Iron, Myelin, and the Brain: Neuroimaging Meets Neurobiology

Although iron is crucial for neuronal functioning, many aspects of cerebral iron biology await clarification. The ability to quantify specific iron forms in the living brain would open new avenues for diagnosis, therapeutic monitoring, and understanding pathogenesis of diseases. A modality that allows assessment of brain tissue composition in vivo, in particular of iron deposits or myelin content on a submillimeter spatial scale, is magnetic resonance imaging (MRI). Multimodal strategies combining MRI with complementary analytical techniques ex vivo have emerged, which may lead to improved specificity. Interdisciplinary collaborations will be key to advance beyond simple correlative analyses in the biological interpretation of MRI data and to gain deeper insights into key factors leading to iron accumulation and/or redistribution associated with neurodegeneration. Emerging MRI techniques are progressing towards a means for the quantification of iron concentration or myelin content over the scale of a whole brain at submillimeter resolutions both ex vivo and in vivo.Complementary techniques borrowed from analytical chemistry and solid-state physics can help in the specification and quantification of iron forms in the brain.Multiparametric imaging approaches yielding quantitative information on both iron and myelin content may provide useful biomarkers to assess white matter integrity in clinical studies that use iron chelation therapy for diseases associated with iron deposition.