Objective: To characterize the dynamics of age-dependent iron accumulation in the brain with susceptibility-weighted imaging (SWI).

Background: Neurodegeneration with brain iron accumulation (NBIA) is characterized by pathological iron accumulation in the subcortical nuclei. Recently, iron deposition lining the putamen and cortex was reported as a diagnostic marker for neuroferritinopathy (subtype of NBIA), however age-related studies in healthy subjects are lacking. Therefore, it is fundamental to first understand the natural age-related dynamics of iron deposition in the healthy brain prior to using iron accumulation as potential prognostic or diagnostic tool in neurodegenerative disorders.

Methods: The quantity of iron accumulation was assessed using the ratio of signal intensity of SWI in five brain nuclei (caudate nucleus, putamen, globus pallidus, red nucleus and dentate nucleus) compared to the lateral ventricle as a background intensity. This was done in 81 healthy volunteers ranging from the first till the eight decade of life. In addition, the presence of pencil lining of the cortex and putamen was scored in these subjects, as well as in two genetically confirmed patients suffering from neurodegeneration with brain iron accumulation (NBIA). All scans were performed on 1.5T MRI and analyzed by an experienced neuroradiologist.

Results: Positive correlations were found between age and SWI intensity, a reflection of iron accumulation, in all subcortical nuclei studied in healthy subjects. Brain iron content over time showed a dynamic course, especially early in life, that differed between the various subcortical nuclei (p < 0.001). Cortical and putaminal pencil lining occurred from the 2nd to the 8th decade of life and was present in 100% of the subjects older than 50 and 20 years of age for the cortex and putamen, respectively.

Conclusions: This study showed that brain iron content is dynamic, especially in early life. Therefore the level of age-related iron content in healthy subjects should be taken into account before using SWI as potential diagnostic or prognostic tool in NBIA. Furthermore, the dichotomous characterization of presence or absence of cortical and/or putaminal pencil lining may not be a useful marker to discriminate between the genetically different NBIA subtypes and between NBIA patients and healthy subjects, but potentially its quantification.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dynamics-of-brain-iron-content-and-cortical-pencil-lining-in-healthy-aging-an-mri-study/