Inter-Site Validation of a Single Breath Hold T2* MR Technique for Heart and Liver Iron Measurement.

Background Approximately 60,000 people are born with thalassaemia major every year. The average life expectancy of thalassaemia major patients is 35 years due to iron overload Cardiomyopathy. The cardiomyopathy is reversible when treated early, but once heart failure is established it is often rapidly progressive, and unresponsive to treatment. The single breath hold (SBH) T2* technique has been validated as the most robust and reproducible non-invasive measurement of myocardial and iron load. Our aim in this study was to validate the transferability and reproducibility of this technique in different scanners worldwide. Methods We aim to compare the reproducibility in six different sites worldwide as part of an NIH funded grant (R01-DK66084-01). So far, two of these sites have been validated: Singapore (Siemens Sonata, 1.5T scanner) and Cagliari, Italy (GE Signa, 1.5 T scanner). At both validation sites, 10 patients were scanned for heart and liver T2*, and scans were repeated for interstudy reproducibility. All patients then flew to London to be rescanned on our reference Siemens Sonata scanner. Results Of the 20 patients scanned, 70% had myocardial iron loading (T2* <20ms) and in 10% the myocardial iron loading was severe. Liver iron loading was present in 65% of patients and in 30% this was severe. The coefficient of variation (COV) for the heart T2* measurements between the local sites and London was 5.9% and 4.9% yielding an average coefficient of variation across both sites of 5.4% (figure 1). The coefficient of variation (COV) for the liver T2* measurements between the local sites and London was 11.3% and 3.9% yielding an average coefficient of variation across both sites of 7.6% (figure 2). There was no significant correlation between liver and myocardial loading. Conclusion These are the first data demonstrating the transferability of the SBH T2* technique and the clinical validation from the 2 collaborating centers were excellent for both heart and liver measurements. Further MR sites confirmed for validation include Children’s Hospital of Philadelphia (USA); Ramathibodi Hospital, Bangkok (Thailand); and Chinese University Hong Kong. Figure 1 Figure 1. Figure 2 Figure 2.

The Effect of Combined Chelation Therapy in the Treatment of Severe Myocardial Iron Loading in Beta Thalassaemia Major.

Introduction: Thalassaemia major ™ is an inherited haemoglobinopathy resulting from mutations of the β-globin gene. Survival is dependent upon lifelong blood transfusions and results in progressive total body iron overload. Cardiac failure secondary to myocardial iron loading is by far the commonest cause of death with only 50% of patients in the UK in recent cohorts surviving beyond the age of 35 years. Conventional treatment with the parenteral iron chelator deferoxamine improves morbidity and mortality but fails to clear the heart of iron in approximately two-thirds of patients. More recently, the oral iron chelator deferiprone has been demonstrated to remove myocardial iron and it has been proposed that in combination with deferoxamine it may have an additive effect. Through the T2* multi-echo cardiac magnetic resonance (CMR) technique, myocardial iron can now be non-invasively and reproducibly quantified, thereby providing a means to assess myocardial iron loading in response to chelation treatment. Purpose: To report the changes in myocardial T2* and cardiac function in patients with severe myocardial iron loading (myocardial T2* &lt;8ms) following treatment with the un-blinded addition of deferiprone to continued deferoxamine chelation therapy. Methods: A mobile CMR scanner (1.5T Siemens Sonata) was transported to Cagliari, Italy. The myocardial T2* was assessed in 167 patients with TM aged 18v42 (30 +/− 5.3years). Of these, 22 patients were identified as having severe myocardial iron loading (T2* &lt;8ms), 15 of whom (at their clinician’s discretion) were subsequently given deferiprone in addition to continued deferoxamine therapy. Patients underwent further CMR assessment at baseline, 6 and 12 months. Results: Over a period of 12 months myocardial T2* improved significantly (6.1+/− 1.0ms to 8.2ms +/−2.5ms, p=0.007) in association with an improvement in cardiac function (LV ejection fraction 52 +/−12% to 65% +/−6.6%, p&lt;0.0001). See Figures 1 and 2. Conclusion: This prospective study shows that patients with severe myocardial iron loading show significant improvement in iron loading and myocardial function with the addition of deferiprone to continued parenteral deferoxamine. Figure 1 Figure 1. Figure 2 Figure 2.

Multi-Centre Validation of the Cardiovascular Magnetic Resonance Multi Breath-Hold T2* Technique for Myocardial Iron Quantification in Thalassaemia Major.

Introduction: Beta thalassaemia major (TM) is a hereditary anaemia affecting 60 000 births worldwide each year. Survival is dependent upon lifelong blood transfusions resulting in iron overload. Cardiac siderosis can result in a cardiomyopathy which is the leading cause of death in TM. The validated cardiac magnetic resonance (CMR) T2* technique allows non-invasive and reproducible quantification of myocardial iron. Assessment of myocardial iron loading is essential in determining appropriate chelation therapy. This technique has the potential to become the new gold standard in the assessment of cardiac siderosis but is currently available at only a few sites worldwide. For maximal healthcare benefit its inter-scanner reproducibility must be demonstrated before being widely disseminated. Objective: To demonstrate that CMR T2* quantification of myocardial iron can be reproducibly transferred to MR scanners of different manufacturers in different centres. This project was sponsored by the Thalassemia International Federation. Methods: The previously described multi breath-hold gradient echo T2* technique was installed on MR scanners (all 1.5Tesla) at 6 different centres. Scanner details were as follows: Site 1, Phillips Intera (Turin, Italy), Site 2, Siemens Sonata (Philadelphia, USA), Site 3 GE Signa (Limassol, Cyprus) Site 4, Phillips Intera (Nicosia, Cyprus), Site 5, GE Signa (Cagliari, Sardinia) and Philips Intera (Genova, Italy). 34 patients (mean age 30+/− 5.7years) were scanned in total. All patients were subsequently re-scanned at the standardization centre in London, UK (Siemens Sonata, 1.5T) within 31 days of their original scan. Results: The T2* sequence was successfully installed on all 6 scanners. Myocardial T2* values ranged from 3.6ms to 51ms (14.2 +/− 11ms). The overall inter-scanner reproducibility (SD/mean) was 5.3% (figure 1). The mean difference between T2* values at the standardization centre and visited sites was 0.32ms. Conclusion: We have demonstrated that the multi breath-hold T2* technique for the quantification of myocardial iron can be reproducibly transferred to 1.5T MR scanners at different sites and of different manufacturers. There is therefore real potential to roll out this technique worldwide to facilitate maximal healthcare impact in the management of patients with iron overload conditions such as thalassaemia. Figure Figure