Hepatic T2 Research Articles

Prognostic Value of Hepatic Native T1 and Extracellular Volume Fraction in Patients with Pulmonary Arterial Hypertension.

Background Right heart failure may lead to impaired liver perfusion and venous congestion, resulting in different extents of liver fibrosis. However, whether hepatic tissue deterioration determined by native T1 mapping and extracellular volume fraction using cardiac magnetic resonance imaging is associated with poor outcomes in patients with pulmonary arterial hypertension remains unclear. Methods and Results A total of 131 participants with pulmonary arterial hypertension (mean age, 36±13 years) and 64 healthy controls (mean age, 44±18) between October 2013 and December 2019 were prospectively enrolled. Hepatic native T1 and extracellular volume fraction values were measured using modified Look-Locker inversion recovery T1 mapping sequences. The primary end point was all-cause mortality; the secondary end point was all-cause mortality and repeat hospitalization attributable to heart failure. Cox regression models and Kaplan-Meier survival analysis were used to identify the association between variables and clinical outcome. During a median follow-up of 34.5 months (interquartile range: 25.3-50.8), hepatic native T1 (hazard ratio per 30-ms increase, 1.22 [95% CI, 1.07-1.39]; P=0.003) and extracellular volume fraction (hazard ratio per 3% increase, 1.18 [95% CI, 1.04-1.34]; P=0.010) values were associated with a higher risk of death. In the multivariate Cox model, hepatic native T1 value (hazard ratio per 30-ms increase, 1.15 [95% CI, 1.04-1.27]; P=0.009) remained as an independent prognostic factor for the secondary end point. Conclusions Hepatic T1 mapping values were predictors of adverse cardiovascular events in participants with pulmonary arterial hypertension and could be novel imaging biomarkers for poor prognosis recognition.

Abstract 12257: Prognostic Value of Liver T1 Mapping and Extracellular Volume in Dilated Cardiomyopathy

Introduction: Cardiac dysfunction closely correlates with liver congestion and effect on liver relaxation time. Liver relaxometry could provide potential prognostic improvement for dilated cardiomyopathy (DCM) patients. Hypothesis: Liver relaxometry might have prognostic significance for DCM patients. Methods: We prospectively enrolled 433 patients diagnosed with DCM. Cardiac and hepatic T1, T2, and extracellular volume (ECV) were measured on the mid-ventricular mappings. The primary endpoint was defined as heart failure death, sudden cardiac death, and heart transplantation. Results: DCM patients who reached primary endpoint showed significantly increased liver native T1 (770.5±103.2ms versus 813.8±137.0ms, p=0.014) and ECV values (30.9±6.8% versus 34.3±10.7%, p=0.009) and decreased liver T2 value (35.8±5.5 versus 34.1±6.2ms, p=0.038). Right ventricular ejection fraction correlated moderately but significantly with liver native T1 (r =-0.293) and ECV (r=-0.245) (both p<0.001). During the follow-up period (median duration 3.9 years) 97 patients reached the primary endpoint. In the Kaplan-Meier survival analysis, DCM patients with elevated liver native T1 or ECV had higher risk of reaching the primary endpoint (cutoff value: 854.9ms, p=0.001 and cutoff value: 34.5%, p<0.001, respectively). Cox analysis indicated that liver ECV was an independent prognostic factor (hazard ratio:1.042, p<0.001) and showed incremental prognostic value to age, sex, NYHA class III-IV, and LVEF. Conclusions: Liver native T1 and ECV correlates with cardiac magnetic resonance parameters. Furthermore, Liver ECV provides incremental prognostic value in DCM patients.

Relationship between Iron deposition and T lymphocytes in children with β-thalassemia with haematopoietic stem cell transplantation.

β-Thalassemia cellular immunity is associated with iron overload. However, the relationship between varying degrees of iron deposition and T cell immune recovery after allogeneic haematopoietic stem cell transplantation(allo-HSCT) in children remain unclear. A retrospective analysis was performed on 84 children with β-Thalassemia undergoing sibling allo-HSCT. According to the degrees of hepatic iron deposition, patients were divided into four classes. T lymphocyte counts were measured. Hepatic iron deposition was assessed by T2* MRI. Epstein-Barr virus and cytomegalovirus infection rates and graft-vs.-host disease incidence were recorded. Immune recovery after allo-HSCT was compared between the two groups. Normal vs. mild group: CD4 cells were higher at 1, 3, and 6 months (P < 0.05), CD3 and CD8 cells were higher at 3 and 6 months, and 1 year in normal group (P < 0.05). Normal vs. moderate group: CD3 and CD4 cells were higher at 1, 3 and 6 months, and 1 year (P < 0.05), CD8 cells were higher at 1 and 3 months, and 1 year in normal group (P < 0.05). Normal vs. severe group: CD3, CD4 and CD8 cell at 1, 3 and 6 months, and 1 year in normal group (P < 0.05). Mild vs. moderate group: CD3, CD4 and CD8 cells were higher at 1 month in mild group (P < 0.05). Mild vs. severe group: CD4 cells were higher at 1, 3 and 6 month, and 1 year (P < 0.05), CD3 and CD8 cells were higher at 1 month in mild group (P < 0.05). Moderate vs. severe group: CD4 cells were higher at 3 months (P < 0.05), CD8 cells were higher at 6 months in moderate group (P < 0.05). The hepatic T2* values were positively correlated with CD3, CD4 and CD8 cells. The infection rates of Epstein-Barr virus and cytomegalovirus were significantly different among the groups (P < 0.05). Iron deposition affects immune recovery of T lymphocytes after allo-HSCT in children with β-thalassemia. The lower the levels of iron deposition, the greater the CD4 cell count.

Assessment of iron overload in a cohort of Sri Lankan patients with transfusion dependent beta thalassaemia and its correlation with pathogenic variants in HBB, HFE, SLC40A1, and TFR2 genes

BackgroundIron overload (IO) is a complication in transfusion dependent beta thalassaemia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka.Materials and MethodsFifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for a period of one year in all. Those who were ≥ 8 years of age (40 patients) underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes.ResultsThe median age of the patients of this cohort was 10 years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The median level of serum ferritin was 2452 ng/dl. Hepatic IO was seen in 37 (92.5%) patients and cardiac IO was seen in 17 (42.5%) patients. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO.Thirty-two (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. Eight (15.4%) and 1 (1.9%) patients were heterozygotes for pathogenic and likely pathogenic variants of HFE genes respectively. There were no pathogenic variants for the TfR2 and SLC40A1 genes. The heterozygotes of the pathogenic variants of the HFE were not at increased risk of IO.ConclusionsCardiac T2* MRI helps to detect cardiac IO in asymptomatic patients. It is important to perform hepatic and cardiac T2* MRI to detect IO in patients with TDT. There was no statistically significant correlation between pathogenic variants of HBB and HFE genes with hepatic and cardiac IO in this cohort of patients.

Assessment of liver cirrhosis severity with extracellular volume fraction MRI.

We aimed to investigate the diagnostic utility of MRI extracellular volume fraction (ECV) for the assessment of liver cirrhosis severity as defined by Child–Pugh class. In this retrospective study, 90 patients (68 cirrhotic patients and 22 controls), who underwent multiparametric liver MRI, were identified. Hepatic T1 relaxation times and ECV were assessed. Clinical scores of liver disease severity were calculated. One-way analysis of variance (ANOVA) followed by Tukey’s multiple comparison test, Spearman’s correlation coefficient, and receiver operating characteristic (ROC) analysis were used for statistical analysis. In cirrhotic patients, hepatic native T1 increased depending on Child–Pugh class (620.5 ± 78.9 ms (Child A) vs. 666.6 ± 73.4 ms (Child B) vs. 828.4 ± 91.2 ms (Child C), P < 0.001). ECV was higher in cirrhotic patients compared to the controls (40.1 ± 11.9% vs. 25.9 ± 4.5%, P < 0.001) and increased depending of Child–Pugh class (33.3 ± 6.0% (Child A) vs. 39.6 ± 4.9% (Child B) vs. 52.8 ± 1.2% (Child C), P < 0.001). ECV correlated with Child–Pugh score (r = 0.64, P < 0.001). ECV allowed differentiating between Child–Pugh classes A and B, and B and C with an AUC of 0.785 and 0.944 (P < 0.001, respectively). The diagnostic performance of ECV for differentiating between Child–Pugh classes A and B, and B and C was higher compared to hepatic native T1 (AUC: 0.651 and 0.910) and MELD score (AUC: 0.740 and 0.795) (P < 0.05, respectively). MRI-derived ECV correlated with Child–Pugh score and had a high diagnostic performance for the discrimination of different Child–Pugh classes. ECV might become a valuable non-invasive biomarker for the assessment of liver cirrhosis severity.

Assessment of dynamic hepatic and renal imaging changes in COVID-19 survivors using T1 mapping and IVIM-DWI.

PurposeTo explore the imaging changes of the liver and kidneys in COVID-19 survivors using variable flip angle (VFA) T1 mapping and intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI).MethodsThis prospective study included 37 discharged COVID-19 participants and 24 age-matched non-COVID-19 volunteers who underwent abdominal MRI with VFA T1 mapping and IVIM-DWI sequencing as a COVID-19 group and control group, respectively. Among those discharged COVID-19 participants, 23 patients underwent two follow-up MRI scans, and were enrolled as the 3-month follow-up group and 1-year follow-up group, respectively. The demographics, clinical characteristics, and laboratory tests were collected. Imaging parameters of the liver and kidneys were measured. All collected values were compared among different groups.ResultsThe 3-month follow-up group had the lowest hepatic T1 value, which was significantly lower than the value in the control group (P < 0.001). Additionally, the 3-month follow-up group had the highest hepatic ADC and D values, cortical ADC and f values, which were significantly higher than those in the control group (for all, P < 0.05). The hepatic D value in the 1-year follow-up group decreased significantly in comparison with that in the 3-month follow-up group (P = 0.001). Compared to non-severe patients, severe cases had significantly higher hepatic D* and f*D* values (P = 0.031, P = 0.015, respectively).ConclusionThe dynamic alterations of hepatic and renal imaging parameters detected with T1 mapping and IVIM-DWI suggested that COVID-19 survivors might develop mild, non-symptomatic liver and kidney impairments, of which liver impairment could probably relieve over time and kidney impairment might be long-existing.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s00261-022-03471-y.

Abstract 10952: Increased Hepatic T1 Mapping Prediction of Elevated Right Atrial Pressure in Patients with Dilated Cardiomyopathy

Introduction: Elevated right atrial pressure (RAP) exhibits residual congestion and poor clinical outcomes in patients with heart failure (HF). In HF patients, persistent high RAP causes liver damage, which leads to liver fibrosis. Recent advances in T1 mapping of the liver using MRI allow the quantification of liver fibrosis. Hypothesis: Hepatic T1 mapping value may predicts high RAP in patients with chronic HF. Methods: We examined the data from the consecutive 40 patients with DCM ( 60 ± 13 years, 27 men) who underwent 3 Tesla cardiac and liver MRI, which were conducted within seven days of right heart catheterization. RV end-diastolic volume (RVEDV), end-systolic volume (RVESV), RV ejection fraction (RVEF), right atrial (RA) and left atrial (LA) volume, left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), LV ejection fraction (LVEF) and LV mass index (LVMI) were calculated from cine cardiac MRI. Native T1 mapping image (T1 short modified look locker inversion recovery-ShMOLLI- sequence) was acquired the heart and the liver (Figure A). Patients were divided into two groups according to RAP; high ( ≥ 8 mmHg; n=10) and low ( &lt;8 mmHg; n=30). Results: Ten patients had high RAP. There were no significant differences in LVEDV,LVESV, LVEF, LVMI, RVEDV, RVESV and RVEF between patients with high RAP group and those without ( 192 ± 54 ml vs 212 ± 57 ml; 136 ± 49 ml vs 154 ± 51 ml; 30 ± 9 % vs 28 ± 8 %; 79 ± 21 g/m 2 vs 81 ± 22 g/m 2 ; 45 ± 27 ml vs 46 ± 19 ml; 27 ± 18 ml vs 25 ± 15 ml; 42 ± 19% vs 46 ± 18%, respectively). The hepatic T1 mapping value was higher in the high RAP group ( 845 ± 47 ms vs 759 ± 90 ms, p &lt; 0.01) and exhibited a positive correlation with RAP ( R = 0.34, P &lt; 0.05). The hepatic T1 mapping value of ≥ 820ms was the optimal cutoff values for identifying high RAP ( T1: sensitivity, 89%; specificity, 72%; AUC, 0.80, Figure B). Conclusion: Increased native T1 mapping value of the liver may be helpful in non-invasively estimating elevated RAP.

Feasibility of Hepatic T1-Mapping and Extracellular Volume Quantification on Routine Cardiac Magnetic Resonance Imaging in Patients with Infiltrative and Systemic Disorders

