Practical Application of Multivendor MRI-Based R2* Mapping for Liver Iron Quantification at 1.5 T and 3.0 T.

BACKGROUND: Recent multicenter, multivendor MRI-based R2* vs. liver iron concentration (LIC) calibrations (i.e., MCMV calibrations) may facilitate broad clinical dissemination of R2*-based LIC quantification. However, these calibrations are based on a centralized offline R2* reconstruction, and their applicability with vendor-provided R2* maps is unclear. PURPOSE: To determine R2* ranges of agreement between the centralized and three MRI vendors' R2* reconstructions. STUDY TYPE: Prospective. SUBJECTS: Two hundred and seven subjects (mean age 37.6 ± 19.6 years; 117 male) with known or suspected iron overload from four academic medical centers. FIELD STRENGTH/SEQUENCE: Standardized multiecho spoiled gradient echo sequence at 1.5 T and 3.0 T for R2* mapping and a multiple spin-echo sequence at 1.5 T for LIC quantification. MRI vendors: GE Healthcare, Philips Healthcare, and Siemens Healthineers. ASSESSMENT: R2* maps were generated using both the centralized and vendor reconstructions, and ranges of agreement were determined. R2*-LIC linear calibrations were determined for each site, field strength, and reconstruction and compared with the MCMV calibrations. STATISTICAL TESTS: Bland-Altman analysis to determine ranges of agreement. Linear regression, analysis of covariance F tests, and Tukey's multiple comparison testing to assess reproducibility of calibrations across sites and vendors. A P value <0.05 was considered significant. RESULTS: The upper limits of R2* ranges of agreement were approximately 500, 375, and 330 s-1 for GE, Philips, and Siemens reconstructions, respectively, at 1.5 T and approximately 700 and 800 s-1 for GE and Philips, respectively, at 3.0 T. Within the R2* ranges of agreement, vendor R2*-LIC calibrations demonstrated high reproducibility (no significant differences between slopes or intercepts; P ≥ 0.06) and agreed with the MCMV calibrations (overlapping 95% confidence intervals). DATA CONCLUSION: Based on the determined upper limits, R2* measurements obtained from vendor-provided R2* maps may be reliably and practically used to quantify LIC less than approximately 8-13 mg/g using the MCMV calibrations and similar acquisition parameters as this study. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

Iron absorption in adults with sickle cell anemia: a stable-isotope approach.

PURPOSE: Iron absorption in sickle cell anemia (SCA) remains unclear and studies in adults with SCA are scarce. The aim of this study was to evaluate the iron absorption SCA adults and its association with iron status and hepcidin concentration. METHODS: SCA patients (n = 13; SCAtotal) and control participants (n = 10) ingested an oral stable iron isotope (57Fe). Iron absorption was measured by inductively coupled plasma mass spectrometry (ICP-MS) 14 days after isotope administration. Patients with ≥ 1000 ng/mL serum ferritin were considered to present iron overload (IO) (SCAio+; n = 3) and others classified without IO (SCAio-; n = 10). RESULTS: Iron absorption in the control group ranged from 0.3 to 26.5% (median = 0.9%), while it varied from 0.3 to 5.4% in SCAio+ (median = 0.5%) and from 0.3 to 64.2% in the SCAio- (median = 6.9%). Hepcidin median values were 14.1 ng/mL (3.0-31.9 ng/mL) in SCAio-, 6.2 ng/mL (3.3-7.8 ng/mL) in SCAio + and 6.2 ng/mL (0.6-9.3 ng/mL) in control. Iron absorption was associated with ferritin level (r = - 0.641; p = 0.018) and liver iron concentration (LIC; r = - 0.786; p = 0.036) in the SCAtotal group. CONCLUSION: Our data suggest that SCAio- individuals may be at risk of developing primary IO. Simultaneously, secondary IO may induce physiological adaptation, resulting in reduced iron absorption. Further studies evaluating intestinal iron absorption using larger sample sizes should be conducted to help establish a safe nutrition approach to be adopted and to ensure the security of food-fortifying public policies for these patients. TRIAL REGISTRATION: This trial was registered at www.ensaiosclinicos.gov.br (Identifier RBR-4b7v8pt).

