Left ventricular diastolic function compared with T2* cardiovascular magnetic resonance for early detection of myocardial iron overload in thalassemia major

PURPOSE: To compare left ventricular (LV) diastolic function with myocardial iron levels in beta thalassemia major (TM) patients, using cardiovascular magnetic resonance (CMR). MATERIALS AND METHODS: We studied 67 regularly transfused patients with TM and 22 controls matched for age, gender, and body surface area. The early peak filling rate (EPFR) and atrial peak filling rate (APFR) were determined from high-temporal-resolution ventricular volume-time curves. Myocardial iron estimation was achieved using myocardial T2* measurements. RESULTS: Myocardial iron loading was found in 46 TM patients (69%), in whom the EPFR correlated poorly with T2* (r = -0.20, P = 0.19). The APFR (r = 0.49, P < 0.001) and EPFR/APFR ratio (r = -0.62, P < 0.001) correlated better with T2*. The sensitivity of the diastolic parameters for detecting myocardial iron loading ranged from 4% (EPFR and APFR) to 17% (EPFR/APFR ratio). CONCLUSION: Myocardial iron overload results in diastolic myocardial dysfunction, but low sensitivity limits the use of a single estimation for early detection of iron overload, for which T2* has a superior categorical limit of normality.     

A single breath-hold multiecho T2* cardiovascular magnetic resonance technique for diagnosis of myocardial iron overload

PURPOSE: To assess tissue iron concentrations by the use of a gradient echo T2* multiecho technique. MATERIALS AND METHODS: We compared the results of measurements of heart T2* from 32 patients using the established multiple breath-hold variable TR technique with a new multiecho sequence that acquires all images within a single breath-hold with constant TR. RESULTS: There was good agreement of myocardial T2* values between both methods in the abnormal range of T2* < 20 msec (mean difference 0.2 msec, 95% CI -1.3 to 0.9 msec, r = 0.97, P < 0.0001). The coefficient of variability between the methods was 3.5%. The interstudy reproducibility using the multiecho sequence had a variability coefficient of 2.3% in the abnormal T2* range and 5.8% over all T2* values. There was good agreement between the techniques for the liver T2* values. CONCLUSIONS: The use of the single breath-hold, multiecho acquisition allowed reliable quantification of myocardial T2*. The good reproducibility, speed, and T1 independence of this technique allows greater accuracy, faster patient throughput, and, therefore, reduced costs (which is important in developing countries where thalassemia is most prevalent).     

Preferential patterns of myocardial iron overload by multislice multiecho T*2 CMR in thalassemia major patients

T*₂ multislice multiecho cardiac MR allows quantification of the segmental distribution of myocardial iron overload. This study aimed to determine if there were preferential patterns of myocardial iron overload in thalassemia major. Five hundred twenty‐three thalassemia major patients underwent cardiac MR. Three short‐axis views of the left ventricle were acquired and analyzed using a 16‐segment standardized model. The T*₂ value on each segment was calculated, as well as the global value. Four main circumferential regions (anterior, septal, inferior, and lateral) were defined. Significant segmental variability was found in the 229 patients with significant myocardial iron overload (global T*₂ <26 ms), subsequently divided into two groups: severe (global T*₂ <10 ms) and mild to moderate (global T*₂ between 10 and 26 ms) myocardial iron overload. A preferential pattern of iron store in anterior and inferior regions was detected in both groups. This pattern was preserved among the slices. The pattern could not be explained by additive susceptibility artifacts, negligible in heavily iron‐loaded patients. A significantly higher T*₂ value in the basal slice was found in patients with severe iron overload. In conclusion, a segmental T*₂ cardiac MR approach could identify early iron deposit, useful for tailoring chelation therapy and preventing myocardial dysfunction in the clinical setting. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Multicenter validation of the magnetic resonance t2* technique for segmental and global quantification of myocardial iron

Purpose

To assess the transferability of the magnetic resonance imaging (MRI) multislice multiecho T2* technique for global and segmental measurement of iron overload in thalassemia patients.

Materials and Methods

Multiecho T2* sequences were installed on six MRI scanners. Five healthy subjects (n = 30) were scanned at each site; five thalassemia major (TM) patients were scanned at the reference site and were rescanned locally (n = 25) within 1 month. T2* images were analyzed using previously validated software.

Results

T2* values of healthy subjects showed intersite homogeneity. On TM patients, for global heart T2* values the correlation coefficient was 0.97, coefficients of variation (CoV_s) ranged from 0.04–0.12, and intraclass coefficients (ICC_s) ranged from 0.94–0.99. The mean CoV and ICC for segmental T2* distribution were 0.198 and 88, respectively.

Conclusion

The multislice multiecho T2* technique is transferable among scanners with good reproducibility. J. Magn. Reson. Imaging 2009;30:62–68. © 2009 Wiley‐Liss, Inc.     

Interscanner reproducibility of cardiovascular magnetic resonance T2* measurements of tissue iron in thalassemia

PURPOSE: To assess interscanner reproducibility of tissue iron measurements in patients with thalassemia using gradient echo T2* measurements on two different MRI scanners. MATERIALS AND METHODS: Twenty-five patients with thalassemia major had liver and myocardial T2* assessment using a Picker Edge 1.5T Scanner and a Siemens Sonata 1.5T scanner, with similar gradient echo sequences. In a subset of 13 patients, two scans on the Siemens scanner were performed to assess interstudy reproducibility. RESULTS: There was a highly significant, linear correlation between T2* values obtained for both the heart (r = 0.95) and the liver (r = 0.99) between scanners. The mean difference, coefficient of variability, and 95% confidence intervals between scanners were 0.8 msec, 9.4% and -5.0 to 6.7 msec for the heart; and 0.9 msec, 7.9% and -2.0 to 3.9 msec for the liver. The interstudy mean difference and coefficient of variability on the Siemens scanner was 0.3 msec and 4.8% (r = 0.99) for the heart, and 0.04 msec and 1.9% (r = 0.99) for the liver. CONCLUSION: The T2* technique for measuring tissue iron is reproducible between the two manufacturers' scanners. This suggests that the widespread implementation of the technique is possible for clinical assessment of myocardial iron loading in thalassemia.     

Black-blood T2* technique for myocardial iron measurement in thalassemia

PURPOSE: To compare the effectiveness and reproducibility of a new black-blood sequence vs. a conventional bright-blood gradient-echo T2* sequence for myocardial iron overload measurement in thalassemia. MATERIALS AND METHODS: Twenty thalassemia patients were studied. Black-blood sequence images were acquired in diastole after a double inversion recovery (DIR) preparation pulse. Bright-blood sequence images were acquired in both early systole and late diastole. The data were randomized and the T2* analysis was performed blindly by two independent observers. RESULTS: The T2* values from the black-blood sequence were comparable to those of the conventional bright-blood sequence (25.7 +/- 12.9 msec vs. 26.4 +/- 14.2 msec in early systole, P = 0.44; and 25.2 +/- 13.1 msec in late diastole, P = 0.41). The coefficient of variation (CV) for black-blood image T2* analysis was 4.1% compared with 8.9% (early systole P = 0.03) and 7.8% (late diastole P = 0.05) for bright-blood image analysis. CONCLUSION: The black-blood T2* technique yields high-contrast myocardial images, provides clearly depicted myocardial borders, and avoids blood signal contamination of the myocardium while yielding improvements in interobserver variability.     

Single region of interest versus multislice T2* MRI approach for the quantification of hepatic iron overload

Purpose

To evaluate the effectiveness of the single ROI approach for the detection of hepatic iron burden in thalassemia major (TM) patients in respect to a whole liver measurement.

Materials and Methods

Five transverse hepatic slices were acquired by a T2* gradient‐echo sequence in 101 TM patients and 20 healthy subjects. The T2* value was calculated in a single region of interest (ROI) defined in the medium‐hepatic slice. Moreover, the T2* value was extracted on each of the eight ROIs defined in the functionally independent segments. The mean hepatic T2* value was calculated.

Results

For patients, the mean T2* values over segments VII and VIII were significantly lower. This pattern was substantially preserved in the two groups identified considering the T2* normal cutoff. All segmental T2* values were correlated with the single ROI T2* value. After the application of a correction map based on T2* fluctuations in the healthy subjects, no significant differences were found in the segmental T2* values.

Conclusion

Hepatic T2* variations are low and due to artifacts and measurement variability. The single ROI approach can be adopted in the clinical arena, taking care to avoid the susceptibility artifacts, occurring mainly in segments VII and VIII. J. Magn. Reson. Imaging 2011;33:348–355. © 2011 Wiley‐Liss, Inc.     

Assessment of hepatic iron content using magnetic resonance imaging

Numerous studies over the past decade have shown that magnetic resonance imaging (MRI) has great potential for detecting and quantifying the distribution of iron in the body. With MRI, tissue iron is indirectly identified by the paramagnetic effects of iron on the shortening of water proton MR relaxation times. However, these effects are complex and involve a number of factors, such as tissue hydration, distribution of iron and water within the tissue, and the amount of iron loading within the iron storage molecules. A coherent understanding of how these factors influence the MRI signal is still lacking. The dependence on experimental conditions, such as magnet field strength, pulse sequences, and data acquisition parameters, further complicates iron quantification with MRI. To date, there is no generally accepted MRI approach available for clinical application. In this review, we first explain the basic MR relaxation mechanisms underlying the detection of iron with MRI. We then review the literature on empirical MRI studies of hepatic iron. Finally, we summarize the critical issues that need to be addressed to develop MRI techniques for non-invasive iron detection in the body.     

Estimation of liver T*2 in transfusion‐related iron overload in patients with weighted least squares T*2 IDEAL

MRI imaging of hepatic iron overload can be achieved by estimating T₂* values using multiple‐echo sequences. The purpose of this work is to develop and clinically evaluate a weighted least squares algorithm based on T₂* Iterative Decomposition of water and fat with Echo Asymmetry and Least‐squares estimation (IDEAL) technique for volumetric estimation of hepatic T₂* in the setting of iron overload. The weighted least squares T₂* IDEAL technique improves T₂* estimation by automatically decreasing the impact of later, noise‐dominated echoes. The technique was evaluated in 37 patients with iron overload. Each patient underwent (i) a standard 2D multiple‐echo gradient echo sequence for T₂* assessment with nonlinear exponential fitting, and (ii) a 3D T₂* IDEAL technique, with and without a weighted least squares fit. Regression and Bland–Altman analysis demonstrated strong correlation between conventional 2D and T₂* IDEAL estimation. In cases of severe iron overload, T₂* IDEAL without weighted least squares reconstruction resulted in a relative overestimation of T₂* compared with weighted least squares. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Feasibility, reproducibility, and reliability for the T*2 iron evaluation at 3 T in comparison with 1.5 T

This study aimed to determine the feasibility, reproducibility, and reliability of the multiecho T*₂ Magnetic resonance imaging technique at 3 T for myocardial and liver iron burden quantification and the relationship between T*₂ values at 3 and 1.5 T. Thirty‐eight transfusion‐dependent patients and 20 healthy subjects were studied. Cardiac segmental and global T*₂ values were calculated after developing a correction map to compensate the artifactual T*₂ variations. The hepatic T*₂ value was determined over a region of interest. The intraoperator and interoperator reproducibility for T*₂ measurements at 3 T was good. A linear relationship was found between patients' R (1000/T*₂) values at 3 and 1.5 T. Segmental correction factors were significantly higher at 3 T. A conversion formula returning T*₂ values at 1.5 T from values at 3 T was proposed. A good diagnostic reliability for T*₂ assessment at 3 T was demonstrated. Lower limits of normal for 3 T T*₂ values were 23.3 ms, 21.1 ms, and 11.7 ms, for the global heart, mid‐ventricular septum, and liver, respectively. In conclusion, T*₂ quantification of iron burden in the mid‐ventricular septum, global heart, and no heavy–moderate livers resulted to be feasible, reproducible, and reliable at 3 T. Segmental heart T*₂ analysis at 3 T may be challenging due to significantly higher susceptibility artifacts. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Automated truncation method for myocardial T2* measurement in thalassemia

Purpose:

To propose an automated truncation method for myocardial T2* measurement and evaluate this method on a large population of patients with iron loading in the heart and scanned at multiple magnetic resonance imaging (MRI) centers.

Materials and Methods:

A total of 550 thalassemia patients were scanned at 20 international centers using a variety of MR scanners (Siemens, Philips, or GE). A single mid‐ventricular short axis slice was imaged. All patient data were anonymized before the T2* were measured by expert observers using standard techniques. These same datasets were then retrospectively processed using the proposed automated truncation method by another independent observer and the resulting T2* measurements were compared with those of expert readings.

Results:

The T2* measurements using the automated method showed good agreement with those measured by expert observers using standard techniques (P = 0.95) with a low coefficient of variation (1.6%).

Conclusion:

This study demonstrates feasibility and good reproducibility of a new automated truncation method for myocardial T2* measurement. This approach simplifies the overall analysis and can be easily incorporated into T2* analysis software to facilitate further development of a fully automated myocardial tissue iron quantification. J. Magn. Reson. Imaging 2013;37:479–483. © 2012 Wiley Periodicals, Inc.     

On using T2 to assess extrinsic magnetic field inhomogeneity effects on T2* measurements in myocardial siderosis in thalassemia

Magnetic resonance T₂* has been validated as a noninvasive means of assessing myocardial iron overload. However, the effect on myocardial T₂* of factors such as shimming, variations in capillary geometry, and susceptibility in relation to the effects of iron has not been fully clarified. Since T₂ is not affected by extrinsic magnetic field inhomogeneity and has different sensitivity to capillary geometry, investigation into the in vivo relationship between myocardial T₂* and T₂ measurements can shed light on this important issue. This study was performed in 136 thalassemia patients. The myocardial T₂ and T₂* thresholds for normality created identical no‐iron‐overload and iron‐overloaded patient groups. In the no‐iron group, there was no correlation between myocardial T₂ and T₂*. In the iron‐overloaded patients, there was a linear correlation (R² = 0.89) between myocardial T₂* and T₂ measurements, which indicates that the iron deposition is the dominant factor in determining these two relaxation values in this scenario. Magn Reson Med, 2009. © 2008 Wiley‐Liss, Inc.     

R2* imaging of transfusional iron burden at 3T and comparison with 1.5T

PURPOSE: To determine normative R2* values in the liver and heart at 3T, and establish the relationship between R2* at 3T and 1.5T over a range of tissue iron concentrations. MATERIALS AND METHODS: A total of 20 healthy control subjects and 14 transfusion-dependent patients were scanned at 1.5T and 3T. At each field strength R2* imaging was performed in the liver and heart. RESULTS: Normative R2* values in the liver were estimated from the control group to be 39.2 +/- 9.0 second(-1) at 1.5T and 69.1 +/- 21.9 second(-1) at 3T. Normative cardiac values were estimated as 23.4 +/- 2.2 second(-1) at 1.5T and 30.0 +/- 3.7 second(-1) at 3T. The combined R2* data from patients and control subjects exhibited a linear relationship between 3T and 1.5T. In the liver, the line of best fit to the 3T vs. 1.5T data had a slope of 2.00 +/- 0.06 and an intercept of -11 +/- 4 second(-1). In the heart, it had a slope of 1.88 +/- 0.14 and an intercept of -15 +/- 4 second(-1). CONCLUSION: These preliminary data suggest that the iron-dependent component of R2* scales linearly with field strength over a wide range of tissue iron concentrations. The incidence of susceptibility artifacts may, however, also increase with field strength.     

Evaluation of iron overload by single voxel MRS measurement of liver T2

PURPOSE: To overcome the difficulty of poor signal-to-noise ratio of magnetic resonance imaging (MRI) in evaluating heavy iron overload by using a single voxel magnetic resonance spectroscopy (MRS) technique. MATERIALS AND METHODS: A single voxel STEAM pulse sequence with a minimum TE of 1.5 msec and a sampling volume of 36.6 cm(3) was developed and applied to 1/T2 measurement of the liver in 14 patients with thalassemia whose liver iron concentration was determined through biopsy. RESULTS: The iron level ranged from 0.23 to 37.15 mg Fe/g dry tissue with a median value of 18.06. In all cases, strong MR signals were obtained. 1/T2 was strongly correlated with the liver iron concentration (r = 0.95, P < 0.00005). CONCLUSION: The single voxel MRS measurement of T2 in liver iron overload overcomes the difficulty of lack of detectable signals in conventional MRI when the iron level is high. There is an excellent correlation between the iron level and 1/T2.     

Myocardial T2 quantitation in patients with iron overload at 3 Tesla

Purpose

To investigate the feasibility of measuring myocardial T2 at 3 Tesla for assessment of tissue iron in thalassemia major and other iron overloaded patients.

Materials and Methods

A single‐breathhold electrocardiogram‐triggered black‐blood multi‐echo spin‐echo (MESE) sequence with a turbo factor of 2 was implemented at 3 Tesla (T). Myocardial and liver T2 values were measured with three repeated breathholds in 8 normal subjects and 24 patients. Their values, together with the T2* values measured using a breathhold multi‐echo gradient‐echo sequence, were compared with those at 1.5T in the same patients.

Results

At 3T, myocardial T2 was found to be 39.6 ± 7.4 ms in normal subjects. In patients, it ranged from 12.9 to 50.1 ms. T2 and T2* were observed to correlate in heart (ρ = 0.93, ρ < 0.0001) and liver (P = 0.95, P < 0.0001). Myocardial T2 and T2* at 3T were also highly correlated with the 1.5T measurements. Preliminary results indicated that myocardial T2 quantitation was relatively insensitive to B1 variation, and reproducible with 3.2% intra‐exam and 3.8% inter‐exam variations.

Conclusion

Myocardial T2 quantitation is feasible at 3T. Given the substantially decreased T2* and increased B0 inhomogeneity, the rapid myocardial T2 measurement protocol demonstrated here may present a robust alternative to study cardiac iron overload at 3T. J. Magn. Reson. Imaging 2009;30:394–400. © 2009 Wiley‐Liss, Inc.     

T2-weighted cardiovascular magnetic resonance imaging

Technical advances in T2-weighted cardiovascular MR (CMR) imaging allow for accurate identification and quantification of tissue injuries that alter myocardial T2 relaxation. Of these, myocardial edema is of special relevance. Increased myocardial water content is an important feature of ischemic as well as nonischemic cardiomyopathies, which are often associated with acute myocardial inflammation. In this article, we review technical considerations and discuss clinical indications of myocardial T2-weighted imaging.     

Measurement of liver iron overload: noninvasive calibration of MRI-R2* by magnetic iron detector susceptometer

An accurate assessment of body iron accumulation is essential for the diagnosis and therapy of iron overload in diseases such as thalassemia or hemochromatosis. Magnetic iron detector susceptometry and MRI are noninvasive techniques capable of detecting iron overload in the liver. Although the transverse relaxation rate measured by MRI can be correlated with the presence of iron, a calibration step is needed to obtain the liver iron concentration. Magnetic iron detector provides an evaluation of the iron overload in the whole liver. In this article, we describe a retrospective observational study comparing magnetic iron detector and MRI examinations performed on the same group of 97 patients with transfusional or congenital iron overload. A biopsy-free linear calibration to convert the average transverse relaxation rate in iron overload (R(2) = 0.72), or in liver iron concentration evaluated in wet tissue (R(2) = 0.68), is presented. This article also compares liver iron concentrations calculated in dry tissue using MRI and the existing biopsy calibration with liver iron concentrations evaluated in wet tissue by magnetic iron detector to obtain an estimate of the wet-to-dry conversion factor of 6.7 ± 0.8 (95% confidence level).