Anna Ramazzotti

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.

Multicenter validation of the magnetic resonance t2* technique for segmental and global quantification of myocardial iron

To assess the transferability of the magnetic resonance imaging (MRI) multislice multiecho T2* technique for global and segmental measurement of iron overload in thalassemia patients.

Evaluation of a web-based network for reproducible T2* MRI assessment of iron overload in thalassemia

PURPOSE To build and evaluate a national network able to improve the care of thalassemia, a genetic disorder in haemoglobin synthesis often associated with iron accumulation in a variety of organs, due to the continuous blood transfusions. METHODS The MIOT (Myocardial Iron Overload in Thalassemia) network is constituted by thalassemia and magnetic resonance imaging (MRI) centers. Thalassemia centers are responsible for patient recruitment and collection of anamnestic and clinical data. MRI centers have been equipped with a standardized acquisition technique and an affordable workstation for image analysis. They are able to perform feasible and reproducible heart and liver iron overload assessments for a consistent number of thalassemia patients in a robust manner. All centers are linked by a web-based network, configured to collect and share patient data. RESULTS On 30th March 2008, 695 thalassemia patients were involved in the network. The completion percentage of the patient records in the database was 85+/-6.5%. Six hundred and thirteen patients (88%) successfully underwent MRI examination. Each MRI center had a specific absorption capacity that remained constant over time, but the network was capable of sustaining an increasing number of patients due to continuous enrollment of new centers. The patients comfort, assessed as the mean distance from the patient home locations to the MRI centers, significantly increased during the networks evolution. CONCLUSION The MIOT network seems to be a robust and scalable system in which T2* MRI-based cardiac and liver iron overload assessment is available, accessible and reachable for a significant and increasing number of thalassemia patients in Italy (about 420 per year), reducing the mean distance from the patient locations to the MRI sites from 951km to 387km. A solid, wide and homogeneous database will constitute an important scientific resource, shortening the time scale for diagnostic, prognostic and therapeutical evidence-based research on the management of thalassemia disease.

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

Standardized T2* map of a normal human heart to correct T2* segmental artefacts; myocardial iron overload and fibrosis in thalassemia intermedia versus thalassemia major patients and electrocardiogram changes in thalassemia major patients.

Studies of the standardized, 3D, 16-segments map of the circumferential distribution of T2* values, of cardiovascular magnetic resonance (CMR) in thalassemia major (TM) and thalassemia intermedia (TI) patients and of electrocardiogram (ECG) changes associated with TM, have been carried out. Similarly, the segment-dependent correction map of the T2* values and the artifactual variations in normal subjects and the T2* correction map to correct segmental measurements in patients with different levels of myocardial iron burden have been evaluated. Cardiovascular magnetic resonance can be a suitable guide to cardiac management in TI, as well as in TM; TI patients show lower myocardial iron burden and more pronounced high cardiac output findings than TM patients. Moreover, it is proposed that, due to its good positive predictive value (PPV) and low cost, ECG can be a suitable guide to orient towards CMR examination in TM cases.

A Robust Method for Assessment of Iron Overload in Liver by Magnetic Resonance Imaging

Assessment of iron overload in liver by T2* magnetic resonance imaging (MRI) is a widely used clinical procedure. In the common clinical practice, measurement is performed locally by manually drawing a small region of interest in liver. This procedure may be affected by a noticeable intra- and inter-observer variability. In this study, a new approach is proposed that performs a global semi-automatic measurement of T2* involving the whole liver extension. Parenchyma is automatically segmented by an adaptive fuzzy-clustering algorithm. The liver T2* global value is evaluated using a pixel-wise approach by introducing an appropriate signal decay model. The proposed method was tested on a synthetic software model and on MR images acquired from 30 thalassemia major patients. The methods was demonstrated to increase the measure precision in T2* assessment and to significantly reduce the intra- and inter- observer variability.

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.