Measurement Of Iron Concentration Research Articles

Enhancing precision through AI-enhanced method verification validating iron determination on the Alinity ci® Analyzer: Experience of the central laboratory of Mohammed VI University Hospital of Oujda

This study meticulously assessed the analytical performance of iron determination on the Alinity ci® analyzer, employing advanced AI-powered method verification techniques. Conducted at Mohammed VI University Hospital's central laboratory in Oujda, Morocco, the validation process strictly adhered to the rigorous guidelines outlined in the French accreditation committee's (COFRAC) Accreditation Technical Guide (GTA) 04. Through comprehensive assessments of repeatability and reproducibility, we definitively confirmed the assay's precision and reliability. Our evaluation yielded highly satisfactory results, consistently exceeding the established criteria set forth by both the instrument manufacturer and esteemed professional organizations like SFBC and RICOS. This unequivocally validates the laboratory's capability to deliver accurate and reproducible iron concentration measurements, crucial for enhanced clinical diagnostics and, ultimately, well-informed patient care decisions. This study underscores the importance of stringent validation processes in ensuring the reliability of diagnostic assays, thereby bolstering confidence in laboratory medicine practices and patient outcomes.

Quantitative susceptibility mapping in the brain reflects spatial expression of genes involved in iron homeostasis and myelination.

Quantitative susceptibility mapping (QSM) is an MRI modality used to non-invasively measure iron content in the brain. Iron exhibits a specific anatomically varying pattern of accumulation in the brain across individuals. The highest regions of accumulation are the deep grey nuclei, where iron is stored in paramagnetic molecule ferritin. This form of iron is considered to be what largely contributes to the signal measured by QSM in the deep grey nuclei. It is also known that QSM is affected by diamagnetic myelin contents. Here, we investigate spatial gene expression of iron and myelin related genes, as measured by the Allen Human Brain Atlas, in relation to QSM images of age-matched subjects. We performed multiple linear regressions between gene expression and the average QSM signal within 34 distinct deep grey nuclei regions. Our results show a positive correlation (p < .05, corrected) between expression of ferritin and the QSM signal in deep grey nuclei regions. We repeated the analysis for other genes that encode proteins thought to be involved in the transport and storage of iron in the brain, as well as myelination. In addition to ferritin, our findings demonstrate a positive correlation (p < .05, corrected) between the expression of ferroportin, transferrin, divalent metal transporter 1, several gene markers of myelinating oligodendrocytes, and the QSM signal in deep grey nuclei regions. Our results suggest that the QSM signal reflects both the storage and active transport of iron in the deep grey nuclei regions of the brain.

Imaging Biomarkers in Prodromal and Earliest Phases of Parkinson’s Disease

Assessing imaging biomarker in the prodromal and early phases of Parkinson’s disease (PD) is of great importance to ensure an early and safe diagnosis. In the last decades, imaging modalities advanced and are now able to assess many different aspects of neurodegeneration in PD. MRI sequences can measure iron content or neuromelanin. Apart from SPECT imaging with Ioflupane, more specific PET tracers to assess degeneration of the dopaminergic system are available. Furthermore, metabolic PET patterns can be used to anticipate a phenoconversion from prodromal PD to manifest PD. In this regard, it is worth mentioning that PET imaging of inflammation will gain significance. Molecular imaging of neurotransmitters like serotonin, noradrenaline and acetylcholine shed more light on non-motor symptoms. Outside of the brain, molecular imaging of the heart and gut is used to measure PD-related degeneration of the autonomous nervous system. Moreover, optical coherence tomography can noninvasively detect degeneration of retinal fibers as a potential biomarker in PD. In this review, we describe these state-of-the-art imaging modalities in early and prodromal PD and point out in how far these techniques can and will be used in the future to pave the way towards a biomarker-based staging of PD.

