Whole-Brain Analysis of Increased Brain Iron in Patients with β-Thalassemia.

RATIONALE AND

OBJECTIVES

β-thalassemia (β-TM) is an inherited hematological disorder characterized by impaired hemoglobin synthesis, leading to chronic anemia and systemic iron overload. While numerous studies have documented widespread iron deposition caused by repeated blood transfusions and disrupted iron metabolism, the impact of iron overload on the brain remains poorly understood. This study aimed to investigate whole-brain iron accumulation in patients with β-TM using quantitative susceptibility mapping (QSM).

METHODS

A total of 88 patients with transfusion-dependent β-TM and 57 age and sex matched healthy controls (HCs) were enrolled. Brain iron levels were assessed using QSM, and voxel-based statistical analyses were conducted to compare intergroup differences in cerebral iron deposition. Statistical significance was determined using family-wise error (FWE) correction for multiple comparisons, with a voxel-level threshold set at p < 0.001 (FWE-corrected) and cluster-level significance at p < 0.05 (FWE-corrected). In addition, a support vector machine (SVM) model was employed to evaluate the discriminatory power of QSM values in distinguishing β-TM patients from HCs.

RESULTS

Compared to HCs, patients with β-TM exhibited significantly increased iron deposition in multiple brain regions, including bilateral cerebellar lobule VIII, right cerebellar lobule III, bilateral middle and superior temporal gyri, left inferior temporal gyrus, right hippocampus, bilateral fusiform gyri, right precuneus, bilateral orbital middle frontal gyri, left orbital inferior frontal gyrus, left medial superior frontal gyrus, right lingual gyrus, bilateral medial and paracingulate gyri, and bilateral supplementary motor areas (p < 0.05). Among β-TM patients, QSM values in several regions showed a positive correlation with Hamilton Anxiety Rating Scale (HAMA) scores and a negative correlation with Montreal Cognitive Assessment (MoCA) scores. Furthermore, the SVM model demonstrated high discriminative performance in separating β-TM patients from HCs (area under the curve [AUC] = 0.937; average classification accuracy = 93.8%).

CONCLUSION

This study provides the first neuroimaging evidence of increased cerebral iron deposition in patients with transfusion-dependent β-TM, suggesting that systemic iron overload may have potential neurobiological effects on the central nervous system. These findings highlight the potential of QSM as a neuroimaging marker for early central nervous system (CNS) involvement in β-TM and support its role in guiding chelation-based interventions.