Non-invasive Quantitative MRI assessment of brain iron overload in patients with BThalassemia and Sickle cell disease

Abstract

Abstract Background B-Thalassemia, sickle cell disease (SCD) and other inherited hemoglobin disorders are considered the most prevalent monogenic diseases worldwide. Secondary iron overload is one of the major complications in such groups of patients affecting many organs (e.g. liver, heart and endocrinal glands). Objective The current study will assess brain iron content ( using R2* values ) in the caudate and thalamic regions through quantitative brain MRI study in B-Thalassemia and SCD patients in comparison to age and sex-matched healthy controls. Also evaluation of the association with LIC (liver iron concentrations) and MIC (myocardial iron concentrations) was done. Methods A case control study on 30 patients (15 with B-thalassemia major and 15 with SCD) and 11 age and sex-matched healthy controls was carried out in the period between August 2018 till August 2019. Brain MRI study using multiecho fast gradient echo sequence was done for all the patients and controls. Brain R2* values of both caudate and thalamic regions (right and left sides) were calculated. Also brain R2* values were correlated with the LIC and HIC in B-thalassemia and SCD groups. Results 15 transfusion dependent B-thalassemia (mean-age: 19.40 ± 4.31 years, 53.3% females), 15 SCD patients (SCD; mean-age: 16.93 ± 3.41 years, 40.6% females) and 11 age and sex matched healthy controls (HC; mean age: 18.73 ± 4.84 years, 54.5% females) were enrolled in the study. No statistically significant differences were found between SCD and control group in all regions of interests No statistically significant differences were found between the three subgroups (p > 0.05) in right thalamus, left and right caudate regions. However, in B-thalassemia subgroup, patients had moderately significantly higher R2* values compared to the controls and SCD patients as regards the left thalamic region with mean R2* values (16.69 ± 1.34) Hz compared to (15.65 ± 1.10) Hz in the control group (p = 0.021) and (15.79 ± 0.77) Hz in the SCD group (p = 0.029). There were no significant correlations between LIC and HIC with brain R2* values of all regions of interests in both B-thalassemia and SCD subgroups. Conclusion MRI is a valuable, reliable, safe and noninvasive method for quantifying iron concentration (in cases of iron overload) in many organs as the liver and heart and it is now used internationally for regular follow up of LIC and HIC for monitoring of the chelation therapy in B-thalassemia and SCD patients. The results of our study showed that even in cases of iron overload which affects vital organs as the liver, cardiac and brain iron overload don't occur. This may be explained by heavy chelation therapy regimens given to our patients due to their poor compliance so as to keep the pre-transfusion hemoglobin level above 10mg/dl to prevent detrimental cardiac affection as cardiac siderosis, arrhythmias including heart block, or even heart failure.