Machine learning-mediated identification of ferroptosis-related genes in osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a condition caused by a disruption or damage to the femoral head's blood supply, which causes the death of bone cells and bone marrow components and prevents future regeneration. Ferroptosis, a type of controlled cell death, is caused by iron-dependent lipid peroxidation. Here, we identified ferroptosis-related genes and infiltrating immune cells involved in ONFH and predicted the underlying molecular mechanisms. The GSE123568 dataset was subjected to differential expression analysis to identify genes related to ferroptosis. Subsequently, GO and KEGG pathway enrichment analyses, as well as protein-protein interaction (PPI) network analysis, were conducted. Hub genes involved in ferroptosis were identified using machine learning and other techniques. Additionally, immune infiltration analysis and lncRNA-miRNA-mRNA network prediction analysis were performed. Finally, we determined whether ferroptosis occurred by measuring iron content. The hub genes were validated by ROC curve analysis and qRT-PCR. Four ferroptosis-related hub genes (MAPK3, PTGS2, STK11, and SLC2A1) were identified. Additionally, immune infiltration analysis revealed a strong correlation among ONFH, hub genes, and various immune cells. Finally, we predicted the network relationship between differentially expressed lncRNAs and hub genes in the lncRNA-miRNA-mRNA network. MAPK3, PTGS2, STK11, and SLC2A1 have been identified as potential ferroptosis-related biomarkers and drug targets for the diagnosis and prognosis of ONFH, while some immune cells, as well as the interaction between lncRNA, miRNA, and mRNA, have also been identified as potential pathogenesis markers and therapeutic targets.

Measurement of Fe and Mn concentrations using image processing techniques based on color intensity approach

Water quality monitoring is an important activity to create a good environment quality with clean and healthy water sources. Various monitoring methods that are generally used such as spectrometry-based instruments certainly have various limitations, such as expensive, requiring a lot of reagents, sensitive instruments, and takes quite a long to get measurement results. Due to the development of population growth and the increasing of water pollutant, water quality monitoring technology that cheap, practical, quick and accurate is important to be made. The main subject in this work was to develop a water quality monitoring method based on multiparameter image processing techniques. This method utilizes the approach of color intensity, light, and number/size/shape of particles. This work will be focus on iron (Fe) and manganese (Mn) concentration measurement by color intensity approach performed using ColorSlurp and Microsoft Excel in its RGB (Red, Green, Blue) matrices. The correlation between the parameter concentration and color intensity was obtained by transforming the RGB into greyscale intensity (GI) value. A linear response was observed in the Fe concentration range 0 to 2.4 mg L−1 with the highest R2 = 0.971, and in the Mn concentration range between 0 to 1.6 mg L−1 with the highest R2 = 0.9432. This work demonstrates that image processing techniques provide a great promise as water quality monitoring method.

Clusterin is upregulated by erastin, a ferroptosis inducer and exerts cytoprotective effects in pancreatic adenocarcinoma cells.

Ferroptosis is a novel form of cell death, which is distinguished from apoptosis and necrosis, and characterized by accumulation of lipid-based reactive oxygen species (ROS) in an iron-dependent manner. Erastin, a small molecule, was widely reported to trigger ferroptosis in various kinds of cancer cells, including pancreatic cancer cells by inducing ROS accumulation. However, how erastin treatment exerts cytotoxicity is not still fully understood. In this study, the effects of erastin in causing pancreatic cancer cell death via inducing ferroptosis and apoptosis are investigated. As expected, erastin treatment caused ROS accumulation, increase in iron concentration and non-apoptotic cell death, which is different from that of induced by apoptosis inducer, staurosporine. Interestingly, erastin treatment caused the upregulation of clusterin, which contributes to the regulation of malignant behaviors of pancreatic cancer, including preventing apoptosis and inducing chemoresistance. Without erastin treatment, overexpressed clusterin significantly promoted cell proliferation, which is consistent with its cytoprotective roles. After erastin treatment, overexpressed clusterin decreased erastin-induced ROS accumulation and cell death. By measuring iron concentration, reduced glutathione (GSH) and glutathione peroxidase 4 (GPX4), it is revealed that clusterin caused resistance to erastin-induced ferroptosis potentially via maintaining the enzymatic activity of GPX4, without disturbing GSH amount. Thus, ferroptosis inducer, erastin, may crosstalk with apoptotic cell death via regulating clusterin, indicating a more complex regulatory network between ferroptosis and apoptosis.

Iron Overload in Dialysis Patients: Serum Ferritin Underestimates Liver Iron Measured By MRI

Background: Parenteral iron supplementation and erythropoietin-stimulating agents are the mainstay management for anemia in patients requiring dialysis. Traditionally, iron status in this patient population is determined by monitoring of widely available and inexpensive serum ferritin level. However, serum ferritin is an acute phase reactant and its usefulness is disease specific. Therefore, several non-invasive methods to evaluate body iron storage have been studied, with measurement of liver iron concentration (LIC) by MRI FDA approved. In this retrospective chart review, we explored the utility of serum ferritin for predicting LIC in a convenience sample of adults on dialysis who had LIC measured by MRI. Methods: Seven adults on dialysis who had been referred to an academic hematology clinic between July 2020 to June 2023 for elevated ferritin and subsequently had completed LIC by MRI were included in this chart review. Liver iron was quantified by T2* Relaxometry in a 1.5 Tesla MRI . Patients age, gender, etiology of end stage renal disease, duration on dialysis, initial LIC, and the ferritin and hemoglobin levels within three month of LIC were collected from patient medical records. Clinical recommendation for holding parenteral iron or starting chelation and patient-follow through were also recorded. In 2 patients, repeat LIC was available. The clinical recommendation for all patients with elevated LICs was to hold parenteral iron and not to start chelation but repeat LIC in 6 month intervals. Result: The median age was 56 years (min 26 years - max 73 years) and 4 of 7 patients were female. The median time of first LIC from initiation of dialysis was 88.5 months (min 19 months - max 130 months). The median of initial LIC was 6.6 mg/g (min 4.6 mg/g - max 12.5 mg/g). The median ferritin was 1120 ng/mL (min 736 ng/mL - max 2650 ng/mL). The median hemoglobin was 10.8 g/dL (min 8.4 g/dL - max 13.7 g/dL). Figure 1A demonstrates that despite similar ferritin levels (bolded group or underlined group), LICs were very variable. Additionally, it is visible in figure 1A that serum ferritin underestimates the LIC (italicized) in this patient population. Holding iron infusion for 2 years in patient 4, resulted in LIC trending down from 6.3 mg/g to 3.2 mg/g (Figure 1B) with minimal impact on hemoglobin. Despite clinical recommendation to hold iron infusion in patient 5 with an initial LIC of 6.8 mg/g, iron infusion was continued. Repeat LIC for this patient 6 months later remained unchanged at 7.0 mg/g, while serum ferritin trended down from 1084 to 843. Conclusion: Ferritin underestimates liver iron concentration in dialysis patients. More investigation is required to determine if liver iron assessment by MRI improves iron management in dialysis patients and optimize serum ferritin utility. This data also suggests that, chelation is not required in iron overloaded dialysis patients, and holding IV iron can result in decline in liver iron concentration.

Impact of Depth-Wise Inhomogeneous Iron Distributions on the Accuracy of Lifetime-Based Interstitial Iron Measurements on Silicon Wafers

This article studies the impact of depth-wise inhomogeneous iron distributions in silicon wafers, and the magnitude of the average iron concentrations, on the accuracy of interstitial iron concentrations extracted from effective lifetime measurements on crystalline silicon wafers. The depth-wise inhomogeneous interstitial iron profiles are generated from simulations of gettering of iron to the wafer surfaces, and are therefore practically relevant for silicon solar cells. Our analysis shows that a considerable amount of error can be introduced into the interstitial iron concentration measurement if the iron profiles are highly inhomogeneous, such as in the early stages of gettering. The absolute interstitial iron concentration also has a determinant role on the magnitude of the error. A “threshold” interstitial iron concentration of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">13</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−3</sup> or below (<10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">13</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−3</sup> ) is recommended for defect studies to avoid significant measurement errors. Other effects such as surface passivation, light source spectrum and wafer thickness are found to also affect the accuracy of the interstitial iron concentration measurement by affecting the uniformity of the carrier profiles.

Evaluation of nano-scaled zero valent iron (nZVI) effects on continuous syngas biomethanation under the thermophilic condition

The nano-scaled zero valent iron (nZVI) particles were applied to strengthen the syngas biomethanation under the thermophilic condition in a continuous bubble column reactor with gas circulation. The CH4 productivity was increased by 6.80% from 71.20 mmol∙Lr−1∙day−1 to the highest 76.04 mmol∙Lr−1∙day−1 at the nZVI concentration of 2.5 g/L. The measurement of iron concentration and the observation of the iron nanoparticles distribution indicate that nZVI can act as an electron conduit to enhance more efficient direct interspecies electron transfer by physically close contact between microorganisms, instead of biological corrosion. Further analysis of metabolic products shows that the nZVI addition can stimulate the EPS secretion, and the direct electron transfer relying on nZVI particles tends to replace other transfer modes. Microbial community analysis reveals that the Bacteria Bacteroidia and Firmicutes, and Archaea Methanothermobacter are the potential dominating enriched syntrophic partners. The expression of functional genes involved in methane production was also found to increase. On the other hand, the nZVI accumulation can lead to the albefaction and inactivation of partial sludge granules due to its toxicity. The negative effects of nZVI at high concentration are also more pronounced. This work shows the feasibility of improving continuous syngas biomethanation by strengthening interspecific association and accelerating electron transfer.