The relationship between liver stiffness by two-dimensional shear wave elastography and iron overload status in transfusion-dependent patients.

Increased liver stiffness (LS) can be result of increased liver iron concentration (LIC) which may not yet be reflected in the liver fibrotic status. The objective of our study was to examine relationship between hemochromatosis, LS, and serum ferritin level in transfusion-dependent patients. We recruited all 70 transfusion-dependent patients, whose median age was 15, referred for evaluating LIC status by magnetic resonance imaging (MRI) followed by two-dimensional ultrasonography shear wave elastography (2D-SWE). Thalassemia beta affected the majority of the patients. The optimal cut point for prediction of severe hemochromatosis using median SWE (kPa) and SWV (m/s) was ≥ 7.0 kPa and ≥ 1.54 m/s, respectively, with sensitivity of 0.76 (95% confidence interval [CI] 0.55, 0.91) and, specificity of 0.69 (95%CI 0.53, 0.82). When combing the optimal cut point of SWE (kPa) at ≥ 7.0 and serum ferritin ≥ 4123 ng/mL, the sensitivity increased to 0.84 (95%CI 0.64, 0.95) with specificity of 0.67 (95%CI 0.50, 0.80), positive predictive value (PPV) of 0.60 (95%CI 0.42, 0.76), and negative predictive value (NPV) of 0.88 (95%CI 0.71, 0.96). Simultaneous tests of 2D-SWE and serum ferritin for prediction of severe hemochromatosis showed the highest sensitivity of 84% (95%CI 0.64-0.95), as compared to 2D-SWE alone at 76% (95%CI 0.55, 0.91) or serum ferritin alone at 44% (95%CI 0.24-0.65). We recommend measuring both 2D-SWE and serum ferritin in short interval follow up patients. Adding 2D-SWE to management guideline will help in deciding for aggressive adjustment of iron chelating medication and increased awareness of patients having severe hemochromatosis.

Estimation of iron overload with T2*MRI in children treated for hematological malignancies.

Iron overload may contribute to long-term complications in childhood cancer survivors. There are limited reports of assessment of tissue iron overload in childhood leukemia by magnetic resonance imaging (MRI). A cross-sectional, observational study in children treated for hematological malignancy was undertaken. Patients ≥6 months from the end of therapy who had received ≥5 red-cell transfusions were included. Iron overload was estimated by serum ferritin (SF) and T2*MRI. Forty-five survivors were enrolled among 431 treated for hematological malignancies. The median age at diagnosis was 7-years. A median of 8 red-cell units was transfused. The median duration from the end of treatment was 15 months. An elevated SF (>1,000 ng/ml), elevated liver iron concentration (LIC) and myocardial iron concentration (MIC) were observed in 5 (11.1%), 20 (45.4%), and 2 (4.5%) patients, respectively. All survivors with SF >1,000 ng/ml had elevated LIC. The LIC correlated with SF (p < 0.001). MIC lacked correlation with SF or LIC. Factors including the number of red-cell units transfused and duration from the last transfusion were associated with elevated SF (p = 0.001, 0.002) and elevated LIC (p = 0.012, 0.005) in multiple linear regression. SF >595 ng/ml predicted elevated LIC with a sensitivity of 85% and specificity of 91.6% (AUC 91.2%). A cutoff >9 units of red cell transfusions had poor sensitivity and specificity of 70% and 75% (AUC 76.6%) to predict abnormal LIC. SF >600 ng/ml is a robust tool to predict iron overload, and T2*MRI should be considered in childhood cancer survivors with SF exceeding 600 ng/ml.

Spectroscopy-based multi-parametric quantification in subjects with liver iron overload at 1.5T and 3T.

