Liver T2 Research Articles

Comparison of iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on liver and cardiac T2* MRI in thalassemia maior.

Background: Cardiac complications due to iron overload are the most common cause of death in patients with thalassemia major. The aim of this study was to compare iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on cardiac and liver iron load measured by T2* MRI.Methods:In this study, 108 patients with thalassemia major aged over 10 years who had iron overload in cardiac T2* MRI were studied in terms of iron chelators efficacy on the reduction of myocardial siderosis. The first group received deferoxamine, the second group only deferasirox, and the third group, a combination of deferoxamine and deferiprone. Myocardial iron was measured at baseline and 12 months later through T2* MRI technique.Results:The three groups were similar in terms of age, gender, ferritin level, and mean myocardial T2* at baseline. In the deferoxamine group, myocardial T2* was increased from 12.0±4.1 ms at baseline to 13.5±8.4 ms at 12 months (p=0.10). Significant improvement was observed in myocardial T2* of the deferasirox group (p<0.001). In the combined treatment group, myocardial T2* was significantly increased (p<0.001). These differences among the three groups were not significant at the 12 months. A significant improvement was observed in liver T2* at 12 months compared to baseline in the deferasirox and the combination group.Conclusion: In comparison to deferoxamine monotherapy, combination therapy and deferasirox monotherapy have a significant impact on reducing iron overload and improvement of myocardial and liver T2* MRI.

Magnetic Resonance Imaging Versus Serum Ferritin Levels in Detection of Liver and Cardiac Iron Overload in Non-Transfusion Dependent Thalassemia

Background: MRI is now established as the non-invasive modality of choice for the diagnosis of liver iron overload. Recently, it has been used to estimate myocardial iron overload in adult patients with acquired anemia. Objective: To assess the value of gradient-echo T2* in monitoring and screening of both liver and cardiac iron overload in non-transfusion dependent thalassemia (NTDT). Material and methods: This prospective study was conducted on children with mean age 11 years. Measurements were obtained in the same 1.5 MRI examination, followed by calculation with the reference spread sheet and then, the results were compared to the standard serum ferritin levels. Results: The study included 31 patients with non-transfusion-dependent thalassemia (NTT); 19 with thalassemiaintermedia, 6 with thalassemia-minor and 6 with hemoglobin-H. Mean serum ferritin was 201.8 ng/mL. Mean liver T2* was measured at 23.7 ms. Mean myocardial T2* was measured at 30 ms. Correlation analysis revealed significant negative correlation between hepatic T2* and serum ferritin (P<0.001*, R=-0.8). Week positive correlation was found for cardiac T2* (P=0.04, r=-0.37) and a week negative correlation was between hepatic and cardiac T2* values (P=0.4, R=-0.37). Statistically significant negative correlation with age was detected for hepatic T2* (P=0.001, R=-0.44) but not for cardiac T2* and serum ferritin. Conclusion: Liver and cardiac T2* measurement is the non-invasive modality of choice for monitoring and screening of both liver and cardiac iron overload in NTDT. From our experience, cardiac iron overload is uncommon in this disease population even in cases with mild and moderate hepatic overload.

Renal Iron Load in Sickle Cell Anemia Patients - a Brazilian Study

Background and Objectives: Sickle cell anemia (SCA) is characterized by chronic haemolysis and frequent painful vaso-occlusive episodes, eventually leading to multiple organ damage, including the kidneys. Chronic haemolysis is frequent in SCA patients receiving regular transfusions. Not all renal disease in patients with SCA is due to sickle cell nephropathy (SCN), but the incidence of renal failure increases as patient survival improves. Since Magnetic Resonance Image can provide a unique evaluation of the abdomen in a single exam, the aim of this study was to assess renal iron deposits in patients with SCA, correlating these values with transfusion burden, liver and heart T2* and blood LDH levels.Material and methods: Twenty patients with SCA older than 20 years of age and transfusion burden were studied in a 1.5T scanner (Avanto, Siemens Medical Systems, Erlangen, Germany) using T2* technique and compared to age- and sex-matched normal controls. For liver T2* analysis, regions of interest (ROI) were manually drawn in the liver, using Viewing software (Leonardo - Siemens) avoiding all major visible vessels. For heart T2* analysis, a full-thickness ROI was manually defined in the interventricular septum (routinely chosen to avoid T2* artifacts from the cardiac veins, liver, and lungs). For renal T2* analysis, ROI were manually drawn in the cortex, using Viewing software (Leonardo - Siemens) avoiding the medullary region. All parameters are presented as mean ± standard deviation. Spearman’s rank test was used to assess the correlation between renal T2* and blood LDH levels. The Ethics Committee for Research approved this trial.Results: Mean renal T2* was significantly lower (p < 0.001) in the SCA patients [16.4 ± 11.8 ms] compared with healthy controls (47.9 ± 11.1 ms). However there was no correlation between renal T2* and heart (p = 0.500) and liver T2* (p= 0.578). Median liver and myocardial T2* in this population was 3.96 ± 3.58 ms and 36.87 ± 8.06 ms. Cortico-medullary signal differences in renal iron loading were observed. Low signal intensity in the cortex relative to the medulla was observed in thirteen patients (65%). SCA patients who showed no cortico-medullary difference in signal intensity had a mean T2* of 30.9 ± 6.5 ms, which was significantly lower (p < 0.001) than that of the group of patients showing a hypointense cortical signal (8.6 ± 2.8 ms). We investigated the relationship between cortico-medullary differences and haemolysis using LDH values as a marker of haemolysis. Renal T2* showed a significant correlation with LDH values. Mean LDH values were significantly different between patients with and without cortico-medullary differences (p = 0.004), being 470.6 ± 123.1 IU/L for those with no cortico-medullary differences, and 1313.0 ± 788.6 IU/L for those with hypointense cortex. The seven highest LDH values in this cohort of 20 patients corresponded to seven patients with cortico-medullary signal intensity differences. Conclusion: Our study in SCA shows that iron deposition in the kidney is not related to systemic iron overload, but to haemolysis. There appears to be a clear localization of iron deposition within the kidney, with the deposits being found in the cortex and not in the medulla, as found by T1 and T2-weighted MRI. Our results suggest that haemolysis is a major determinant of renal iron load in SCA patiests. DisclosuresNo relevant conflicts of interest to declare.

Observational Study of Magnetic Resonance Imaging Monitoring in Patients with Aplastic Anemia (AA) and Low or Int-1 Risk of Myelodysplastic Syndromes(MDS) Complicated with Iron Overload

▪Objective: To observe the clinical characters and magnetic resonance imaging (MRI) T2* change in patients with aplastic anemia (AA) and low or int-1 risk of myelodysplastic syndromes(MDS) complicated with iron overload.Methods:This is a prospective study. Patients with AA and low and intermediate-1 risk factors of MDS complicated with iron overload were enrolled. Clinical parameters and T2* of liver, heart and pancreas were collected regularly.Results: Of all the 92 recruited patients (54 males and 38 females), the median age was 47.5 (15~18) year-old, median disease duration was 26 (3~407) months. There were 54 AA patients and 38 MDS patients. SF was related to liver T2* and pancreatic T2*(AA group r=-0.476,-0.509, respectively, P<0.05; MDS group r=-0.401, -0.565, respectively, P<0.05) in both groups, but not related to cardiac T2* in either group. SF level was correlated with transfusion amount in AA patients (r=0.403, P<0.05), but not in MDS patients (r=0.234, P>0.05. Of the 20 patients who received iron-chelation therapy, 3 (15%) had diarrheas, 2 (10%) decreased in hemoglobin, 2 (10%) decreased in platelet, 2 (10%) had increased creatinine, 1 (5%) had allergic dermatitis, but the symptoms relieved after drug withdrawal. 2 patients died of bone marrow failure during the follow-up period. 38 patients finished the half-year evaluation. Those (18 cases) who chelated adequately had significant decrease in SF (3354.9±3287.3 vs 2119.3±1742.0 ng/ml, P=0.044). Meanwhile an increase in hemoglobin level (83.5±30.0 vs 96.7±31.6 g/L, P=0.01) was noticed in those with decreased SF. 26 patients finished one year follow-up, those (15 cases) who chelated adequately had significant decrease in SF (3583.9±3543.8 vs 1693.9±1532.5 ng/ml, P=0.006), increase in cardiac T2* (25.0±13.4 vs 32.3±15.7 ms, P=0.015) and left ventricular ejection fraction (LVEF) (63.6±8.6 vs 67.1±5.2 %, P=0.028) , whereas no such changes were found in those did not chelate adequately. No change was found either in chelated or non-chelated groups in hemoglobin, WBC count, platelet count, SGPT, TBil, creatinine level, liver or pancreas T2* value. For those with decreased SF, even without chelation, increase in hemoglobin level (91.1 ±29.9 vs 108.4±31.4 g/L, P=0.046),cardiac T2* (25.5±13.7 vs 33.1±15.9 ms, P=0.014)) and LVEF level (63.6±8.6 vs 67.2±5.4 %, P=0.027) were also documented.Conclusion: SF was related to liver T2* and pancreatic T2* in both AA and MDS groups. SF was relevant to transfusion amount in patients with AA but not MDS. Adequate iron chelation can decrease the SF level, and might bring improvement in cardiac T2* and LVEF level. Decrease of SF even without chelation might also benefit patients. DisclosuresNo relevant conflicts of interest to declare.

A MRI Prospective Survey on Heart and Liver Iron and Cardiac Function in Thalassemia Major Patients Treated with Deferasirox Versus Deferiprone and Desferrioxamine in Monotherapy

Background: No prospective data are available about the efficacy of deferasirox versus deferiprone and desferrioxamine in monotherapy. Our study aimed to prospectively assess the efficacy of deferasirox versus deferiprone and desferrioxamine in monotherapy in a large cohort of thalassemia major (TM) patients by quantitative Magnetic Resonance (MR).Methods: Among the 2551 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we selected those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans. We identified three groups of patients: 235 treated with DFX, 142 with DFP and 162 with DFO. Iron overload was measured by T2* multiecho technique. Liver T2* values were converted into liver iron concentration (LIC) values. Biventricular function parameters were quantitatively evaluated by cine images.Results: Excellent/good levels of compliance were similar in the DFX (98.7%) vs DFP (96.3%) and DFO (97.5%) groups.Among the patients with myocardial iron overload at baseline, in all three groups there was a significant improvement in the global heart T2* value (DFX: +4.58±5.91ms P<0.0001, DFP: 8.53±6.97ms P<0.0001 and DFO: +3.93±5.21 ms P<0.0001) and a reduction in the number of pathological segments (DFX: -4.49±4.55 P<0.0001, DFP: -8.08±5.5.84 ms P=0.001 and DFO: -3.65±3.81 ms P<0.0001). In DFP and in DFO groups there was a significant improvement in left ventricular ejection function (LVEF) (+4.86±6.99% P=0.044 and +3.87±7.48% P=0.004, respectively). Only in the DFP group there was a significant improvement in right ventricular ejection function (RVEF) (6.69±4.61% P=0.001). The improvement in the global heart T2* was significantly lower in the DFX versus the DFP group , but it was not significantly different in the DFX versus the DFO group (Figure 1). The improvement in the LVEF was significantly higher in both DFP and DFO groups than in the DFX group while the improvement in the RVEF was significantly higher in the DFP than in DFX group (Figure 2).Among the patients with hepatic iron at baseline (LIC≥3mg/g dw) the changes were not significantly different in DFX versus the other groups.Conclusions: Prospectively in a large clinical setting of TM patients, DFX monotherapy was significantly less effective than DFP in improving myocardial siderosis and biventricular function and it was significantly less effective than DFO in improving the LVEF. [Display omitted] [Display omitted] DisclosuresPepe:Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc..

Correlation of Serum Ferritin Levels with Liver and Heart Mri T2 and Liver Iron Concentration in Beta Thalassemia Intermediate Patients: A Contemporary Issue

▪Background: B-Thalassemia intermediate (B-TI) is a genetic disease that is milder than beta thalassemia major. The accumulation of iron in different organs causes tissue damage. The T2* magnetic resonance imaging (MRI) technique is currently the gold standard for iron load detection. However, it is expensive and needs an expert radiologist to report findings. Therefore, we conducted this study to determine an optimal cut-off value of ferritin in proportion to T2 MRI for early detection of cardiac and hepatic iron overload in patients with beta thalassemia intermediate.Methods: This cross-sectional study was conducted on 108 patients with B-TI who referred to tertiary Hospital, Shiraz University of Medical Sciences, Shiraz, Iran. Serum ferritin, hepatic and cardiac T2 MRI were assessed. The ROC curve was used to determine the sensitivity and specificity of cut-off value.Results: Serum ferritin levels showed a statistically significant negative correlation with T2 hepatic MRI (r= -0.290, P value=0.003) and positive correlation with LIC (r= 0.426, P value < 0.001) in the patients with BTI. However, T2 cardiac MRI was not significantly correlated with serum ferritin levels (P value= 0.073).According to the analysis of ROC curves, the best cut-off value for ferritin to show early diagnosis of liver iron overload was 412 ng/ml. calculated sensitivities and specificities were 0.78 and 0.82 for T2 liver MRI and 0.76 and 0.86 for liver iron concentration (LIC) respectively.Conclusion: Serum ferritin levels of 412 ng/ml might be considered as a cut-off point to evaluate hepatic iron overload before using expensive, not readily available T2 MRI. This level of serum ferritin (around 500 ng/ml) could be considered for starting iron chelation therapy in patients with B-TI in areas where T2 MRI is not available. DisclosuresNo relevant conflicts of interest to declare.

