Brain iron content in systemic iron overload: A beta-thalassemia quantitative MRI study

Objective: Multisystem iron poisoning is a major concern for long-term beta-thalassemia management. Quantitative MRI-based techniques routinely show iron overload in heart, liver, endocrine glands and kidneys. However, data on the brain are conflicting and monitoring of brain iron content is still matter of debate. Methods: This 3T-MRI study applied a well validated high-resolution whole-brain quantitative MRI assessment of iron content on 47 transfusion-dependent (mean-age: 36.9 +/- 10.3 years, 63% females), 23 non-transfusion dependent (mean-age: 29.2 +/- 11.7 years, 56% females) and 57 healthy controls (mean-age: 33.9 +/- 10.8 years, 65% females). Clinical data, Wechsler Adult Intelligence Scale scores and treatment regimens were recorded. Beside whole-brain R2* analyses, regional R2*-values were extracted in putamen, globus pallidum, caudate nucleus, thalamus and red nucleus; hippocampal volumes were also determined. Results: Regional analyses yielded no significant differences between patients and controls, except in those treated with deferiprone that showed lower R2*-values (p< 0.05). Whole-brain analyses of R2*-maps revealed strong age-R2* correlations (r(2) =0.51) in both groups and clusters of significantly increased R2*-values in betathalassemia patients in the hippocampal formations and around the Luschka foramina; transfusion treatment was associated with additional R2* increase in dorsal thalami. Hippocampal formation R2*-values did not correlate with hippocampal volume; hippocampal volume did not differ between patients and controls. All regions with increased R2*-values shared a strict anatomical contiguity with choroid plexuses suggesting a blooming effect as the likely cause of R2* increase, in agreement with the available histopathologic literature evidence. Conclusion: According to our MRI findings and the available histopathologic literature evidence, concerns about neural tissue iron overload in beta-thalassemia appear to be unjustified.