Cardiac magnetic resonance imaging (CMR) is commonly obtained to evaluate for myocardial infiltrative disorders and fibrosis. Pre- and post-Gadolinium contrast T1-mapping sequences are employed to estimate interstitial expansion using extracellular volume fraction (ECV). Given the proximity of the liver to the heart, T1 and ECV quantification of the liver is feasible on CMR. The purpose of this study was to evaluate for hepatic measures of fibrosis and interstitial expansion in patients with amyloidosis or systemic disease on CMR. Myocardial and hepatic native T1 values were measured retrospectively using a cardiac short axis modified Look-Locker inversion recovery sequence. Myocardial and hepatic ECV were calculated using pre- and post-contrast T1 and blood pool values according to the following formula: ECV=(Δ(1/T1) myocardium or liver and/or Δ(1/T1) blood)x(1 - hematocrit). Patients were divided into three cohorts by final diagnosis: amyloidosis, systemic disease (e.g. sarcoid, scleroderma), and controls (EF > 50, no ischemia). Of the 135 patients who underwent CMR, 22 had cardiac amyloidosis (age 59.9 ± 12.6 yrs, 41% female), 20 had systemic disease (age 50.9 ± 13.4 yrs, 35% female), and 93 were controls (age 49.5 ± 17.3 yrs, 50% female). Myocardial T1 and ECV values were highest for patients with amyloid, second highest for systemic disease, and least for controls (T1: 1169 ± 92 vs 1101 ± 53 vs 1027 ± 73 ms, p < 0.0001; ECV: 0.47 ± 0.11 vs 0.31 ± 0.05 vs 0.27 ± 0.04, p < 0.0001). Hepatic T1 and ECV were similarly higher in patients with amyloid and systemic disease compared to controls (T1: 646 ± 101 vs 660 ± 93 vs 595 ± 58 ms, p < 0.0001; ECV: 0.38 ± 0.08 vs 0.37 ± 0.05 vs 0.31 ± 0.03, p < 0.0001). There was a positive correlation between hepatic T1 and ECV (R2=0.282, p < 0.0001). No patients had abnormal liver function tests or clinical liver disease. Hepatic ECV quantification on CMR in patients with amyloidosis and systemic disorders is feasible. Further longitudinal investigation regarding detection of early or subclinical liver disease is warranted.

Evaluation of liver T1 using MOLLI gradient echo readout under the influence of fat

BackgroundThe effect of hepatic steatosis on the gradient-echo (GRE) based Modified Look-Locker Inversion Recovery (MOLLI) technique for T1 mapping has not been evaluated. The purpose of this study was to evaluate a GRE based MOLLI technique for hepatic T1 mapping and determine the relationship of T1 differences (ΔT1) on in-phase (IP) and out-of-phase (OP) to fat fraction (FF) measurement. Materials and methods3 T MRI included MOLLI T1 mapping with TE = 1.3 (OP), 2.4 (IP), and 1.8 ms, and chemical-shift-encoded sequence with spectral modeling of fat to generate FF map as a reference. Bloch simulations and oil/water phantoms were used to characterize the response of the MOLLI T1 in various FF < 30% since MOLLI T1 estimation was erratic beyond this limit. Curve fit between ΔT1 and FF from simulation was applied to validate the phantom and the in-vivo results. Thirty-eight normal volunteers were included (16 women, Age 44 ± 12 years, BMI 27 ± 5.3 kg/m2). MOLLI water images were reconstructed by the average of OP and IP images, and the T1 values on water images served as the reference for T1 bias calculation defined as the percent difference between OP, IP, TE = 1.8 ms and the referenced water T1. Linear regression was performed to correlate the FF quantified by the reference and MOLLI methods. ResultsPhantom results were consistent with the Bloch simulations. The simulated relationship between FF (0–30%) and ΔT1 could be modeled precisely by a cubic equation with R2 = 1. In-vivo MOLLI ΔT1 and estimated FF were correlated to the reference FF (both R2 ≥ 0.96 and P < 0.001). TE = 1.8 ms demonstrated less T1 bias (−1.34%) compared to TE = OP (5.32%) or IP (−3.8%, both P < 0.001). ConclusionAt 3 T, TE of 1.8 ms can be used to reduce the T1 bias and deliver consistent T1 values when FF is <30%.

Turnover Rates of the Low-Density Lipoprotein Receptor and PCSK9: Added Dimension to the Cholesterol Homeostasis Model.

We measured the turnover rates of the LDLR (low-density lipoprotein receptor) and PCSK9 (proprotein convertase subtilisin/kexin type 9) in mice by metabolic labeling with heavy water and mass spectrometry. Approach and Results: In liver of mice fed high-cholesterol diets, LDLR mRNA levels and synthesis rates were markedly lower with complete suppression of cholesterol synthesis and higher cholesterol content, consistent with the Brown-Goldstein model of tissue cholesterol homeostasis. We observed markedly lower PCSK9 mRNA levels and synthesis rates in liver and lower concentrations and synthesis rates in plasma. Hepatic LDLR half-life (t½) was prolonged, consistent with an effect of reduced PCSK9, and resulted in no reduction in hepatic LDLR content despite reduced mRNA levels and LDLR synthesis rates. These changes in PCSK9 synthesis complement and expand the well-established model of tissue cholesterol homeostasis in mouse liver, in that reduced synthesis and levels of PCSK9 counterbalance lower LDLR synthesis by promoting less LDLR catabolism, thereby maintaining uptake of LDL cholesterol into liver despite high intracellular cholesterol concentrations. Lower hepatic synthesis and secretion of PCSK9, an SREBP2 (sterol response element binding protein) target gene, results in longer hepatic LDLR t½ in response to cholesterol feeding in mice in the face of high intracellular cholesterol content. PCSK9 modulation opposes the canonical lowering of LDLR mRNA and synthesis by cholesterol surplus and preserves LDLR levels. The physiological and therapeutic implications of these opposing control mechanisms over liver LDLR are of interest and may reflect subservience of hepatic cholesterol homeostasis to whole body cholesterol needs.

