Association of intraplacental oxygenation patterns on dual-contrast MRI with placental abnormality and fetal brain oxygenation.

OBJECTIVES: Most human in-vivo placental imaging techniques are unable to distinguish and characterize various placental compartments, such as the intervillous space (IVS), placental vessels (PV) and placental tissue (PT), limiting their specificity. We describe a method that employs T2* and diffusion-weighted magnetic resonance imaging (MRI) data to differentiate automatically placental compartments, quantify their oxygenation properties and identify placental lesions (PL) in vivo. We also investigate the association between placental oxygenation patterns and fetal brain oxygenation. METHODS: This was a prospective study conducted between 2018 and 2021 in which dual-contrast clinical MRI data (T2* and diffusion-weighted MRI) were acquired from patients between 20 and 38 weeks' gestation. We trained a fuzzy clustering method to analyze T2* and diffusion-weighted MRI data and assign placental voxels to one of four clusters, based on their distinct imaging domain features. The new method divided automatically the placenta into IVS, PV, PT and PL compartments and characterized their oxygenation changes throughout pregnancy. RESULTS: A total of 27 patients were recruited, of whom five developed pregnancy complications. Total placental oxygenation level and T2* did not demonstrate a statistically significant temporal correlation with gestational age (GA) (R2 = 0.060, P = 0.27). In contrast, the oxygenation level reflected by T2* values in the placental IVS (R2 = 0.51, P = 0.0002) and PV (R2 = 0.76, P = 1.1 × 10-7 ) decreased significantly with advancing GA. Oxygenation levels in the PT did not show any temporal change during pregnancy (R2 = 0.00044, P = 0.93). A strong spatial-dependent correlation between PV oxygenation level and GA was observed. The strongest negative correlation between PV oxygenation and GA (R2 = 0.73, P = 4.5 × 10-7 ) was found at the fetal-vessel-dominated region close to the chorionic plate. The location and extent of the placental abnormality were automatically delineated and quantified in the five women with clinically confirmed placental pathology. Compared to the averaged total placental oxygenation, placental IVS oxygenation level best reflected fetal brain oxygenation level during fetal development. CONCLUSION: Based on clinically feasible dual-MRI, our method enables accurate spatiotemporal quantification of placental compartment and fetal brain oxygenation across different GAs. This information should improve our knowledge of human placenta development and its relationship with normal and abnormal pregnancy. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Can biomarkers predict myocardial iron overload in children with thalassemia major?

AIM: Beta-thalassemia major requires regular blood transfusions throughout life, which in turn leads to iron accumulation in the body. While cardiac T2* MRI is the gold standard in determining cardiac iron accumulation, it is not always feasible, which has led to the search for new biomarkers. Herein, the value of growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide in predicting cardiac iron accumulation is investigated in asymptomatic children with beta-thalassemia major. MATERIALS AND METHOD: Forty-one patients aged 11-21 years and 41 age-, gender-, body mass index-matched healthy controls were included. Serum growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were compared between the patients and controls. Additionally, the relations of these biomarkers with cardiac and liver T2 * MRI were investigated in the patients. RESULTS: In the patients, growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were higher than healthy controls (p < 0.001, p = 0.025, p < 0.001, respectively). There were no significant correlations of growth differentiation factor-15 and N-terminal pro-B-type natriuretic peptide levels with both cardiac and liver T2 * MRI measurements. While there was no significant correlation of serum galectin-3 with cardiac T2 * MRI measurements, a negative correlation was found with liver T2 * MRI measurements (p = 0.040, rho = -0.325). CONCLUSION: All three biomarkers investigated in this study failed to predict myocardial iron accumulation in asymptomatic children with beta-thalassemia major. However, a weak relation between serum galectin-3 level and hepatic iron accumulation was demonstrated.

Evaluation of the efficacy of signal-averaged electrocardiogram testing in the cardiac assessment of beta-thalassemia major patients.

BACKGROUND: More than 70% of thalassemia's major mortality is due to the cardiac complications of this syndrome, mostly consequent to myocardial Iron overload; therefore, evaluation of such complications is of utmost importance. T2*MRI is used to assess hepatic and myocardial Iron load in thalassemia patients, which is not always available. Signal-Averaged Electrocardiography is a rather easy method of evaluating major thalassemia patients regarding their risk for sudden cardiac death. METHODS AND MATERIALS: In this cross-sectional study, 48 patients with thalassemia major underwent evaluation with electrocardiography, signal-averaged electrocardiography, echocardiography, T2*MRI, and ferritin level. The association of the existence of ventricular late potentials in SAECG and other cardiac variables was evaluated. Moreover, the association between myocardial and hepatic Iron load and cardiac characteristics was assessed. RESULTS: 48 patients with a mean age of 30.31 ± 7.22 years old entered the study. 27 (56.3%) of the patients had ventricular late potentials, which were associated with myocardial dry Iron weight (P = 0.011). Nonspecific ST-T changes and premature atrial and ventricular contractions were seen more frequently in patients with late potentials (P = 0.002, 0.031, and 0.031, respectively). Patients with higher myocardial and hepatic Iron loads had longer QTc in their 12-lead surface electrocardiograms. CONCLUSION: Patients with ventricular late potentials assessed by SAECG had a higher myocardial Iron load. Higher myocardial Iron load is associated with higher cardiac complications in patients with beta-thalassemia major; therefore, SAECG can be used as a screening test for cardiac complications in beta-thalassemia major patients.

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.

BACKGROUND: Iron 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 METHODS: Fifty-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. RESULTS: The 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. CONCLUSIONS: Cardiac 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.

Prediction of Heart and Liver Iron Overload in ß-Thalassemia Major Patients Using Machine Learning Methods.

Patients with ß-thalassemia major (ß-TM) face a wide range of complications as a result of excess iron in vital organs, including the heart and liver. Our aim was to find the best predictive machine learning (ML) model for assessing heart and liver iron overload in patients with ß-TM. Data from 624 ß-TM patients were entered into three ML models using random forest (RF), gradient boost model (GBM), and logistic regression (LR). The data were classified and analyzed by R software. Four evaluation metrics of predictive performance were measured: sensitivity, specificity, accuracy, and area under the curve (AUC), operating characteristic curve. For heart iron overload, the LR had the highest predictive performance based on AUC: 0.68 [95% CI (95% confidence interval): 0.60, 0.75]. The GBM also had the highest specificity (69.0%) and accuracy (67.0%). Most sensitivity is also acquired with LR (75.0%). For liver iron overload, the highest performance based on AUC was observed with RF, AUC: 0.68 (95% CI: 0.59, 0.76). The RF showed the highest accuracy (66.0%) and specificity (66.0%), while the LR had the highest sensitivity (84.0%). Ferritin, duration of transfusion, and age were determined as the most effective predictors of iron overload in both heart and liver. Logistic regression LR was determined to be the strongest method to predict cardiac and RF values for liver iron overload in patients with ß-TM. Older thalassemia patients with a high serum ferritin (SF) level and a longer duration of transfusion therapy were more prone to heart and liver iron overload.

Safety, feasibility, and efficacy of strengthening exercise in Duchenne muscular dystrophy.

BACKGROUND: This two-part study explored the safety, feasibility, and efficacy of a mild-moderate resistance isometric leg exercise program in ambulatory boys with Duchenne muscular dystrophy (DMD). METHODS: First, we used a dose escalation paradigm with varying intensity and frequency of leg isometric exercise to determine the dose response and safety in 10 boys. Second, we examined safety and feasibility of a 12-wk in-home, remotely supervised, mild-moderate intensity strengthening program in eight boys. Safety measures included T2 MRI, creatine kinase levels, and pain. Peak strength and function (time to ascend/descend four stairs) were also measured. RESULTS: Dose-escalation revealed no signs of muscle damage. Seven of the eight boys completed the 12-wk in-home program with a compliance of 84.9%, no signs of muscle damage, and improvements in strength (knee extensors P < .01; knee flexors P < .05) and function (descending steps P < .05). CONCLUSIONS: An in-home, mild-moderate intensity leg exercise program is safe with potential to positively impact both strength and function in ambulatory boys with DMD.

Assessment of intramyocardial hemorrhage with dark-blood T2*-weighted cardiovascular magnetic resonance.

BACKGROUND: Intramyocardial hemorrhage (IMH) within myocardial infarction (MI) is associated with major adverse cardiovascular events. Bright-blood T2*-based cardiovascular magnetic resonance (CMR) has emerged as the reference standard for non-invasive IMH detection. Despite this, the dark-blood T2*-based CMR is becoming interchangeably used with bright-blood T2*-weighted CMR in both clinical and preclinical settings for IMH detection. To date however, the relative merits of dark-blood T2*-weighted with respect to bright-blood T2*-weighted CMR for IMH characterization has not been studied. We investigated the diagnostic capacity of dark-blood T2*-weighted CMR against bright-blood T2*-weighted CMR for IMH characterization in clinical and preclinical settings. MATERIALS AND METHODS: Hemorrhagic MI patients (n = 20) and canines (n = 11) were imaged in the acute and chronic phases at 1.5 and 3 T with dark- and bright-blood T2*-weighted CMR. Imaging characteristics (Relative signal-to-noise (SNR), Relative contrast-to-noise (CNR), IMH Extent) and diagnostic performance (sensitivity, specificity, accuracy, area-under-the-curve, and inter-observer variability) of dark-blood T2*-weighted CMR for IMH characterization were assessed relative to bright-blood T2*-weighted CMR. RESULTS: At both clinical and preclinical settings, compared to bright-blood T2*-weighted CMR, dark-blood T2*-weighted images had significantly lower SNR, CNR and reduced IMH extent (all p < 0.05). Dark-blood T2*-weighted CMR also demonstrated weaker sensitivity, specificity, accuracy, and inter-observer variability compared to bright-blood T2*-weighted CMR (all p < 0.05). These observations were consistent across infarct age and imaging field strengths. CONCLUSION: While IMH can be visible on dark-blood T2*-weighted CMR, the overall conspicuity of IMH is significantly reduced compared to that observed in bright-blood T2*-weighted images, across infarct age in clinical and preclinical settings at 1.5 and 3 T. Hence, bright-blood T2*-weighted CMR would be preferable for clinical use since dark-blood T2*-weighted CMR carries the potential to misclassify hemorrhagic MIs as non-hemorrhagic MIs.

The effect of measurement area size on the reliability of myocardial iron load measurement in cardiac magnetic resonance imaging examinations of thalassemia patients

Background/aim: The aim of this study was to evaluate the intraobserver and interobserver reliability of cardiac T2* MRI measurements in different region of interest (ROI) sizes. Materials and methods: Cardiac T2* MRIs of 24 thalassemia major patients were evaluated. Two different ROI sizes were used for measurement. In the first measurement, an ROI approximately 5 mm in diameter was used in the interventricular septal myocardium. In the other method, the whole ventricular septal myocardium was used as the measurement. The intraobserver and interobserver variabilities were assessed with the intraclass correlation coefficient (ICC). Results: The measurement of the first observer, the ICC of the small-sized ROI (ssROI), was 0.869, and the measurement for the second observer, the ICC of the ssROI, was 0.659. The ICC of the whole-septal ROI (wsROI) was 0.991 for the first observer and 0.980 for the second observer. Interobserver variability, for the mean measurement, was 0.442 for the ICC of ssROI and 0.883 for the ICC of wsROI. Conclusion: For the evaluation of myocardial iron load with T2* MRI we suggest making measurements with ROI, including all of the interventricular septum, as a consequence of high intraobserver and interobserver consistency.

Prevalence and Risk Factors for Cardiac and Liver Iron Overload in Adults with Thalassemia in Malaysia.

We explored the severity and risk factors for cardiac and liver iron overload (IOL) in 69 thalassemia patients who underwent T2* magnetic resonance imaging (T2* MRI) in a Malaysian tertiary hospital from 2011 to 2015. Fifty-three patients (76.8%) had transfusion-dependent thalassemia (TDT) and 16 (23.2%) had non transfusion-dependent thalassemia (NTDT). Median serum ferritin prior to T2* MRI was 3848.0 µg/L (TDT) and 3971.0 µg/L (NTDT). Cardiac IOL was present in 16 (30.2%) TDT patients and two (12.5%) NTDT patients, in whom severe cardiac IOL defined as T2* <10 ms affected six (11.3%) TDT patients. Liver IOL was present in 51 (96.2%) TDT and 16 (100%) NTDT patients, 37 (69.8%) TDT and 13 (81.3%) NTDT patients were in the most severe category (>15 mgFe/gm dry weight). Serum ferritin showed a significantly strong negative correlation with liver T2* in both TDT (rs = -0.507, p = 0.001) and NTDT (r = -0.762, p = 0.002) but no correlation to cardiac T2* in TDT (r = -0.252, p = 0.099) as well as NTDT (r = -0.457, p = 0.100). For the TDT group, regression analysis showed that cardiac IOL was more severe in males (p = 0.022) and liver IOL was more severe in the Malay ethnic group (p = 0.028) and those with higher serum ferritin levels (p = 0.030). The high prevalence of IOL in our study and the poor correlation between serum ferritin and cardiac T2* underline the need to routinely screen thalassemia patients using T2* MRI to enable the early detection of cardiac IOL.

