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Background: Small artery occlusion (SAO) is a common ischemic stroke subtype. However, its clinical outcome can be more severe than commonly understood. The severity of SAO can vary, ranging from mild to moderate. Iron deposition has been associated with the development and progression of stroke. However, its specific distribution and relationship with stroke severity in SAO remain unclear. The study's purpose is to investigate the differences in iron deposition between mild stroke with SAO (SAO-MiS) and moderate stroke with SAO (SAO-MoS) through quantitative susceptibility mapping (QSM) and its association with neurological deficits. Methods: Sixty-eight SAO participants within 24 hours of first onset were enrolled and separated into SAO-MiS and SAO-MoS according to the National Institutes of Health Stroke Scale (NIHSS) scores. QSM helped calculate the susceptibility maps, reflecting the iron content within the brain. The susceptibility maps were analyzed using voxel-wise statistical analysis to compare the iron deposition between SAO-MiS and SAO-MoS. Then, differentially distributed iron deposition helped differentiate between mild and moderate stroke using support vector machine (SVM) methods. Results: Compared with SAO-MiS, SAO-MoS depicted elevated iron deposition in the left pallidum, parahippocampal gyrus, and superior frontal gyrus medial region, and is lower in the right superior/middle frontal gyrus and bilateral supplementary motor area. Based on iron deposition, the SVM classifier's analysis revealed a high power to discriminate SAO-MoS from SAO-MiS. In addition, fibrinogen, triglyceride (TG), and total cholesterol (TC) were linked with QSM values in specific brain regions. Conclusions: Our study first revealed the brain iron distribution after SAO and differently distributed iron deposition in SAO-MiS and SAO-MoS. The results indicate that iron deposition could play a role in the pathophysiology of SAO and its correlation with stroke severity. [ABSTRACT FROM AUTHOR]

Background and aims: This study aimed to investigate the effect of iron overload on acetylcholinesterase activity in the frontal lobe tissue of rats with minimal hepatic encephalopathy (MHE) and its relation to cognitive ability. By elucidating the potential mechanisms of cognitive impairment, this study may offer insights into novel therapeutic targets for MHE. Materials and methods: Twelve Sprague-Dawley rats were purchased and randomly assigned to either the experimental or control group with six rats in each group. Following the induction of MHE, the Morris Water Maze (MWM) was utilized to assess spatial orientation and memory capacity. Subsequently, Magnetic Resonance Imaging (MRI) scans were performed to capture Quantitative Susceptibility Mapping (QSM) images of all rats' heads. Results: Compared to the control group rats, the MHE model rats showed significantly reduced learning and memory capabilities as well as spatial orientation abilities (P < 0.05). Furthermore, the susceptibility values in the frontal lobe tissue of MHE model rats was significantly higher than that of the control group rats (P < 0.05), and the corresponding BuChE activity in the frontal lobe extract of model rats was significantly increased while BuChE activity in the peripheral blood serum was significantly decreased compared to the control group rats (P < 0.05). Meanwhile, our findings indicate a significant positive correlation between latency period and BuChE activity with susceptibility values in the MHE group. Conclusion: The changes in BuChE activity in frontal lobe extract may be related to changes in spatial orientation and behavioral changes in MHE, and iron overload in the frontal lobe tissue may regulate changes in BuChE activity, BuChE levels appear to be iron-dependent. [ABSTRACT FROM AUTHOR]

Background: The pathophysiological mechanisms underlying migraine without aura (MwoA) in females remain incompletely elucidated. Currently, the association between headache laterality and iron deposition (ID), and functional connectivity (FC) in female MwoA patients has not been fully studied. Methods: We prospectively recruited 63 female patients with MwoA and 31 matched healthy controls (HC) from the hospital. ID and FC among the four groups were analyzed using two‐sample t‐tests (with cluster‐wise family‐wise error [FWE] correction). Pearson correlation analysis was used to evaluate the relationships between clinical variables and both ID and FC values. Significance level: p < 0.05. Results: Compared to HC, left‐sided MwoA exhibited differences in ID in various brain regions, including the cerebellum, left orbital inferior frontal gyrus, left calcarine gyrus, right putamen, and left caudate nucleus, as well as exhibited enhanced FC between the left lobule III of the cerebellum and the right superior temporal gyrus. Compared to bilateral MwoA, left‐sided MwoA showed significantly enhanced in FC values in the left calcarine gyrus, the right precentral gyrus, the right postcentral gyrus, and the right lingual gyrus. Additionally, significant differences were observed in the Pearson correlations between clinical variables and both ID and FC in the female MwoA subgroups. Conclusion: Our study provided preliminary evidence indicating significant differences in ID, FC, and correlations among subgroups of female MwoA. This provides neuroimaging references for further subclassifying MwoA patients. This offers valuable insights into potential pathophysiological mechanisms linked to the brain functional impairment in female MwoA. [ABSTRACT FROM AUTHOR]

ABSTRACT Background The pathophysiological mechanisms underlying migraine without aura (MwoA) in females remain incompletely elucidated. Currently, the association between headache laterality and iron deposition (ID), and functional connectivity (FC) in female MwoA patients has not been fully studied. Methods We prospectively recruited 63 female patients with MwoA and 31 matched healthy controls (HC) from the hospital. ID and FC among the four groups were analyzed using two‐sample t‐tests (with cluster‐wise family‐wise error [FWE] correction). Pearson correlation analysis was used to evaluate the relationships between clinical variables and both ID and FC values. Significance level: p

This study aims to analyse hyperechoic substantia nigra (HSN) characteristics and the correlation of HSN with clinical features and blood biomarkers in patients with Parkinson's disease (PD). Transcranial sonography (TCS) evaluations of the substantia nigra (SN) were performed in 40 healthy controls and 71 patients with PD, including patients with SN hyperechogenicity (SN+) and those with normal SN echogenicity (SN−). Evaluation of motor and non‐motor symptoms was assessed by a series of rating scales. The uricase method was used to determine serum uric acid (UA) levels, and enzyme‐linked immunosorbent assay (ELISA) was used to measure plasma interleukin (IL)‐1β levels. TCS showed 92.50% specificity and 61.97% sensitivity in differentiating PD patients from controls. The area of SN+ contralateral to the side of initial motor symptoms (SNcontra) was larger than that ipsilateral to the side of initial motor symptoms (SNipsi). The PDSN+ group had lower Argentine Hyposmia Rating Scale (AHRS) scores and UA levels than the PDSN− group. Binary logistic regression analysis revealed that AHRS scores and UA levels could be independent predictors for HSN. The larger SN echogenic area (SNL) sizes positively correlated with plasma IL‐1β levels in PD patients with SN+. The present study provides further evidence of the potential of SN echogenicity as an imaging biomarker for PD diagnosis. PD patients with HSN have more severe non‐motor symptoms of hyposmia. HSN in PD patients is related to the mechanism of abnormal iron metabolism and microglial activation. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic steatohepatitis (NASH) is a rapidly progressing chronic liver disease of global significance. However, the underlying mechanisms responsible for NASH remain unknown. Indoleamine 2,3-dioxygenase 1 (IDO1) has been recognized as essential factor in immune response and metabolic regulation. Here we aimed to investigate the functions and mechanisms of the IDO1 in macrophages on hepatic lipid deposition and iron metabolism in NASH. Methods: The effect of IDO1 in NASH was evaluated by WT and IDO1−/− mice model fed with methionine/choline-deficient (MCD) diet in vivo. Macrophages scavenger clodronate liposomes (CL) and overexpressing of IDO1 in macrophages by virus were employed as well. Lipid deposition was assessed through pathological examination and lipid droplet staining, while iron levels were measured using an iron assay kit and western blotting. Primary hepatocytes and bone marrow-derived macrophages were treated with oleic acid/palmitic acid (OA/PA) to assess IDO1 expression via Oil Red O staining and immunofluorescence staining in vitro. Results: Pathological images demonstrated that the increase of IDO1 exacerbated lipid accumulation in the livers of mice with MCD diet, while reduction of iron accumulation was observed in the liver and the serum of MCD-fed mice. Scavenging of macrophages effectively mitigated both lipid and iron accumulation. In addition, the deficiency of IDO1 in macrophages significantly mitigated lipid accumulation and iron overload in hepatic parenchymal cells. Finally, lentivirus-mediated overexpression of IDO1 in liver macrophages exacerbated hepatic steatosis and iron deposition in NASH. Conclusions: Our results demonstrated that effective inhibition of IDO1 expression in macrophages in NASH alleviated hepatic parenchymal cell lipid accumulation and iron deposition, which provided new insights for the future treatment of NASH. [ABSTRACT FROM AUTHOR]