Quercetin alleviates subarachnoid hemorrhage-induced early brain injury via inhibiting ferroptosis in the rat model.

Early brain injury (EBI) refers to a series of pathophysiological brain lesions that occur within 72 hr after subarachnoid hemorrhage (SAH), which is an extremely crucial factor in the poor prognosis of patients. In EBI, ferroptosis has been proven to cause neuronal death. Quercetin (QCT) is effective in deactivating reactive oxygen species (ROS), inhibiting lipid peroxidation, and even chelating iron, but its role in SAH remains unclear. In this study, the mortality rate, severity grade of SAH, brain water content (BWC), blood-brain barrier permeability, and neurological function of the rats were detected. Moreover, mitochondrial morphology in cortical neurons were observed and their sizes were subsequently quantified. The levels of lipid peroxidation on glutathione and malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were determined, whereas the protein expressions of glutathione peroxidase 4 (GPX4), SLC7A11 (xCT), transferrin receptor 1 (TfR1), and ferroportin-1 (FPN1) were analyzed by western immunoblotting. The neurodegeneration involved in EBI was investigated by fluoro-Jade C staining, while iron staining was utilized to measure iron content. Our results showed that inhibition of ferroptosis by QCT could suppress EBI and improve neurological function in SAH rats. QCT increased the expression levels of GPX4, xCT, and FPN1, while downregulated TfR1, and exerted protective effects on neurons as well as alleviated iron accumulation and lipid peroxidation in the cortex of SAH rats. In conclusion, our study revealed that QCT might alleviate the EBI by inhibiting ferroptosis in SAH rats.

Applications of strategically acquired gradient echo imaging to neurodegenerative diseases

Background: One major thrust in radiology today is image standardization with a focus on rapid, quantitative, multi-contrast data collection and processing.&#x0D; Methods: Strategically acquired gradient echo (STAGE) imaging1-4 is one such method that uses multiple flip angles and multiple echo times. It can provide 8 qualitative and 7 quantitative images as well as transmit field B1 transmit field and B1 receive field maps in 4-6 minutes or less on a 3T magnetic resonance (MR) scanner. STAGE provides qualitative images in the form of proton density-weighted images, T1 weighted images and T2* weighted images. STAGE provides quantitative data in the form of proton spin density (PSD), T1, T2* and susceptibility maps as well as segmentation of white matter, gray matter and cerebrospinal fluid via simulated double inversion recovery (sDIR) images. STAGE has been tested using the NIST phantom and yields intrasubject errors of only 1-2% and intrasubject variation of 2 to 5%. Contrast-to-noise ratio (CNR) measurements show that the T1WE images are comparable to the conventional T1W MP-RAGE images. Today these quantitative measures are providing new biomarkers for imaging a variety of neurodegenerative diseases (Figure 1).&#x0D; Results: During the last few years, we have focused on measuring iron content and neuromelanin (NM) in the substantia nigra (SN) for comparing idiopathic Parkinson’s disease (PD) with healthy controls and patients with other movement disorders. We have found that the volume of NM, the iron content of the SN, the volume of the SN and the N1 sign all together can provide an area under the curve of 95% in distinguishing PD from healthy controls.5 We have developed a template of the midbrain to allow for automatic detection and quantification of these properties. We use tSWI to enhance the N1 sign visibility. We have also used STAGE to study multiple sclerosis (MS) lesions. QSM can be used to map changes in white matter susceptibility and potentially correlated with demyelination. We provide a composite image using tSWI combined with fluid-attenuated inversion recovery (FLAIR) to highlight those lesions that are purely inflammatory from inflammatory demyelinating lesions. Recently we have begun to study the use of absolute water content as a measure of lesion atrophy. Higher water content means a higher likelihood of tissue damage. This also explains why the presence of “black holes” seen in T1W images of MS patients tends to correlate with the expanded disability status score.&#x0D; Conclusions: In summary, STAGE provides a comprehensive clinical imaging protocol that, combined with diffusion-weighted imaging (DWI) and FLAIR, can yield a standardized 10-minute (3T) o 15-minute (1.5T) imaging protocol of the entire brain across all manufacturers.

Decreased Clinical Toxicity and Two-Phase Elimination Kinetics Observed After Intravenous Iron Sucrose Overdose

BackgroundManagement of oral iron overdoses is well-established, but there is limited literature regarding intravenous iron sucrose overdoses. Indications for administering deferoxamine after oral iron overdoses include clinical signs and symptoms of toxicity, along with a serum iron concentration ≥ 500 μg/dL. Reported signs and symptoms of iron sucrose overdose do not appear to correlate with those of oral iron overdoses. Case ReportWe present a case of intravenous iron sucrose overdose in a clinically well-appearing patient with a presenting serum iron concentration that was several times higher than the usual threshold concentration for initiating deferoxamine treatment. A 21-year-old woman presented to the emergency department after an accidental intravenous iron sucrose overdose. The patient received a home infusion of 1000 mg iron sucrose, which was five times the prescribed dose. Her presenting serum iron concentration was 1799 μg/dL, with bicarbonate and anion gap both within normal limits and an unremarkable physical examination. Because she did not have evidence of severe iron toxicity, she was treated supportively and deferoxamine was not administered. Her serum iron concentration decreased below the toxic range over the next 14 h, and she was discharged home the next day. Why Should an Emergency Physician Be Aware of This?This patient was managed successfully with expectant care alone, suggesting that iron sucrose overdose has much lower toxicity than oral iron salt overdose. This discrepancy between measured iron concentrations and clinical presentation may be explained by the elimination kinetics of iron sucrose having separate redistribution and elimination phases.

Distribution Indices of Magnetic Susceptibility Values in the Primary Motor Cortex Enable to Classify Patients with Amyotrophic Lateral Sclerosis.

Quantitative Susceptibility Mapping (QSM) can measure iron concentration increase in the primary motor cortex (M1) of patients with Amyotrophic Lateral Sclerosis (ALS). However, such alteration is confined to only specific regions interested by upper motor neuron pathology; therefore, mean QSM values in the entire M1 have limited diagnostic accuracy in discriminating between ALS patients and control subjects. This study investigates the diagnostic accuracy of a broader set of M1 QSM distribution indices in classifying ALS patients and controls. Mean, standard deviation, skewness and kurtosis of M1 QSM values were used either individually or as combined predictors in support vector machines. The classification performance was compared to that obtained by the radiological assessment of T2* signal hypo-intensity of M1 in susceptibility-weighted MRI. The least informative index for the classification of ALS patients and controls was the subject’s mean QSM value in M1. The highest diagnostic performance was obtained when all the distribution indices of positive QSM values in M1 were considered, which yielded a diagnostic accuracy of 0.90, with sensitivity = 0.89 and specificity = 1. The radiological assessment of M1 yielded a diagnostic accuracy of 0.79, with sensitivity = 0.76 and specificity = 0.90. The joint evaluation of QSM distribution indices could support the clinical examination in ALS diagnosis and patient monitoring.

Reductive dissolution of jarosite by inorganic sulfur compounds catalyzed by Acidithiobacillus thiooxidans

The adsorption of jarosite and the resulting passivation of mineral surfaces can negatively influence metal extraction from sulfidic ores as well as the fate of other elements in biohydrometallurgical processes. Some bioleaching microorganisms mediate dissimilatory iron reduction coupled to sulfur oxidation (DIRSO), a process utilized predominantly in continuously enhanced leaching of metals from sulfide and/or oxidized ores. In this study, the reductive dissolution of jarosite (biosynthesized by the iron-oxidizing archaeon Acidianus manzaensis) catalyzed by the mesophilic acidophilic bacterium Acidithiobacillus (At.) thiooxidans oxidizing different inorganic sulfur compounds was investigated. Kinetic measurements of pH, ORP, iron concentrations, and planktonic cell counts were performed to describe the reductive dissolution of jarosite. Moreover, the solid leaching residues were analyzed using X-ray absorption near edge structure (XANES), Inductively coupled plasma - optical emission spectrometry (ICP-OES), scanning electron microscopy (SEM), X-ray diffraction (XRD), and Raman spectroscopy. The dissolution rates of jarosite after 34 days of bioleaching by At. thiooxidans with S0, Na2S2O3, and Na2SO3 were 41.7, 76.3, and 98.4%, respectively, while negligible jarosite dissolution was detected in abiotic controls. The presence of Na2S2O3 and Na2SO3 resulted in structural modifications on the jarosite surfaces, but the dissolution of jarosite was not promoted in the absence of At. thiooxidans. In the biotic assays with Na2SO3, jarosite was completely dissolved, indicating that Na2SO3 was the most suitable electron donor (out of those tested) for DIRSO by At. thiooxidans. The findings obtained in this study can contribute to designing suitable bioleaching strategies for oxidized ores. They also highlight the potential of microbially catalyzed DIRSO to mitigate jarosite formation that often hinders bioleaching of sulfidic ores.

