 1 are not well understood, hindering the development of powerful biomarkers. We demonstrate that the dominant contribution to the effective transverse MRI relaxation rate ![Graphic][1] in nigrosome 1 originates from iron accumulated in dopaminergic neurons. We link ![Graphic][2] 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. It is now theoretically possible to monitor dopaminergic neuron depletion, in vivo , as an early diagnostic tool for Parkinson’s disease. ### Competing Interest Statement The 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. [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif