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author:("He, taihang")
1.  How Early Can Myocardial Iron Overload Occur in Beta Thalassemia Major? 
PLoS ONE  2014;9(1):e85379.
Myocardial siderosis is the most common cause of death in patients with beta thalassemia major(TM). This study aimed at investigating the occurrence, prevalence and severity of cardiac iron overload in a young Chinese population with beta TM.
Methods and Results
We analyzed T2* cardiac magnetic resonance (CMR), left ventricular ejection fraction (LVEF) and serum ferritin (SF) in 201 beta TM patients. The median age was 9 years old. Patients received an average of 13 units of blood per year. The median SF level was 4536 ng/ml and 165 patients (82.1%) had SF>2500 ng/ml. Myocardial iron overload was detected in 68 patients (33.8%) and severe myocardial iron overload was detected in 26 patients (12.6%). Twenty-two patients ≤10 years old had myocardial iron overload, three of whom were only 6 years old. No myocardial iron overload was detected under the age of 6 years. Median LVEF was 64% (measured by CMR in 175 patients). Five of 6 patients with a LVEF<56% and 8 of 10 patients with cardiac disease had myocardial iron overload.
The TM patients under follow-up at this regional centre in China patients are younger than other reported cohorts, more poorly-chelated, and have a high burden of iron overload. Myocardial siderosis occurred in patients younger than previously reported, and was strongly associated with impaired LVEF and cardiac disease. For such poorly-chelated TM patients, our data shows that the first assessment of cardiac T2* should be performed as early as 6 years old.
PMCID: PMC3899006  PMID: 24465548
3.  On T2* Magnetic Resonance and Cardiac Iron 
Circulation  2011;123(14):1519-1528.
Measurement of myocardial iron is key to the clinical management of patients at risk of siderotic cardiomyopathy. The cardiovascular magnetic resonance (CMR) relaxation parameter R2* (assessed clinically via its reciprocal T2*) measured in the ventricular septum is used to assess cardiac iron, but iron calibration and distribution data in humans is limited.
Methods and Results
Twelve human hearts were studied from transfusion dependent patients following either death (heart failure n=7, stroke n=1) or transplantation for end-stage heart failure (n=4). After CMR R2* measurement, tissue iron concentration was measured in multiple samples of each heart using inductively coupled plasma atomic emission spectroscopy. Iron distribution throughout the heart showed no systematic variation between segments, but epicardial iron concentration was higher than in the endocardium. The mean (±SD) global myocardial iron causing severe heart failure in 10 patients was 5.98 ±2.42mg/g dw (range 3.19–9.50), but in 1 outlier case of heart failure was 25.9mg/g dw. Myocardial ln[R2*] was strongly linearly correlated with ln[Fe] (R2=0.910, p<0.001) leading to [Fe]=45.0•(T2*)−1.22 for the clinical calibration equation with [Fe] in mg/g dw and T2* in ms. Mid-ventricular septal iron concentration and R2* were both highly representative of mean global myocardial iron.
These data detail the iron distribution throughout the heart in iron overload and provide calibration in humans for CMR R2* against myocardial iron concentration. The iron values are of considerable interest with regard to the level of cardiac iron associated with iron-related death and indicate that the heart is more sensitive to iron loading than the liver. The results also validate the current clinical practice of monitoring cardiac iron in-vivo by CMR of the mid septum.
PMCID: PMC3435874  PMID: 21444881
Magnetic resonance imaging; heart; iron overload; siderosis; thalassemia
10.  International Reproducibility of Single Breath-hold T2* Magnetic Resonance for Cardiac and Liver Iron Assessment among Five Thalassemia Centers 
To examine the reproducibility of the single breath-hold T2* technique from different scanners, after installation of standard methodology in 5 international centers.
Materials and Methods
Up to 10 patients from each center were scanned twice locally for local interstudy reproducibility of heart and liver T2*, and then flown to a central MR facility to be rescanned on a reference scanner for intercenter reproducibility. Interobserver reproducibility for all scans was also assessed.
Of the 49 patients scanned, the intercenter reproducibility for T2* was 5.9% for the heart and 5.8% for the liver. Local interstudy reproducibility for T2* was 7.4% for the heart and 4.6% for the liver. Interobserver reproducibility for T2* was 5.4% for the heart and 4.4% for the liver.
These data indicate that T2* MR may be developed into a widespread test for tissue siderosis providing that well defined and approved imaging and analysis techniques are used.
PMCID: PMC2946327  PMID: 20677256
Thalassaemia; Cardiac siderosis; cardiomyopathy; Cardiovascular MR
11.  Value of black blood T2* cardiovascular magnetic resonance 
To assess whether black blood T2* cardiovascular magnetic resonance is superior to conventional white blood imaging of cardiac iron in patients with thalassaemia major (TM).
Materials and methods
We performed both conventional white blood and black blood T2* CMR sequences in 100 TM patients to determine intra and inter-observer variability and presence of artefacts. In 23 patients, 2 separate studies of both techniques were performed to assess interstudy reproducibility.
