High-resolution iron mapping to study the role of brain iron complexes in the basal forebrain in neuropsychiatric disorders.

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The mechanisms of brain iron changes underlying neurodegenerative diseases are largely unknown. One hypothesis suggests that erythrocytes leak through an impaired blood-brain barrier leading to activation of microglia. This results in intracellular deposition of haemosiderin, a disorganised iron storage complex which contains unbound iron ions. In this state, iron is neurotoxic producing free radicals and causing oxidative stress. The nucleus basalis of Meynert is a cholinergic basal forebrain nucleus which is affected early in the course of many neuropsychiatric disorders. Brain iron can be detected using gradient-echo MRI with areas of high iron appearing hypo-intense in magnitude images. Advanced susceptibility mapping at high field is needed for reliable quantification. Disentangling the mechanisms that lead to iron-mediated neurotoxicity is at the frontier of multidisciplinary research and clinical imaging. Moreover, non-invasive iron mapping using MRI provides a mechanistic biomarker for disease prediction that can be exploited in future clinical trials.