TU33. FAMILIAL LIABILITY FOR ENDOCRINE-METABOLIC DISORDERS AND DEPRESSION

Patients with transfusion dependent anemia are at risk of complications from iron overload. Quantitative T2* magnetic resonance imaging (MRI) is the best non-invasive method to assess iron deposition in the liver and heart and to guide chelation therapy.To investigate the image quality and inter-observer variations in T2* measurements of the myocardium and the liver, and to obtain the lower limit of cardiac and hepatic quantitative T2* values in patients without suspicion of iron overload.Thirty-eight patients referred for cardiac MRI were prospectively included in the study. Three patients were referred with, and 35 without suspicion of iron overload. Quantitative T2* parametric maps were obtained on a 1.5 T MRI system in the cardiac short axis and liver axial view. Two readers independently assessed the image quality and the representative and the lowest T2* value in the myocardium and the liver.The normal range of representative T2* values in the myocardium and liver was 24−45 ms and 14−37 ms, respectively. None of the 35 participants (0 %, 95 % confidence interval 0–11 %) in the normal reference group demonstrated representative T2* values below previously reported lower limits in the myocardium (20 ms) or the liver (8 ms). Focal myocardial areas with T2* values near the lower normal range, 19−20 ms, were seen in two patients. The readers generally reported good image quality.T2* imaging for assessing iron overload can be performed in a non-dedicated center with sufficient image quality.

ROLE OF CARDIOVASCULAR MAGNETIC RESONANCE IMAGING IN ASSESSMENT OF MYOCARDIAL IRON OVERLOAD IN THALASSEMIA PATIENTS

Background: Thalassemia major anemia patients require repeated blood transfusions, which improves their survival and quality of life, however it leads to iron overload and cellular damage. Serum ferritin and liver biopsy were used classically to measure iron overload and to monitor patient response to chelation therapy. Magnetic resonance imaging (MRI T2*) has proven to be a non-invasive, effective technique in detecting and quantifying myocardial and hepatic iron overload and in adjustment of iron chelation therapy.Aim of Work: To assess myocardial siderosis among our patients using MRI T2* technique and to correlate it with hepatic iron load and left ventricular ejection fraction (LVEF).Patients and methods: Our study included 42 cases of regularly transfused patients. Hepatic and myocardial iron overload were measured by multi-breath-hold MRI T2* technique and a cine view sequence was used to assess left ventricular function (EF).Results: Myocardial and hepatic iron overload were inter-correlated to each other and correlated to left ventricular function (LVEF). There was insignificant correlation between cardiac and hepatic T2* value results (k = 0.014, P > 0.05). However, there was a progressive and significant decline in left ventricular ejection fraction (r = 0·61, P < 0·001) in patients with low cardiac T2* values (T2* < 20 ms).Conclusion: MRI T2* technique is a precise, reproducible, and non-invasive technique for measuring tissue iron concentration and sparing the patients from an invasive biopsy technique. It also benefits in early detection of cardiac dysfunction and provides a follow up tool helping in chelation therapy adjustment.

Longer sustained Fontan circulation is associated with prolonged hepatic T1 relaxation time on T1 mapping