Central Obesity and Liver Iron Content: A Noninvasive Assessment in General Population by Magnetic Resonance Imaging

Background/Aim: Existing evidence points to an altered status of iron metabolism in obesity. We aimed to investigate whether central obesity is independently associated with estimated liver iron content (liver T2* value) in general population that used the noninvasive assessment method by MRI. Methods: The study was carried out on 200 subjects randomly selected from the Golestan Cohort Study who underwent abdominal MRI. Quantitative T2* maps of entire cross-sectional area of liver were calculated using a semi-automated software for estimating the levels of iron content. Segmentation and calculation of visceral (VFA) and subcutaneous fat area (SFA) were also performed. Results: There was no significant difference in mean liver T2* values between obese (body mass index, BMI >30 kg/m²) and non-obese (BMI ≤30 kg/m²) subjects. After controlling for other covariates, no statistically significant association was detected between liver T2* values and VFA, SFA and VFA/SFA ratio. The drop in the relative signal intensity as an indicator of steatosis and serum ferritin predicted liver T2* values that almost had the same strength (standardized β of -0.41 and -0.41, respectively). Conclusions: Central obesity indices are not correlated with estimated liver iron content by MRI. Hepatic steatosis and serum ferritin seem to be the best predictors of hepatic T2* value. Since central obesity indices were not direct predictors of hepatic T2* value after the adjustment for confounding factors, it is possible that lipid accumulation in the liver locally, but not systematically, influences hepatic iron metabolism.

Abstract 13421: Liver T1 Mapping MRI and Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Fatty liver disease and liver fibrosis are associated with cardiovascular disease (CVD) metabolic risk factors and events. However direct imaging of liver abnormalities using T1 mapping MRI in relation to CVD has not been investigated in large epidemiological cohorts. Hypothesis: Liver abnormalities (inflammation and/or fibrosis) by T1 mapping MRI are associated with CVD events. Methods: MESA enrolled 6814 participants free of clinical CVD at baseline, MESA1 (2000-2002). A subsample of participants underwent Modified Look-Locker T1 mapping MRI at the fifth follow-up exam, MESA5 (2010 -2012). T1 maps were analyzed avoiding vessels and biliary ducts, and pre- and post-contrast T1 times (25 minutes after injection) were calculated. Liver extracellular volume fraction (ECV) was calculated using the pre- and post-contrast T1 times of the liver and cardiac blood pool. Higher ECV and pre-contrast T1 time (PreT1) were indicative of liver abnormalities. Coronary heart disease (CHD), heart failure (HF) and atrial fibrillation (AF) events were ascertained between MESA 1 and MESA 5. Multivariable linear regression analysis evaluated the cross-sectional relationship between liver ECV and T1 time with cardiac events adjusted for ASCVD/AHA risk score, liver fat content by computed tomography, alcohol use, socioeconomic status and BMI. Results: In 888 participants (67.83±8 years, 51% female, 60% Caucasian, 4% Chinese, 26% African-American, 10% Hispanic) there were 63 cardiac events (44 CHD, 13 CHF and 18 AF) between MESA1 and 5. Compared to controls, PreT1 and ECV were significantly higher in those with any cardiac event and AF. In multivariable analysis, PreT1 (standardized β=0.08, p=0.018) and ECV (standardized β=0.09, p=0.008) were associated with composite cardiac events. Conclusion: Liver abnormalities (most likely inflammation and/or fibrosis) estimated by greater liver PreT1 and ECV, are associated with cardiac events in a multi-ethnic cohort.

Quantitative Liver Function Analysis: Volumetric T1 Mapping with Fast Multisection B1 Inhomogeneity Correction in Hepatocyte-specific Contrast-enhanced Liver MR Imaging.

