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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 in nigrosome 1 originates from iron accumulated in dopaminergic neurons. We link 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.
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