Decursin ameliorates carbon-tetrachloride-induced liver fibrosis by facilitating ferroptosis of hepatic stellate cells.

Decursin possesses the potential to alleviate transforming growth factor (TGF)-β-induced hepatic stellate cells (HSCs) activation. However, the mechanisms by which decursin alleviates hepatic fibrosis remain not fully understood. Our aim is to explore the function of decursin on regulating HSCs' activation and hepatic fibrosis. The anti-fibrotic effect of decursin was evaluated by Masson and Sirius red staining, and immunohistochemical (IHC) and quantitative real-time PCR (qRT-PCR) analyses for alpha-smooth muscle actin (α-SMA) and collagen type I(Col1α1) expression. Ferroptosis was assessed by measuring iron concentration, glutathioneperoxidase4 (Gpx4), and prostaglandin endoperoxide synthase 2 (Ptgs2) expression, glutathione (GSH) level, lipid peroxidation, and reactive oxygen species (ROS) level. We found that decursin treatment decreased carbon tetrachloride (CCl4)-induced liver fibrosis. The primary HSCs isolated from decursin-treated group showed an increased Fe2+, lipid ROS level, and decreased Gpx4 and GSH levels compared with HSCs from the model group. Moreover, decursin promoted ferroptosis in activated HSCs in vitro, as evidenced by declined Gpx4 and GSH levels, increased Fe2+, ROS, and Ptgs2 levels compared with control. More important, ferroptosis inhibitor destroyed the anti-fibrosis effect of decursin on HSCs. In summary, these data suggest that decursin has potential to treat hepatic fibrosis.

Minimally Invasive Surgery for ICH Evacuation Combined With Deferoxamine Treatment Increased Perihematomal Claudin-5 and ZO-1 Expression Levels and Decreased BBB Permeability in Rabbits.

ObjectiveTo investigate the role of minimally invasive surgery (MIS) in intracerebral hemorrhage (ICH) evacuation combined with deferoxamine (DFX) treatment on perihematomal tight junction protein (claudin-5 and ZO-1) expression levels and blood-brain barrier (BBB) permeability in rabbits.MethodsWe randomly assigned 65 male rabbits (weight: 1.9–2.6 kg) to a normal control group (NC group, 13 rabbits), hemorrhage model group (HM group, 13), DFX treatment group (DFX group, 13 rabbits), MIS group (MIS group, 13 rabbits), or MIS combined with DFX treatment group (MIS + DFX group, 13 rabbits). ICH was established in all of the groups except the NC group. MIS was performed to evacuate the hematoma 6 h after the ICH model was created in the MIS and MIS + DFX groups. The DFX and MIS + DFX groups were treated with DFX (100 mg/kg, dissolved in 2 mL of 0.9% saline solution, administered intramuscularly) at 2 h, and then every 12 h for 7 d. The same dose of 0.9% saline solution was administered to the NC, HM, and MIS groups at the same time points. Sixty-five rabbits were divided into 5 groups, and 13 rabbits in each group. Neurological deficit (i.e., Purdy's score) was recorded in all rabbits before euthanasia (N total = 65). In each group, 2 rabbits were used for iron concentration measurement (N total = 10), 2 rabbits were used for brain water content measurement (N total = 10), 3 rabbits were used for BBB permeability measurement (N total = 15), 3 rabbits were used for claudin-5, ZO-1 expression detection by Western Blotting (N total = 15), and 3 rabbits were used for claudin-5, ZO-1 mRNA detection by real-time PCR (N total = 15). On day 7, the rabbits were sacrificed and the perihematomal brain tissue was harvested to test the iron concentration, brain water content (BWC), tight junction proteins (claudin-5 and ZO-1) expression, and BBB permeability.ResultsPurdy's score, iron concentration, and BWC were lower in the MIS and MIS + DFX groups compared to the HM and DFX groups. The MIS + DFX group showed a significant decrease in these indicators. The use of MIS to evacuate the hematoma led to increased expression levels of claudin-5 and ZO-1, as well as decreased BBB permeability. The MIS + DFX group exhibited a remarkable increase in claudin-5 and ZO-1 expression levels and a significant decrease in BBB permeability.ConclusionsMIS combined with DFX treatment could increase the expression levels of perihematomal tight junction proteins (claudin-5 and ZO-1) expression, reduce BBB permeability, and improve the neurological function. MIS combined with DFX treatment may also prevent secondary brain damage following ICH.

