Abstract
Strict iron regulation is essential for normal brain function. The main iron compounds responsible for iron homeostasis, transferrin and ferritin, are distributed heterogeneously across the brain and are implicated in aging, neurodegenerative diseases and cancer. However, non-invasive discrimination between iron compounds, such as transferrin and ferritin, remains a challenge. We present a novel magnetic resonance imaging (MRI) technology for mapping of iron compounds in the living brain (the r1-r2* relaxivity). The specificity of the r1-r2* relaxivity to the presence of ferritin and transferrin is validated by both bottom-up and top-down approaches, incorporating in vitro, in vivo and ex vivo analyses. In vitro, our MRI approach reveals the distinct paramagnetic properties of ferritin and transferrin. In the in vivo human brain, we validate our approach against ex vivo iron compounds quantification and gene expression. Our approach predicts the transferrin-ferritin fraction across brain regions and in aging. It reveals brain tumors’ iron homeostasis, and enhances the distinction between tumor tissue and non-pathological tissue without contrast agents. Therefore, our approach may allow for non-invasive research and diagnosis of iron homeostasis in living human brains.
Competing Interest Statement
The authors have declared no competing interest.