Purpose To determine whether B1 inhomogeneity-corrected volumetric T1 maps of gadoxetic acid-enhanced liver magnetic resonance (MR) imaging are able to demonstrate global liver function and functional heterogeneity in patients with cirrhosis and to investigate their relationship with the development of hepatic insufficiency and decompensation. Materials and Methods This institutional review board-approved retrospective study with waiver of informed consent included 234 consecutive patients who underwent gadoxetic acid-enhanced liver MR imaging, including B1 inhomogeneity-corrected volumetric T1 mapping. For all patients, T1 relaxation times of the liver and liver volumes were measured on T1 maps. Liver T1 and functional liver volume-to-weight ratio (liver volume divided by liver T1 and the patient's weight) were compared between Child-Pugh class A and class B cirrhosis. Associations between serum markers, MR parameters, hepatic insufficiency, and decompensation were investigated by using Cox proportional hazards analysis. Results Patients with Child-Pugh class B disease showed significantly longer liver T1 (548.2 msec ± 257.7 vs 372.2 msec ± 77.5, P < .0001) and lower kurtosis of liver T1 (29.1 ± 39.6 vs 43.9 ± 64.9, P = .016) than patients with Child-Pugh class A disease. Prolonged liver T1 (≥462 msec) (hazard ratio [HR], 5.9; 95% confidence interval [CI]: 1.1, 62.8) and an albumin level of less than 3.5 g/dL (HR, 20.7; 95% CI: 3.9, 221.9) were independently associated with the development of hepatic insufficiency. Functional liver volume-to-weight ratio was associated with the development of hepatic decompensation in patients with Child-Pugh class A disease (HR, 0.03; 95% CI: 0.004, 0.23). Conclusion B1 inhomogeneity-corrected volumetric T1 mapping provided information on global liver function and demonstrated functional heterogeneity. In addition, prolonged liver T1 (≥462 msec) was associated with the development of hepatic insufficiency, and functional liver volume-to-weight ratio was negatively related with the development of decompensation in compensated cirrhosis. © RSNA, 2016 Online supplemental material is available for this article.

Visual morphometry and three non-invasive markers in the evaluation of liver fibrosis in chronic liver disease

Objective: Liver fibrosis is traditionally graded into categorical stages with cirrhosis as the highest stage. However, cirrhosis stage may vary between individuals widely in terms of the amount of fibrosis which is not assessed by traditional staging systems. We aimed to utilise visual morphometry to quantify the amount of fibrosis in liver biopsy and compare how non-invasive methods of quantifying liver fibrosis correlated with histological measures.Materials and methods: Liver biopsy specimens from 115 consecutive chronic liver disease patients were assessed by a single pathologist for fibrosis stage by the Clinical Research Network and METAVIR systems as well as percentage fibrosis by visual morphometry. Liver T1 relaxation times, liver stiffness measurement (LSM) by transient elastography and enhanced liver fibrosis (ELF) score were compared between fibrosis stages. In addition, these parameters were correlated with pathologist’s visual estimate of percentage fibrosis and their predictive ability for advanced fibrosis and cirrhosis assessed by area under receiver operating curve (AUROC).Results: All four parameters increased sequentially from fibrosis stage F0 to F4 (p<.001 for each). AUROCs for advanced fibrosis and cirrhosis were 0.931 and 1.000 respectively for pathologist’s estimate of fibrosis, 0.707 and 0.926 for ELF score, 0.763 and 0.972 for T1 and 0.881 and 0.989 for LSM. LSM, ELF score and T1 correlated significantly with pathologist’s estimate of percentage fibrosis.Conclusion: Non-invasive markers of fibrosis LSM, ELF and T1 relaxation time provide continuous surrogates for categorical histopathological staging of fibrosis which can be useful as markers of progression and regression of fibrosis on follow-up.

Black blood T1rho MR imaging may diagnose early stage liver fibrosis: a proof-of-principle study with rat biliary duct ligation model.

To explore black blood T1rho (T1ρ) liver imaging and investigate the earliest stage when biliary duct ligation (BDL) induced liver fibrosis can be diagnosed. MR was performed at 3 Tesla. A T1ρ prepared 2D fast spin echo (FSE) sequence with acquisition of four spin lock times (TSLs: 1, 10, 30, and 50 msec) and spin-lock frequency of 500 Hz was applied. Inherent black blood effect of FSE and double inversion recovery (DIR) achieved blood signal suppression, and 3 axial sections per liver were obtained. Male Sprague-Dawley rats were scanned at baseline (n=32), and on day-3 (n=13), day-5 (n=11), day-7 (n=10), day-10 (n=4) respectively after BDL. Hematoxylin-eosin (HE) and picrosirius red staining liver histology was obtained at these time points. The physiological liver parenchyma T1ρ was 38.38±1.53 msec (range, 36.05-41.53 msec). Liver T1ρ value elevated progressively after BDL. On day-10 after BDL all experimental animals can be separated from normal liver based on T1ρ measurement with lowest value being 42.82 msec. Day-7 and day-10 liver resembled METAVIR stage-F1/F2 fibrosis, and fibrous area counted for 0.22%±0.13% and 0.38%±0.44% of liver parenchyma area, respectively. This study provides the first proof-of-principle that T1ρ might diagnose early stage liver fibrosis.