PURPOSE: To evaluate the precision profile (repeatability and reproducibility) of quantitative STEAM-MRS and to determine the relationships between multiple MR biomarkers of chronic liver disease in subjects with iron overload at both 1.5 Tesla (T) and 3T. METHODS: MRS data were acquired in patients with known or suspected liver iron overload. Two STEAM-MRS sequences (multi-TE and multi-TE-TR) were acquired at both 1.5T and 3T (same day), including test-retest acquisition. Each acquisition enabled estimation of R1, R2, and FWHM (each separately for water and fat); and proton density fat fraction. The test-retest repeatability and reproducibility across acquisition modes (multi-TE vs. multi-TE-TR) of the estimates were evaluated using intraclass correlation coefficients, linear regression, and Bland-Altman analyses. Multi-parametric relationships between parameters at each field strength, across field strengths, and with liver iron concentration were also evaluated using linear and nonlinear regression. RESULTS: Fifty-six (n = 56) subjects (10 to 73 years, 37 males/19 females) were successfully recruited. Both STEAM-MRS sequences demonstrated good-to-excellent precision (intraclass correlation coefficient ≥ 0.81) for the quantification of R1water , R2water , FWHMwater , and proton density fat fraction at both 1.5T and 3T. Additionally, several moderate (R2 = 0.50 to 0.69) to high (R2 ≥ 0.70) correlations were observed between biomarkers, across field strengths, and with liver iron concentration. CONCLUSIONS: Over a broad range of liver iron concentration, STEAM-MRS enables rapid and precise measurement of multiple biomarkers of chronic liver disease. By evaluating the multi-parametric relationships between biomarkers, this work may advance the comprehensive MRS-based assessment of chronic liver disease and may help establish biomarkers of chronic liver disease.

Comparison of the effects of calcium channel blockers plus iron chelation therapy versus chelation therapy only on iron overload in children and young adults with transfusion-dependent thalassemia: A randomized double-blind placebo-controlled trial.

BACKGROUND: Myocardial iron deposition is a significant cause of morbidity and mortality in patients with transfusion-dependent thalassemia (TDT). Amlodipine, L-type calcium channel blocker with regular chelation therapy may reduce myocardial iron overload. Lack of randomized trials prompted this study to assess the effect of calcium channel blocker (amlodipine) in combination with iron chelation therapy on iron overload in patients with TDT. METHODS: Sixty-four eligible patients were randomized to receive either amlodipine and chelation (group A) or chelation alone (group B) in double-blind placebo-controlled trial. Myocardial iron concentration (MIC) using T2* magnetic resonance imaging (MRI), liver iron concentration (LIC), left ventricular ejection fraction (LVEF), and serum ferritin were measured at baseline and 12 months. RESULTS: In the amlodipine group, mean cardiac T2* value significantly increased from 18.11 ± 8.47 to 22.15 ± 7.61 (p = .002) at 12 months, whereas in control group, there was a nonsignificant increase (p = .62) in cardiac T2* value from 19.50 ± 8.84 to 20.03 ± 9.07. There was a significant decrease in MRI-derived MIC in the amlodipine group compared to control group (1.93 ± 1.61 to 1.29 ± 0.90, p = .01). Changes in the LVEF (p = .45), MRI-derived LIC (p = .09), and serum ferritin (p = .81) were not significant between the two groups. CONCLUSION: Amlodipine is safe and when combined with chelation therapy appears to be more effective in reducing cardiac iron overload than chelation only in children and young adults with TDT.

Biopsy-based optimization and calibration of a signal-intensity-ratio-based MRI method (1.5 Tesla) in a dextran-iron loaded mini-pig model, enabling estimation of very high liver iron concentrations.

