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.     

Distribution of cardiac iron measured by magnetic resonance imaging (MRI)-R*2

Purpose

To assess regional iron distribution by magnetic resonance imaging (MRI)‐R₂* within the heart of patients with β‐thalassemia major (TM) and other iron overload diseases.

Materials and Methods

Breathhold electrocardiogram (ECG)‐gated MRI (1.5 T) of the heart was used for the measurement of transverse relaxation rates R₂* in 32 patients (11–79 years). In a mid‐papillary short‐axis slice divided into septal, anterior, lateral, and posterior quadrants, R₂* was analyzed from region of interest (ROI)‐based signal intensities from 12 echo times (TE = 1.3–26 msec). Typical boundary effects were evaluated in detail.

Results

The segmentation of the cardiac wall resulted in highly significant correlations of R₂* between septal and all other quadrants. In the patient group with R₂* < 50 s^?1 (normal), all quadrants show higher normalized median rates (126%–174%) than the septum (P < 10^?4), while this was relatively smaller in the group with septal R₂* > 50 s^?1. Typical boundary effects on segmental R₂* from blood, lung tissue, epicardial fat, and hepatic iron could not be easily separated from segmental iron distribution.

Conclusion

The measurement of MRI‐R2* in the interventricular septum is the least affected method by boundary effects to detect patients with iron overload at risk of developing heart failure. J. Magn. Reson. Imaging 2010;32:1104–1109. © 2010 Wiley‐Liss, Inc.

     

Multislice multiecho T2* cardiovascular magnetic resonance for detection of the heterogeneous distribution of myocardial iron overload

PURPOSE: To assess the tissue iron concentration of the left ventricle (LV) using a multislice, multiecho T2* MR technique and a segmental analysis. MATERIALS AND METHODS: T2* multiecho MRI was performed in 53 thalassemia major patients. Three short-axis views of the LV were obtained and analyzed with custom-written software. The myocardium was automatically segmented into 12 segments. The T2* value on each segment as well as the global T2* value were calculated. Cine dynamic images were also obtained to evaluate biventricular function parameters by quantitative analysis. RESULTS: For the T2* global value, the coefficient of variation (CoV) for intra-/interobserver and interstudy reproducibility was 3.9% (r = 0.98), 5.5% (r = 0.98), and 4.7% (r = 0.99) respectively. Three groups were identified based on analysis of myocardial T2*: homogeneous (21%), heterogeneous (38%), and no myocardial iron overload (41%). The mean serum ferritin, liver iron concentration, and urinary iron excretion were significantly different among the groups. We did not find significant differences among groups in biventricular function. There was a correlation between the global T2* value and the T2* value in the mid-ventricular septum (r = 0.95, P < 0.0001). CONCLUSION: Multislice multiecho T2* MRI provides a noninvasive, fast, reproducible means of assessing myocardial iron distribution. The single measurement of mid-septal T2* correlated well with the global T2* value.     

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.     

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.     

R2 relaxometry with MRI for the quantification of tissue iron overload in beta-thalassemic patients

PURPOSE: To evaluate the usefulness of a time-efficient MRI method for the quantitative determination of tissue iron in the liver and heart of beta-thalassemic patients using spin-spin relaxation rate, R2, measurements. MATERIALS AND METHODS: Images were obtained at 1.5 T from aqueous Gd-DTPA solutions (0.106-8 mM) and from the liver and heart of 46 beta-thalassemic patients and 10 controls. The imaging sequence used was a respiratory-triggered 16-echo Carr-Purcell-Meiboom-Gill (CPMG) spin-echo (SE) pulse sequence (TR = 2000 msec, TE(min) = 5 msec, echo spacing (ES) = 5 msec, matrix = 192 x 256, slice thickness = 10 mm). Liver iron concentration (LIC) measurements were obtained for 22 patients through biopsy specimens excised from the relevant liver segment. Biopsy specimens were also evaluated regarding iron grade and fibrosis. Serum ferritin (SF) measurements were obtained in all patients. RESULTS: A statistically significant difference was found between patients and healthy controls in mean liver (P < 0.004) and myocardium (P < 0.004) R2 values. The R2 values correlated well with Gd DTPA concentration (r = 0.996, P < 0.0001) and LIC (r = 0.874, P < 0.0001). A less significant relationship (r = 0.791, P < 0.0001) was found between LIC measurements and SF levels. R2 measurements appear to be significantly affected (P = 0.04) by different degrees of hepatic fibrosis. The patients' liver R2 values did not correlate with myocardial R2 values (r = 0.038, P < 0.21). CONCLUSION: Tissue iron deposition in beta-thalassemic patients may be adequately quantified using R2 measurements obtained with a 16-echo MRI sequence with short ES (5 msec), even in patients with a relatively increased iron burden.     

Influence of iron chelation on R1 and R2 calibration curves in gerbil liver and heart.

MRI is gaining increasing importance for the noninvasive quantification of organ iron burden. Since transverse relaxation rates depend on iron distribution as well as iron concentration, physiologic and pharmacologic processes that alter iron distribution could change MRI calibration curves. This article compares the effect of three iron chelators, deferoxamine, deferiprone, and deferasirox, on R1 and R2 calibration curves according to two iron loading and chelation strategies. Thirty-three Mongolian gerbils underwent iron loading (iron dextran 500 mg/kg/wk) for 3 weeks followed by 4 weeks of chelation. An additional 56 animals received less aggressive loading (200 mg/kg/week) for 10 weeks, followed by 12 weeks of chelation. R1 and R2 calibration curves were compared to results from 23 iron-loaded animals that had not received chelation. Acute iron loading and chelation-biased R1 and R2 from the unchelated reference calibration curves but chelator-specific changes were not observed, suggesting physiologic rather than pharmacologic differences in iron distribution. Long-term chelation deferiprone treatment increased liver R1 50% (P < 0.01), while long-term deferasirox lowered liver R2 30.9% (P < 0.0001). The relationship between R1 and R2 and organ iron concentration may depend on the acuity of iron loading and unloading as well as the iron chelator administered.     

ΔR2* gadolinium‐diethylenetriaminepentacetic acid relaxivity in venous blood

The accuracy of perfusion measurements using dynamic, susceptibility‐weighted, contrast‐enhanced MRI depends on estimating contrast agent concentration in an artery, i.e., the arterial input function. One of the difficulties associated with obtaining an arterial input function are partial volume effects when both blood and brain parenchyma occupy the same pixel. Previous studies have attempted to correct arterial input functions which suffer from partial volume effects using contrast concentration in venous blood. However, the relationship between relaxation and concentration (C) in venous blood has not been determined in vivo. In this note, a previously employed fitting approach is used to determine venous relaxivity in vivo. In vivo relaxivity is compared with venous relaxivity measured in vitro in bulk blood. The results show that the fitting approach produces relaxivity calibration curves which give excellent agreement with arterial measurements. Magn Reson Med 69:1104–1108, 2013. © 2012 Wiley Periodicals, Inc.     

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.     

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.     

Multiple gradient echo sequence optimized for rapid, single-scan mapping of R(2)(*) at high B0.

A multiple-gradient-echo sequence is proposed for accurately mapping R(2)(*) in the presence of in-slice macroscopic susceptibility gradients. In-slice signal loss caused by background macroscopic susceptibility gradients is mitigated by combining three successive gradient-echo images whose slice refocus gradients are successively incremented. The optimum incrementation of slice-refocusing gradients was determined by numerical simulation. By repeating further cycles of three images in the same sequence, artifact-compensated data spanning a range of echo times (TEs) was acquired leading to single-scan, R(2) (*) maps that are quantitatively reflective of microscopic field inhomogeneities. The performance of the sequence was demonstrated at 3.0T, first with a doped aqueous phantom, and then on the head of a normal volunteer. That performance is compared quantitatively with previously published work.     

Relaxivity‐iron calibration in hepatic iron overload: Probing underlying biophysical mechanisms using a Monte Carlo model

Iron overload is a serious condition for patients with β‐thalassemia, transfusion‐dependent sickle cell anemia, and inherited disorders of iron metabolism. MRI is becoming increasingly important in noninvasive quantification of tissue iron, overcoming the drawbacks of traditional techniques (liver biopsy). Effective transverse relaxation rate (1/effective transverse relaxation time) rises linearly with iron while transverse relaxation rate (1/T₂) has a curvilinear relationship in human liver. Although recent work has demonstrated clinically valid estimates of human liver iron, the calibration varies with MRI sequence, field strength, iron chelation therapy, and organ imaged, forcing recalibration in patients. To understand and correct these limitations, a thorough understanding of the underlying biophysics is of critical importance. Toward this end, a Monte Carlo‐based approach, using human liver as a “model” tissue system, was used to determine the contribution of particle size and distribution on MRI signal relaxation. Relaxivities were determined for hepatic iron concentrations ranging from 0.5 to 40 mg iron per gram dry tissue weight. Model predictions captured the linear and curvilinear relationship of effective transverse relaxation rate and transverse relaxation rate with hepatic iron concentrations, respectively, and were within in vivo confidence bounds; contact or chemical exchange mechanisms were not necessary. A validated and optimized model will aid understanding and quantification of iron‐mediated relaxivity in tissues where biopsy is not feasible (heart and spleen). Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Enhancement of gas‐filled microbubble R2* by iron oxide nanoparticles for MRI

Gas‐filled microbubbles have the potential to become a unique intravascular MR contrast agent due to their magnetic susceptibility effect, biocompatibility, and localized manipulation via ultrasound cavitation. However, microbubble susceptibility effect is relatively weak when compared with other intravascular MR susceptibility contrast agents. In this study, enhancement of microbubble susceptibility effect by entrapping monocrystalline iron oxide nanoparticles (MIONs) into polymeric microbubbles was investigated at 7 T in vitro. Apparent T₂ enhancement (ΔR₂*) induced by microbubbles was measured to be 79.2 ± 17.5 sec^?1 and 301.2 ± 16.8 sec^?1 for MION‐free and MION‐entrapped polymeric microbubbles at 5% volume fraction, respectively. ΔR₂* and apparent transverse relaxivities (r₂*) for MION‐entrapped polymeric microbubbles and MION‐entrapped solid microspheres (without gas core) were also compared, showing the synergistic effect of the gas core with MIONs. This is the first experimental demonstration of microbubble susceptibility enhancement for MRI application. This study indicates that gas‐filled polymeric microbubble susceptibility effect can be substantially increased by incorporating iron oxide nanoparticles into microbubble shells. With such an approach, microbubbles can potentially be visualized with higher sensitivity and lower concentrations by MRI. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.