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Abstract #1313

Lifespan Iron Accumulation in Dopaminergic Neurons Studied by Quantitative MRI and X-ray Fluorescence

Felix Büttner1, Tilo Reinert1,2, Carsten Jäger1,2, Malte Brammerloh1, Markus Morawski2, Ilona Lipp1, Gerald Falkenberg3, Dennis Brückner3, Pierre-Louis Bazin4, Catherine Crockford5, Roman Wittig5,6, Evgeniya Kirilina1, and Nik Weiskopf1,7,8
1Neurophysics Department, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, 2Paul Flechsig Institute of Neuropathology and Brain Research, Medical Faculty University Leipzig, Leipzig, Germany, 3Deutsches Elektronen-Synchrotron DESY, Hamburg, Germany, 4Full brain picture Analytics, Leiden, Netherlands, 5Ape Social Mind Lab, Institute of Cognitive Science Marc Jeannerod, Lyon, France, 6Taï Chimpanzee Project, Centre Suisse de Recherches Scientifiques, Abidjan, Cote D'ivoire, 7Felix Bloch Institute for Solid State Physics, Faculty of Physics and Earth System Sciences, Leipzig University, Leipzig, Germany, 8Wellcome Centre for Human Neuroimaging, Institute of Neurology, University College London, London, United Kingdom

Synopsis

Keywords: Microstructure, Quantitative Imaging, Iron, Substantia nigra, R2*

Motivation: Dopaminergic neurons require iron for their function but suffer from iron overload in age.

Goal(s): To non-invasively monitor the age-related iron accumulation in dopaminergic neurons, we investigated mechanisms of iron-induced MR contrast in the substantia nigra across the lifespan.

Approach: We combined quantitative MRI, X-ray fluorescence imaging and biophysical modelling in a unique animal model: ethically collected postmortem chimpanzee brains.

Results: The iron load of dopaminergic neurons and the effective transverse relaxation rates in the substantia nigra increased with age. The biophysical model accurately links the relaxation rate to the iron load and neuronal density, which demonstrated its suitability for ages above puberty.

Impact: Monitoring cell-specific iron concentrations of dopaminergic neurons and neuronal densities in the substantia nigra throughout the lifespan holds potential of an early neuroimaging biomarker for Parkinson’s disease.

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Abstract

Keywords