Quantitative MR Imaging of Brain Iron: A Postmortem Validation Study

Abstract

To investigate the relationship between transverse relaxation rates R2 and R2*, the most frequently used surrogate markers for iron in brain tissue, and chemically determined iron concentrations. This study was approved by the local ethics committee, and informed consent was obtained from each individual's next of kin. Quantitative magnetic resonance (MR) imaging was performed at 3.0 T in seven human postmortem brains in situ (age range at death, 38-81 years). Following brain extraction, iron concentrations were determined with inductively coupled plasma mass spectrometry in prespecified gray and white matter regions and correlated with R2 and R2* by using linear regression analysis. Hemispheric differences were tested with paired t tests. The highest iron concentrations were found in the globus pallidus (mean ± standard deviation, 205 mg/kg wet mass ± 32), followed by the putamen (mean, 153 mg/kg wet mass ± 29), caudate nucleus (mean, 92 mg/kg wet mass ± 15), thalamus (mean, 49 mg/kg wet mass ± 11), and white matter regions. When all tissue samples were considered, transverse relaxation rates showed a strong linear correlation with iron concentration throughout the brain (r² = 0.67 for R2, r² = 0.90 for R2*; P < .001). In white matter structures, only R2* showed a linear correlation with iron concentration. Chemical analysis revealed significantly higher iron concentrations in the left hemisphere than in the right hemisphere, a finding that was not reflected in the relaxation rates. Because of their strong linear correlation with iron concentration, both R2 and R2* can be used to measure iron deposition in the brain. Because R2* is more sensitive than R2 to variations in brain iron concentration and can detect differences in white matter, it is the preferred parameter for the assessment of iron concentration in vivo.