Introduction: Iron deposition is vital for damaging neurons and causing different cognitive disorders. Today, using the quantitative susceptibility mapping (QSM) technique, iron deposits in other brain areas can be assessed and measured. This study aimed to identify changes in iron deposition of 12 brain nuclei through different stages of dementia using the QSM technique to introduce biomarkers for the early detection of cognitive disorders. Material and Methods: The Alzheimer’s Disease Neuroimaging Initiative (ADNI) database was used to download data. A 3T MRI scanner scanned thirty-five participants with normal cognition and forty-six patients with cognitive disorders who were classified into four groups based on the severity of the condition. QSM processing determined twelve regions of interest (ROIs) by automatic nuclei segmentation and statistical analysis performed in these groups’ MRI images. Results: Based on previous findings, QSM values ​​increase proportionally to iron deposition.In this study, the increase in the QSM values ​​of different nuclei of the early mild cognitive impairment (EMCI) stage indicates iron deposition in these participants. In the EMCI group, The QSM value of the bilateral thalamus (P

Introduction: While patients who experience improved cognition following carotid endarterectomy (CEA) typically demonstrate restored brain perfusion after the procedure, it is worth noting that less than 50% of patients in whom postoperative cerebral blood flow (CBF) restoration is achieved actually show improved cognition after postoperatively. This suggests that factors beyond the mere restoration of CBF may play a role in postoperative cognitive improvement. Increased iron deposition in the cerebral cortex may cause neural damage, and quantitative susceptibility mapping (QSM) obtained using magnetic resonance imaging (MRI) quantifies magnetic susceptibility in the cerebral cortex, allowing for the assessment of iron deposition in vivo. The purpose of the present study was to determine whether preoperative cortical magnetic susceptibility as well as postoperative changes in CBF are associated with cognitive improvement after CEA. Methods: Brain MRI with a three-dimensional gradient echo sequence was preoperatively performed in 53 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≥70%), and QSM with brain surface correction and vein removal was obtained. Cortical magnetic susceptibility was measured in the cerebral hemisphere ipsilateral to surgery on QSM. Preoperatively and at 2 months after the surgery, brain perfusion single-photon emission computed tomography and neuropsychological assessments were conducted. Using these collected data, we evaluated alterations in CBF within the affected hemisphere and assessed cognitive improvements following the operation. Results: A logistic regression analysis showed that a postoperative greater increase in CBF (95% confidence interval [CI], 1.06–1.90; p = 0.0186) and preoperative lower cortical magnetic susceptibility (95% CI, 0.03–0.74; p = 0.0201) were significantly associated with postoperatively improved cognition. Although sensitivity, specificity, and positive and negative predictive values with the cutoff value lying closest to the upper left corner of a receiver operating characteristic curve for the prediction of postoperatively improved cognition did not differ between postoperative changes in CBF and preoperative cortical magnetic susceptibility, the specificity and the positive predictive value were significantly greater for the combination of postoperative changes in CBF and preoperative cortical magnetic susceptibility (specificity, 95% CI, 93–100%; positive predictive value 95% CI, 68–100%) than for the former parameter alone (specificity, 95% CI, 63–88%; positive predictive value 95% CI, 20–64%). Conclusion: Preoperative cortical magnetic susceptibility as well as postoperative changes in CBF are associated with cognitive improvement after CEA. [ABSTRACT FROM AUTHOR]

Iron deposition is crucial pathological changes observed in patients with Parkinson's disease (PD). Recently, scientists have actively explored therapeutic approaches targeting iron deposition in PD. However, several clinical studies have failed to yield consistent results. In this review, we provide an overview of iron deposition in PD, from both basic research and clinical perspectives. PD patients exhibit abnormalities in various iron metabolism-related proteins, leading to disruptions in iron distribution, transport, storage, and circulation, ultimately resulting in iron deposition. Excess iron can induce oxidative stress and iron-related cell death, and exacerbate mitochondrial dysfunction, contributing to the progression of PD pathology. Magnetic resonance imaging studies have indicated that the characteristics of iron deposition in the brains of PD patients vary. Iron deposition correlates with the clinical symptoms of PD, and patients with different disease courses and clinical presentations display distinct patterns of iron deposition. These iron deposition patterns may contribute to PD diagnosis. Iron deposition is a promising target for PD treatment. However, further research is required to elucidate the underlying mechanisms and their impacts on PD. Iron deposition in the Substantia nigra (SN) is a crucial pathological alteration in Parkinson's disease (PD). This article provides a review of the mechanisms and effects of iron deposition, as well as research on brain iron deposition in PD patients using magnetic resonance imaging (MRI). These findings elucidate the role of iron deposition in PD. [ABSTRACT FROM AUTHOR]

Introduction: Iron deposition is vital for damaging neurons and causing different cognitive disorders. Today, using the quantitative susceptibility mapping (QSM) technique, iron deposits in other brain areas can be assessed and measured. This study aimed to identify changes in iron deposition of 12 brain nuclei through different stages of dementia using the QSM technique to introduce biomarkers for the early detection of cognitive disorders. Material and Methods: The Alzheimer's Disease Neuroimaging Initiative (ADNI) database was used to download data. A 3T MRI scanner scanned thirty-five participants with normal cognition and forty-six patients with cognitive disorders who were classified into four groups based on the severity of the condition. QSM processing determined twelve regions of interest (ROIs) by automatic nuclei segmentation and statistical analysis performed in these groups' MRI images. Results: Based on previous findings, QSM values increase proportionally to iron deposition. In this study, the increase in the QSM values of different nuclei of the early mild cognitive impairment (EMCI) stage indicates iron deposition in these participants. In the EMCI group, The QSM value of the bilateral thalamus (P<0.05) and left amygdala (P=0.006) nuclei were higher than in the control group. Based on the results of the receiver operating characteristic curve (ROC) analysis, the left amygdala (P=0.005), left putamen (P=0.002), left thalamus (P=0.05), and right thalamus (P<0.05) have an appropriate sensitivity and specificity to identify the different stages of cognitive disorders. Conclusion: The left amygdala and bilateral thalamic nuclei are the first areas exposed to iron deposition during cognitive impairment. Mentioned nuclei, especially the left amygdala, have high efficiency and sensitivity for the early detection of cognitive disorders. [ABSTRACT FROM AUTHOR]

Background: Detection and quantification of liver iron overload are significant to initiate treatment and monitoring of iron overload. This study aimed to quantify liver iron deposits in β-thalassemia major patients using MRI T2* and its correlation with age and heart iron deposition. Methods and Results: This retrospective study included 54 records of patients between 5-16 years of age with hepatic iron deposition due to β-thalassemia major. Data were collected from MRI reports in Picture Archiving and Communication Systems-Radiology Information System (PACS-RIS) and serum ferritin (SF) test results obtained from Hospital Information Systems and written into a dedicated datasheet. The information was recorded on a data collection sheet. The datasheet included all the required data, demographic data, lab results, T2* mapping for iron deposition in the liver and heart, and liver measurements. All subjects had high SF (from 1120 to 9850 ng/ml) with an average of 4317.93±2779.9 ng/ml. Age and SF correlated positively (r=0.368, P=0.0006). A negative correlation was observed between SF and liver T2* (r= -0578, P=0.000) (Table 3), whereas between liver T2* and heart T2* correlation had a positive direction (r= 0.329, P=0.015) Conclusion: MRI provides accurate, non-invasive, valid, and repeatable techniques, which are more acceptable to patients for assessing iron load. Furthermore, MRI T2* methods measure iron overload within the target organ precisely.

