Comparison between different software programs and techniques for liver iron concentration assessment with MRI in thalassemic patients

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1 Comparison between different software programs and techniques for liver iron concentration assessment with MRI in thalassemic patients Poster No.: C-1580 Congress: ECR 2015 Type: Scientific Exhibit Authors: A. Casaleggio 1, C. Conforti 2, F. Paparo 1, L. Bacigalupo 1, D. Zefiro 1, C. M. viberti 1, G. Forni 1, G. A. Rollandi 1 ; 1 Genoa/IT, 2 Genova/IT Keywords: DOI: Liver, MR, Computer Applications-General, Hematologic diseases /ecr2015/C-1580 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 14

2 Aims and objectives The quantification and monitoring of body iron burden play a pivotal role in the clinical management of patients affected by inherited hemoglobin disorders, including thalassemia, hereditary hemochromatosis and sickle cell disease. The total amount of iron deposited in the organs well correlates with serum ferritin levels (expressed in ng/ml); however, serum ferritin lacks of specificity, since it may be affected by other factors such as fever or inflammation. Liver iron content (LIC), expressed as mg Fe/g dry tissue, is considered a reliable biomarker of the total iron stored in the body [Angelucci 2000]; therefore, direct or indirect methods for measuring LIC are used as surrogates for assessing the whole-body iron burden. Currently, chemical analysis of percutaneous liver biopsy specimens remains the reference standard for the diagnosis and quantification of LIC, but its routine clinical application for purposes of screening, treatment monitoring, and epidemiologic studies is limited by the significant risk of bleeding, infection and sampling errors, due to the heterogeneous distribution of iron deposits throughout the liver [Butensky 2005]. In the last decade, magnetic resonance imaging (MRI) has become an effective alternative for the noninvasive assessment of liver iron overload [Wood 2011]. MRI is able to produce LIC estimates over the entire range of clinically relevant values. MRI quantifies iron indirectly, by detecting the paramagnetic effects of the interactions between iron, stored as ferritin and hemosiderin, and nearby hydrogen nuclei. MRI-based methods to provide estimates of LIC include signal intensity ratios, based on T2 or T2*-weighted imaging, and relaxometry, based on T2 or T2* relaxation times (or R2 and R2* relaxation rates). Relaxometry methods calculate T2 or T2* by fitting a decay model to the average signal intensity at various echo times (TEs); these methods have been proven to be more robust than signal intensity ratios. The St Pierre method is a T2-based technique marketed with the name of FerriScan TM [Figure 1]. It is an FDA-approved technique that is currently used as surrogate of liver biopsy in different clinical trials. The aim of this work was to compare the T2-derived LIC measurements (FerriScan TM ) with LIC values obtained by T2* relaxometry using three different commercial software programs. Images for this section: Page 2 of 14

3 Fig. 1: 43-year-old woman with beta-thalassemia intermedia and severe hepatic iron overload (>15mg/g): the FerriScanTM report contains the patient's liver iron concentration, including an R2 image and histogram of the distribution of R2 in the liver. Page 3 of 14

4 Methods and materials This retrospective observational study was performed on 15 thalassemic patients undergoing MRI examinations under chelation therapy and about fifty FerriScan TM -T2 and T2* MRI examinations were performed and compared. Exams were done with a 1.5T General Electric Hdx scanner using an eightelement cardiac/torso coil. Breath-hold T2*-MRI measurements were performed and the whole liver was scanned employing a multi-echo gradient echo sequence. T2- MRI measurements were performed with a multislice single spin-echo pulse sequence according to the FerriScan TM protocol and the images acquired were sent via a secure electronic link to the FerriScan TM central for processing. The LICdw reports produced were considered as a reference standard. Three commercial software programs performing T2* relaxometry were used for the LIC estimation: Quanta Hematology (Camelot Biomedical Systems, Genoa, Italy) [Figure 2,3,4,5]; CMRTools (Cardiovascular Imaging Solutions, London, UK) [Figure 6]; FuncTool (General Electric Medical Systems, Milwaukee, WI) [Figure 7,8,9]. To perform a direct comparison with the average LICdw of the FerriScan TM report, a radiologist with 7 year experience in MRI (FP) selected the slice on multi-echo gradient images which was corresponding to the slice shown in the FerriScan TM report. Correlations among LICdw measurements were subjected to linear regression analysis and the regression coefficient R2 was used to evaluate the correlation between the techniques; the software were also compared using Bland-Altman plots. Images for this section: Page 4 of 14

