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Title: Cardiovascular magnetic resonance and iron measurement
Author: Carpenter, John-Paul
ISNI:       0000 0004 2706 3327
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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INTRODUCTION: The magnetic resonance (MR) relaxation parameter T2* is used for non-invasive assessment of cardiac iron, with low cardiac T2* being associated with left ventricular (LV) impairment and the development of heart failure. However, there is very little data calibrating cardiac T2* and other MR relaxation parameters to human cardiac iron concentration, and the effects of cardiac iron on the right ventricle (RV) are little known. METHODS AND RESULTS: We studied the distribution of cardiac iron in a series of post-mortem hearts from transfusion-dependent patients using mass spectrometry derived iron concentration, and compared the results against the MR relaxation parameters T1, T2 and T2*. We found variable iron loading between cardiac tissues, but a mainly homogeneous deposition of iron in the LV myocardium, apart from a transmural gradient. We established a calibration equation for cardiac iron using T2*. Septal iron and T2* were very representative of whole-heart values. Cardiac iron was also measurable using T2, but T1 measurement was unreliable. Clinical studies of the RV showed a progressive fall in ejection fraction (EF) as iron loading increased and we established normal ranges for RV volumes and EF in patients with beta thalassaemia major (TM). Finally, a worldwide survey of the clinical use of T2* in over 3000 TM patients showed a high prevalence of cardiac iron loading with large regional variation, and confirmed that low T2* values are associated with heart failure and death. CONCLUSION: In transfusion dependent patients, cardiac iron is deposited variably in the cardiac tissues, but is mainly homogenous in the myocardium and can be calculated from cardiac T2* using the obtained calibration equation. There is similarity in myocardial response to iron loading between the RV and LV. Worldwide data shows a high prevalence of cardiac iron loading, but significant variation suggests that undetermined factors may influence the loading, of which genetic modulation is a prime candidate.
Supervisor: Pennell, Dudley ; Prasad, Sanjay Sponsor: National Institutes of Health
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral