MR contrast mechanisms in human locus coeruleus were studied combining high-resolution post mortem MRI, histology, ion-beam microscopy, and electron paramagnetic resonance. We demonstrate that the main source of MR contrast in formalin fixed LC is paramagnetic iron accumulated in noradrinergic neurons. However, we show that MR contrast in LC drastically changes during the first six months of tissue fixation. We assign these changes to iron been scavenged by neuromelanin and the change of its paramagnetic state. The results have major consequences for MRI of the locus coeruleus, demonstrating a fundamental change rather than the commonly known gradual changes in contrast due to formalin fixation.
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