Liver steatosis in patients with transfusion-dependent thalassaemia.

We evaluated the prevalence and the clinical associations of liver steatosis (LS) in patients with transfusion-dependent thalassaemia (TDT). We considered 301 TDT patients (177 females, median age = 40.61 years) enrolled in the Extension-Myocardial Iron Overload in Thalassaemia Network, and 25 healthy subjects. Magnetic resonance imaging was used to quantify iron overload and hepatic fat fraction (FF) by T2* technique and cardiac function by cine images. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Hepatic FF was significantly higher in TDT patients than in healthy subjects (median value: 1.48% vs. 0.55%; p = 0.013). In TDT, hepatic FF was not associated with age, gender, serum ferritin levels or liver function parameters, but showed a weak inverse correlation with high-density lipoprotein cholesterol. The 36.4% of TDT patients showed LS (FF >3.7%). Active hepatitis C virus (HCV) infection, increased body mass index and hepatic iron were independent determinants of LS. A hepatic FF >3.53% predicted the presence of an abnormal OGTT. Hepatic FF was not correlated with cardiac iron, biventricular volumes or ejection fractions, but was correlated with left ventricular mass index. In TDT, LS is a frequent finding, associated with iron overload, increased weight and HCV, and conveying an increased risk for the alterations of glucose metabolism.

Pancreatic fatty replacement as risk marker for altered glucose metabolism and cardiac iron and complications in thalassemia major.

OBJECTIVES: This multicenter study assessed the extent of pancreatic fatty replacement and its correlation with demographics, iron overload, glucose metabolism, and cardiac complications in a cohort of well-treated patients with thalassemia major (TM). METHODS: We considered 308 TM patients (median age: 39.79 years; 182 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Magnetic resonance imaging was used to quantify iron overload (IO) and pancreatic fat fraction (FF) by T2* technique, cardiac function by cine images, and to detect replacement myocardial fibrosis by late gadolinium enhancement technique. The glucose metabolism was assessed by the oral glucose tolerance test. RESULTS: Pancreatic FF was associated with age, body mass index, and history of hepatitis C virus infection. Patients with normal glucose metabolism showed a significantly lower pancreatic FF than patients with impaired fasting glucose (p = 0.030), impaired glucose tolerance (p < 0.0001), and diabetes (p < 0.0001). A normal pancreatic FF (< 6.6%) showed a negative predictive value of 100% for abnormal glucose metabolism. A pancreatic FF > 15.33% predicted the presence of abnormal glucose metabolism. Pancreas FF was inversely correlated with global pancreas and heart T2* values. A normal pancreatic FF showed a negative predictive value of 100% for cardiac iron. Pancreatic FF was significantly higher in patients with myocardial fibrosis (p = 0.002). All patients with cardiac complications had fatty replacement, and they showed a significantly higher pancreatic FF than complications-free patients (p = 0.002). CONCLUSION: Pancreatic FF is a risk marker not only for alterations of glucose metabolism, but also for cardiac iron and complications, further supporting the close link between pancreatic and cardiac disease. KEY POINTS: • In thalassemia major, pancreatic fatty replacement by MRI is a frequent clinical entity, predicted by a pancreas T2* < 20.81 ms and associated with a higher risk of alterations in glucose metabolism. • In thalassemia major, pancreatic fatty replacement is a strong risk marker for cardiac iron, replacement fibrosis, and complications, highlighting a deep connection between pancreatic and cardiac impairment.

Myocardial T2 values at 1.5 T by a segmental approach with healthy aging and gender.

OBJECTIVES: Our aims were to obtain myocardial regional and global T2 values as a reference for normality for the first time using a GE scanner and to assess their association with physiological variables. METHODS: One hundred healthy volunteers aged 20-70 years (50% females) underwent cardiovascular magnetic resonance. Basal, mid-ventricular, and apical short-axis slices of the left ventricle were acquired by a multi-echo fast-spin-echo (MEFSE) sequence. Image analysis was performed with a commercially available software package. The T2 value was assessed in all 16 myocardial segments and the global value was the mean. RESULTS: The global T2 value averaged across all subjects was 52.2 ± 2.5 ms (range: 47.0-59.9 ms). Inter-study, intra-observer, and inter-observer reproducibility was good (coefficient of variation < 5%). 3.6% of the segments was excluded because of artifacts and/or partial-volume effects. Segmental T2 values differed significantly (p < 0.0001), with the lowest value in the basal anterolateral segment (50.0 ± 3.5 ms) and the highest in the apical lateral segment (54.9 ± 5.1 ms). Mean T2 was significantly lower in the basal slice compared to both mid-ventricular and apical slices and in the mid-ventricular slice than in the apical slice. Aging was associated with increased segmental and global T2 values. Females showed higher T2 values than males. T2 values were not correlated to heart rate. A significant inverse correlation was detected between global T2 values and mean wall thickness. CONCLUSIONS: The optimized MEFSE sequence allows for robust and reproducible quantification of segmental T2 values. Gender- and age-specific segmental reference values must be defined for distinguishing healthy and diseased myocardium. KEY POINTS: • In healthy subjects, T2 values differ among myocardial segments and are influenced by age and gender. • Normal T2 values in the myocardium, usable as a benchmark by other GE sites, were established.

Locus Coeruleus magnetic resonance imaging in cognitively intact elderly subjects.

The locus coeruleus is the main noradrenergic nucleus of the brain and is often affected in neurodegenerative diseases. Recently, magnetic resonance imaging with specific T1-weighted sequences for neuromelanin has been used to evaluate locus coeruleus integrity in patients with these conditions. In some of these studies, abnormalities in locus coeruleus signal have also been found in healthy controls and related to ageing. However, this would be at variance with recent post-mortem studies showing that the nucleus is not affected during normal ageing. The present study aimed at evaluating locus coeruleus features in a well-defined cohort of cognitively healthy subjects who remained cognitively intact on a one-year follow-up. An ad-hoc semiautomatic analysis of locus coeruleus magnetic resonance was applied. Sixty-two cognitively intact subjects aged 60-80 years, without significant comorbidities, underwent 3 T magnetic resonance with specific sequences for locus coeruleus. A semi-automatic tool was used to estimate the number of voxels belonging to locus coeruleus and its intensity was obtained for each subject. Each subject underwent extensive neuropsychological testing at baseline and 12 months after magnetic resonance scan. Based on neuropsychological testing 53 subjects were cognitively normal at baseline and follow up. No significant age-related differences in locus coeruleus parameters were found in this cohort. In line with recent post-mortem studies, our in vivo study confirms that locus coeruleus magnetic resonance features are not statistically significantly affected by age between 60 and 80 years, the age range usually evaluated in studies on neurodegenerative diseases. A significant alteration of locus coeruleus features in a cognitively intact elderly subject might be an early sign of pathology.

Absence of T1 Hyperintensity in the Brain of High-risk Patients After Multiple Administrations of High-dose Gadobutrol for Cardiac Magnetic Resonance.

PURPOSE: A prospective study was conducted to evaluate signal changes in the dentate nucleus, globus pallidus, pons, and thalamus (normalized to the deep cerebellum white matter) in T1-weighted magnetic resonance (MR) images after serial injections of gadobutrol in patients with thalassemia without neurological lesions. METHODS: In this study three groups were scanned at both 1.5 T and 3 T: 15 thalassemia patients transfused and chelated with ≥4 gadobutrol administrations at a high dose (0.2 mmol/kg per scan) for late gadolinium enhancement (LGE) cardiovascular MR, 8 thalassemia patients and 13 healthy subjects who had never received gadolinium-based contrast agents (GBCA). RESULTS: Signal intensity (SI) ratios at 1.5 T in all regions were comparable among the three groups and were not correlated with the number of gadobutrol administrations. In healthy subjects SI ratios were significantly different among the 4 regions, being higher in the pallidus. The SI ratios at 1.5 T were significantly higher and not correlated with SI ratios at 3 T or with iron overload in the same regions assessed by the T2* technique. CONCLUSION: This article describes the lack of increased SI in T1-weighted MR images after repeated administration of gadobutrol for cardiovascular MR studies in a high-risk population (high dose per scan, iron overload that can facilitate the transmetalation of gadolinium) scanned at 3 T and 1.5 T.

Effective Cardiac Index and Systemic-Pulmonary Collaterals Evaluated by Cardiac Magnetic Resonance Late After Fontan Palliation.

The regulation of cardiac output in the Fontan circuit is not completely understood. Systemic-pulmonary collaterals (SPCs) are frequent in patients with univentricular heart, and their clinical significance and management remain controversial. The aims of our study were to identify factors associated with SPCs' flow at late follow-up after Fontan and evaluate the relation between SPCs flow (QSPCs) and the effective cardiac index (CI). From our cardiac magnetic resonance database, we identified all Fontan patients with a complete set of flow measurements allowing calculation of QSPCs and effective CI. QSPCs was calculated as (left pulmonary veins flow + right pulmonary veins flow) - (right pulmonary artery flow + left pulmonary artery flow). Effective CI was calculated as (Aortic flow (QAo) - QSPCs)/BSA. Medical, surgical history, and clinical status were recorded. Sixty-four post-Fontan patients (36 male; mean age 19 ± 10 years) were included in the study. Median QSPCs was 0.7 L/min/m2 (interquartile [IQ] range 0.386-0.983) accounting for a median of 21% (IQ range 13-28) of aortic flow. The effective CI in our population was 2.4 ± 0.6 L/min/m2. QSPCs inversely correlate with left pulmonary artery area (r = -0.37, p = 0.004) and total antegrade pulmonary flow (r = -0.32, p = 0.01). QSPCs correlate with indexed aortic flow (r = 0.6, p <0.001) and inversely correlate with effective CI (r = -0.39, p = 0.002). Effective CI inversely correlates with age at study and age at the Fontan palliation (r = -0.35, p = 0.005, and r = -0.29, p = 0.02, respectively) and positively with ventricular ejection fraction (r = 0.3, p = 0.01). In conclusion, SPCs are common in Fontan patients, correlate inversely with effective CI, and are associated with a reduced antegrade pulmonary flow. In cardiac magnetic resonance evaluation of post-Fontan patients, effective CI should be taken into account rather than the total CI.

Accurate estimate of pancreatic T2* values: how to deal with fat infiltration.

PURPOSE: We examined different approaches aimed to deal with the signal fluctuation of pancreatic T2* values due to fat infiltration in order to obtain accurate estimates of iron overload. METHODS: Pancreatic T2* values were assessed in 20 patients (13 females, 37.24 ± 9.12 years) enrolled in the Myocardial Iron Overload in Thalassemia network without and with the application of fat suppression-FS (T2*-NoFS and T2*-FS). T2* values were assessed in three different ways: (1) from the immediate fit (original T2*); (2) discarding the echoes until the achievement of a good visual concordance between the signal and the model (final_vis T2*); (3) eliminating the echoes until the achievement of a fitting error (known) <5% (final_thres T2*). RESULTS: For the T2*-NoFS sequence the original T2* values were significantly higher than the final_vis T2* values (difference:4.8 ± 6.1 ms; P < 0.0001) and the final_thres T2* values (difference:4.3 ± 6.1 ms; P = 0.006). For the T2*-FS sequence the original T2* values were comparable to final_vis and final_thres T2* values. The original T2*-FS values were significantly different from the original T2*-NoFS values. The final_vis T2*-FS values were comparable to the final_vis T2*-NoFS values and the final_thresh T2*-FS values were comparable to the final_thresh T2*-NoFS values. For both T2*-FS and T2*-NoFS sequences, the final_thres T2* values were not significantly different from the final_vis T2* values and no bias was present. CONCLUSIONS: In the clinical practice, an accurate pancreatic iron overload assessment should be done by applying FS and, when needed, by discarding the TEs until the fitting error goes below 5%.

Improvement of heart iron with preserved patterns of iron store by CMR-guided chelation therapy.

AIMS: [Formula: see text] multislice multiecho cardiac magnetic resonance (CMR) allows quantification of the segmental distribution of myocardial iron overload (MIO). We evaluated whether a preferential pattern MIO was preserved between two CMR scans in regularly chelated thalassaemia major (TM) patients. METHODS AND RESULTS: We evaluated prospectively 259 TM patients enrolled in the MIO in Thalassaemia (MIOT) network with a CMR follow-up (FU) study at 18 ± 3 months and significant MIO at baseline. The [Formula: see text] in the 16 segments and the global value were calculated. Four main circumferential regions (anterior, septal, inferior and lateral) were defined. We identified two groups: severe (n = 80, global [Formula: see text] <10 ms) and mild-moderate MIO (n = 179, global [Formula: see text] = 10-26 ms). Based on the CMR reports, 56.4% of patients changed the chelation regimen. For each group, there was a significant improvement in the global heart as well as in regional [Formula: see text] values (P < 0.0001). At the baseline, the mean [Formula: see text] value over the anterior region was significantly lower than the values over the other regions, and the mean [Formula: see text] over the inferior region was significantly lower than the values over the septal and the lateral regions. The same pattern was present at the FU, with a little difference for patients with mild-moderate MIO. CONCLUSION: A preferential pattern of iron store in anterior and inferior regions was present at both CMRs, with an increment of [Formula: see text] values at FU due to a baseline CMR-guided chelation therapy. The anterior region seems the region in which the iron accumulates first and is removed later.

