A Scalable fMRI Estimate of Basal Ganglia Brain Tissue Iron for Use in Developmental and Translational Neuroscience

assessment of the DA system remains limited in youth. Brain tissue iron is a developmentally sensitive marker of DA-related neurobiology that can be measured non-invasively via magnetic resonance imaging (MRI). Iron is an essential co-factor for DA synthesis and a foundational metabolic resource that supports cellular metabolism, myelination, and energetic demands of the basal ganglia. T2*-weighted echo-planar imaging (EPI), collected during functional MRI (fMRI), is sensitive to magnetic susceptibility of non-heme brain iron. Leveraging this property, we demonstrate the validity and broad applicability of an iron-sensitive metric that can be derived from conventional single-echo fMRI: ΔR2*. In a longitudinal developmental dataset (N = 151; age range 12-31), ΔR2* showed high reliability, strong longitudinal stability, and validity via robust convergence with established quantitative relaxometry-based iron measures (R2* and R2'). Critically, ΔR2* can be retrospectively estimated from extant fMRI data and derived in large-scale consortium data repositories, demonstrated here in the Adolescent Brain and Cognitive Development (ABCD) baseline cohort (N = 8,366; ages 9-11). We show that ΔR2* captures known age-related increases in basal ganglia iron, highlighting neurodevelopmental sensitivity at population-scale. Together, these findings establish ΔR2* as a reliable, widely accessible marker of basal ganglia iron, enabling scalable investigation of lifespan trajectories and neuropsychiatric risk in existing and future datasets.