Non-invasive assessment of portal hypertension using quantitative magnetic resonance imaging

Hepatic venous pressure gradient (HVPG) measurement is currently the only validated technique to accurately evaluate changes in portal pressure. In this study, we evaluate the use of non-contrast quantitative magnetic resonance imaging (MRI) as a surrogate measure of portal pressure. Thirty patients undergoing HVPG measurement were prospectively recruited. MR parameters of longitudinal relaxation time (T1), perfusion of the liver and spleen (by arterial spin labelling), and blood flow in the portal, splanchnic and collateral circulation (by phase contrast MRI) were assessed. We estimated the liver stiffness measurement (LSM) and enhanced liver fibrosis (ELF) score. The correlation of all non-invasive parameters with HVPG was evaluated. The mean (range) HVPG of the patients was 9.8 (1-22) mmHg, and 14 patients (48%) had clinically significant portal hypertension (CSPH, HVPG ⩾10mmHg). Liver T1 relaxation time, splenic artery and superior mesenteric artery velocity correlated significantly with HVPG. Using multiple linear regression, liver T1 and splenic artery velocity remained as the two parameters in the multivariate model significantly associated with HVPG (R=0.90, p<0.001). This correlation was maintained in patients with CSPH (R=0.85, p<0.001). A validation cohort (n=10) showed this linear model provided a good prediction of HVPG. LSM and ELF score correlated significantly with HVPG in the whole population but the correlation was absent in CSPH. MR parameters related to both hepatic architecture and splanchnic haemodynamics correlate significantly with HVPG. This proposed model, confirmed in a validation cohort, could replace the invasive HVPG measurement. In patients with cirrhosis, the development and progression of portal hypertension is related to worse outcomes. However, the standard technique of assessing portal pressure is invasive and not widely used in clinical practice. Here, we have studied the use of non-invasive MRI in evaluating portal pressure. The MRI measures of liver architecture and blood flow in the splenic artery correlated well with portal pressure. Therefore, this non-invasive method can potentially be used to assess portal pressure in clinical trials and monitoring treatment in practice.

A model for hepatic fibrosis: the competing effects of cell loss and iron on shortened modified Look-Locker inversion recovery T1 (shMOLLI-T1 ) in the liver.

To propose a simple multicompartment model of the liver and use Bloch-McConnell simulations to demonstrate the effects of iron and fibrosis on shortened-MOLLI (shMOLLI) T1 measurements. Liver T1 values have shown sensitivity to inflammation and fibrosis, but are also affected by hepatic iron content. Modified Look-Locker inversion recovery (MOLLI) T1 measurements are biased by the lower T2 associated with high iron. A tissue model was generated consisting of liver cells and extracellular fluid (ECF), with iron-dependent relaxation rates. Fibrosis was imitated by increasing the ECF proportion. Simulations of the shMOLLI sequence produced a look-up table (LUT) of shMOLLI-T1 for a given ECF fraction and iron content. The LUT was used to calculate ECF(shMOLLI-T1 ), assuming normal hepatic iron content (HIC), and ECF(shMOLLI- T1,T2*), accounting for HIC determined by T2*, for 77 patients and compared to fibrosis assessed by liver biopsy. Simulations showed that increasing HIC decreases shMOLLI-T1 , with an increase in HIC from 1.0 to 2.5 mg/g at normal ECF fraction decreasing shMOLLI-T1 by 160 msec, while increasing ECF increased ShMOLLI-T1 , with an increase of 20% ECF at normal iron increasing shMOLLI-T1 by 200 msec. Calculated patient ECF(shMOLLI-T1 ) showed a strong dependence on Ishak score (3.3 ± 0.8 %ECF/Ishak stage) and 1/T2* (-0.23 ± 0.04 %ECF/Hz). However, when iron was accounted for to produce ECF(shMOLLI- T1,T2*), it was independent of HIC but retained sensitivity to Ishak score. Use of this multicompartment model of the liver with Bloch-McConnell simulation should enable compensation of iron effects when using shMOLLI-T1 to assess fibrosis. 1 J. Magn. Reson. Imaging 2017;45:450-462.

Correlation between liver iron concentration determined by magnetic resonance imaging and serum ferritin in adolescents with thalassaemia disease

