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Synopsis

Toquantify the iron loading in the whole body among transfusion-dependentpatients, 32 transfusion-dependent patients and 32 healthy volunteers wererecruited to participate in this study. The quantitative susceptibility mappingwas processed to get the susceptibility of the ROIs in the brain, and T2*valuesof their livers, pancreas and myocardium. Significantly higher iron levels inthe putamen were found in transfusion-dependent patients(right/left=0.147±0.066/0.149±0.811ppm) compared withhealthy controls(right/left=0.064±0.037/0.060±0.326ppm) (P=0.021/0.011). A ROC curve was performed, and the results suggested thatliver T2* and pancreas T2* values can be great predictors to diagnose the ironoverload in the brain ( AUC=0.877, 0.974, P<0.01).

Target audience

Thoseinterested in hematological disease and radiologists, scientist and MRIresearchers.

PURPOSE

Transfusion-dependentdisease (TDD) is a kind of chronic disease which includes β-thalassemiamajor, myelodysplastic syndromes (MDS), and aplastic anemia(AA). Patientswith this disease depend on regular transfusions of packedred blood cells (PRBC) during the course of treatment. Long-term transfusion treatment can lead to iron deposits indifferent organs, including the brain, heart, liver and pancreas, and causes organdysfunction. Serum ferritin (SF), despite being the biomarker of choice forestimating blood iron concentration, cannot measure the organs’ iron depositionand can be easily affected by inflammation, alcohol-related cirrhosis or theonset of viral infection. Needle biopsy cannot be widely used because it isinvasive and carries a high risk of bleeding among patients with TDD. In thisstudy, we used quantitative susceptibility mapping (QSM)1 in brainiron evaluation, and quantified iron loading in the different brain areas amongpatients with TDD We found a relationship between the brain iron and pancreas,heart or liver iron. Furthermore, we want to find the bestpredictor for brain iron among liver, pancreas or myocardiumT2* value.

METHODS

32 TDD patients and 32 healthy volunteers participated in this study. Thegroups were matched for age. Patients in the acute inflammation or infection stageand patients with tumors were excluded. Venous blood was collected to test SFon the day of the MR scan. The MRI examincluded 6-echo gradient-echo SWI sequence covering the full brain, 8-echo Dixon sequence in the abdominal and 8-echo FLASH sequence in the heart. All data were collectedon a Siemens MAGNETOM Trio Tim system 3.0T MR scanner (SiemensHealthcare, Erlangen, Germany). The parameters are as follows: Brain SWI: TR=28ms,TE=20ms, flip angle=15°, 64 slices, slicethickness=2 mm, distance factor=20%, FOV=230×172.5 mm2, Voxel size: 1.0×0.5×2.0 mm3,measurements=1. Abdominal 8echo-Dixon sequence: TR=11.4 ms, TE= 1.17/2.39/3.68/4.92/6.14/7.36/8.58/9.80 ms,flip angle=10°, 40 slices, slice thickness=5 mm, distance factor=20%, FOV=420×315 mm2,Voxel size: 2.4×1.6×5.0mm3, measurements=1, Resp. control:Breath-hold, Dimension=3D; Myocardium FLASH sequence: TR=730ms, TE= 2.7/5/7.3/9.6/11.9/14.2/16.5/18.80ms,flip angle=18°, 1 slices, slice thickness=8.0 mm, distance factor=20%, FOV=380×285mm2,Voxel size: 2.5×1.5×8.0mm3, measurements=1, ECG/Trigger. The T2*(R2*) values of liverpancreas and myocardium were analyzed from R2*map using the Siemens syngo workstation.MEDI Toolbox (Cornell MRI Research Lab, USA) and MATLAB R2014a (MathWorks, Inc,US) were used to reconstruct the Quantitative Susceptibility Map (QSM) in figure1. Then the susceptibility ofbrain areas were analyzed from QSM using ImageJ 1.48v software (NationalInstitutes of Health,USA). The ROIs of brain included head of nucleus caudate (HNC),putamen (PT), globuspallidus (GP), red nucleus(RN),substantia nigra (SN) and corpora dentatum (CD).Two sampled t-test was usedto compare between TDD and healthy controls. Then we investigated the diagnosticvalue of liver, pancreas and myocardium T2* (figure2) cutoff points based onROC curve.

RESULTS

Significantly higher levels of PT were present in transfusion-dependentpatients (right/left=0.147±0.066/0.149±0.811ppm) compared with healthy controls(right/left=0.064±0.037/0.060±0.326ppm)(P=0.021/0.011). No differences were found in HNC, GP, RN, SN and CD betweenTDD patient group and the control group (P>0.05). ROC curve analysis wasperformed (Figure 3) and suggested that liver T2* and pancreas T2* values canbe great predictors to diagnose the iron overload in the brain (AUC=0.877,0.974, P<0.01). The T2* values ofliver and pancreas at the best cut-off point are 11.9 ms and 34.8ms, respectively.

DISCUSSION

MRI was gradually acceptedfor clinical use as a non-invasive method and can be used for monitoring thechanges of iron concentration in different organs. In this study, we comparedthe iron loading in different organs. The results could show the iron loading processin the whole system.

CONCLUSION

TDD can lead to iron overload in the brain, especially in the putamen. The T2* values of liver and pancreas can be a great predictor for iron overload in the brain.

Acknowledgements

No acknowledgement found.

References

1. Wang Y, Liu T. Quantitative susceptibilitymapping (QSM): decoding MRI data for a tissue magnetic biomarker[J]. MagneticResonance in Medicine, 2015, 73(1): 82-101.
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