Polyneuropathy and myopathy in beta-thalassemia major patients.

The thalassemias are the most common single gene disorder in the world. Nowadays, the average life expectancy of patients in developed countries has increased significantly, while, there was an increase of complications. We aimed to investigate peripheral neuropathy and myopathy in this patient group using a neurophysiological study. We performed nerve conduction studies and electromyography of upper and lower extremities on 36 beta-thalassemia major (ß-thal) patients. The electrophysiological findings were correlated with demographic data and laboratory parameters of the disease. Patients with ß-thal present polyneuropathy or myopathy at (50%). Polyneuropathy was detected in (38.9%) and myopathy in (27.8%), while polyneuropathy and myopathy were present at (16.7%) with an overlap of the diseases in 1/3 of the patients. There was not a statistically significant correlation of polyneuropathy and myopathy with age, sex, splenectomy, nor with respect to laboratory parameters, hemoglobin, and ferritin. However, there was a statistically significant correlation of polyneuropathy and myopathy with iron overload, as recorded by the magnetic resonance imaging (MRI) of the heart and the liver. Our findings suggest that iron overload plays a key role in the pathogenesis of polyneuropathy and myopathy in ß-thal patients, and performing heart and liver MRI for the prediction of such lesions in an annual basis is warranted.

Localization of muscle damage within the quadriceps femoris induced by different types of eccentric exercises.

This study examined localization of muscle damage within the quadriceps femoris induced by different types of eccentric exercises by using transverse relaxation time (T2 )-weighted magnetic resonance imaging (MRI). Thirty-three young males performed either of the following three exercises: single-joint eccentric contraction of the knee extensors (KE), eccentric squat (S), or downhill walking (DW) (n=11/exercise). KE and S consisted of 5-set×10-lowering of 90% one-repetition maximum load. DW was performed for 60 minutes with -10% slope, 6 km/h velocity, and 20% body mass load carried. At pre- and 24-, 48-, and 72-hours post-exercise, T2 -MRI was scanned and T2 values for the rectus femoris (RF), vastus intermedius (VI), vastus lateralis (VL), and vastus medialis (VM) at proximal, middle, and distal sites were calculated. Additionally, soreness felt when static pressure was applied to these sites and maximal isometric knee extension torque were measured. Maximal torque significantly (P<.05) decreased (7%-15%) at 24-48 hours after all exercises. T2 significantly increased (3%-9%) at 24-72 hours after all exercises, with heterogeneities within the muscles found in each exercise. Effect size and peak change of T2 , as well as soreness, overall indicated that the proximal RF after KE and middle VM after S and DW were most affected by these exercises. The VL did not show any significant T2 increase after all exercises. These results suggest that muscle damage specifically localizes at the proximal RF by KE and at the middle VM by S and DW, while the VL is least damaged regardless of the exercises.

Iron-chelating effect of silymarin in patients with ß-thalassemia major: A crossover randomised control trial.

This study aimed to determine the potential iron-chelating effects of silymarin in patients with ß-thalassemia major receiving standard iron-chelation therapy. We evaluated whether addition of silymarin to standard iron-chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo-controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other groups. Silymarin efficacy was assessed by measuring serum iron level, ferritin level, total iron-binding capacity and liver and cardiac function on magnetic resonance imaging. Silymarin treatment resulted in a negative change in the serum iron and ferritin levels and a positive change in the total iron-binding capacity levels (treatment effect, p < .001, p = .06, and p = .05, respectively). Silymarin treatment led to positive changes in cardiac and liver function in both treatment sequences of study; however, this was not statistically significant. There was a negative change in liver iron concentration in both treatment sequences (treatment effect, p = .02). In conclusion, combined iron-chelation and silymarin therapy was effective for improving the iron-burden status in patients with ß-thalassemia major.