Proton density fat fraction: magnetic resonance imaging applications beyond the liver.

Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is an emerging quantitative imaging biomarker that accurately measures the fat fraction of tissue by correcting factors influencing magnetic resonance signal intensity. Beyond fat quantification, it also measures R2* which is a direct measure of iron concentration. The utilization of MRI-PDFF in liver diseases is well established. In the present review, we focused on applications of MRI-PDFF in different body areas including pancreas, bone, muscle, spleen, testis, visceral, and subcutaneous adipose tissue. Future studies can enable tracking of quantitative fat fraction changes in different organs simultaneously, which can be critical in understanding fat metabolism.

Elevated iron concentration in putamen and cortical speech motor network in developmental stuttering.

Theoretical accounts of developmental stuttering implicate dysfunctional cortico-striatal-thalamo-cortical motor loops through the putamen. However, the analysis of conventional MRI brain scans in individuals who stutter has failed to yield strong support for this theory in terms of reliable differences in the structure or function of the basal ganglia.Here, we performed quantitative mapping of brain tissue, which can be used to measure iron content alongside markers sensitive to myelin and thereby offers particular sensitivity to the measurement of iron-rich structures such as the basal ganglia.Analysis of these quantitative maps in 41 men and women who stutter and 32 individuals who are typically fluent revealed significant group differences in maps of R2*, indicative of higher iron content in individuals who stutter in the left putamen and in left hemisphere cortical regions important for speech motor control. Higher iron levels in brain tissue in individuals who stutter could reflect elevated dopamine levels or lysosomal dysfunction, both of which are implicated in stuttering.This study represents the first use of these quantitative measures in developmental stuttering and provides new evidence of microstructural differences in the basal ganglia and connected frontal cortical regions.

Intracerebral Iron Accumulation may be Associated with Secondary Brain Injury in Patients with Poor Grade Subarachnoid Hemorrhage

BackgroundThe amount of intracranial blood is a strong predictor of poor outcome after subarachnoid hemorrhage (SAH). Here, we aimed to measure iron concentrations in the cerebral white matter, using the cerebral microdialysis (CMD) technique, and to associate iron levels with the local metabolic profile, complications, and functional outcome.MethodsFor the observational cohort study, 36 patients with consecutive poor grade SAH (Hunt & Hess grade of 4 or 5, Glasgow Coma Scale Score ≤ 8) undergoing multimodal neuromonitoring were analyzed for brain metabolic changes, including CMD iron levels quantified by graphite furnace atomic absorption spectrometry. The study time encompassed 14 days after admission. Statistical analysis was performed using generalized estimating equations.ResultsPatients were admitted in a poor clinical grade (n = 26, 72%) or deteriorated within 24 h (n = 10, 28%). The median blood volume in the subarachnoid space was high (SAH sum score = 26, interquartile range 20–28). Initial CMD iron was 44 µg/L (25–65 µg/L), which significantly decreased to a level of 25 µg/L (14–30 µg/L) at day 4 and then constantly increased over the remaining neuromonitoring days (p < 0.01). A higher intraventricular hemorrhage sum score (≥ 5) was associated with higher CMD iron levels (Wald-statistic = 4.1, df = 1, p = 0.04) but not with the hemorrhage load in the subarachnoid space (p = 0.8). In patients developing vasospasm, the CMD iron load was higher, compared with patients without vasospasm (Wald-statistic = 4.1, degree of freedom = 1, p = 0.04), which was not true for delayed cerebral infarction (p = 0.4). Higher iron concentrations in the brain extracellular fluid (34 µg/L, 36–56 µg/L vs. 23 µg/L, 15–37 µg/L) were associated with mitochondrial dysfunction (CMD lactate to pyruvate ratio > 30 and CMD-pyruvate > 70 µM/L, p < 0.001). Brain extracellular iron load was not associated with functional outcome after 3 months (p > 0.5).ConclusionsThis study suggests that iron accumulates in the cerebral white matter in patients with poor grade SAH. These findings may support trials aiming to scavenger brain extracellular iron based on the hypothesis that iron-mediated neurotoxicity may contribute to acute and secondary brain injury following SAH.