OBJECTIVE: Magnetic resonance imaging (MRI)-based techniques for non-invasive assessing liver iron concentration (LIC) in patients with iron overload have a limited upper measuring range around 35 mg/g dry weight, caused by signal loss from accelerated T1-, T2-, T2* shortening with increasing LIC. Expansion of this range is necessary to allow evaluation of patients with very high LIC. AIM: To assess measuring range of a gradient-echo R2* method and a T1-weighted spin-echo (SE), signal intensity ratio (SIR)-based method (TE = 25 ms, TR = 560 ms), and to extend the upper measuring range of the SIR method by optimizing echo time (TE) and repetition time (TR) in iron-loaded minipigs. METHODS: Thirteen mini pigs were followed up during dextran-iron loading with repeated percutaneous liver biopsies for chemical LIC measurement and MRIs for parallel non-invasive estimation of LIC (81 examinations) using different TEs and TRs. RESULTS: SIR and R2* method had similar upper measuring range around 34 mg/g and similar method agreement. Using TE = 12 ms and TR = 1200 ms extended the upper measuring range to 115 mg/g and yielded good method of agreement. DISCUSSION: The wider measuring range is likely caused by lesser sensitivity of the SE sequence to iron, due to shorter TE, leading to later signal loss at high LIC, allowing evaluation of most severe hepatic iron overload. Validation in iron-loaded patients is necessary.

Iron Chelators, Such as Deferasirox, When Combined With Hydroxyurea, Provide an Additional Benefit of Iron Chelation in Patients Receiving Chronic Transfusion Therapy.

Red blood cell (RBC) transfusions have been established as one of the primary therapies in treating sickle cell anemia. However, they are not free of side effects, with overloading the body with iron being one of the most important. Iron chelation therapy greatly reduces the iron load of the body. In addition, hydroxyurea (HU), an oral chemotherapeutic drug also has a significant role in the treatment of the disease with beneficial effects on many of the clinical problems that arise, mainly in reducing painful crises. The aim of this study was to investigate the effect of synergistic transfusion therapy and HU on the response to deferasirox (DFX) chelation therapy. Eighteen patients with sickle cell disease were divided into two groups based on their treatment, either with simple transfusions and DFX or with a combination of transfusion therapy, DFX and HU, and were evaluated with magnetic resonance imaging (MRI) for liver iron concentration (LIC) and biochemistry. All patients completed the study. The results of the study showed improvement in serum ferritin (FER) levels and LIC after 12 months of therapy in both groups, especially in the group receiving the combination therapy with HU. In addition, there was a noteworthy improvement in serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and lactate dehydrogenase (LDH) levels with serum creatinine (Cr) levels remaining stable during the study in both groups. Hydroxyurea, when combined with iron chelators such as DFX, provides an additional benefit of iron chelation in patients receiving chronic transfusion therapy.

Thalassemia Intermedia: Chelator or Not?

Thalassemia is the most common genetic disorder worldwide. Thalassemia intermedia (TI) is non-transfusion-dependent thalassemia (NTDT), which includes ß-TI hemoglobin, E/ß-thalassemia and hemoglobin H (HbH) disease. Due to the availability of iron chelation therapy, the life expectancy of thalassemia major (TM) patients is now close to that of TI patients. Iron overload is noted in TI due to the increasing iron absorption from the intestine. Questions are raised regarding the relationship between iron chelation therapy and decreased patient morbidity/mortality, as well as the starting threshold for chelation therapy. Searching all the available articles up to 12 August 2022, iron-chelation-related TI was reviewed. In addition to splenectomized patients, osteoporosis was the most common morbidity among TI cases. Most study designs related to ferritin level and morbidities were cross-sectional and most were from the same Italian study groups. Intervention studies of iron chelation therapy included a subgroup of TI that required regular transfusion. Liver iron concentration (LIC) ≥ 5 mg/g/dw measured by MRI and ferritin level > 300 ng/mL were suggested as indicators to start iron chelation therapy, and iron chelation therapy was suggested to be stopped at a ferritin level ≤ 300 ng/mL. No studies showed improved overall survival rates by iron chelation therapy. TI morbidities and mortalities cannot be explained by iron overload alone. Hypoxemia and hemolysis may play a role. Head-to-head studies comparing different treatment methods, including hydroxyurea, fetal hemoglobin-inducing agents, hypertransfusion as well as iron chelation therapy are needed for TI, hopefully separating ß-TI and HbH disease. In addition, the target hemoglobin level should be determined for ß-TI and HbH disease.

Zinc and iron adequacy and relative importance of zinc/iron storage and intakes among breastfed infants.