Comparison of Deferiprone to Deferasirox and Deferoxamine to Cardiac and Hepatic T2* MRI in Thalassemia Patients: Evidence-based Case Report.

BACKGROUND: there are currently three iron chelator readily available for patients Indonesia; deferiprone/DFP (branded as Ferriprox), deferasirox/DFX (branded as Exjade) and deferoxamine/DFO (branded as Desferal). This study aims to determine which iron chelator is the most efficient in reducing cardiac and hepatic iron overload (measured by means of T2* MRI). METHODS: journal search with determined MeSH term was done in PubMed and Scopus. Studies that looked upon thalassemia major patient in all ages with usage of monotherapy iron chelation and its effect on myocardial T2* MRI and/or liver T2* MRI was included. Appraisal of studies was done using Oxford's CEBM appraisal tools and Joanna Brigs Institute critical appraisal tools. RESULTS: total of 11 studies with grand total of 611 samples were included. Mean T2* MRI value or (when available) mean changes in T2* MRI value after usage of specific iron chelator was gained from all the studies included. Comparison study and individual studies shows better control and increase of myocardial T2* MRI in those with DFP, and of liver T2* in those with good adherence to DFO chelation. CONCLUSION: DFP is superior in controlling or reducing myocardial iron load (as proven by mT2* MRI) and DFO had better capabilities in controlling or reducing hepatic iron load (as proven by liver T2* MRI). Studies with longer observation and larger samples is needed to see a significant changes of T2* MRI in DFX.

Addition of T2-guided optical tomography improves noncontrast breast magnetic resonance imaging diagnosis.

BACKGROUND: While dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is recognized as the most sensitive examination for breast cancer detection, it has a substantial false positive rate and gadolinium (Gd) contrast agents are not universally well tolerated. As a result, alternatives to diagnosing breast cancer based on endogenous contrast are of growing interest. In this study, endogenous near-infrared spectral tomography (NIRST) guided by T2 MRI was evaluated to explore whether the combined imaging modality, which does not require contrast injection or involve ionizing radiation, can achieve acceptable diagnostic performance. METHODS: Twenty-four subjects-16 with pathologically confirmed malignancy and 8 with benign abnormalities-were simultaneously imaged with MRI and NIRST prior to definitive pathological diagnosis. MRIs were evaluated independently by three breast radiologists blinded to the pathological results. Optical image reconstructions were constrained by grayscale values in the T2 MRI. MRI and NIRST images were used, alone and in combination, to estimate the diagnostic performance of the data. Outcomes were compared to DCE results. RESULTS: Sensitivity, specificity, accuracy, and area under the curve (AUC) of noncontrast MRI when combined with T2-guided NIRST were 94%, 100%, 96%, and 0.95, respectively, whereas these values were 94%, 63%, 88%, and 0.81 for DCE MRI alone, and 88%, 88%, 88%, and 0.94 when DCE-guided NIRST was added. CONCLUSION: In this study, the overall accuracy of imaging diagnosis improved to 96% when T2-guided NIRST was added to noncontrast MRI alone, relative to 88% for DCE MRI, suggesting that similar or better diagnostic accuracy can be achieved without requiring a contrast agent.

Efficacy of hepatic T2* MRI values and serum ferritin concentration in predicting thalassemia major classification for hematopoietic stem cell transplantation.

Liver biopsy has been performed for many decades for classifying the patients with TM. Meanwhile, using non-invasive methods such as T2* MRI technique has been recently much more considered to determine the hepatic iron overload. Ninety-three pediatric HSCT candidates with TM who underwent liver biopsy were included in this study. Hepatic T2* MRI values and serum ferritin concentrations were assessed to investigate and determine the useful method in detection of patients with TM class III whom received different conditioning regimens, in comparison with class I and II. Twenty (21.5%) patients were categorized as class III. Hepatic T2* MRI could detect TM class III patients with 60% sensitivity and 87.67% specificity (LR+: 4.867, accuracy: 81.72%), while predictive feature of ferritin values for distinguishing patients with TM class III was not statistically significant (p-value >0.01). Combination of T2*MRI with age (T2*-age) could detect TM class III with 85% sensitivity and 72.6% specificity (LR+: 3.1, accuracy: 75.27%).T2*-age may be considered as an alternative and non-invasive method to liver biopsy for differentiation and classification of patients with TM before transplantation.

