Does quantitative susceptibility mapping elucidate age-related alterations in deep gray matter iron deposition? A systematic review.

Age-related iron accumulation in the brain is linked to neurodegenerative processes, contributing to neuronal damage and functional decline. Quantitative Susceptibility Mapping (QSM), an advanced MRI technique, provides superior sensitivity for assessing iron deposition in vivo compared to traditional methods like R2* and susceptibility-weighted imaging (SWI). This systematic review evaluates QSM's ability to detect age-related iron changes in healthy aging populations, focusing on technical and methodological considerations. Following PRISMA guidelines, we searched Embase, MEDLINE, Scopus, and Web of Science for studies (2015-2025) using QSM to assess brain iron in healthy aging. Included studies reported susceptibility changes in brain nuclei. Data on study characteristics, QSM values, reference regions, and processing methods were extracted. Quality was assessed using the Newcastle-Ottawa Scale. A narrative synthesis was conducted due to methodological heterogeneity. From 110 records, 12 studies with 2,178 participants were included. Consistent increases in magnetic susceptibility, indicating iron accumulation, were observed in the caudate nucleus and putamen. The red nucleus, substantia nigra, and dentate nucleus showed increased susceptibility in most studies, while the hippocampus and thalamus exhibited variable, age-dependent patterns. Methodological diversity in QSM acquisition and processing (phase unwrapping, background field removal, dipole inversion) contributed to variability. QSM could effectively detect age-related cerebral iron deposition, especially in deep gray matter nuclei, with implications for understanding brain aging and neurodegenerative risk. Standardized protocols and longitudinal studies are needed to improve comparability and clarify temporal dynamics. QSM's sensitivity makes it a valuable biomarker for distinguishing normal aging from pathological processes, informing future diagnostic and therapeutic strategies.