The study cohort consisted predominantly of males (73.6%) with a mean age of 12.2 years and diverse anthropometric characteristics. Most patients (55.6%) received blood transfusions every three weeks, while Deferasirox was the primary chelation therapy, administered to 93.1% of patients, with 91.7% following a once-daily regimen. The mean ages at diagnosis, initiation of blood transfusions, and start of chelation therapy were 13.23 months, 15.64 months, and 4.73 years, respectively.

The mothers of 70 patients (97.2%) reported that they had not undergone prenatal testing for the disease. 16 patients (22.2%) had a sibling affected with either beta-thalassemia major or minor. The majority of the patients, sixty-one (84.7%), had undergone a splenectomy.

Hemoglobin levels ranged from 5.2 to 13 g/dL (mean: 8.26), serum ferritin from 536.27 to 33,477.78 ng/mL (mean: 4150.55), and total bilirubin from 0.5 to 6.5 mg/dL (mean: 1.9). AST/SGOT and ALT/SGPT levels varied between 12–178 U/L (mean: 44.07) and 6–164 U/L (mean: 42.56), respectively. ALP ranged from 47 to 1801.5 U/L (mean: 227.04).

A significant proportion of patients exhibited moderate to severe iron accumulation across multiple organs. Myocardial iron loading was moderate in 25% and severe in 30.6% of patients. Liver iron loading, assessed by the mFFE method, was severe in 62.5% of patients, with similar trends observed using the mDIXON method (55.6% severe). Pancreatic iron loading was moderate in 44.4% and severe in 31.9% of patients.

Fig 7: Pie graphs showing frequency of myocardial iron loading (top left), pancreatic iron loading (top right), liver iron loading by mFFE (bottom left) and liver iron loading by mDIXON method (bottom right) respectively.

Myocardial, liver, and pancreatic iron loading showed significant positive correlations with serum ferritin and liver function tests.

Table 12: Summary of the correlation between different parameters along with their Pearson correlation coefficient (r) and Significance value (p value) (2-tailed).

Fig 8: 3-D stacked column showing correlation between serum ferritin levels and myocardial iron loading.

Fig 9: 3-D stacked column showing correlation between serum ferritin levels and liver iron loading by mFFE.

Fig 10: 3-D stacked column showing correlation between serum ferritin levels and liver iron loading by mDIXON.

Fig 11: 3-D stacked column showing correlation between serum ferritin levels and pancreatic iron loading.

Fig 14: Scatter plots illustrating the correlation between serum ferritin levels and LIC by mFFE (left) and by mDIXON (right).

Fig 15: Scatter plots illustrating the correlation between serum ferritin levels and pancreatic R2* (left) and between LIC and MIC (right).

Fig 16: Scatter plot illustrating the correlation between LIC and LIC by mDIXON (left) and between pancreatic R2* and MIC (right).

Among the cohort, 9.7% of patients had abnormal 2D ECHO results, while 55.6% had normal 2D ECHO findings. However, within the group with normal 2D ECHO, only 10% had normal myocardial iron levels, whereas 50% had mild iron loading, and 40% exhibited moderate to severe myocardial iron overload. Additionally, a significant proportion of these patients also showed moderate to severe iron accumulation in other organs—70% in the liver (mFFE method) (65% by mDIXON method) and 75% in the pancreas.

Fig 13: 3-D column showing frequency of patients with normal and abnormal 2D ECHOs.

Fig 22: A 14-year-old boy, diagnosed with thalassemia major at 15 days of life. mFFE T2* cardiac (bottom left), mFFE R2* cardiac (bottom right). Upon presentation, he had a serum ferritin level of 2720 ng/mL with an MIC value of 1.61 mg/g, indicating light cardiac iron loading. Notably, he had a normal 2D ECHO. He commenced blood transfusion at 15 days of life, has been regular in receiving treatment, and is currently on a low dose of chelation (Deferasirox 100 mg OD).

