Improved T2* assessment in liver iron overload by magnetic resonance imaging Vincenzo Positano a, , Benedetta Salani a , Alessia Pepe a , Maria Filomena Santarelli a,b , Daniele De Marchi a , Anna Ramazzotti a,b , Brunella Favilli a,b , Eliana Cracolici c , Massimo Midiri c , Paolo Cianciulli d , Massimo Lombardi a , Luigi Landini a,e a MRI Laboratory, Gabriele Monasterio Foundation, Via Moruzzi, 1 56124 Pisa, Italy b Institute of Clinical Physiology, CNR, 56124 Pisa, Italy c Department of Radiology, University of Palermo, 90010 Palermo, Italy d Sant'Eugenio PapaHospital, Centro Talassemie, 00100 Rome, Italy e Department of Information Engineering, University of Pisa, 56126 Pisa, Italy Received 13 February 2008; revised 10 June 2008; accepted 12 June 2008 Abstract 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. © 2009 Elsevier Inc. All rights reserved. Keywords: Liver; Thalassemia; MRI; Iron overload; Multi-echo T2* 1. Introduction Iron overload represents a critical health problem in patients with primary and secondary hemosiderosis. The most important of these conditions is beta thalassemia major, the most common genetic disorder worldwide [1]. Although heart failure remains the main cause of mortality in thalassemia major patients, clinical management of these patients is also based on the assessment of liver iron stores, for several reasons. First, liver iron was shown to correlate closely with total body iron [2]. Second, liver iron concentration is a proven prognostic indicator in thalassemic patients [3], although it is poorly correlated with heart iron and heart failure. Moreover, to date, three chelator agents are commercially available for use alone or in combination therapy and they seem to have different efficacies on Available online at www.sciencedirect.com Magnetic Resonance Imaging 27 (2009) 188 197 Dr. Alessia Pepe was supported by a grant from the Centro per la lotta contro l'infarto Onlus Fondation. Corresponding author. Tel.: +39 050 315 2613; fax: +39 050 315 2166. E-mail address: positano@ifc.cnr.it (V. Positano). 0730-725X/$ see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.mri.2008.06.004