Neonatal nutrient storage and supplies from breast milk contribute to nutrient status and growth of infants during their early life. This study investigated the adequacy of zinc and iron intakes among breastfed infants during the first 4 months and determined the relative importance of zinc/iron storage versus nutrient intakes with infant's biochemical status and growth. A longitudinal study followed lactating women and their breastfed infants from birth to 4 months postpartum. Cord zinc and ferritin concentrations, as indicators of nutrient storages, were determined. Zinc and iron intakes from breast milk were determined by measurement of breast milk volume together with milk zinc and iron concentrations at 2 and 4 months postpartum. Inadequacy of nutrient intakes was determined using average requirement (AR) which were 1.6 and 0.24 mg/day for zinc and iron respectively. Infant's serum zinc and ferritin were determined at 4 months of age. The data were collected from 64 and 56 participants at 2 months and 4 months postpartum. Inadequate zinc intake was found in 14.5 and 40% of infants at 2 and 4 months old, respectively. The prevalence of biochemical zinc and iron deficiency in infants were 76 and 11%, respectively. Iron endowment was significantly associated with serum ferritin at 4 months. The cumulative zinc intake was positively associated with weight gain and weight-for-length Z-score, but not length. This study provides quantitative data on zinc and iron intakes, and demonstrates the relative importance of nutrient storage versus intakes on biochemical status and growth of breastfed infants.

Iron Availability Modulates the Response of Endosymbiotic Dinoflagellates to Heat Stress.

Warming and nutrient limitation are stressors known to weaken the health of microalgae. In situations of stress, access to energy reserves can minimize physiological damage. Because of its widespread requirements in biochemical processes, iron is an important trace metal, especially for photosynthetic organisms. Lowered iron availability in oceans experiencing rising temperatures may contribute to the thermal sensitivity of reef-building corals, which rely on mutualisms with dinoflagellates to survive. To test the influence of iron concentration on thermal sensitivity, the physiological responses of cultured symbiotic dinoflagellates (genus Breviolum; family Symbiodiniaceae) were evaluated when exposed to increasing temperatures (26 to 30°C) and iron concentrations ranging from replete (500 pM Fe') to limiting (50 pM Fe') under a diurnal light cycle with saturating radiance. Declines in photosynthetic efficiency at elevated temperatures indicated sensitivity to heat stress. Furthermore, five times the amount of iron was needed to reach exponential growth during heat stress (50 pM Fe' at 26-28°C vs. 250 pM Fe' at 30°C). In treatments where exponential growth was reached, Breviolum psygmophilum grew faster than B.minutum, possibly due to greater cellular contents of iron and other trace metals. The metal composition of B.psygmophilum shifted only at the highest temperature (30°C), whereas changes in B.minutum were observed at lower temperatures (28°C). The influence of iron availability in modulating each alga's response to thermal stress suggests the importance of trace metals to the health of coral-algal mutualisms. Ultimately, a greater ability to acquire scarce metals may improve the tolerance of corals to physiological stressors and contribute to the differences in performance associated with hosting one symbiont species over another.

An automated liver segmentation in liver iron concentration map using fuzzy c-means clustering combined with anatomical landmark data.

BACKGROUND: To estimate median liver iron concentration (LIC) calculated from magnetic resonance imaging, excluded vessels of the liver parenchyma region were defined manually. Previous works proposed the automated method for excluding vessels from the liver region. However, only user-defined liver region remained a manual process. Therefore, this work aimed to develop an automated liver region segmentation technique to automate the whole process of median LIC calculation. METHODS: 553 MR examinations from 471 thalassemia major patients were used in this study. LIC maps (in mg/g dry weight) were calculated and used as the input of segmentation procedures. Anatomical landmark data were detected and used to restrict ROI. After that, the liver region was segmented using fuzzy c-means clustering and reduced segmentation errors by morphological processes. According to the clinical application, erosion with a suitable size of the structuring element was applied to reduce the segmented liver region to avoid uncertainty around the edge of the liver. The segmentation results were evaluated by comparing with manual segmentation performed by a board-certified radiologist. RESULTS: The proposed method was able to produce a good grade output in approximately 81% of all data. Approximately 11% of all data required an easy modification step. The rest of the output, approximately 8%, was an unsuccessful grade and required manual intervention by a user. For the evaluation matrices, percent dice similarity coefficient (%DSC) was in the range 86-92, percent Jaccard index (%JC) was 78-86, and Hausdorff distance (H) was 14-28 mm, respectively. In this study, percent false positive (%FP) and percent false negative (%FN) were applied to evaluate under- and over-segmentation that other evaluation matrices could not handle. The average of operation times could be reduced from 10 s per case using traditional method, to 1.5 s per case using our proposed method. CONCLUSION: The experimental results showed that the proposed method provided an effective automated liver segmentation technique, which can be applied clinically for automated median LIC calculation in thalassemia major patients.