Background:MRI imaging is an alternative to serum ferritin for assessing iron overload in patients with thalassaemia disease.Aims:To correlate liver iron concentration (LIC) determined by MRI and clinical and biochemical parameters.Methods:An MRI study using cardiovascular magnetic resonance (CMR) tools to determine cardiac and liver iron was undertaken in adolescents with thalassaemia disease.Results:Eighty-nine patients (48 males) with thalassaemia disease were enrolled. Seventy patients had been transfusion-dependent since a mean (SD) age of 3.8 (3.0) years, and 19 patients were not transfusiondependent. Mean (SD) haematocrit was 27.3 (2.9)%. Twenty-eight patients were splenectomized. Mean (SD) serum ferritin was 1673 (1506) μg/L. All transfusion-dependent patients received iron chelation at the mean (SD) age of 8.4 (3.5) years with either monotherapy of desferrioxamine, deferiprone, deferasirox or combined therapy of desferrioxamine and deferiprone, while only 5 of 19 patients who were not transfusion-dependent received oral chelation. The 89 patients underwent an MRI scan at the mean (SD) age of 14.8 (3.2) years. No patients had myocardial iron overload, but nine had severe liver iron overload, 27 had moderate liver iron overload, and 36 had mild liver iron overload. A significant correlation between liver T2* and serum ferritin was expressed as the equation: T2* (ms) = 28.080–7.629 log ferritin (μg/L) (r2 0.424, P = 0.0001). Patients with serum ferritin of >1000 to >2500 μg/L risked moderate and severe liver iron loading with the odds ratio ranging from 6.8 to 13.3 (95% CI 2.5–50.8).Conclusion:In thalassaemia, MRI is an alternative means of assessing iron stores, but when it is not available serum ferritin can be used to estimate liver T2*.

Evaluation of Iron Deposition in the Adrenal Glands of β Thalassemia Major Patients Using 3-Tesla MRI.

BackgroundBeta-thalassemia major (β-TM) patients need blood transfusions, which result in iron deposition. To regulate chelation therapy, iron load has to be measured. With MRI, the amount of signal loss and T2* decay time shortening are used for iron quantification.ObjectivesThe aim was to measure adrenal iron load with T2* relaxometry using MRI, and to compare it with liver and cardiac iron and serum ferritin, and to find out whether adrenal iron could be predicted from those parameters.Patients and MethodsBetween October 2014 and March 2015, MRI was performed in 21 patients with β-TM, recieving blood transfusions and chelation therapy. The control group (n = 11) included healthy volunteers with no known history of adrenal, hematologic, chronic disease, and blood transfusion.ResultsAmong patients, there was no significant correlation between plasma ferritin and adrenal T2*. Significant difference was detected among T2* values of adrenals between the patient and control groups. There was no significant correlation between adrenal gland and liver T2* in β-TM patients, moderate correlation was detected between adrenal T2* and cardiac T2*.ConclusionAdrenal iron in β-TM can be reliably measured in 3 Tesla MRI. The results highlight the absence of correlation between adrenal iron deposition both with serum ferritin and hepatic iron.

Quantification of maceration changes using post mortem MRI in fetuses.

BackgroundPost mortem imaging is playing an increasingly important role in perinatal autopsy, and correct interpretation of imaging changes is paramount. This is particularly important following intra-uterine fetal death, where there may be fetal maceration. The aim of this study was to investigate whether any changes seen on a whole body fetal post mortem magnetic resonance imaging (PMMR) correspond to maceration at conventional autopsy.MethodsWe performed pre-autopsy PMMR in 75 fetuses using a 1.5 Tesla Siemens Avanto MR scanner (Erlangen, Germany). PMMR images were reported blinded to the clinical history and autopsy data using a numerical severity scale (0 = no maceration changes to 2 = severe maceration changes) for 6 different visceral organs (total 12). The degree of maceration at autopsy was categorized according to severity on a numerical scale (1 = no maceration to 4 = severe maceration). We also generated quantitative maps to measure the liver and lung T2.ResultsThe mean PMMR maceration score correlated well with the autopsy maceration score (R2 = 0.93). A PMMR score of ≥4.5 had a sensitivity of 91 %, specificity of 64 %, for detecting moderate or severe maceration at autopsy. Liver and lung T2 were increased in fetuses with maceration scores of 3–4 in comparison to those with 1–2 (liver p = 0.03, lung p = 0.02).ConclusionsThere was a good correlation between PMMR maceration score and the extent of maceration seen at conventional autopsy. This score may be useful in interpretation of fetal PMMR.

Value of severe liver iron overload for assessing heart iron levels in thalassemia major patients.

The relationship between severe liver iron overload (LIO) and heart iron overload (HIO) in transfusion-dependent patients with thalassemia major (TM) is uncertain. Whether severe LIO can serve as an index for assessing heart iron deposition has vital clinical significance. Therefore, our aim is to determine if a close relationship exists between severe LIO and HIO. We examined 110 TM patients who underwent T2* measurement in the liver and heart on a 1.5 Tesla MRI scanner. Various statistical analysis methods were used to assess the relationship. Most of these patients suffered from severe LIO (58.18%, liver T2* < 1.4 ms). Both Pearson's and Spearman's tests showed a significant correlation between liver T2* and heart T2* values (with a correlation coefficient of 0.408 and 0.550, respectively, both P < 0.0001). A nonlinear model, with the equation of Heart T2* = 37.974-17.684 / Liver T2*, was found to be the best model to indicate the relationship between liver T2* and heart T2*. Receiver operating characteristic (ROC) analysis showed the area under the ROC curve of liver T2* and serum ferritin for predicting HIO was 0.812 (95% confidence interval [CI]: 0.731-0.892; P < 0.0001) and 0.69 (95% CI: 0.585-0.795; P = 0.001), respectively. Our preliminary data suggest the existence of a close relationship between severe LIO and HIO. High liver iron levels appear to increase the risk of heart iron deposition. This further supports the concept of critical liver iron concentration, above which elevated heart iron is present. J. MAGN. RESON. IMAGING 2016;44:880-889.