Physical activity (PA) is linked to better cognitive and brain health, though its mechanisms are unknown. While brain iron is essential for normal function, levels increase with age and, when excessive, can cause detrimental neural effects. We examined how objectively measured PA relates to cerebral iron deposition and memory functioning in normal older adults. Sixty-eight cognitively unimpaired older adults from the UCSF Memory and Aging Center completed neuropsychological testing and brain magnetic resonance imaging, followed by 30-day Fitbit monitoring. Magnetic resonance imaging quantitative susceptibility mapping (QSM) quantified iron deposition. PA was operationalized as average daily steps. Linear regression models examined memory as a function of hippocampal QSM, PA, and their interaction. Higher bilateral hippocampal iron deposition correlated with worse memory but was not strongly related to PA. Covarying for demographics, PA moderated the relationship between bilateral hippocampal iron deposition and memory such that the negative effect of hippocampal QSM on memory performances was no longer significant above 9120 daily steps. PA may mitigate adverse iron-related pathways for memory health. • Brain iron deposition occurs with age and increases the risk for cognitive decline. • The role of physical activity (PA) on brain iron deposition is unknown. • Hippocampal iron deposition is related to poorer memory in cognitively normal adults. • PA attenuated the relationship between iron deposition and memory. • PA may mitigate adverse iron-related pathways for memory health. [ABSTRACT FROM AUTHOR]

A comprehensive study of the impact of electrode design and iron deposition mechanism on the enhancement of the capacity of an all-iron redox flow battery (AIFB) has been conducted. The research is focused on revealing the complex interaction between electrode architecture, iron deposition behaviour, and battery capacity. Using a developed experimental setup, five different electrode designs are investigated. These designs include variations in the arrangement of carbon felt (CF) and non-woven fabric (NWF) layers and critical factors affecting iron deposition. Battery charge and discharge experiments were carried out under controlled conditions, simulating practical operating regimes with a current density of 50 mA/cm² and a compression ratio of 80 %. The results demonstrate the influence of electrode design on iron deposition and, consequently, on battery capacity. The electrode configuration with two layers of CF and two layers of NWF exhibits a specific capacity exceeding 700 mA•h/cm². Analysis using scanning electron microscopy (SEM) complements the capacity determination results by providing valuable information about the spatial distribution of iron on the electrode surfaces. Furthermore, quantitative analysis using ZAF correction reveals uniform models of iron deposition on the surface of electrode E, indicating its potential for optimizing AIFB performance. This study provides a comprehensive understanding of the relationship between electrode design, iron deposition behaviour, and AIFB capacity. The results offer insights for improving electrode configurations, ultimately contributing to the development of efficient energy storage solutions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Respiratory functions in thalassemia major (TM) patients concerning poor chelation are a frequently researched issue. Our study aims to evaluate the lung functions of our patients with TM in the chronic transfusion program and to correlate them with their age, ferritin levels, and pre-transfusion hemoglobin values. METHODS: Height, weight, pulmonary function test (PFT) results, pre-transfusion hemoglobin levels, and ferritin levels of 97 patients (55 boys and 42 girls) without any underlying cardiac or chronic respiratory disease were recorded. PFT is consisted of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), the ratio of FEV1/FVC to peak expiratory flow (PEF), and forced mid-exhaled flow between 25% and 75% of mid-expiratory flow (MEF25-75). Data were analyzed with IBM SPSS V25. ESULTS: Low FVC was observed in 58 patients (60%), and low FEV1 was observed in 26 patients (27.6%). Low PEF was observed in 62 patients (64.5%), and low MEF25-75 was observed in 8 (8.3%). PFT was affected in 75 patients (78.1%). The pattern of involvement was restrictive. Age, height, and ferritin values significantly affected the MEF25-75 (p<0.05). Age and pre-transfusion hemoglobin values had a significant effect on the FVC test (p<0.05). There was a weak negative correlation between ferritin values and MEF25-75 (r=-0.221) and a weak positive correlation between pre-transfusion hemoglobin and FVC (r=0.222). CONCLUSION: Age and height are the main risk factors affecting FEV1, MEF25-75, and PEF. Serum ferritin has only an effect on MEF25-75 in our study. The respiratory functions of TM patients were affected in a restrictive pattern. [ABSTRACT FROM AUTHOR]

Background: Iron overload is connected with an expanded prevalence of thalassemia due to heart impairment. This considers pointing to survey changes in thalassemia's aortic elasticity due to iron deposition in the heart and liver of children. Methods: This case-control study was performed on 80 healthy and 160 thalassemia patients. The subjects gathered from educational pediatric hospital of Ali Asghar in Zahedan, Iran, from 2019 to 2021. Echocardiography parameters were measured. Ferritin, lipids profile, cardiac and liver MRI T2 * measured in patients only. Aortic elasticity parameters were aortic strain, aortic stiffness β index, aortic distensibility and pressure strain elastic modulus. Data analyzed by SPSS,p

Abstract Background Migraine is one of the world’s most prevalent and disabling diseases. Despite huge advances in neuroimaging research, more valuable neuroimaging markers are still urgently needed to provide important insights into the brain mechanisms that underlie migraine symptoms. We therefore aim to investigate the regional iron deposition in subcortical nuclei of migraineurs as compared to controls and its association with migraine-related pathophysiological assessments. Methods A total of 200 migraineurs (56 chronic migraine [CM], 144 episodic migraine [EM]) and 41 matched controls were recruited. All subjects underwent MRI and clinical variables including frequency/duration of migraine, intensity of migraine, 6-item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and Pittsburgh Sleep Quality Index (PSQI) were recorded. Quantitative susceptibility mapping was employed to quantify the regional iron content in subcortical regions. Associations between clinical variables and regional iron deposition were studied as well. Results Increased iron deposition in the putamen, caudate, and nucleus accumbens (NAC) was observed in migraineurs more than controls. Meanwhile, patients with CM had a significantly higher volume of iron deposits compared to EM in multiple subcortical nuclei, especially in NAC. Volume of iron in NAC can be used to distinguish patients with CM from EM with a sensitivity of 85.45% and specificity of 71.53%. As the most valuable neuroimaging markers in all of the subcortical nuclei, higher iron deposition in NAC was significantly associated with disease progression, and higher HIT-6, MIDAS, and PSQI. Conclusions These findings provide evidence that iron deposition in NAC may be a biomarker for migraine chronicity and migraine-related dysfunctions, thus may help to understand the underlying vascular and neural mechanisms of migraine. Trial registration ClinicalTrials.gov, number NCT04939922.

Introduction: Previous studies have revealed structural, functional, and metabolic changes in brain regions inside the cortico-striatal-thalamo-cortical (CSTC) loop in patients with paroxysmal kinesigenic dyskinesia (PKD), whereas no quantitative susceptibility mapping (QSM)-related studies have explored brain iron deposition in these areas. Methods: A total of eight familial PKD patients and 10 of their healthy family members (normal controls) were recruited and underwent QSM on a 3Tmagnetic resonance imaging system. Magnetic susceptibility maps were reconstructed using amulti-scale dipole inversion algorithm. Thereafter, we specifically analyzed changes in local mean susceptibility values in cortical regions and subcortical nuclei inside the motor CSTC loop. Results: Compared with normal controls, PKD patients had altered brain iron levels. In the cortical gray matter area involved with the motor CSTC loop, susceptibility values were generally elevated, especially in the bilateral M1 and PMv regions. In the subcortical nuclei regions involved with the motor CSTC loop, susceptibility values were generally lower, especially in the bilateral substantia nigra regions. Conclusion: Our results provide new evidence for the neuropathogenesis of PKD and suggest that an imbalance in brain iron levels may play a role in PKD. [ABSTRACT FROM AUTHOR]

Introduction: The ventral tegmental area (VTA) is less affected compared to substantia nigra pars compacta (SNc) in Parkinson's disease (PD). This study aimed to quantitatively evaluate iron content in the VTA across different stages of PD in order to help explain the selective loss of dopamine neurons in PD. Methods: Quantitative susceptibility mapping (QSM) data were obtained from 101 PD patients, 35 idiopathic rapid eye movement sleep behavior disorder (RBD) patients, and 62 healthy controls (HCs). The mean QSM values in the VTA and SNc were calculated and compared among the groups. Results: Both RBD and PD patients had increased iron values in the bilateral SNc compared with HCs. RBD and PD patients in the Hoehn-Yahr (H & Y) stage 1 did not show elevated iron values in the VTA, while PD patients with more than 1.5 H & Y staging had increased iron values in bilateral VTA compared to HCs. Discussion: This study shows that there is no increased iron accumulation in the VTA during the prodromal and early clinical stages of PD, but iron deposition increases significantly as the disease becomes more severe. [ABSTRACT FROM AUTHOR]