Microstructural and compositional variation in pacu and piranha teeth related to diet specialization (Teleostei: Serrasalmidae).

In any vertebrate group, tooth shape is known to fit with a biological function related to diet. However, little is known about the relationships between diet and tooth microstructure and composition in teleost fishes. In this work, we describe the external morphology, internal microstructure and elemental composition of the oral teeth of three representative species of the family Serrasalmidae having different feeding habits (herbivorous vs. omnivorous vs. carnivorous). We used backscattered-electron imaging and low vacuum environmental scanning electron microscope to compare the organization and mineralization of tooth layers as well as energy dispersive X-ray microanalysis and Raman microspectrometry to investigate the elemental composition, Ca/P ratio and mineralogy of the most superficial layers. Oral teeth of each serrasalmid species have the same internal organization based on five distinctive layers (i.e. pulp, dentine, inner enameloid, outer enameloid and cuticle) but the general tooth morphology is different according to diet. Microstructural and compositional variation of the cuticle and iron-enrichment of superficial layers were highlighted between herbivorous and carnivorous species. Iron is more concentrated in teeth of the herbivorous species where it is associated with a thicker cuticle explaining the more intense red-pigmentation of the cutting edges of oral teeth. The iron-enrichment is interpreted as a substitution of Ca by Fe in the hydroxyapatite. These traits are discussed in the light of the evolutionary history of the family. Further considerations and hypotheses about the formation and origin of the mineralized tooth layers and especially the iron-rich superficial layers in teleost fishes are suggested.

B0-field dependence of MRI T1 relaxation in human brain.

Tissue longitudinal relaxation characterized by recovery time T1 or rate R1 is a fundamental MRI contrast mechanism that is increasingly being used to study the brain's myelination patterns in both health and disease. Nevertheless, the quantitative relationship between T1 and myelination, and its dependence on B0 field strength, is still not well known. It has been theorized that in much of brain tissue, T1 field-dependence is driven by that of macromolecular protons (MP) through a mechanism called magnetization transfer (MT). Despite the explanatory power of this theory and substantial support from in-vitro experiments at low fields (<3 â€‹T), in-vivo evidence across clinically relevant field strengths is lacking. In this study, T1-weighted MRI was acquired in a group of eight healthy volunteers at four clinically relevant field strengths (0.55, 1.5, 3 and 7 â€‹T) using the same pulse sequence at a single site, and jointly analyzed based on the two-pool model of MT. MP fraction and free-water pool T1 were obtained in several brain structures at 3 and 7 â€‹T, which allowed distinguishing between contributions from macromolecular content and iron to tissue T1. Based on this, the T1 of MP in white matter, indirectly determined by assuming a field independent T1 of free water, was shown to increase approximately linearly with B0. This study advances our understanding of the T1 contrast mechanism and its relation to brain myelin content across the wide range of currently available MRI strengths, and it has the potential to inform design of T1 mapping methods for improved reproducibility in the human brain.

Effect of four kinds of complexing iron on the process of iron uptake by Anabaena flos-aquae.

