Eliana Cracolici

Multislice multiecho T2* cardiovascular magnetic resonance for detection of the heterogeneous distribution of myocardial iron overload

To assess the tissue iron concentration of the left ventricle (LV) using a multislice, multiecho T2* MR technique and a segmental analysis.

Evaluation of the efficacy of oral deferiprone in β-thalassemia major by multislice multiecho T2

Abstract:  Objectives: Oral deferiprone (L1) appears to be promising in the treatment of β‐thalassemia major (TM) patients. T2* magnetic resonance imaging (MRI) with a single measurement in the mid‐ventricular septum was validated as a quantitative evaluation of myocardial iron overload. Previous studies suggested a marked heterogeneity of iron distribution in the myocardium. We set up a multislice multiecho T2* MRI for the detection of this heterogeneity. The aim of our study was to investigate differences between the L1 vs. the subcutaneous desferrioxamine (DF)‐treated patients using this new approach.Methods: Thirty‐six β‐TM patients (age 29 ± 8 yr) underwent MRI. Eighteen patients received long‐term L1, and 18 other patients matched for age and sex received DF. T2* multiecho sequences on three short axis views of the left ventricle were obtained and analyzed by custom‐made software. In each slice, the myocardium was automatically segmented into four segments. Cine‐dynamic images were also obtained to evaluate biventricular function.Results: For multislice T2* technique, the coefficient of variation for intra‐ and inter‐observer, and inter‐study reproducibility was 3.9%, 4.7%, and 5.5%, respectively. The global heart T2* value was significantly higher in the L1 vs. DF group (35 ± 7 vs. 27 ± 2 ms; P = 0.02). The number of segments with normal T2* value (>20 ms) was significantly higher in the L1 vs. the DF group (11 ± 1 vs. 8 ± 5 segments; P = 0.03). We did not detect significant differences in biventricular function parameters.Conclusions: This new approach confirms that L1 could be more effective than DF in removal of myocardial iron.

Improved T2* assessment in liver iron overload by magnetic resonance imaging

In the clinical MRI practice, it is common to assess liver iron overload by T2* multi-echo gradient-echo images. However, there is no full consensus about the best image analysis approach for the T2* measurements. The currently used methods involve manual drawing of a region of interest (ROI) within MR images of the liver. Evaluation of a representative liver T2* value is done by fitting an appropriate model to the signal decay within the ROIs vs. the echo time. The resulting T2* value may depend on both ROI placement and choice of the signal decay model. The aim of this study was to understand how the choice of the analysis methodology may affect the accuracy of T2* measurements. A software model of the iron overloaded liver was inferred from MR images acquired from 40 thalassemia major patients. Different image analysis methods were compared exploiting the developed software model. Moreover, a method for global semiautomatic T2* measurement involving the whole liver was developed. The global method included automatic segmentation of parenchyma by an adaptive fuzzy-clustering algorithm able to compensate for signal inhomogeneities. Global liver T2* value was evaluated using a pixel-wise technique and an optimized signal decay model. The global approach was compared with the ROI-based approach used in the clinical practice. For the ROI-based approach, the intra-observer and inter-observer coefficients of variation (CoVs) were 3.7% and 5.6%, respectively. For the global analysis, the CoVs for intra-observers and inter-observers reproducibility were 0.85% and 2.87%, respectively. The variability shown by the ROI-based approach was acceptable for use in the clinical practice; however, the developed global method increased the accuracy in T2* assessment and significantly reduced the operator dependence and sampling errors. This global approach could be useful in the clinical arena for patients with borderline liver iron overload and/or requiring follow-up studies.

CARDIAC IRON AND CARDIAC DISEASE IN MALES AND FEMALES WITH TRANSFUSION-DEPENDENT THALASSEMIA MAJOR: A T2* MAGNETIC RESONANCE IMAGING STUDY

Background It has been repeatedly reported that female patients with thalassemia major survive longer than males and that the difference is due to a lower rate of cardiac disease in females. Design and Methods We compared the cardiac iron load as measured by T2* magnetic resonance imaging in 776 patients (370 males) examined at the National Research Council as part of an Italian cooperative study. We also established normal left ventricular ejection fraction values for our population. Results The prevalence of cardiac disease was higher in males than in females (105 males versus 69 females; P<0.0001). Cardiac T2* was significantly lower in patients with heart dysfunction (P<0.0001), but no difference was observed according to sex. Twenty males and five females had a history of cardiac arrhythmias. Their cardiac T2* was not significantly lower than that of patients without arrhythmias (24 ms versus 26 ms; P=0.381), nor was there a difference between sexes. Liver T2* was significantly lower in males and females with heart dysfunction compared to those without. Ferritin levels were higher in patients of both sexes with heart dysfunction without significant differences between males and females. Conclusions Males and females are at the same risk of accumulating iron in their hearts, but females tolerate iron toxicity better, possibly as an effect of reduced sensitivity to chronic oxidative stress.

