PETRA III Science Seminar | In situ magnetometry of iron in human dopaminergic neurons using super-resolution MRI and ion-beam microscopy

by Malte Brammerloh (Max Planck Institute for Human Cognitive and Brain Sciences)

Tuesday 9 Apr 2024, 14:15 → 15:00 Europe/Berlin

Online

While paramagnetic transition metals play a crucial role in cellular catalytic processes, they can induce oxidative stress, resulting in cell dysfunction or death. Hence, it is vital to have methods to monitor cellular metals for medicine and cell biology. Here we present a novel multimodal method for in-cell magnetometry, enabling direct measurement of metal magnetic properties within individual cells in tissue, without prior isolation and at room temperature. Individual cell magnetic moments are measured using super-resolution MRI microscopy. The cellular metal content is quantified using ion-beam microscopy and synchrotron micro X-ray fluorescence on the same cells.

The metal magnetic susceptibility is then obtained from the slope of the cell magnetic moments' dependence on cell metal content. We applied the new method to determine the susceptibility of iron accumulated in human dopaminergic neurons inside neuromelanin, the byproduct of dopamine synthesis. This susceptibility was \chi = 2.98(19)e-6 m³/kg, providing unique insights into iron binding in dopaminergic neurons. Furthermore, this susceptibility value establishes a quantitative relationship between cellular iron concentration and iron-sensitive MRI parameters, which can be non-invasively measured /in vivo/. This breakthrough paves the way for the /in vivo/ detection of dopaminergic neuron density and iron load, requiring a standard clinical MRI scanner only. It promises to facilitate early diagnosis of Parkinson's disease.