AbstractIron (Fe), which is a necessary micronutrient for algal growth, plays an important role in the physiological metabolism and enzymatic reactions of algae. This study aimed to investigate the absorption process of four kinds of complexing iron absorbed by Anabaena flos-aquae. Results showed that the absorptive capacity of A. flos-aquae to complex iron was inversely proportional to the stability of the complex bond of complex iron. Complex iron with weak binding ability can be quickly adsorbed by A. flos-aquae. The absorptive rate was as follows: ferric humate, ferric oxalate >ammonium ferric citrate >EDTA Fe. For EDTA-Fe with a strong binding ability, a moderate iron concentration (e.g. 0.6 mg l-1) is favourable for iron uptake by A. flos-aquae. Our experiments also revealed that the process of separating iron from complex iron before entering algal cells was probably as follows: iron complexed with organic ligands were firstly adsorbed on the surface of algae cells; afterwards, iron ions were captured by organic matter on the surface of algae cells, accompanied by the rupture of the bond between Fe3+ and ligand; finally, the Fe3+ entered into the cell of algae while the organic ligands returned to the medium.

Selenite mitigates cadmium-induced oxidative stress and affects Cd uptake in rice seedlings under different water management systems.

Cadmium (Cd) is toxic throughout the food chain. Selenium (Se) can mitigate Cd accumulation in rice plants, although it is unclear why it has such effect. The objectives of this study were to investigate the effects of Se application on Cd-induced oxidative stress and antioxidant activities, and the combined effects of Se application and water management on the formation of iron plaque on the rice surface and Fe, Cd, and Se accumulation in rice plants. Rice seedlings were grown in Cd-contaminated soil with or without the addition of Se, and in aerobic or flooded conditions. Exogenous Se reduced Cd-induced oxidative stress. In the flooded treatment, exogenous selenite significantly decreased Cd concentrations in rice tissues, whereas it noticeably enhanced Cd concentrations in rice tissues in the aerobic treatment. Furthermore, selenite addition and flooding promote the formation of iron plaque and increase Fe concentrations in rice tissues. Pearson correlation analysis shows that plant Cd was significantly negatively correlated with Fe concentrations in rice tissues, and plant Fe was significantly positively correlated with Se concentrations in rice tissues, but no significant correlation was found between Cd and Se concentrations Thus, exogenous selenite may indirectly affect Cd uptake by influencing the formation of iron plaque on rice root surface, Fe uptake and Fe levels in rice.

The value of magnetic resonance imaging in evaluation of myocardial and liver iron overload in a thalassaemia endemic population: a report from Northeastern Thailand.

PURPOSE: Patients with chronic haemolytic anaemia, such as in thalassaemia, require repeated blood transfusions, which leads to iron overload and cellular damage, especially in the heart and liver. Classically, serum ferritin and liver biopsy have been used to monitor patient response to chelation therapy. Magnetic resonance imaging (MRI) has proven to be effective in detecting and quantifying iron in the heart and liver. The aim of the paper is to evaluate the accuracy of the MRI T2* procedure in the assessment of liver iron concentration and myocardial iron overload. MATERIAL AND METHODS: In 210 cases of monthly transfused patients, hepatic and myocardial iron overload was measured by multi-breath-hold MRI T2* and compared to serum ferritin (a traditional marker of iron overload). RESULTS: No significant correlation was observed between serum ferritin level and cardiac T2* MRI (p = 0.68, r = 0.06). However, a significant correlation was observed between serum ferritin and liver iron concentration evaluated by MRI (p = 0.04, r = 0.68). CONCLUSION: Routine evaluation of liver and heart iron content using MRI T2* is suggested to better evaluate the haemosiderosis status in thalassaemic patients.

Simultaneous quantitative susceptibility mapping (QSM) and R2* for high iron concentration quantification with 3D ultrashort echo time sequences: An echo dependence study.