Fig 23: His mFFE T2* liver (top left), mFFE R2* liver (top right), mFFE T2* pancreas (bottom left), mFFE R2* pancreas (bottom right). Upon presentation, he had a serum ferritin of 2720 ng/mL, with LFT parameters as follows: Total serum bilirubin—1.72 mg/dL, AST/SGOT—56.5 U/L, ALT/SGPT—85.7 U/L, and ALP—267 U/L. His MRI revealed severe liver iron loading (LIC—16 mg/g) and moderate pancreatic iron loading (R2*—307.37/s).

Our study revealed that the mDIXON method successfully identified iron overload in cases where the mFFE method failed, particularly in severe iron overload scenarios. According to Henninger et al, R2* relaxometry can accurately quantify liver iron concentration (LIC) only till 20 mg/g when using 1.5 Tesla MRIs. [10]

Fig 17: A 15-year-old boy diagnosed with thalassemia major at the age of 3 months. Note the signal drop on the first echo of the native mFFE T2*/R2*.

Fig 18: His mFFE T2* showed negative values (top left), and both T2* and R2* (top right) displayed poor image quality, making it challenging to assess vessels and place the ROIs. In this case, mDIXON T2* R2* (bottom left, bottom right) enabled us to determine the LIC value (27.9 mg/g), indicative of severe liver iron loading.

Fig 29: mDIXON QUANT Liver images a 13-year-old boy with Thalassemia Major. T1FFE/W (top left), T1FFE/F (top middle), T1FFE/T2* (top right), T1FFE/R2* (bottom left), T1FFE/FF (bottom middle).

Here are some illustrative cases that highlight key findings from the study:

Fig 19: A 12-year-old boy with thalassemia major, diagnosed at 18 months of age. T1 axial (top left), BTFE cardiac 2 chamber (top right), and BTFE cardiac 4 chamber (bottom).

Fig 20: His T2W axial shows the liver (top left), T2W axial shows the pancreas (top right), and T2W coronal shows the liver, pancreas, and spleen (bottom). Note the intensity of these organs.

Fig 21: His mFFE R2* liver axial (left) and mFFE T2* liver axial (right). He had a serum ferritin of 3824 ng/mL and severe liver iron loading by both mFFE and mDIXON methods, with LIC values of 17.8 mg/g and 16.9 mg/g, respectively.

Fig 24: A 15-year-old boy, diagnosed with thalassemia major at 6 months of age. mFFE T2* liver (top left), mFFE R2* liver (top right), mFFE T2* pancreas (bottom left), mFFE R2* pancreas (bottom right) with ROI placement. He had a serum ferritin level of 2720 ng/mL with LFTs: total serum bilirubin—2.73 mg/dL, AST/SGOT—37.01 U/L, ALT/SGPT—8.88 U/L, and ALP—233.99 U/L. His MRI revealed moderate liver iron loading (LIC—14.4 mg/g) and light pancreatic iron loading (R2*—94.19/s). He began blood transfusions at the age of 6 months and is currently receiving them every 3 weeks. He commenced chelation therapy at 7 years of age and is currently on Deferasirox 1500 mg OD.

Fig 25: A 13-year-old boy diagnosed with thalassemia major at 6 months of age. mFFE T2* cardiac (left), mFFE R2* cardiac (right) with single ROI placement in the mid-portion of the interventricular septum. Upon presentation, he had a serum ferritin level of 2409 ng/mL and a normal 2D ECHO. His MRI showed a T2* of 24.62 ms, R2* of 41.17, and MIC of 1.24 mg/g, indicative of light cardiac iron loading. He began blood transfusions at the age of 6 months and is currently receiving them every 3 weeks. He commenced chelation therapy at 5 years and is currently on Deferasirox 1000 mg OD.

Fig 26: His mDIXON T2* liver (left), mDIXON R2* liver (right) with ROI placement. The mean values were used. Upon presentation, he had a serum ferritin level of 2409 ng/mL with LFT parameters as follows: Total serum bilirubin—1.1 mg/dL, AST/SGOT—28.3 U/L, ALT/SGPT—22.65 U/L, and ALP—114.2 U/L. His MRI revealed T2* of 1.18 ms, R2* of 842.77/s, and LIC of 1.24 mg/g, suggestive of severe liver iron loading.