Beta-Thalassemia major (thalassemia) is a common genetic condition causing profound anemia which is very widespread in the world, particularly in countries where malaria has been prevalent, because single copies of the gene, which are insufficient to cause the major disease, offer protection against malaria. Some 93 million worldwide carry one copy of this gene, and one-quarter of children will inherit the major condition if 2 carriers reproduce. About 60,000 children are born annually with thalassemia and treatment is invasive and expensive. Regular blood transfusions are required to keep the children alive, but this leads to iron overload in the tissues which causes death at a young age in many sufferers. Treatment with iron chelation is helpful, but requires sometimes daily injections and is very expensive especially in developing countries. In 70% of cases, death is due to heart failure, the onset of which is difficult to predict and often has a rapid downhill course. Therefore our long term aim is to prevent death from heart failure caused by myocardial iron overload in thalassemia by using magnetic resonance (MR) imaging to identify early iron loading, and establish effective and well tolerated myocardial chelation regimes. Thus there is great scope for helping large numbers of sufferers, and also finding more acceptable and cost-effective treatments. In this grant application, we have 4 major aims: first, to understand how iron affects the signal from the MR scanner; second, to optimize MR acquisition sequences so that measurements taken from the images accurately reflect the magnetic relaxation in the tissues; third, to calibrate the MR relaxation measurements against both heart and liver, so that we understand how the measurements made by the scanner relate to the amount of iron in these organs; fourth, to roll-out MR sequences to 6 sites world-wide and validate their use, so that these sites can in principle act as local distributors of the expertise within their own regions, whilst promoting research into improved care in thalassemia. These centers are Philadelphia (USA), Cagliari (Italy), Athens (Greece), Nicosia (Cyprus), Mumbai (India) and Singapore.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK066084-03
Application #
6901871
Study Section
Special Emphasis Panel (ZDK1-GRB-3 (O1))
Program Officer
Wright, Daniel G
Project Start
2003-09-15
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$270,000
Indirect Cost
Name
U of L Imperial Col of Sci/Technlgy/Med
Department
Type
DUNS #
227092590
City
London
State
Country
United Kingdom
Zip Code
SW7 2-AZ
Carpenter, John-Paul; He, Taigang; Kirk, Paul et al. (2014) Calibration of myocardial T2 and T1 against iron concentration. J Cardiovasc Magn Reson 16:62
Kirk, Paul; Carpenter, John Paul; Tanner, Mark A et al. (2011) Low prevalence of fibrosis in thalassemia major assessed by late gadolinium enhancement cardiovascular magnetic resonance. J Cardiovasc Magn Reson 13:8
Carpenter, John-Paul; He, Taigang; Kirk, Paul et al. (2011) On T2* magnetic resonance and cardiac iron. Circulation 123:1519-28
Kirk, Paul; He, Taigang; Anderson, Lisa J et al. (2010) International reproducibility of single breathhold T2* MR for cardiac and liver iron assessment among five thalassemia centers. J Magn Reson Imaging 32:315-9
He, Taigang; Smith, Gillian C; Gatehouse, Peter D et al. (2009) On using T2 to assess extrinsic magnetic field inhomogeneity effects on T2* measurements in myocardial siderosis in thalassemia. Magn Reson Med 61:501-6
Kirk, P; Roughton, M; Porter, J B et al. (2009) Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major. Circulation 120:1961-8
He, Taigang; Gatehouse, Peter D; Smith, Gillian C et al. (2008) Myocardial T2* measurements in iron-overloaded thalassemia: An in vivo study to investigate optimal methods of quantification. Magn Reson Med 60:1082-9
He, Taigang; Kirk, Paul; Firmin, David N et al. (2008) Multi-center transferability of a breath-hold T2 technique for myocardial iron assessment. J Cardiovasc Magn Reson 10:11
He, Taigang; Gatehouse, Peter D; Kirk, Paul et al. (2008) Myocardial T*2 measurement in iron-overloaded thalassemia: an ex vivo study to investigate optimal methods of quantification. Magn Reson Med 60:350-6
He, Taigang; Gatehouse, Peter D; Kirk, Paul et al. (2007) Black-blood T2* technique for myocardial iron measurement in thalassemia. J Magn Reson Imaging 25:1205-9

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