Detailing magnetic field strength dependence and segmental artifact distribution of myocardial effective transverse relaxation rate at 1.5, 3.0, and 7.0 T.

PURPOSE: Realizing the challenges and opportunities of effective transverse relaxation rate (R2 *) mapping at high and ultrahigh fields, this work examines magnetic field strength (B0 ) dependence and segmental artifact distribution of myocardial R2 * at 1.5, 3.0, and 7.0 T. METHODS: Healthy subjects were considered. Three short-axis views of the left ventricle were examined. R2 * was calculated for 16 standard myocardial segments. Global and mid-septum R2 * were determined. For each segment, an artifactual factor was estimated as the deviation of segmental from global R2 * value. RESULTS: The global artifactual factor was significantly enlarged at 7.0 T versus 1.5 T (P = 0.010) but not versus 3.0 T. At 7.0 T, the most severe susceptibility artifacts were detected in the inferior lateral wall. The mid-septum showed minor artifactual factors at 7.0 T, similar to those at 1.5 and 3.0 T. Mean R2 * increased linearly with the field strength, with larger changes for global heart R2 * values. CONCLUSION: At 7.0 T, segmental heart R2 * analysis is challenging due to macroscopic susceptibility artifacts induced by the heart-lung interface and the posterior vein. Myocardial R2 * depends linearly on the magnetic field strength. The increased R2 * sensitivity at 7.0 T might offer means for susceptibility-weighted and oxygenation level-dependent MR imaging of the myocardium.

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 *2 (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.

Regional and global pancreatic T*2 MRI for iron overload assessment in a large cohort of healthy subjects: normal values and correlation with age and gender.

Multiecho gradient-echo T*2 magnetic resonance imaging is a well-established technique for iron overload assessment but there are few reports concerning the pancreas. The aim of this work was to assess the feasibility and reproducibility of the magnetic resonance imaging for measuring pancreatic regional and global T*2 values, to establish the lower limit of normal in a large cohort of healthy subjects and to correlate the measured values with age and gender. One hundred and twenty healthy subjects (61 males, 51±17 years) underwent magnetic resonance imaging (1.5T) using a multiecho gradient-echo T*2 sequence. T*2 measurements were performed in pancreatic head, body, and tail. The global value was calculated as the mean. Measurement of pancreatic T*2 values was feasible in all subjects. For the T*2 global value the coefficient of variation for intraoperator and interoperator reproducibility were 7.7% and 13%, respectively. The global T*2 values ranged from 24 to 52 ms with the lower limit of normal of 26 ms. There were no significant differences among the regional pancreatic T*2 values. No significant correlation was found between T*2 and patient age or gender. In conclusion, pancreatic T*2 measurements appear to be feasible, reproducible, nontime-consuming and reliable. Gender- and age-related differences concerning pancreatic T*2 were not found.

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.

Standardized T2* map of a normal human heart to correct T2* segmental artefacts; myocardial iron overload and fibrosis in thalassemia intermedia versus thalassemia major patients and electrocardiogram changes in thalassemia major patients.

Studies of the standardized, 3D, 16-segments map of the circumferential distribution of T2* values, of cardiovascular magnetic resonance (CMR) in thalassemia major (TM) and thalassemia intermedia (TI) patients and of electrocardiogram (ECG) changes associated with TM, have been carried out. Similarly, the segment-dependent correction map of the T2* values and the artifactual variations in normal subjects and the T2* correction map to correct segmental measurements in patients with different levels of myocardial iron burden have been evaluated. Cardiovascular magnetic resonance can be a suitable guide to cardiac management in TI, as well as in TM; TI patients show lower myocardial iron burden and more pronounced high cardiac output findings than TM patients. Moreover, it is proposed that, due to its good positive predictive value (PPV) and low cost, ECG can be a suitable guide to orient towards CMR examination in TM cases.