Segmentation of pelvic structures in T2 MRI via MR-to-CT synthesis.

Segmentation of multiple pelvic structures in MRI volumes is a prerequisite for many clinical applications, such as sarcopenia assessment, bone density measurement, and muscle-to-fat volume ratio estimation. While many CT-specific datasets and automated CT-based multi-structure pelvis segmentation methods exist, there are few MRI-specific multi-structure segmentation methods in literature. In this pilot work, we propose a lightweight and annotation-free pipeline to synthetically translate T2 MRI volumes of the pelvis to CT, and subsequently leverage an existing CT-only tool called TotalSegmentator to segment 8 pelvic structures in the generated CT volumes. The predicted masks were then mapped back to the original MR volumes as segmentation masks. We compared the predicted masks against the expert annotations of the public TCGA-UCEC dataset and an internal dataset. Experiments demonstrated that the proposed pipeline achieved Dice measures ≥65% for 8 pelvic structures in T2 MRI. The proposed pipeline is an alternative method to obtain multi-organ and structure segmentations without being encumbered by time-consuming manual annotations. By exploiting the significant research progress in CTs, it is possible to extend the proposed pipeline to other MRI sequences in principle. Our research bridges the chasm between the current CT-based multi-structure segmentation and MRI-based segmentation. The manually segmented structures in the TCGA-UCEC dataset are publicly available.

Design and fabrication of dysprosium impregnated polyvinyl alcohol hydrogels. Physiochemical, mechanical, bioimaging and in vitro evaluation.

Tissue engineering has gained prominence during the past decade since it offers a key solution to defects associated with the tissue regeneration. The limited healing potential of the cartilage tissue damage has significant clinical implications. Herein, dysprosium (Dy3+) impregnated polyvinyl alcohol (PVA) hydrogels have been developed to enhance the therapeutic efficacy, enabling simultaneous diagnostic imaging and antibacterial drug delivery for potential applications in articular cartilage. Based on the favorable imaging features, Dy3+ impregnated PVA hydrogels with enhanced stability were formed through successive steps of repeated cycles of freezing at - 30 °C for 21 h, thawing at 25 °C for 4 h and lyophilization. The tensile and compression tests of the hydrogels respectively determined a maximum of 3.88 and 1.58 MPa, which reflected better compatibility towards cartilage. The hydrogels fetched a sustained drug release for a period of 12 h with an associated swelling ratio of 80%. The potential of the resultant hydrogels in image diagnosis has been deliberated through their blue and yellow emissions in the visible region. Further, the computed tomography (CT) and magnetic resonance imaging characteristics of the hydrogels respectively accomplished a maximum of 343 Hounsfiled units (HU) and relaxivity of 7.25 mM-1s-1. The cytocompatibility of the hydrogels is also determined through in vitro tests performed in Murine pro B cell line (BA/F3) and human Megakaryocyte cell line (Mo7e) cell lines.

Correlation of Magnesium Level with Cardiac and Hepatic Hemosiderosis Measured by T2*MRI Technique and Age in Patients with Thalassemia Major.

Background: Given the association of hypomagnesemia with cardiac arrhythmia, the aim of this study was to investigate the relationship between serum magnesium levels with age and T2* magnetic resonance imaging (MRI) findings of the heart and liver in patients with thalassemia major (TM). Materials and Methods: In a descriptive cross-sectional study, a total of 62 patients with ß-thalassemia major aged 11-48 years were selected at the Amir-Kabir Hospital, Arak, Iran. Serum magnesium, ferritin, and iron levels of patients were measured, and the rate of cardiac and hepatic hemosiderosis of patients was extracted according to the routine T2*MRI method. Results: The mean age of the patients at diagnosis was 32.6 years. The comparison of TM patients with and without hepatic/cardiac hemosiderosis demonstrated that mean levels of serum ferritin, serum iron, and age were significantly higher in TM patients with cardiac hemosiderosis than in hepatic/cardiac non-hemosiderosis (P < 0.05); however, there was no significant difference in mean levels of serum magnesium in TM patients with and without hepatic/cardiac hemosiderosis (P = 0.279). Interestingly, the correlation of age with serum magnesium levels in TM patients revealed a statistically significant and moderate inverse correlation (r = -0.56, P = 0.013). Conclusion: Hypomagnesemia may occur in a time-dependent manner. It is recommended that, in addition to cardiac and hepatic T2*MRI, serum magnesium levels be measured by using magnesium replacement if necessary.