While iron over‐accumulation has been reported in late stage Alzheimer's disease (AD), whether this occurs early in the asymptomatic stage of AD remains unknown. We aimed to assess brain iron levels in asymptomatic AD using quantitative MR relaxometry of effective transverse relaxation rate (R2*) and longitudinal relaxation rate (R1), and recruited 118 participants comprised of three groups including healthy young participants, and cognitively normal older individuals without or with positive AD biomarkers based on cerebrospinal fluid (CSF) proteomics analysis. Compared with the healthy young group, increased R2* was found in widespread cortical and subcortical regions in the older groups. Further, significantly higher levels of R2* were found in the cognitively normal older subjects with positive CSF AD biomarker (i.e., asymptomatic AD) compared with those with negative AD biomarker in subcortical regions including the left and right caudate, left and right putamen, and left and right globus pallidus (p <.05 for all regions), suggesting increased iron content in these regions. Subcortical R2* of some regions was found to significantly correlate with CSF AD biomarkers and neuropsychological assessments of visuospatial functions. In conclusion, R2* could be a valuable biomarker for studying early pathophysiological changes in AD. [ABSTRACT FROM AUTHOR]

Background and purpose: Postmortem brain study indicated that cerebellar Purkinje cell (PC) loss might be a pathological finding in patients with inherited and idiopathic cervical dystonia (ICD). The analysis of conventional magnetic resonance imaging brain scans failed to yield support for this finding. Previous studies have identified that iron overload can be the consequence of neuron death. The objectives of this study were to investigate iron distribution and demonstrate changes in axons in the cerebellum, providing evidence for PC loss in patients with ICD. Methods: Twenty‐eight patients with ICD (20 females) and 28 age‐ and sex‐matched healthy controls were recruited. A spatially unbiased infratentorial template was applied to perform cerebellum optimized quantitative susceptibility mapping and diffusion tensor analysis based on magnetic resonance imaging. Voxel‐wise analysis was performed to assess cerebellar tissue magnetic susceptibility and fractional anisotropy (FA) alterations, and the clinical relevance of these findings was investigated in the patients with ICD. Results: Increased susceptibility values revealed by quantitative susceptibility mapping in the right lobule CrusI, CrusII, VIIb, VIIIa, VIIIb and IX were found in the patients with ICD. A reduced FA value was found across almost all the cerebellum; an FA value of the significant clusters within the right lobule VIIIa significantly correlated with the motor severity of patients with ICD (r = −0.575, p = 0.002). Conclusions: Our study provided evidence for cerebellar iron overload and axonal damage in patients with ICD, which may indicate PC loss and related axonal changes. These results provide evidence for the neuropathological findings in patients with ICD and further highlight the cerebellar involvement in the pathophysiology of dystonia. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate susceptibility values associated with iron accumulation in the deep gray matter during postnatal development and to compare magnetic susceptibility between patients with normal and delayed development. Methods: Patients with postmenstrual age (PMA) ≤ 1000 days underwent MR scans between August 2015 and April 2020 at our hospital. Quantitative susceptibility mapping (QSM) was performed, and magnetic susceptibility was measured using three-dimensional volumes of interest (VOIs) for the caudate nucleus (CN), globus pallidus (GP), putamen (PT), and ventrolateral thalamic nucleus (VL). Cross-sectional analysis was performed for 99 patients with normal development and 39 patients with delayed development. Longitudinal analysis was also performed to interpret changes over time in 13 patients with normal development. Correlations between magnetic susceptibility in VOIs and PMA or chronological age (CA) were assessed. Results: Susceptibility values for CN, GP, PT, and VL showed positive moderate correlations with both PMA (ρ = 0.45, 0.69, 0.62, and 0.33, respectively) and CA (ρ = 0.53, 0.69, 0.66, and 0.39, respectively). The slope of the correlation between susceptibility values and age was highest in the GP among the four gray matter areas. Susceptibility values for the CN, GP, PT, and VL were higher with normal development than with delayed development at early postnatal age, although a significant difference was only observed for the CN. Susceptibility values also increased with age in the longitudinal analysis. Conclusions: Magnetic susceptibility values in deep gray matter increased with age ≤ 1000 days. The normal development group showed higher susceptibility values than the delayed development group at early postnatal age (PMA ≤ 285 days). Key Points: • Magnetic susceptibilities in deep gray matter nuclei increased with age (postmenstrual age ≤ 1000 days) in a large number of pediatric patients. • The normal development group showed higher susceptibility values than the delayed development group in the basal ganglia and ventrolateral thalamic nucleus at early postnatal age (PMA ≤ 285 days). [ABSTRACT FROM AUTHOR]

Locus coeruleus (LC) and substantia nigra pars compacta (SNpc) degrade with normal aging, but not much is known regarding how these changes manifest in MRI images, or whether these markers predict aspects of cognition. Here, we use high-resolution diffusion-weighted MRI to investigate microstructural and compositional changes in LC and SNpc in young and older adult cohorts, as well as their relationship with cognition. In LC, the older cohort exhibited a significant reduction in mean and radial diffusivity, but a significant increase in fractional anisotropy compared with the young cohort. We observed a significant correlation between the decrease in LC mean, axial, and radial diffusivities and measures examining cognition (Rey Auditory Verbal Learning Test delayed recall) in the older adult cohort. This observation suggests that LC is involved in retaining cognitive abilities. In addition, we observed that iron deposition in SNpc occurs early in life and continues during normal aging.

Iron deposition is closely related to developing haemophilic arthropathy (HA). Studying the relationship between ferroptosis signal expression and iron overload in HA synovium facilitates understanding the pathogenesis of joint synovial hyperplasia in bloodborne arthritis and the development of new protective methods. The knee synovium was collected from HA and osteoarthritis (OA) patients, and pathological changes were analysed by HE and Prussian blue staining. Ferroptosis phenotypes were examined by immunohistochemistry and western blotting. Moreover, ferric ammonium citrate (FAC)-induced was used to construct an in vitro iron overload model to investigate the relationship between iron overload and ferroptosis in synovial fibroblasts (FLS). Furthermore, the factors influencing ferroptosis in FLS were explored. Iron deposition, cell proliferation, and vascular proliferation in the synovium of HA were more obvious. Ferroptosis in HA synovium appears to inhibit. FLS ferroptosis increased with iron accumulation, malondialdehyde (MDA) in cells, and glutathione (GSH) depletion. TNF-α plays a protective role in this process. Blocking the action of TNF-α and inducing ferroptosis significantly reduced synovial proliferation. TNF-α inhibitors combined with a ferroptosis inducer may be a new therapeutic method for HA synovitis. [ABSTRACT FROM AUTHOR]

Hemodialysis patients exhibit anemia-related cerebral hyperperfusion and iron deposition (ID). However, the mechanisms underlying the pathology of cerebral ID are not clear. We investigated the role of cerebral blood flow (CBF) in the pathophysiology of cerebral ID in hemodialysis patients with anemia. This study recruited 33 hemodialysis patients with anemia and thirty-three healthy controls (HCs). All the subjects underwent quantitative susceptibility mapping (QSM) and arterial spin labeling (ASL) to measure ID and CBF in the cerebral nuclei. Furthermore, we evaluated lacunar infarction (LI), cerebral microbleeds, and total white matter hyperintensity volume (TWMHV). Hemodialysis patients with anemia showed significantly higher ID and CBF in some nuclei compared to the HCs after adjusting for age, sex, and total intracranial volume (TIV) [ P < 0.05, false discovery rate (FDR) corrected]. CBF showed a positive correlation with ID in both patients and HCs after adjustments for age, gender, and TIV (P < 0.05, FDR corrected). Serum phosphorus, calcium, TWMHV, hypertension, and dialysis duration were independently associated with ID (P < 0.05). Hemoglobin, serum phosphorus, and LI were independently associated with CBF (P < 0.05). Mediation analysis demonstrated that CBF mediated the effects between hemoglobin and ID. Our study demonstrated that CBF mediated aberrant cerebral ID in hemodialysis patients with anemia. [ABSTRACT FROM AUTHOR]