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with single ventricle defects may develop Fontan-associated liver disease. T1 mapping has been successfully used for evaluating chronic liver disease in adults. Liver T1 mapping has been also studied in the pediatric patients with single ventricles, and these patients show higher T1 relaxation times compared to the healthy controls. Purpose Our objective was to study the relationship between the cardiac MRI (CMR) T1 mapping relaxation time of the liver and 1) CMR derived hemodynamic parameters, 2) peripheral venous pressure (PVP) measured from a cubital cannula 3) systemic ventricle morphology [LV vs. RV], 4) the age of patient, and 5) alanine transaminase (P-ALAT) levels. Methods This retrospective study included 46 patients with functional single ventricle, which underwent routine CMR at our hospital. Table 1 shows demographic and clinical data of the study population. Statistical analysis were performed with IBM SPSS Statistics v.25 software using independent samples t test, Mann-Whitney U-test or Pearson correlation as appropriate. A p-value less than 0.05 was considered significant. Results The average T1 relaxation time of the liver was longer in patients with RV morphology (p = 0.004). There was a significant moderate positive correlation between the age of the patients and hepatic T1 relaxation time (r = 0.45, p = 0.002), and between hepatic T1 relaxation time and P-ALAT levels (r = 0.5, p = 0.016) (Fig.1). No significant correlations were detected between the T1 times of the liver and hemodynamic parameters of the heart (all tested parameters are listed in the Table1). Ejection fraction and PVP showed a non-significant weak correlation with a hepatic T1 relaxation times (r=-0.3, p = 0,056 and r = 0.3, p = 0,070, respectively). Conclusions T1 mapping times of the liver may reflect Fontan-associated liver disease. We observed connections between the hepatic T1 relaxation times and 1) patients age, 2) systemic ventricle morphology and 3) P-ALAT levels.

Pancreatic MR imaging and endocrine complications in patients with beta-thalassemia: a single-center experience.

Iron deposition in various organs can cause endocrine complications in patients with transfusion-dependent beta-thalassemia. The aim was to investigate the relationship between endocrine complications and pancreatic iron overload using magnetic resonance imaging (MRI). Forty patients with transfusion-dependent thalassemia (TDT) were enrolled in the study. The magnetic resonance imagings of the patients were performed using a 1.5 Tesla Philips MRI scanner. Two out of three patients had at least one clinical endocrine complication. The rate of iron deposition was 62.5% in liver, and 45% in pancreas tissue, and was 12.5% in heart tissue. Pancreatic T2* and hepatic T2* values were significantly positively correlated (p = 0.006). Pancreatic T2* and ferritin were significantly negatively correlated (p = 0.03). Cardiac T2* values were negatively correlated with fasting blood glucose (p = 0.03). Patients with short stature had significantly higher cardiac iron burden (22.3 vs. 36.6 T2*ms; p 0.01), and patients with hypothyroidism had higher liver iron concentrations (9.9 vs. 6.4 LIC mg/g; p = 0.05). The ferritin level of 841ng/mL and liver iron concentration (LIC) value of 8.7mg/g were detected as the threshold level for severe pancreatic iron burden (AUC 70%, p:0.04, AUC 80%, p = 0.002, respectively). Moreover, males were found to have decreased pancreas T2* values compared with the values in females (T2* 19.3 vs. 29.9, p = 0.05). Patients with higher ferritin levels over than 840ng/mL should be closely monitored for pancreatic iron deposition, and patients with endocrine complications should be assessed in terms of cardiac iron burden.

The relationships between pancreatic T2* values and pancreatic iron loading with cardiac dysfunctions, hepatic and cardiac iron siderosis among Egyptian children and young adults with β-thalassaemia major and sickle cell disease: a cross-sectional study

Background: Cardiac, hepatic and pancreatic T2* measured by magnetic resonance imaging (MRI) has been proven to be an accurate and non-invasive method for measuring iron overload in iron overload conditions. There is accumulating evidence that pancreatic iron can predict cardiac iron in young children because the pancreas loads earlier than the heart. The aim of our study was to assess the relationships between pancreatic T2* values and pancreatic iron loading with cardiac dysfunctions and liver and cardiac iron among patients with β-thalassaemia major (βTM) and sickle cell disease (SCD). Methods: 40 βTM and 20 transfusion-dependant SCD patients were included along with 60 healthy age and sex-matched controls. Echocardiography and Tissue Doppler Imaging were performed for all subjects as well as the control group. Hepatic, cardiac and pancreatic iron overload in cases were assessed by MRI T2*. Results: The mean age of our patients was 13.7 years with mean frequency of transfusion/year 12. Mean cardiac T2* was 32.9 ms and mean myocardial iron concentration was 0.7 mg/g; One patient had cardiac iron overload of moderate severity. Mean pancreatic T2* was 22.3 ms with 20 patients having mild pancreatic iron overload. Pancreatic T2* correlated positively peak late diastolic velocity at septal mitral annulus (r=0.269, p=0.038), peak early diastolic velocity at tricuspid annulus (r=0.430, p=0.001) and mitral annular plane systolic excursion (r=0.326, p=0.01); and negatively with end systolic pulmonary artery pressure (r=-0.343, p=0.007) and main pulmonary artery diameter (MPA) (r=-0.259, p=0.046). We couldn’t test the predictability of pancreatic T2* in relation to cardiac T2* as only one patient had cardiac T2*&lt;20 ms. Conclusion: There was a relationship between pancreatic iron siderosis with cardiac dysfunction in multi-transfused patients with βTM and SCD. No direct relation between pancreatic iron and cardiac siderosis was detected.