PURPOSE: To evaluate the echo dependence of 3D ultrashort echo time (TE) quantitative susceptibility mapping (3D UTE-QSM) and effective transverse relaxation rate ( R2*) measurement in the setting of high concentrations of iron oxide nanoparticles. METHODS: A phantom study with iron concentrations ranging from 2 to 22 mM was performed using a 3D UTE Cones sequence. Simultaneous QSM processing with morphology-enabled dipole inversion (MEDI) and R2* single exponential fitting was conducted offline with the acquired 3D UTE data. The dependence of UTE-QSM and R2* on echo spacing (ΔTE) and first TE (TE1 ) was investigated. RESULTS: A linear relationship was observed between UTE-QSM measurement and iron concentration up to 22 mM only, with the minimal TE1 of 0.032 ms and ΔTE of less than 0.1 ms. A linear relationship was observed between R2* and iron concentration up to 22 mM only when TE1 was less than 0.132 ms and ΔTE was less than 1.2 ms. UTE-QSM with MEDI processing showed strong dependence on ΔTE and TE1 , especially at high iron concentrations. CONCLUSION: UTE-QSM is more sensitive than R2* measurement to TE selection. Both an ultrashort TE1 and a small ΔTE are needed to achieve accurate QSM for high iron concentrations. Magn Reson Med 79:2315-2322, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Improved liver R2* mapping by pixel-wise curve fitting with adaptive neighborhood regularization.

PURPOSE: To improve liver R2* mapping by incorporating adaptive neighborhood regularization into pixel-wise curve fitting. METHODS: Magnetic resonance imaging R2* mapping remains challenging because of the serial images with low signal-to-noise ratio. In this study, we proposed to exploit the neighboring pixels as regularization terms and adaptively determine the regularization parameters according to the interpixel signal similarity. The proposed algorithm, called the pixel-wise curve fitting with adaptive neighborhood regularization (PCANR), was compared with the conventional nonlinear least squares (NLS) and nonlocal means filter-based NLS algorithms on simulated, phantom, and in vivo data. RESULTS: Visually, the PCANR algorithm generates R2* maps with significantly reduced noise and well-preserved tiny structures. Quantitatively, the PCANR algorithm produces R2* maps with lower root mean square errors at varying R2* values and signal-to-noise-ratio levels compared with the NLS and nonlocal means filter-based NLS algorithms. For the high R2* values under low signal-to-noise-ratio levels, the PCANR algorithm outperforms the NLS and nonlocal means filter-based NLS algorithms in the accuracy and precision, in terms of mean and standard deviation of R2* measurements in selected region of interests, respectively. CONCLUSIONS: The PCANR algorithm can reduce the effect of noise on liver R2* mapping, and the improved measurement precision will benefit the assessment of hepatic iron in clinical practice. Magn Reson Med 80:792-801, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Assessment of MR-based R2* and quantitative susceptibility mapping for the quantification of liver iron concentration in a mouse model at 7T.

PURPOSE: To assess the feasibility of quantifying liver iron concentration (LIC) using R2* and quantitative susceptibility mapping (QSM) at a high field strength of 7 Tesla (T). METHODS: Five different concentrations of Fe-dextran were injected into 12 mice to produce various degrees of liver iron overload. After mice were sacrificed, blood and liver samples were harvested. Ferritin enzyme-linked immunosorbent assay (ELISA) and inductively coupled plasma mass spectrometry were performed to quantify serum ferritin concentration and LIC. Multiecho gradient echo MRI was conducted to estimate R2* and the magnetic susceptibility of each liver sample through complex nonlinear least squares fitting and a morphology enabled dipole inversion method, respectively. RESULTS: Average estimates of serum ferritin concentration, LIC, R2*, and susceptibility all show good linear correlations with injected Fe-dextran concentration; however, the standard deviations in the estimates of R2* and susceptibility increase with injected Fe-dextran concentration. Both R2* and susceptibility measurements also show good linear correlations with LIC (R2 = 0.78 and R2 = 0.91, respectively), and a susceptibility-to-LIC conversion factor of 0.829 ppm/(mg/g wet) is derived. CONCLUSION: The feasibility of quantifying LIC using MR-based  R2* and QSM at a high field strength of 7T is demonstrated. Susceptibility quantification, which is an intrinsic property of tissues and benefits from being field-strength independent, is more robust than R2* quantification in this ex vivo study. A susceptibility-to-LIC conversion factor is presented that agrees relatively well with previously published QSM derived results obtained at 1.5T and 3T.