This study aimed to explore the effect of iron deposition on native T1 mapping and blood oxygen level-dependent (BOLD) imaging in detecting liver fibrosis (LF) in a rabbit model. An LF group (n = 100) was established by subcutaneously injecting 50% carbon tetrachloride (CCl 4) oil solution, and 20 normal rabbits composed a control group. Native T1 mapping and BOLD were performed, and the T1 native and R 2 * quantitative parameters were analyzed by receiver operating characteristic (ROC) and multiple logistic regression analyses, with histopathological results and liver iron content (LIC) serving as reference standards. In total, 18, 17, 16, 18, and 15 rabbits were histopathologically diagnosed with LF stages F0, F1, F2, F3, and F4, respectively. T1 native (r = 0.47), R 2 * (r = 0.75) and LIC (r = 0.61) increased with LF stage progression (p < 0.001). Compared to T1 native values, R 2 * performed better in diagnosing the LF stage, especially for distinguishing F1-F2 from F3-F4 (AUC = 0.66 vs. 0.91, p = 0.01). Combined with the LIC, both T1 native and R 2 * showed improved diagnostic value in comparison to the individual imaging techniques, particularly for diagnosing F0 vs. F1-F2 and F0 vs. F1-F4, with AUC values of 0.90 vs. 0.70 (p = 0.01) and 0.93 vs. 0.77 (p = 0.01) for T1 native + LIC vs. LIC, respectively. BOLD imaging performed better than native T1 mapping in predicting and diagnosing LF stage progression. The decrease in diagnostic accuracy caused by the deposition of liver iron is a potential pitfall in the assessment of LF with BOLD imaging and native T1 mapping. [ABSTRACT FROM AUTHOR]

Background: Migraine is one of the world's most prevalent and disabling diseases. Despite huge advances in neuroimaging research, more valuable neuroimaging markers are still urgently needed to provide important insights into the brain mechanisms that underlie migraine symptoms. We therefore aim to investigate the regional iron deposition in subcortical nuclei of migraineurs as compared to controls and its association with migraine-related pathophysiological assessments. Methods: A total of 200 migraineurs (56 chronic migraine [CM], 144 episodic migraine [EM]) and 41 matched controls were recruited. All subjects underwent MRI and clinical variables including frequency/duration of migraine, intensity of migraine, 6-item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and Pittsburgh Sleep Quality Index (PSQI) were recorded. Quantitative susceptibility mapping was employed to quantify the regional iron content in subcortical regions. Associations between clinical variables and regional iron deposition were studied as well. Results: Increased iron deposition in the putamen, caudate, and nucleus accumbens (NAC) was observed in migraineurs more than controls. Meanwhile, patients with CM had a significantly higher volume of iron deposits compared to EM in multiple subcortical nuclei, especially in NAC. Volume of iron in NAC can be used to distinguish patients with CM from EM with a sensitivity of 85.45% and specificity of 71.53%. As the most valuable neuroimaging markers in all of the subcortical nuclei, higher iron deposition in NAC was significantly associated with disease progression, and higher HIT-6, MIDAS, and PSQI. Conclusions: These findings provide evidence that iron deposition in NAC may be a biomarker for migraine chronicity and migraine-related dysfunctions, thus may help to understand the underlying vascular and neural mechanisms of migraine. Trial registration: ClinicalTrials.gov, number NCT04939922. [ABSTRACT FROM AUTHOR]

Neurodegeneration with brain iron accumulation (NBIA) is an umbrella term encompassing various inherited neurological disorders characterised by abnormal iron accumulation in basal ganglia. We aimed to study the clinical, radiological and molecular spectrum of disorders with NBIA. All molecular-proven cases of NBIA presented in the last 5 years at 2 tertiary care genetic centres were compiled. Demographic details and clinical and neuroimaging findings were collated. We describe 27 individuals from 20 unrelated Indian families with causative variants in 5 NBIA-associated genes. PLA2G6-associated neurodegeneration (PLAN) was the most common, observed in 13 individuals from 9 families. They mainly presented in infancy with neuroregression and hypotonia. A recurrent pathogenic variant in COASY was observed in two neonates with prenatal-onset severe neurodegeneration. Pathogenic bi-allelic variants in PANK2, FA2H and C19ORF12 genes were observed in the rest, and these individuals presented in late childhood and adolescence with gait abnormalities and extrapyramidal symptoms. No intrafamilial and interfamilial variability were observed. Iron deposition on neuroimaging was seen in only 6/17 (35.3%) patients. A total of 22 causative variants across 5 genes were detected including a multiexonic duplication in PLA2G6. The variants c.1799G > A and c.2370 T > G in PLA2G6 were observed in three unrelated families. In silico assessments of 8 amongst 9 novel variants were also performed. We present a comprehensive compilation of the phenotypic and genotypic spectrum of various subtypes of NBIA from the Indian subcontinent. Clinical presentation of NBIAs is varied and not restricted to extrapyramidal symptoms or iron accumulation on neuroimaging. [ABSTRACT FROM AUTHOR]

Hemodialysis (HD) is the most regularly applied replacement therapy for end-stage renal disease, but it may result in brain injuries. The correlation between cerebral blood flow (CBF) alteration and iron deposition has not been investigated in patients undergoing HD. Ferritin level may be a dominant factor in CBF and iron deposition change. We hypothesize that ferritin level might be the key mediator between iron deposition and CBF alteration. The correlation in the putamen was estimated between the susceptibility values and CBF in patients undergoing HD. Compared with healthy controls, patients showed more altered global susceptibility values and CBF. The susceptibility value was negatively correlated with CBF in the putamen in patients. Moreover, the susceptibility value was negatively correlated with ferritin level and positively correlated with serum iron level in the putamen of patients. CBF was positively correlated with ferritin level and negatively correlated with serum iron level in the putamen of patients. These findings indicate that iron dyshomeostasis and vascular damage might exist in the putamen in patients. The results revealed that iron dyshomeostasis and vascular damage in the putamen may be potential neural mechanisms for neurodegenerative processes in patients undergoing HD. [ABSTRACT FROM AUTHOR]

Background: A putative role for iron in driving Alzheimer's disease (AD) progression is complicated by previously reported associations with neuroinflammation, apolipoprotein E and AD proteinopathy. To establish how iron interacts with clinicopathological features of AD and at what disease stage iron influences cognitive outcomes, we investigated the association of cerebrospinal fluid (CSF) biomarkers of iron (ferritin), inflammation (acute phase response proteins) and apolipoproteins with pathological biomarkers (CSF Aβ42/t-tau, p-tau181), clinical staging and longitudinal cognitive deterioration in subjects from the BioFINDER cohort, with replication of key results in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.Methods: Ferritin, acute phase response proteins (n=9) and apolipoproteins (n=6) were measured in CSF samples from BioFINDER (n=1239; 4 years cognitive follow-up) participants stratified by cognitive status (cognitively unimpaired, mild cognitive impairment, AD) and for the presence of amyloid and tangle pathology using CSF Aβ42/t-tau (A+) and p-tau181 (T+). The ferritin and apolipoprotein E associations were replicated in the ADNI (n=264) cohort.Results: In both cohorts, ferritin and apoE were elevated in A-T+ and A+T+ subjects (16%-40%), but not clinical diagnosis. Other apolipoproteins and acute phase response proteins increased with clinical diagnosis, not pathology. CSF ferritin was positively associated with p-tau181, which was mediated by apolipoprotein E. An optimised threshold of ferritin predicted cognitive deterioration in mild cognitive impairment subjects in the BioFINDER cohort, especially those people classified as A-T- and A+T-.Conclusions: CSF markers of iron and neuroinflammation have distinct associations with disease stages, while iron may be more intimately associated with apolipoprotein E and tau pathology. [ABSTRACT FROM AUTHOR]

Hydroxyurea is a chemotherapeutic agent that is used in the treatment of various hematological diseases including chronic myelogenous leukemia, polycythemia vera, and sickle cell anemia. Hydroxyurea is also used to treat psoriasis. Drug-induced hyperpigmentation is a known cutaneous side effect of hydroxyurea along with xerosis, dermal ulcers, and dermatomyositis-like eruptions. Hyperpigmentation has been observed in the oral mucosa, nails, and in a generalized or a diffuse pattern. The mechanism of hyperpigmentation related to hydroxyurea is believed to be correlated with increased melanin. Classically, clinical types of diffuse hyperpigmentation owing to iron deposition in the dermis have been associated with minocycline and not with hydroxyurea. We report a novel case in which hydroxyurea hyperpigmentation is associated with iron deposition.