Cardiac T2* values ranged from 4.5 to 43.8 ms. The mean T2* values were not different between black blood and white blood acquisitions (20.5 vs 21.6 ms, p = 0.26). Compared with the conventional white blood diastolic acquisition, the coefficient of variance of the black blood CMR technique was superior for intra-observer reproducibility (1.47% vs 4.23%, p < 0.001), inter-observer reproducibility (2.54% vs 4.50%, p < 0.001) and inter-study reproducibility (4.07% vs 8.42%, p = 0.001). Assessment of artefacts showed a superior score for black blood vs white blood scans (4.57 vs 4.25; p < 0.001).
Black blood T2* CMR has superior reproducibility and reduced imaging artefacts for the assessment of cardiac iron, in comparison with the conventional white blood technique, which make it the preferred technique for clinical practice.
PMCID: PMC3062187  PMID: 21401929
14.  Right ventricular volumes and function in thalassemia major patients in the absence of myocardial iron overload 
We aimed to define reference ranges for right ventricular (RV) volumes, ejection fraction (EF) in thalassemia major patients (TM) without myocardial iron overload.
Methods and results
RV volumes, EF and mass were measured in 80 TM patients who had no myocardial iron overload (myocardial T2* > 20 ms by cardiovascular magnetic resonance). All patients were receiving deferoxamine chelation and none had evidence of pulmonary hypertension or other cardiovascular comorbidity. Forty age and sex matched healthy non-anemic volunteers acted as controls. The mean RV EF was higher in TM patients than controls (males 66.2 ± 4.1% vs 61.6 ± 6%, p = 0.0009; females 66.3 ± 5.1% vs 62.6 ± 6.4%, p = 0.017), which yielded a raised lower threshold of normality for RV EF in TM patients (males 58.0% vs 50.0% and females 56.4% vs 50.1%). RV end-diastolic volume index was higher in male TM patients (mean 98.1 ± 17.3 mL vs 88.4 ± 11.2 mL/m2, p = 0.027), with a higher upper limit (132 vs 110 mL/m2) but this difference was of borderline significance for females (mean 86.5 ± 13.6 mL vs 80.3 ± 12.8 mL/m2, p = 0.09, with upper limit of 113 vs 105 mL/m2). The cardiac index was raised in TM patients (males 4.8 ± 1.0 L/min vs 3.4 ± 0.7 L/min, p < 0.0001; females 4.5 ± 0.8 L/min vs 3.2 ± 0.8 L/min, p < 0.0001). No differences in RV mass index were identified.
The normal ranges for functional RV parameters in TM patients with no evidence of myocardial iron overload differ from healthy non-anemic controls. The new reference RV ranges are important for determining the functional effects of myocardial iron overload in TM patients.
PMCID: PMC2867986  PMID: 20416084
15.  Myocardial T2* Measurements in Iron Overloaded Thalassemia 
Reproducible and accurate myocardial T2* measurement is required for the quantification of iron in the tissue of heart in transfused thalassemia. The aim of this study was to determine the best method to measure the myocardial T2* from multi-gradient echo data acquired both with and without black blood preparation. Sixteen thalassemia patients from six centres were scanned twice locally, within 1 week, using an optimised bright blood T2* sequence and then subsequently scanned at the standardization centre in London within 4 weeks, using a T2* sequence both with and without black blood preparation. Different curve fitting models (Mono-exponential, Truncation, and Offset) were applied to the data and the results were compared by means of reproducibility. The T2* measurements using both the bright and black blood techniques were also compared. The black blood data was well fitted by the mono-exponential model, which suggests a more accurate measure of T2* by removing the main source of errors in the bright blood data. For bright blood data, the offset model appeared to underestimate T2* values substantially and was less reproducible; the truncation model gave rise to more reproducible T2* measurements, which were also closer to the values obtained from the black blood data.
PMCID: PMC2593631  PMID: 18956471
MRI; T2* relaxation; curve fitting; accuracy; reproducibility; iron overload
16.  Multi-center transferability of a breath-hold T2 technique for myocardial iron assessment 
Cardiac iron overload is the leading cause of death in thalassemia major and is usually assessed using myocardial T2* measurements. Recently a cardiovascular magnetic resonance (CMR) breath-hold T2 sequence has been developed as a possible alternative. This cardiac T2 technique has good interstudy reproducibility, but its transferability to different centres has not yet been investigated.
Methods and Results
The breath-hold black blood spin echo T2 sequence was installed and validated on 1.5T Siemens MR scanners at 4 different centres across the world. Using this sequence, 5–10 thalassemia patients from each centre were scanned twice locally within a week for local interstudy reproducibility (n = 34) and all were rescanned within one month at the standardization centre in London (intersite reproducibility). The local interstudy reproducibility (coefficient of variance) and mean difference were 4.4% and -0.06 ms. The intersite reproducibility and mean difference between scanners were 5.2% and -0.07 ms.
The breath-hold myocardial T2 technique is transferable between Siemens scanners with good intersite and local interstudy reproducibility. This technique may have value in the diagnosis and management of patients with iron overload conditions such as thalassemia.
PMCID: PMC2279115  PMID: 18291040

Results 1-16 (16)