Magnetic Properties of Ferritin at Different Levels of Degradation: Implications for MRI‐Based Iron Quantification in the Brain

TL;DR

This study investigates how ferritin's magnetic properties change as it degrades, which is important for accurately measuring brain iron levels using MRI.

Contribution

The study provides new insights into the magnetic behavior of ferritin and its implications for postmortem MRI-based iron quantification.

Findings

Ferritin molecules degrade rapidly postmortem, with less than one-third detectable after 24 hours.

R2* relaxation rates correlate with total iron content, not ferritin degradation.

Ferritin behaves as a simple paramagnet, not an antiferromagnet, at room temperature.

Abstract

Ferritin's iron core exhibits complex magnetic properties, as suggested by magnetometry and Mössbauer spectroscopy, which remain incompletely understood. In particular, the antiferromagnetic inner core could influence the accuracy of iron quantification using MRI and raise concerns about postmortem validation studies involving degraded ferritin cores.

Fresh postmortem brain samples from six deceased human subjects were analyzed using energy‐filtered transmission electron microscopy (EFTEM) and electron energy loss spectrometry in scanning mode of the TEM (STEM‐EELS) to visualize and quantify the iron cores of ferritin proteins and estimate their iron content. EFTEM findings were compared with results from mass spectrometry and R2* mapping at 3T. Analyses focused on three gray matter regions including the frontal cortex, putamen, and globus pallidus.

Autolysis led to a rapid degradation of ferritin molecules, with fewer than one‐third remaining detectable via EFTEM 24 h postmortem. The degradation followed a single‐exponential decay pattern, suggesting that almost the entire non‐heme iron is stored in ferritin. However, R2* relaxation rates did not follow this degradation pattern but instead correlated strongly with total iron content as measured by mass spectrometry.

R2* mapping‐derived magnetic susceptibility of ferritin appears to be independent of the structural and magnetic organization of its iron core and shows a linear relationship with total iron content. These findings support the interpretation of ferritin as a simple paramagnet at room temperature, without significant antiferromagnetic contributions. Consequently, susceptibility based postmortem studies focusing on iron accumulation are not affected by autolysis.

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