Quantitative MR Imaging of Brain Iron: A Postmortem Validation Study

Abstract

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.