Correlation between Heart and Liver Iron Levels Measured by MRI T2* and Serum Ferritin in Patients with β-thalassemia Major

Background Transfusion-induced iron overload leads to many complications in patients with β-thalassemia major. This study aimed to compare the level of iron stored in the liver and heart measured by MRI T2 * with ferritin levels in these patients. Materials and Methods This study was done on 52 patients with β-thalassemia major aged 7 to 29 years. Serum ferritin level was checked and heart and liver MRI T2* operation was performed, then the liver and heart iron level measured by MRI T2 * was compared with serum ferritin levels. Results 150-180 cc/kg packed cells were received on average. The mean ± SD serum ferritin level was 2644.8±1988.3 ng/mL. The mean ± SD relaxation times in liver and heart MRI T2* were 4.39±5.8 and 26.59±10.62 millisecond, respectively. A negative significant correlation was found between serum ferritin levels and liver MRI T2* (P 0.05). Conclusion Since there was no correlation between serum ferritin levels and cardiac iron levels, accurate assessment of cardiac iron load using MRI T2* is necessary in patients with β-thalassemia major. Serum ferritin level is reliable for assessing liver iron levels.

Correlation between Heart, Liver and Pancreas Hemosiderosis Measured by MRI T2* among Thalassemia Major Patients from Iran.

Major thalassemia patients need lifelong transfusions. The consequence of these repeated transfusions is iron accumulation in different organs. The main aim of the present study was to investigate the correlation between heart, liver and pancreas hemosiderosis in thalassemic patients from Iran. This cross-sectional study was conducted on 164 major thalassemia patients at Zafar Adult Thalassemia Center, a referral thalassemia center in Tehran, Iran, from May to November 2014. All patients were on regular blood transfusion at 2-4 week intervals to keep their hemoglobin at a level of 7-9 gr/dL before each transfusion. Demographic data were gathered from patients' history. MRI T2* of liver, heart and pancreas were performed for all patients. There were a moderate correlation between pancreatic T2* and cardiac T2* relaxation times (r = 0.42, P < 0.001), a moderate correlation between T2* of pancreas and liver (r = 0.41, P < 0.001), and a weak correlation between T2* relaxation times of heart and liver (r = 0.31, P < 0.001). Poor correlation between liver and heart, as well as a weak to moderate correlation between pancreas and liver T2* relaxation times indicate that relying on liver MRI T2* to predict the exact condition of pancreas or heart iron overload might not be a reliable approach in thalassemia major patients. Our findings suggest the advantage of using pancreas and heart MRI T2* as a non-invasive method for estimation of iron overload instead of relying on liver MRI T2*.

Influence of fat on liver T1 measurements using modified Look-Locker inversion recovery (MOLLI) methods at 3T.

PurposeTo characterize the effect of fat on modified Look–Locker inversion recovery (MOLLI) T 1 maps of the liver. The balanced steady‐state free precession (bSSFP) sequence causes water and fat signals to have opposite phase when repetition time (TR) = 2.3 msec at 3T. In voxels that contain both fat and water, the MOLLI T 1 measurement is influenced by the choice of TR.Materials and MethodsMOLLI T 1 measurements of the liver were simulated using the Bloch equations while varying the hepatic lipid content (HLC). Phantom scans were performed on margarine phantoms, using both MOLLI and spin echo inversion recovery sequences. MOLLI T 1 at 3T and HLC were determined in patients (n = 8) before and after bariatric surgery.ResultsAt 3T, with HLC in the 0–35% range, higher fat fraction values lead to longer MOLLI T 1 values when TR = 2.3 msec. Patients were found to have higher MOLLI T 1 at elevated HLC (T 1 = 929 ± 97 msec) than at low HLC (T 1 = 870 ± 44 msec).ConclusionAt 3T, MOLLI T 1 values are affected by HLC, substantially changing MOLLI T 1 in a clinically relevant range of fat content. J. Magn. Reson. Imaging 2016;44:105–111.