Imaging of Cerebral Iron as an Emerging Marker for Brain Aging, Neurodegeneration, and Cerebrovascular Diseases

Abstract

Iron is critical for brain development, metabolism, and function; however, dysregulated iron disposition contributes to neurological diseases. Many neuroimaging techniques have enabled detection of iron susceptibility, and quantitative susceptibility mapping (QSM) offers a sensitive magnetic resonance imaging (MRI) technique for quantifying brain iron. To elucidate the functional role of cerebral iron and clarify the utility of QSM in establishing iron as a potential biomarker, this review synthesizes cellular and regional behaviours of iron from physiological aging to disease conditions, with a focus on neurodegeneration such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS), as well as cerebral small vessel disease (CSVD) as cerebrovascular manifestation. Distinct patterns of iron distribution in deep gray matter and selective cortical regions are associated with motor and cognitive impairment, while the interaction between iron, vascular integrity, and glial function further stresses its pathological relevance. QSM of iron may, thereby, serve as a marker to monitor iron-related disease progression and facilitate intervention. Temporal dynamics of iron in brain pathology remain underexplored, and we emphasized the need for longitudinal mapping and multi-modality biomarker integration. Establishing iron as a clinically relevant imaging biomarker requires continued investigation into its topographical, molecular, and functional correlates across aging and disease trajectories.