Background: Microstructural changes in deep gray matter (DGM) nuclei are related to physiological behavior, cognition, and memory. Therefore, it is critical to study age-dependent trajectories of biomarkers in DGM nuclei for understanding brain development and aging, as well as predicting cognitive or neurodegenerative diseases. Objectives: We aimed to (1) characterize age-dependent trajectories of mean susceptibility, adjusted volume, and total iron content simultaneously in DGM nuclei using quantitative susceptibility mapping (QSM); (2) examine potential contributions of sex related effects to the different age-dependence trajectories of volume and iron deposition; and (3) evaluate the ability of brain age prediction by combining mean magnetic susceptibility and volume of DGM nuclei. Methods: Magnetic susceptibilities and volumetric values of DGM nuclei were obtained from 220 healthy participants (aged 10–70 years) scanned on a 3T MRI system. Regions of interest (ROIs) were drawn manually on the QSM images. Univariate regression analysis between age and each of the MRI measurements in a single ROI was performed. Pearson correlation coefficients were calculated between magnetic susceptibility and adjusted volume in a single ROI. The statistical significance of sex differences in age-dependent trajectories of magnetic susceptibilities and adjusted volumes were determined using one-way ANCOVA. Multiple regression analysis was used to evaluate the ability to estimate brain age using a combination of the mean susceptibilities and adjusted volumes in multiple DGM nuclei. Results: Mean susceptibility and total iron content increased linearly, quadratically, or exponentially with age in all six DGM nuclei. Negative linear correlation was observed between adjusted volume and age in the head of the caudate nucleus (CN; R2 = 0.196, p < 0.001). Quadratic relationships were found between adjusted volume and age in the putamen (PUT; R2 = 0.335, p < 0.001), globus pallidus (GP; R2 = 0.062, p = 0.001), and dentate nucleus (DN; R2 = 0.077, p < 0.001). Males had higher mean magnetic susceptibility than females in the PUT (p = 0.001), red nucleus (RN; p = 0.002), and substantia nigra (SN; p < 0.001). Adjusted volumes of the CN (p < 0.001), PUT (p = 0.030), GP (p = 0.007), SN (p = 0.021), and DN (p < 0.001) were higher in females than those in males throughout the entire age range (10–70 years old). The total iron content of females was higher than that of males in the CN (p < 0.001), but lower than that of males in the PUT (p = 0.014) and RN (p = 0.043) throughout the entire age range (10–70 years old). Multiple regression analyses revealed that the combination of the mean susceptibility value of the PUT, and the volumes of the CN and PUT had the strongest associations with brain age (R2 = 0.586). Conclusions: QSM can be used to simultaneously investigate age- and sex- dependent changes in magnetic susceptibility and volume of DGM nuclei, thus enabling a comprehensive understanding of the developmental trajectories of iron accumulation and volume in DGM nuclei during brain development and aging.

Objective: To explore alterations in thalamic subfield volume and iron accumulation in individuals with post‐traumatic headache (PTH) relative to healthy controls. Background: The thalamus plays a pivotal role in the pathomechanism of pain and headache, yet the role of the thalamus in PTH attributed to mild traumatic brain injury (mTBI) remains unclear. Methods: A total of 107 participants underwent multimodal T1‐weighted and T2* brain magnetic resonance imaging. Using a clinic‐based observational study, thalamic subfield volume and thalamic iron accumulation were explored in 52 individuals with acute PTH (mean age = 41.3; standard deviation [SD] = 13.5), imaged on average 24 days post mTBI, and compared to 55 healthy controls (mean age = 38.3; SD = 11.7) without history of mTBI or migraine. Symptoms of mTBI and headache characteristics were assessed at baseline (0–59 days post mTBI) (n = 52) and 3 months later (n = 46) using the Symptom Evaluation of the Sports Concussion Assessment Tool (SCAT‐5) and a detailed headache history questionnaire. Results: Relative to controls, individuals with acute PTH had significantly less volume in the lateral geniculate nucleus (LGN) (mean volume: PTH = 254.1, SD = 43.4 vs. controls = 278.2, SD = 39.8; p = 0.003) as well as more iron deposition in the left LGN (PTH: T2* signal = 38.6, SD = 6.5 vs. controls: T2* signal = 45.3, SD = 2.3; p = 0.048). Correlations in individuals with PTH revealed a positive relationship between left LGN T2* iron deposition and SCAT‐5 symptom severity score at baseline (r = −0.29, p = 0.019) and maximum headache intensity at the 3‐month follow‐up (r = −0.47, p = 0.002). Conclusion: Relative to healthy controls, individuals with acute PTH had less volume and higher iron deposition in the left LGN. Higher iron deposition in the left LGN might reflect mTBI severity and poor headache recovery. [ABSTRACT FROM AUTHOR]

Background: Widespread white matter (WM) injury is a hallmark feature of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, controversies about the mechanism of WM tract injury exist persistently. Excessive iron accumulation, frequently reported in CADASIL patients, might cause WM tract injury. Purpose: To test the association between iron accumulation and WM tract injury in CADASIL patients. Study Type: Retrospective. Population: A total of 35 CADASIL patients (age = 50.4 ± 6.4, 62.9% female) and 48 healthy controls (age = 55.7 ± 8.0, 68.8% female). Field Strength/Sequence: Diffusion‐weighted spin‐echo echo‐planar sequence; enhanced susceptibility‐weighted angiography (ESWAN) gradient echo sequence on a 3 T scanner. Assessment: The phase images acquired by ESWAN were used to calculate quantitative susceptibility mapping (QSM). Iron accumulation was evaluated in deep gray matters using QSM. WM tract injury was quantified by diffusion metrics based on WM major tracts skeleton. We compared iron deposition between groups and analyzed the correlation between WM tract injury and iron deposition in regions showing significant differences from healthy controls. Exploratory analysis was carried out to investigate whether WM tract injury mediated the relationship between iron deposition and cognitive impairment evaluated by Mini‐Mental State Examination (MMSE). Statistical Tests: General linear model (GLM), partial correlation, stepwise linear regression and mediation analysis were used. The threshold of statistical significance was set as p < 0.05. Results: Compared with healthy controls, CADASIL patients had significantly increased iron deposition in the caudate and putamen. Aberrant iron deposition in these two regions was significantly associated with decreased WM fractional anisotropy (FA) (caudate, r = −0.373； putamen, r = − 0.421), and increased radial diffusivity (RD) (caudate, r = 0.372; putamen, r = 0.386). Furthermore, WM tract injury mediated the relationship between iron deposition and cognitive impairment. Data Conclusion: Patients with CADASIL show increased iron deposition in the caudate and putamen that is correlated to WM tract injury, which may in turn mediate the association with cognitive impairment. Evidence Level: 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Decomposition of methane is the most efficient method for obtaining pure hydrogen. As catalysts for decomposition of methane, in this work, Ni-foam and Ni–Fe composites obtained by the electrochemical method were used for the first time. Thin iron films were electrochemically grown by potential cycling on the Ni-foam surface. The obtained catalysts were tested for decomposition of methane in the temperature range of 650–850 °C and characterized using XRD, RAMAN, SEM, TGA/DTA, H2-TPR and BET analysis of specific surface area and pore size. The effect of cycles (75, 150, and 250) of iron deposition on Ni-foam on its activity in methane decomposition was studied. It has been determined that the highest catalytic activity is observed for the composite, where the iron deposition cycle on nickel foam is 150. The Ni-Fe150 catalyst showed an initial methane conversion of 91% at a temperature of 850 °C, which increased from 60 min to 96.7% and from 180 min to 98.6%, and was stable for 540 min, while the hydrogen yield was 76%. It has been stated that graphite-like carbon is formed on all catalysts, and the largest amount (32%) is formed on Ni-Fe150. The data obtained in the work indicate that the increase in the activity of Ni-Fe150 in the decomposition of methane is associated with the formation of a Ni–Fe alloy and an increase in the reducibility of iron cations in the composition of the Ni–Fe alloy. In addition, the formation of graphite-like carbon with a high defectiveness on the surface of the Ni-Fe150 catalyst promotes the decomposition of methane in areas not covered with carbon. [ABSTRACT FROM AUTHOR]