Diagnostic value of magnetic resonance parametric mapping for non-invasive assessment of liver fibrosis in patients with primary sclerosing cholangitis

BackgroundPrimary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, characterized by bile duct inflammation and destruction, leading to biliary fibrosis and cirrhosis. The purpose of this study was to investigate the utility of T1 and T2 mapping parameters, including extracellular volume fraction (ECV) for non-invasive assessment of fibrosis severity in patients with PSC.MethodsIn this prospective study, patients with PSC diagnosis were consecutively enrolled from January 2019 to July 2020 and underwent liver MRI. Besides morphological sequences, MR elastography (MRE), and T1 and T2 mapping were performed. ECV was calculated from T1 relaxation times. The presence of significant fibrosis (≥ F2) was defined as MRE-derived liver stiffness ≥ 3.66 kPa and used as the reference standard, against which the diagnostic performance of MRI mapping parameters was tested. Student t test, ROC analysis and Pearson correlation were used for statistical analysis.Results32 patients with PSC (age range 19–77 years) were analyzed. Both, hepatic native T1 (r = 0.66; P < 0.001) and ECV (r = 0.69; P < 0.001) correlated with MRE-derived liver stiffness. To diagnose significant fibrosis (≥ F2), ECV revealed a sensitivity of 84.2% (95% confidence interval (CI) 62.4–94.5%) and a specificity of 84.6% (CI 57.8–95.7%); hepatic native T1 revealed a sensitivity of 52.6% (CI 31.7–72.7%) and a specificity of 100.0% (CI 77.2–100.0%). Hepatic ECV (area under the curve (AUC) 0.858) and native T1 (AUC 0.711) had an equal or higher diagnostic performance for the assessment of significant fibrosis compared to serologic fibrosis scores (APRI (AUC 0.787), FIB-4 (AUC 0.588), AAR (0.570)).ConclusionsHepatic T1 and ECV can diagnose significant fibrosis in patients with PSC. Quantitative mapping has the potential to be a new non-invasive biomarker for liver fibrosis assessment and quantification in PSC patients.

The effect of bone marrow-derived mesenchymal stem cell co-transplantation with hematopoietic stem cells on liver fibrosis alleviation and survival in patients with class III \u03b2-thalassemia major

BackgroundHepatic fibrosis is a common complication in transfusion-dependent thalassemia patients. Data on the co-transplantation of mesenchymal stem cells (MSCs) with hematopoietic stem cells (HSCs) in beta-thalassemia major patients are scarce. Therefore, we aimed to evaluate the effect of co-transplantation of bone marrow-derived MSC with HSCs on the liver fibrosis alleviation and transplant outcomes in class III beta-thalassemia major.MethodsBetween April 1998 and January 2017, a total of 224 consecutive patients with class III beta-thalassemia major underwent allogeneic HSCT in the Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran. To assess liver fibrotic changes after transplantation, 47 patients participated in the MSC plus HSC group and 30 patients in the HSC only group at the end of the follow-up period. All patients underwent laboratory tests, especially serum ferritin and liver function testing, hepatic T2* MRI, liver biopsy, and FibroScan before and 2 years after transplantation. Kaplan-Meier curves were derived to determine survival and were compared using the log-rank test. Repeated-measure, mixed-effect linear regression models were used to examine the changes in liver fibrosis over time.ResultsThe 10-year OS rate was 71.84% in the mesenchymal group and 61.89% in the non-mesenchymal group (P value = 0.294), while the 10-year TFS rate was 63.64% in the mesenchymal group and 52.78% in the non-mesenchymal group (P value = 0.285). No significant difference was observed in the 10-year NRM, rejection rate, ANC engraftment, platelet engraftment, acute GvHD, and chronic GvHD between the two groups. In addition, the results of repeated-measure, mixed-effect linear regression models showed that none of the variables determining hepatic fibrosis had a significant difference between patients receiving MSCs and patients who did not receive MSCs.ConclusionsBased on the results of this study, a single infusion of MSCs at the time of HSCT to patients with class III beta-thalassemia major could not significantly improve the liver fibrosis alleviation and transplantation outcomes, including OS, TFS, TRM, rejection rate, ANC engraftment, platelet engraftment, acute GvHD, and chronic GvHD.

Evaluation of iron overload by cardiac and liver T2* in β-thalassemia: Correlation with serum ferritin, heart function and liver enzymes.

