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|Number 10-15: T2* CMR to Tailor Chelation Therapy in Thalassemia Major|
Number 10-15: T2* CMR to Tailor Chelation Therapy in Thalassemia Major
Case from: Alessia Pepe, Vincenzo Positano, Massimo Lombardi
History: A 35 year old male with beta-thalassemia major, regularly transfused since the age of 30 months, started chelation treatment with subcutaneous desferrioxamine at the age of 4 years. He is currently asymptomatic. Due to his age and the history of poor compliance with the chelation therapy during childhood, he was referred to our unit for quantitative evaluation of myocardial and liver iron load and assessment of biventricular function. The last echocardiogram 6 months prior to the current CMR showed normal LV size and ejection fraction.
CMR I: Standard SSFP cines images (Movie 1) showed a dilated LV (EDVi = 113 ml/m2) with global systolic dysfunction (EF 49%, indicative of a moderate impairment considering the chronic anaemic status of the patient). The RV was borderline in terms of size and ejection fraction. Of note, references ranges for LV function in thalassaemia major patients are different to the usual reference ranges, related to the chronic anaemia.
Cardiac and liver T2* iron load measurements I:
The iron, when present in an intracellular location in the form of haemosiderin, forms focal clusters of magnetic inhomogeneity. The presence of these clusters results in a dramatic reduction in the protons' transverse relaxation time T2*. T2* imaging is accomplished using a breath-hold multiple echo gradient pulse sequence to acquire a series of images with increasing echo times (Movie 2). The mean signal intensity within the region of interest is determined for each image in the series and is then plotted as a function of echo times (Figure 1). T2* values are then calculated by fitting the mean signal intensity data to a decay curve. The higher the slope of the decay curve, the lower the T2* value is, indicating higher iron burden.
In our institution we use the following reference tables for determining iron loading burden (Table 1)
In our patient, heart T2* images to assess iron loading were analyzed using the HIPPO MIOT® software (Movie 2). The bull's eye plot maps into a 2D representation the 3D distribution of the T2* values over the left ventricle. Each ring of the bull's eye corresponds to a short axis slice. The apical slice corresponds to the internal ring, the basal slices to the external ring. Radial segmentation of the Bull's eye follows the American Heart Association guidelines (6 segments for basal and middle slices, four segments for apical slice).
Cardiac and liver T2* iron load measurements II: Heart T2* measurements on the follow-up CMR scan (Figure 2) 12 months later showed a significant reduction of myocardial iron overload. There was still a persistent and homogeneous myocardial iron burden with all cardiac LV segments having T2* values < 20 ms. However, the global heart T2* measurement was 13ms, confirming moderate overall myocardial iron loading, which was improved since the initial evaluation 12 months earlier.
Cardiac and liver T2* iron load measurements III: Heart T2* measurements on the follow-up CMR scan (Figure 3) 24 months after the initiation of the combined therapy showed a dramatic reduction of the cardiac iron burden, with the absence of myocardial iron loading. All LV segments showed T2* values > 20 ms, and the global heart T2* measurement was 30 ms (Figure 2).
CMR III: Standard SSFP cine images on follow-up CMR examination 24-months after the initiation of the intensive chelation regimen, demonstrated a significant improvement in LV systolic function with an LVEF of 60% (Movie 3).
Figure 4 compares the normalized decay curve of the patient in the three follow up CMR examinations. The slowing of the signal decay with the increase of the T2* value is well visible.
2) Ramazzotti A, Pepe A, Positano V, Rossi G, De Marchi D, Brizi MG, Midiri M, Valeri G, Sallustio G, Luciani A, Caruso V, Centra M, Cianciulli P, De Sanctis V, Maggio A, Lombardi M. Multicenter validation of the magnetic resonance T2* technique for segmental and global quantification of myocardial iron. J Magn Reson Imaging. 2009 Jun 25;30(1):62-8.
3) Noetzli LJ, Carson SM, Nord AS, Coates TD, Wood JC. Longitudinal analysis of heart and liver iron in thalassemia major. Blood. 2008 Oct 1;112(7):2973-8.
4) Modell B, Khan M, Darlison M, Westwood MA, Ingram D, Pennell DJ. Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2008;10(1):42.
5) Wood JC, Enriquez C, Ghugre N, Tyzka JM, Carson S, Nelson MD et al. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood. 2005 Aug;106:1460-5.