Myocardial scarring by delayed enhancement cardiovascular magnetic resonance in thalassaemia major

Background: Cardiovascular magnetic resonance (CMR) by delayed enhancement (DE) enables visualisation of myocardial scarring, but no dedicated studies are available in thalassaemia major. Objective: To investigate the prevalence, extent, clinical and instrumental correlates of myocardial fibrosis or necrosis by DE CMR in patients with thalassaemia major. Patients: 115 Patients with thalassaemia major consecutively examined at an MRI laboratory. Methods: DE images were acquired to quantify myocardial scarring. Myocardial iron overload was determined by multislice multiecho T2*. Cine images were obtained to evaluate biventricular function. Results: DE areas were present in 28/115 patients (24%). The mean (SD) extent of DE was 3.9 (2.4)%. In 26 patients the location of fibrosis was not specific and patchy distribution was prevalent. Two patients showed transmural DE following coronary distribution. The DE group was significantly older than the no-DE group (31 (7.7) years vs 26 (7.7) years, p = 0.004). No significant relation with heart T2* values and biventricular function was found. A significant correlation was found between the presence of DE and changes in ECG (ECG abnormal in the DE group 22/28 patients and in the no-DE group 30/87 patients; χ2 = 14.9; p<0.001). Conclusions: In patients with thalassaemia the significant presence of myocardial fibrosis/necrosis seems to be a time-dependent process correlating with cardiovascular risk factors and cardiac complications. Levels of HCV antibodies are significantly higher in the serum of patients with thalassaemia with myocardial fibrosis/necrosis. ECG changes showed a good accuracy in predicting myocardial scarring.

Single region of interest versus multislice T2* MRI approach for the quantification of hepatic iron overload

To evaluate the effectiveness of the single ROI approach for the detection of hepatic iron burden in thalassemia major (TM) patients in respect to a whole liver measurement.

Multislice multiecho T2* cardiac magnetic resonance for the detection of heterogeneous myocardial iron distribution in thalassaemia patients

The present study investigated myocardial T2* heterogeneity in thalassaemia major (TM) patients by cardiac magnetic resonance (CMR), to determine whether is related to inhomogeneous iron overload distribution. A total of 230 TM patients consecutively referred to our laboratory were studied retrospectively. Three short‐axis views (basal, medium and apical) of the left ventricle (LV) were obtained by multislice multiecho T2* CMR. T2* segmental distribution was mapped on a 16‐segment LV model. The level of heterogeneity of the T2* segmental distribution, evaluated by the coefficient of variation (CoV), was compared with that of a surrogate data set, to determine whether the inhomogeneous segmental distribution of T2* could be generated by susceptibility artefacts. Susceptibility artefacts offer an explanation for the T2* heterogeneity observed in patients without iron overload. In subjects with global T2* below the lower limit of the normal, T2* heterogeneity increased abruptly which could not be explained by artefactual effects. Some segmental T2* values were below and others above the limit of normal threshold (20 ms) in 104 (45%) TM patients. Among these patients, 74% showed a normal T2* global value. In conclusion, a true heterogeneity in the iron overload distribution may be present in TM patients. Heterogeneity seemingly appears in the borderline myocardial iron and stabilizes at moderate to severe iron burden. Copyright

A T2* MRI prospective survey on heart iron in thalassemia major patients treated with deferasirox versus deferiprone and desferrioxamine in monotherapy

Excellent/good levels of compliance were similar in the 3 groups (DFX 99%, DFP 95%; DFO 96%, P =0 .6). There were no significant differences in all 3 groups to maintain the patients without significant myocardial iron overload (global heart T2*≥20 ms) (DFX 98%; DFP 100%; DFO 98%; P=1.0). The percentage of patients that maintained a normal LVEF (>57%) was significantly lower in DFX (77%) versus DFP (100%) (P=0.018), it was no significantly different in DFX and DFO group (82%) (P=0.59). Among the patients with myocardial iron overload at baseline in all 3 groups, there was a significant improvement in the global heart T2* value and in the number of segment with a normal T2* value; only in the DFP group there was a significant improvement in the right global systolic function (+ 6.8% P =0.016). The improvement in the global heart T2* was significantly lower in the DFX versus the DFP group (P=0.0026), but it was not significantly different in the DFX versus the DFO group (mean difference global heart T2* 3.5±4.7 ms versus 8.8±8.6 ms and versus 3.7±5.5 ms, respectively; P=0.90) (Figure 1). The changes in the global systolic biventricular function were not significantly different among groups. Conclusions

Prospective comparison on cardiac iron by MR in thalassemia major patients treated with combination deferipron-desferrioxamine versus deferipron and desferrioxamine in monoterapy

Background Combination therapy with deferipron and desferrioxamine (DFP+DFO) seems more effective than DFP and DFO in monotherapy in removing myocardial iron. However, no data are available in literature about prospective comparisons on cardiac iron and function in TM patients treated with DFP+DFO versus DFP and DFO in monotherapy. Aim: The aim of this multi-centre study was to assess prospectively in a large clinical setting the efficacy of the DFP+DFO versus DFP and DFO in TM patients by quantitative MR. Methods

CMR T2* technique for segmental and global quantification of myocardial iron: multi-centre transfereability and healtcare impact evalaution

in each patient for both sequences. Differences between functional parameters and LV mass were made with a paired Student’s T test; correlation between parameters was assessed with Pearson’s correlation coefficient. A Bland-Altman analysis was used to investigate the limits of agreement between the measurements. Differences between time-efficiency related parameters were made with a paired Student’s T test. Results: Functional parameters and mass were significantly different in the two sequences (p < 0.05) but a strong correlation was found for LVejection fraction (r = 0.96) and good correlation for other functional parameters (r between 0.83 and 0.93). Scan time was significantly lower for 3D sequence, report timewas significantly higher for 3D sequence. Conclusion: 3D k-t BLAST sequence can be used to assess EF in patients who have poor compliance in performing multiple apnoeas and in patients who are not able to remain in the scanner for a long time. Conversely report time is significantly higher for 3D sequence.