Introduction: In this study, we aimed to assess the relationship of cardiac and hepatic T2* magnetic resonance imaging (MRI) values as a gold standard for detecting iron overload with serum ferritin level, heart function, and liver enzymes as alternative diagnostic methods. Methods: A total 58 patients with beta-thalassemia major who were all transfusion dependent were evaluated for the study. T2* MRI of heart and liver, echocardiography, serum ferritin level, and liver enzymes measurement were performed. The relationship between T2* MRI findings and other assessments were examined. Cardiac and hepatic T2* findings were categorized as normal, mild, moderate, and severe iron overload. Results: 22% and 11% of the patients were suffering from severe iron overload in heart and liver, respectively. The echocardiographic findings were not significantly different among different iron load categories in heart or liver. ALT level was significantly higher in patient with severe iron overload than those with normal iron load in heart (P =0.005). Also, AST level was significantly lower in normal iron load group than mild, moderate, and severe iron load groups in liver (P <0.05). The serum ferritin level was significantly inversely correlated with cardiac T2* values (r = -0.34, P =0.035) and hepatic T2* values (r = -0.52, P =0.001). Conclusion: Cardiac and hepatic T2* MRI indicated significant correlation with serum ferritin level.

Relationship Between Pituitary Siderosis and Endocrinological Disorders in Pediatric Patients with Beta-Thalassemia.

IntroductionExcess iron accumulation occurs mainly in organs such as reticuloendothelial cells, the pituitary gland, and the pancreas in beta-thalassemia because of blood transfusions. In the present study, it was aimed to investigate the relationship between T2* values on magnetic resonance imaging (MRI) and clinically diagnosed pituitary endocrinological disorders in children with thalassemia major.MethodsThis study enrolled patients diagnosed with beta-thalassemia at pediatric hematology outpatient clinics. In the study, in addition to the medical history of the patients, routinely performed tests, including hemoglobin electrophoresis, routine biochemical tests, and tests for pubertal development (follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, etc.), as well as iron deposition measured by hepatic MRI T2* (STAR) sequence, were retrospectively assessed. A total of 29 patients were enrolled.ResultsHypothyroidism was detected in 34.6% (9/26) of patients, short stature in 37% (10/27), and pubertal retardation in 50% (14/28) of the patients. There was no significant correlation between hypothyroidism and pituitary MRI T2* values. No significant correlation was found between laboratory parameters and pituitary MRI examination. Although the sensitivity of T2* levels could rise above 80%, their specificity remained low. This is one of the major limitations of the pituitary MR T2* study for the prediction of short stature. The best lower cut-off level of MR T2* to predict short stature was found 14.6 ms.ConclusionThe diagnostic specificity pituitary MR examination levels for short stature were detected as low. Thus, the clinical standardization and validation of pituitary MR T2* values examination are needed before clinical follow-up and multifaceted studies are needed.

MRI quantification techniques in fatty liver: the diagnostic performance of hepatic T1, T2, and stiffness measurements in relation to the proton density fat fraction.

Nonalcoholic fatty liver disease (NAFLD) can progress to liver cirrhosis and is predicted to become the most frequent indication for liver transplantation in the near future. Noninvasive assessment of NAFLD is important for diagnosis and patient management. This study aims to prospectively determine the liver stiffness and T1 and T2 values in patients with NAFLD and to compare the diagnostic performance of magnetic resonance elastography (MRE) and mapping techniques in relation to the proton density fat fraction (PDFF). Eighty-three patients with NAFLD and 26 participants with normal livers were imaged with a 1.5 T scanner. PDFF measurements obtained from the multiecho Dixon technique were used to quantify the liver fat. MRE, native T1 mapping (modified Look-Locker inversion recovery [MOLLI] schemes 5(3)3, 3(3)3(3)5, and 3(2)3(2)5 and the B1-corrected variable flip angle [VFA] method), and T2 mapping values were correlated with PDFF. The diagnostic performance of MRE and the mapping techniques were analyzed and compared. T1 values measured with the MOLLI schemes and the B1-corrected VFA (P < 0.001), and the stiffness values from MRE (P = 0.047) were significantly higher in the NAFLD group. No significant difference was found between the groups in terms of T2 values (P = 0.127). In differentiation of the NAFLD and control groups, the B1-corrected VFA technique had slightly higher accuracy and area under the curve (AUC) than the MOLLI schemes. In the NAFLD group, there was a good correlation between the PDFF, MOLLI 3(3)3(3)5 and 3(2)3(2)5, and VFA T1 measurements (r=0.732; r=0.735; r=0.716, P < 0.001, respectively). Liver T1 mapping techniques have the potential to distinguish steatotic from nonsteatotic livers, and T1 values seem to have a strong correlation with the liver fat content.