MR Quantitative Susceptibility Imaging for the Evaluation of Iron Loading in the Brains of Patients with β-Thalassemia Major

BACKGROUND AND PURPOSE:Patients with β-thalassemia require blood transfusion to prolong their survival, which could cause iron overload in multiple organs, including the heart, liver, and brain. In this study, we aimed to quantify iron loading in the brains of patients with β-thalassemia major through the use of MR quantitative susceptibility imaging.MATERIALS AND METHODS:Thirty-one patients with thalassemia with a mean (± standard deviation) age of 25.3 (±5.9) years and 33 age-matched healthy volunteers were recruited and underwent MR imaging at 3T. Quantitative susceptibility images were reconstructed from a 3D gradient-echo sequence. Susceptibility values were measured in the caudate nucleus, putamen, globus pallidus, red nucleus, substantia nigra, dentate nucleus, and choroid plexus. General linear model analyses were performed to compare susceptibility values of different ROIs between the patients with thalassemia and healthy volunteers.RESULTS:Of the 31 patients, 27 (87.1%) had abnormal iron deposition in one of the ROIs examined. Significant positive age effect on susceptibility value was found in the putamen, dentate nucleus, substantia nigra, and red nucleus (P = .002, P = .017, P = .044, and P = .014, respectively) in the control subjects. Compared with healthy control subjects, patients with thalassemia showed significantly lower susceptibility value in the globus pallidus (P < .001) and substantia nigra (P = .003) and significantly higher susceptibility value in the red nucleus (P = .021) and choroid plexus (P < .001).CONCLUSIONS:A wide range of abnormal susceptibility values, indicating iron overloading or low iron content, was found in patients with thalassemia. MR susceptibility imaging is a sensitive method for quantifying iron concentration in the brain and can be used as a potentially valuable tool for brain iron assessment.

Beta-thalassemia major is a disease caused by genetic defects that lead to reduced production of hemoglobin. The patients require blood transfusion to prolong their survival, which could cause iron overload in multiple organs, including the heart, liver, and brain.¹ Iron chelation therapy is administrated to clear the excess iron. Whereas iron overload in the heart and liver may cause death, alterations of iron content in the brain may contribute to cognitive impairment, as observed in some patients with thalassemia,^2,3 which has not been found to correlate with age and blood ferritin levels. Accurate assessment of iron content in the brains of patients with thalassemia could provide valuable information for individualized patient treatment. Conventionally, MR relaxometry on the basis of methods that use T2 and T2* mapping has been used to quantify iron in the brain.⁴ Recently, the application of measuring brain iron by use of phase value of MR imaging with SWI^5,6 and quantitative susceptibility mapping (QSM)^7–12 has been evaluated for the quantification of iron content in patients with Parkinson disease.¹³ QSM is an MR imaging technique that measures the magnetic susceptibility of tissues, such as blood or iron content, through mathematically modeling their induced effects on the phase of signal. Although the derivation of a magnetic susceptibility image from the phase information obtained from MR imaging is an ill-posed problem, techniques have been established to overcome this by imposing smoothness or sparseness constraints on the susceptibility images.^9–11 QSM has been successfully applied in multiple sclerosis, Parkinson disease, and so forth. A recent study¹⁴ has also established positive correlation between magnetic susceptibility values measured by use of QSM and iron content measured by x-ray fluorescence imaging and inductively coupled plasma mass spectrometry. In the present study, we quantified the brain iron content in a cohort of patients with β-thalassemia major and compared this with healthy age-matched subjects. We hypothesize that there are significant differences in iron loading between patients with thalassemia and healthy control subjects as measured by QSM.