Hepatic and cardiac iron overload quantified by magnetic resonance imaging in patients on hemodialysis: A systematic review and meta-analysis.

INTRODUCTION: Few studies have reported hepatic and cardiac iron overload in patients with end-stage renal disease (ESRD), and the current evidence regarding the prevalence is still scarce. AIM: This review aims to estimate the prevalence of hepatic and/or cardiac iron overload quantified by magnetic resonance imaging (MRI) in patients with ESRD who receive hemodialysis (HD), peritoneal dialysis (PD), or have undergone a kidney transplant. METHODS: A systematic review with meta-analysis was conducted and reported in line with PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. MEDLINE and Embase bibliographic databases were searched using a comprehensive list of controlled vocabulary and keywords to identify relevant studies. All studies reporting the prevalence of hepatic and/or cardiac iron overload quantified by MRI in ESRD patients were considered. The Newcastle-Ottawa scale was used to assess the methodological quality of included studies. To investigate the heterogeneity between studies, random-effect meta-analyses for proportions were used. RESULTS: The review comprised seven studies that included 339 patients. Using meta-analysis, the pooled prevalence of severe and mild to moderate hepatic iron overload quantified by MRI was 0.23 [95% CI: 0.08-0.43] and 0.52 [95% CI: 0.47-0.57], respectively. Only three studies included cardiac iron quantification, and none reported iron overload. CONCLUSIONS: This review has revealed a high prevalence of severe hepatic iron overload in patients with ESRD treated by HD. Further studies with a larger sample size are needed to determine the impact of iron overload on vital organs in patients with ESRD and guide future research in this understudied field. Proper use of iron chelation and continuous monitoring will help in the early detection of unsolicited complications; however, the low renal clearance of most iron chelators limits the options for treating iron excess in patients with ESRD.

A single closed head injury in male adult mice induces chronic, progressive white matter atrophy and increased phospho-tau expressing oligodendrocytes.

Traumatic brain injury (TBI) acutely damages the brain; this injury can evolve into chronic neurodegeneration. While much is known about the chronic effects arising from multiple mild TBIs, far less is known about the long-term effects of a single moderate to severe TBI. We found that a single moderate closed head injury to mice induces diffuse axonal injury within 1-day post-injury (DPI). At 14 DPI, injured animals have atrophy of ipsilesional cortex, thalamus, and corpus callosum, with bilateral atrophy of the dorsal fornix. Atrophy of the ipsilesional corpus callosum is accompanied by decreased fractional anisotropy and increased mean and radial diffusivity that remains unchanged between 14 and 180 DPI. Injured animals show an increased density of phospho-tau immunoreactive (pTau+) cells in the ipsilesional cortex and thalamus, and bilaterally in corpus callosum. Between 14 and 180 DPI, atrophy occurs in the ipsilesional ventral fornix, contralesional corpus callosum, and bilateral internal capsule. Diffusion tensor MRI parameters remain unchanged in white matter regions with delayed atrophy. Between 14 and 180 DPI, pTau+ cell density increases bilaterally in corpus callosum, but decreases in cortex and thalamus. The location of pTau+ cells within the ipsilesional corpus callosum changes between 14 and 180 DPI; density of all cells increases including pTau+ or pTau- cells. >90% of the pTau+ cells are in the oligodendrocyte lineage in both gray and white matter. Density of thioflavin-S+ cells in thalamus increases by 180 DPI. These data suggest a single closed head impact produces multiple forms of chronic neurodegeneration. Gray and white matter regions proximal to the impact site undergo early atrophy. More distal white matter regions undergo chronic, progressive white matter atrophy with an increasing density of oligodendrocytes containing pTau. These data suggest a complex chronic neurodegenerative process arising from a single moderate closed head injury.