5 Fig. 2: 43-year-old woman with beta-thalassemia intermedia and severe hepatic iron overload (>15mg/g): QuantaHematology LICdw map avg mg-g sd 7.68 mg-g median mg-g Page 5 of 14

6 Fig. 3: 43-year-old woman with beta-thalassemia intermedia and severe hepatic iron overload (>15mg/g): QuantaHematology R2 star map avg Hz sd median Hz Page 6 of 14

7 Fig. 4: 43-year-old woman with beta-thalassemia intermedia and severe hepatic iron overload (>15mg/g): QuantaHematology ROI positioning Page 7 of 14

8 Fig. 5: 43-year-old woman with beta-thalassemia intermedia and severe hepatic iron overload (>15mg/g): QuantaHematology T2 star map avg 2.03ms sd 7.78ms median 1.38ms Page 8 of 14

9 Fig. 6: 43-year-old woman with beta-thalassemia intermedia and severe hepatic iron overload (>15mg/g): CMRtools for the assessment of iron loading in liver provides a stepby-step approach to calculating T2* from CMR images. Page 9 of 14

10 Fig. 7: 43-year-old woman with beta-thalassemia intermedia and severe hepatic iron overload (>15mg/g): FuncTool GE R2star map Page 10 of 14

11 Fig. 8: 43-year-old woman with beta-thalassemia intermedia and severe hepatic iron overload (>15mg/g): FuncTool GE time-intensity curve Page 11 of 14

12 Fig. 9: 43-year-old woman with beta-thalassemia intermedia and severe hepatic iron overload (>15mg/g): FuncTool GE T2 star map Page 12 of 14

13 Results The time evolution of liver iron content was analyzed and clinically discussed case-bycase for the patients which had at least one point outside the ±1 SD interval in the Bland- Altman plot. Although all T2* methods are in good agreement with the FerriScan TM results, the best accordance with LICdw deriving from FerriScan TM is reached by the measurement obtained from Quanta Hematology; the corresponding Bland-Altman analysis has mean of 0.1 mg/g and a standard deviation (SD) of 1.5 mg/g. Conclusion The good agreement observed between the T2* method and the goldstandard (FerriScan TM T2), makes suitable in our opinion the use of different commercial software for liver iron concentration monitoring in clinical routine. In our series of patients and measurements we observed two cases where FerriScan TM appeared to overestimate the LIC, particularly when the LIC had higher values. In these cases we don't have a biopsy to allow direct quantification of LIC but we consider that FerriScan TM could have overestimated the LIC because the decrease over time of the LIC showed by FerriScan TM was too large. In fact it is assumed that LIC decrease under chelation therapy should be approximately 3mg/g of LIC dry weight over 1 year of time. Personal information References 1. Wood et al., "MRI R2 and R2-star mapping accurately estimates hepatic iron concentration" (2005) 2. StPierre et al., "Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance" (2005) 3. Meloni et al., "The use of appropriate calibration curves systematic differences in liver R2star values measured using different software packages" (2013) Page 13 of 14

14 4. Fernandes et al., "Heart and liver T2 assessment for iron overload using different software programs" (2011) 5. Wood et al., "Disparities Between Two Common MRI Metrics of Liver Iron Concentration in Transfusional Siderosis" (2011) Page 14 of 14

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