Objective: To investigate the metabolic pattern of different types of iron accumulation in multiple sclerosis (MS) lesions, and compare metabolic alterations within and at the periphery of lesions and newly emerging lesions in vivo according to iron deposition. Methods: 7 T MR spectroscopic imaging and susceptibility-weighted imaging was performed in 31 patients with relapsing-remitting MS (16 female/15 male; mean age, 36.9 ± 10.3 years). Mean metabolic ratios of four neuro-metabolites were calculated for regions of interest (ROI) of normal appearing white matter (NAWM), “non-iron” (lesion without iron accumulation on SWI), and three distinct types of iron-laden lesions (“rim”: distinct rim-shaped iron accumulation; “area”: iron deposition across the entire lesions; “transition”: transition between “area” and “rim” accumulation shape), and for lesion layers of “non-iron” and “rim” lesions. Furthermore, newly emerging “non-iron” and “iron” lesions were compared longitudinally, as measured before their appearance and one year later. Results: Thirty-nine of 75 iron-containing lesions showed no distinct paramagnetic rim. Of these, “area” lesions exhibited a 65% higher mIns/tNAA (p = 0.035) than “rim” lesions. Comparing lesion layers of both “non-iron” and “rim” lesions, a steeper metabolic gradient of mIns/tNAA (“non-iron” +15%, “rim” +40%) and tNAA/tCr (“non-iron” −15%, “rim” −35%) was found in “iron” lesions, with the lesion core showing +22% higher mIns/tNAA (p = 0.005) and –23% lower tNAA/tCr (p = 0.048) in “iron” compared to “non-iron” lesions. In newly emerging lesions, 18 of 39 showed iron accumulation, with the drop in tNAA/tCr after lesion formation remaining significantly lower compared to pre-lesional tissue over time in “iron” lesions (year 0: p = 0.013, year 1: p = 0.041) as opposed to “non-iron” lesions (year 0: p = 0.022, year 1: p = 0.231). Conclusion: 7 T MRSI allows in vivo characterization of different iron accumulation types each presenting with a distinct metabolic profile. Furthermore, the larger extent of neuronal damage in lesions with a distinct iron rim was reconfirmed via reduced tNAA/tCr concentrations, but with metabolic differences in lesion development between (non)-iron-containing lesions. This highlights the ability of MRSI to further investigate different types of iron accumulation and suggests possible implications for disease monitoring.

Iron dysregulation may attenuate cognitive performance in patients with CADASIL. However, the underlying pathophysiological mechanisms remain incompletely understood. Whether white matter microstructural changes mediate these processes is largely unclear. In the present study, 30 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients were confirmed via genetic analysis and 30 sex- and age-matched healthy controls underwent multimodal MRI examinations and neuropsychological assessments. Quantitative susceptibility mapping and peak width of skeletonized mean diffusivity (PSMD) were analyzed. Mediation effect analysis was performed to explore the interrelationship between iron deposition, white matter microstructural changes and cognitive deficits in CADASIL. Cognitive deterioration was most affected in memory and executive function, followed by attention and working memory in CADASIL. Excessive iron in the temporal-precuneus pathway and deep gray matter specific to CADASIL were identified. Mediation analysis further revealed that PSMD mediated the relationship between iron concentration and cognitive profile in CADASIL. The present findings provide a new perspective on iron deposition in the corticosubcortical circuit and its contribution to disease-related selective cognitive decline, in which iron concentration may affect cognition by white matter microstructural changes in CADASIL.

Lumbar spinal stenosis (LSS) is defined as spinal canal narrowing, resulting in the compression of the nerves traversing the lower back into the leg. Inflammation is the most common cause of LSS. Elevated iron stores are often associated with chronic inflammation resulting in nerve damage-induced pain. Macrophage polarization to either the M1 (inflammatory) or M2 (anti-inflammatory) type is essential for regulating host defenses and promoting tissue repair. However, the precise role of macrophage polarization in iron release or retention in LSS pathophysiology remains elusive. Melittin, a component of bee venom, modulates iron metabolism-related macrophage polarization and is beneficial in LSS. We treated primary peritoneal macrophages with melittin and assessed macrophage polarization by immunofluorescence staining. Melittin (100 and 250 µg/kg) effects on iron deposition-induced macrophage polarization were also evaluated using immunochemistry, real-time PCR, and flow cytometry in an LSS rat model. Locomotor function was assessed using the Basso–Beattie–Bresnahan (BBB) locomotor rating scale, ladder scoring, and von Frey test for up to 3 weeks. Melittin induced M2 polarization of iron-insulted primary macrophages in vitro and increased the proportion of M2 macrophages in the damaged spinal cord in vivo. Moreover, melittin attenuated iron overload-induced M1 polarization by regulating iron metabolism-related genes in rats with LSS. In conclusion, melittin improves locomotor recovery and stimulates axonal growth following LSS. Additionally, it promotes functional recovery in LSS rat models by regulating macrophage iron metabolism, thereby activating M2 macrophages, suggesting its potential application in LSS treatment.

Objective To perform quantitative evaluation of fat and iron deposition in the pancreas of patients with acute pancreatitis (AP) based on the IDEAL-IQ quantitative parameters fat fraction (FF) and relaxation rate (R2*), and to investigate the efficacy of this technique in the diagnosis of AP. Methods A total of 72 patients with AP who were diagnosed and treated in The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from October 2020 to October 2021, were enrolled as case group, and 82 healthy controls who underwent physical examination during the same period of time were enrolled as control group. The abdominal IDEAL-IQ sequence test was performed for both groups using GE 3.0T magnetic resonance instrument, and FF and R2* values were measured on post-processing workstation. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. A receiver operating characteristic (ROC) curve analysis was performed for the parameters with statistical significance, and area under the ROC curve (AUC) was used to evaluate the diagnostic efficacy of parameters. Results Compared with the control group, the case group had significantly higher FF value (Z=-10.01, P < 0.001) and R2* value (Z=-3.73, P < 0.001), while there were no significant differences in FF and R2* values between mild AP and moderate-to-severe AP (P > 0.05). FF value had a sensitivity of 100% and a specificity of 90.2% in the diagnosis of AP, while R2* value had a sensitivity of 48.6% and a specificity of 86.6% in the diagnosis of AP. Conclusion The quantitative parameter FF value of magnetic resonance IDEAL-IQ technique has relatively high sensitivity and specificity in the diagnosis of AP, and it is a specific index for the diagnosis of AP and holds promise for clinical application. [ABSTRACT FROM AUTHOR]

Stroke is a major cause of death and disability worldwide, with the majority of cases resulting from ischemic events due to arterial occlusion. Current therapeutic approaches focus on rapid reperfusion through intravenous thrombolysis and intravascular thrombectomy. Although these interventions can mitigate long-term disability, reperfusion itself may induce neuronal injury. The exact mechanisms underlying neuronal damage following cerebral ischemia have yet to be reported. Recent research suggests that ferroptosis may play a significant role in post-ischemic neuronal death, which can be targeted to prevent neuronal loss. This review explores the three essential hallmarks of ferroptosis: the presence of redox-active iron, the peroxidation of polyunsaturated fatty acid-containing phospholipids, and the loss of lipid peroxide repair capacity. The involvement of ferroptosis in neuronal injury following ischemic stroke is also explored, along with an overview of ferroptosis-associated changes in different ischemic stroke animal models. Furthermore, recent therapeutic interventions targeting the ferroptosis pathway, as well as the opportunities, difficulties, and future directions of ferroptosis-targeted therapies in ischemic stroke, are discussed.

