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

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.