Measurement of Liver Iron Concentration in a Population of Non-Transfusion Dependent Thalassemia Patients Using a Trained Artificial Neural Network to Analyse Magnetic Resonance Images

Background: Measurements of liver iron concentration (LIC) by magnetic resonance imaging (MRI) have become established and validated in several research intensive centers. However, challenges remain with translating these measurement methodologies for routine clinical use. Current methods involve many steps presenting multiple opportunities for human error and can lead to systematic severe measurement error. Artificial neural networks (ANNs) can be trained to replace human input into image processing and may have a role in providing a simple, robust, and low cost solution for LIC measurement.Aims: The aim of the study wasto determine the limits of agreement between measurements of LIC by a reference standard spin-density-projection-assisted (SDPA) R2-MRI method (FerriScan) and a method using trained ANNs to analyse image data. MR image datasets (400) previously acquired from Siemens scanners were pre-processed and then, together with their corresponding SDPA R2-MRI LIC values, were filtered through publically available ANNs. The ANNs had been pre-trained on large image sets (ImageNet). Relevant features were extracted and then used to train a machine learning (gradient boosting) algorithm to predict LIC values from previously unseen MR image datasets.Methods: Thalassemia patients (N=100) referred by the National Institute of Haematology and Blood Transfusion, Hanoi, Vietnam for routine LIC measurement by MRI were prospectively recruited with informed consent. Patients were randomised to be scanned in either a Philips Ingenia or a Siemens Avanto 1.5T scanner. Image data were acquired using the FerriScan protocol. Images were then processed (1) using a quality controlled core laboratory data analysis service using the SDPA R2-MRI method and (2) by a non-radiologically-trained technician using the trained artificial neural network to generate LIC values. The technician was required to trace the outline of the torso and then click a mouse button. The technician using the ANN was blinded from the SDPA R2-MRI results and the analysts generating the SDPA R2-MRI results were blinded from the ANN results. Reported data were analysed using the statistical methods of Bland and Altman.Results: A plot of the ANN-predicted LIC values against the SDPA R2-MRI LIC values (Figure) shows the data scattered about the line of equivalence indicating that the ANN method is generating results that correlate with the validated SDPA R2-MRI reference standard. The geometric mean ratio of ANN LIC to SDPA R2-MRI LIC was 0.93 (95% CI 0.91 -0.96) indicating a small but statistically significant systematic underestimation of LIC by the ANN. The geometric mean ratios of the two LIC measurements were significantly different for the two scanners (0.98 for Philips and 0.90 for Siemens, p = 0.006) indicating that the bias of the ANN method against the reference standard is not universal but is dependent on scanner. Bland Altman analysis indicates that 95% of pairs of measurements are predicted to have ratios between 1.23 and 0.69 indicating a modest random variability between the ANN method and the reference standard that is better than that between biopsy and the reference standard. The performance of the ANN method in predicting SDPA R2-MRI LIC values above the clinically relevant thresholds of 7 and 15 mg Fe/g dw is characterized in Table 1 showing positive predictive values (PPVs) and negative predictive values (NPVs) together with their 95% CIs.Conclusion: The data indicate that the ANN method of measurement of LIC has potential to be used as a fast and robust method of analysing MR image data to generate LIC values. Further testing is required on a wider range of scanner types and with more patients with lower LICs. The performance of the ANN will also likely be improved through training on a larger number of datasets. [Display omitted] DisclosuresSt Pierre:Resonance Health Ltd: Consultancy, Equity Ownership, Speakers Bureau. Cooper:Resonance Health Ltd: Consultancy. Boulos:Resonance Health Ltd: Employment. House:Resonance Health Ltd: Employment. Pang:Resonance Health Ltd: Employment. Bangma:Resonance Health Ltd: Employment. Taher:Novartis Pharmaceuticals: Honoraria, Research Funding; Celgene: Research Funding.