Background and Aims: This study aimed to investigate the effect of iron overload on acetylcholinesterase activity in the frontal lobe tissue of rats with minimal hepatic encephalopathy (MHE) and its relation to cognitive ability. By elucidating the potential mechanisms of cognitive impairment, this study may offer insights into novel therapeutic targets for MHE., Materials and Methods: Twelve Sprague-Dawley rats were purchased and randomly assigned to either the experimental or control group with six rats in each group. Following the induction of MHE, the Morris Water Maze (MWM) was utilized to assess spatial orientation and memory capacity. Subsequently, Magnetic Resonance Imaging (MRI) scans were performed to capture Quantitative Susceptibility Mapping (QSM) images of all rats' heads., Results: Compared to the control group rats, the MHE model rats showed significantly reduced learning and memory capabilities as well as spatial orientation abilities ( P < 0.05). Furthermore, the susceptibility values in the frontal lobe tissue of MHE model rats was significantly higher than that of the control group rats ( P < 0.05), and the corresponding BuChE activity in the frontal lobe extract of model rats was significantly increased while BuChE activity in the peripheral blood serum was significantly decreased compared to the control group rats ( P < 0.05). Meanwhile, our findings indicate a significant positive correlation between latency period and BuChE activity with susceptibility values in the MHE group., Conclusion: The changes in BuChE activity in frontal lobe extract may be related to changes in spatial orientation and behavioral changes in MHE, and iron overload in the frontal lobe tissue may regulate changes in BuChE activity, BuChE levels appear to be iron-dependent., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lan, Yang, Wang, Wang, Huang and Wang.)

Hepatic splenosis, a rare entity, is the ectopic implantation of splenic tissue into the hepatic parenchyma, most often incidentally seen in patients with a history of splenic trauma and splenectomy. We present a unique case of hepatic splenosis in a patient with hemosiderosis and splenectomy following the incidental finding of hepatic masses on pretransplant imaging. Final diagnosis was made based on cross-sectional imaging characteristics matching that of the left upper quadrant splenules alone. We discuss common characteristics of hepatic splenosis on multiple modalities, the effect of iron deposition on the imaging characteristics of hepatic and splenic tissue and how that impacts the differential and diagnosis. This case highlights the unique imaging characteristics hepatic splenosis can have particularly in the setting of hemosiderosis. Hepatic splenosis imaging diagnosis has a significant advantage over tissue diagnosis in terms of decreased risk, time and cost.

Backgroundβ-Thalassemia cellular immunity is associated with iron overload. However, the relationship between varying degrees of iron deposition and T cell immune recovery after allogeneic haematopoietic stem cell transplantation(allo-HSCT) in children remain unclear.MethodsA retrospective analysis was performed on 84 children with β-Thalassemia undergoing sibling allo-HSCT. According to the degrees of hepatic iron deposition, patients were divided into four classes. T lymphocyte counts were measured. Hepatic iron deposition was assessed by T2* MRI. Epstein–Barr virus and cytomegalovirus infection rates and graft-vs.-host disease incidence were recorded.ResultsImmune recovery after allo-HSCT was compared between the two groups. Normal vs. mild group: CD4 cells were higher at 1, 3, and 6 months (P

Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies, such as Parkinson's disease (PD), which are characterized by the loss of dopaminergic neurons in substantia nigra, associated with abnormal iron load. The assessment of presymptomatic biomarkers predicting the onset of neurodegenerative disorders is critical for monitoring early signs, screening patients for neuroprotective clinical trials and understanding the causal relationship between iron accumulation processes and disease development. Here, we used Quantitative Susceptibility Mapping (QSM) and 7T MRI to quantify iron deposition in Nigrosome 1 (N1) in early PD (ePD) patients, iRBD patients and healthy controls and investigated group differences and correlation with disease progression. We evaluated the radiological appearance of N1 and analyzed its iron content in 35 ePD, 30 iRBD patients and 14 healthy controls via T2*-weighted sequences and susceptibility (χ) maps. N1 regions of interest (ROIs) were manually drawn on control subjects and warped onto a study-specific template to obtain probabilistic N1 ROIs. For each subject the N1 with the highest mean χ was considered for statistical analysis. The appearance of N1 was rated pathological in 45% of iRBD patients. ePD patients showed increased N1 χ compared to iRBD patients and HC but no correlation with disease duration, indicating that iron load remains stable during the early stages of disease progression. Although no difference was reported in iron content between iRBD and HC, N1 χ in the iRBD group increases as the disease evolves. QSM can reveal temporal changes in N1 iron content and its quantification may represent a valuable presymptomatic biomarker to assess neurodegeneration in the prodromal stages of PD.

Excessive iron released by hemoglobin and necrotic tissues is the predominant factor that aggravates the outcome of traumatic brain injury (TBI). Regulating the levels of iron and its metabolism is a feasible way to alleviate damage due to TBI. However, the spatial-temporal iron metabolism and iron deposition in neurons and glial cells after TBI remains unclear. In our study, male C57BL/6 mice (8-12 weeks old, weighing 20-26 g) were conducted using controlled cortical impact (CCI) models, combined with treatment of iron chelator deferoxamine (DFO), followed by systematical evaluation on iron deposition, cell-specific expression of iron metabolic proteins and ferroptosis in ipsilateral cortex. Herein, ferroptosis manifest by iron overload and lipid peroxidation was noticed in ipsilateral cortex. Furthermore, iron deposition and cell-specific expression of iron metabolic proteins were observed in the ipsilateral cortical neurons at 1-3 days post-injury. However, iron overload was absent in astrocytes, even though they had intense TBI-induced oxidative stress. In addition, iron accumulation in oligodendrocytes was only observed at 7-14 days post-injury, which was in accordance with the corresponding interval of cellular repair. Microglia play significant roles in iron engulfment and metabolism after TBI, and excessive affects the transformation of M1 and M2 subtypes and activation of microglial cells. Our study revealed that TBI led to ferroptosis in ipsilateral cortex, iron deposition and metabolism exhibited cell-type-specific spatial-temporal changes in neurons and glial cells after TBI. The different effects and dynamic changes in iron deposition and iron metabolism in neurons and glial cells are conducive to providing new insights into the iron-metabolic mechanism and strategies for improving the treatment of TBI. [ABSTRACT FROM AUTHOR]

Objectives: We employed quantitative susceptibility mapping (QSM) to assess iron deposition in parkinsonian disorders and explored whether combining QSM values and neurofilament light (NfL) chain levels can improve the accuracy of distinguishing Parkinson's disease (PD) from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Materials and methods: Forty-seven patients with PD, 28 patients with MSA, 18 patients with PSP, and 28 healthy controls (HC) were enrolled, and QSM data were reconstructed. Susceptibility values in the bilateral globus pallidus (GP), putamen (PUT), caudate nucleus (CN), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN) were obtained. Plasma NfL levels of 47 PD, 18 MSA, and 14 PSP patients and 22 HC were measured by ultrasensitive Simoa technology. Results: The highest diagnostic accuracy distinguishing MSA from PD patients was observed with increased susceptibility values in CN (AUC: 0.740). The susceptibility values in RN yielded the highest diagnostic performance for distinguishing PSP from PD patients (AUC: 0.829). Plasma NfL levels were significantly higher in the MSA and PSP groups than in PD and HC groups. Combining the susceptibility values in the RN and plasma NfL levels improved the diagnostic performance for PSP vs. PD (AUC: 0.904), whereas plasma NfL levels had higher diagnostic accuracy for MSA vs. PD (AUC: 0.877). Conclusion: The exploratory study indicates different patterns of iron accumulation in deep gray matter nuclei in Parkinsonian disorders. Combining QSM values with NfL levels may be a promising biomarker for distinguishing PSP from PD, whereas plasma NfL may be a reliable biomarker for differentiating MSA from PD. QSM and NfL measures appeared to have low accuracy for separating PD from controls. [ABSTRACT FROM AUTHOR]

Background: PLA2G6-associated neurodegeneration (PLAN) is a heterogeneous group of neurodegenerative diseases caused by biallelic PLA2G6 mutations, covering diseases such as infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD), dystonia parkinsonism (DP), and autosomal recessive early-onset parkinsonism (AREP). The study aims to report the clinical and genetic features of a series of PLAN patients. Methods: The clinical and radiological findings of five Chinese patients from three families were collected. Whole-exome next generation sequencing (NGS) was applied to identify the genetic causes. Co-segregation analysis of the detected candidate variants were performed in their families. The pathogenicity of identified novel variants was predicted by in silico analysis. Results: NGS revealed compound heterozygous variants of PLA2G6 gene in all five patients. There were six PLA2G6 variants identified, including two known variants (c.116G>A, c.238G>A) and four novel variants (c.2120dupA, c.2071C>G, c.967G>A, c1534T>A). ACMG predicts c.2120dupA to be pathogenic, c.2071C>G and c.1534T>A to be likely pathogenic, and c1534T>A to be of uncertain significance. Clinically, four patients fell into the diagnosis of ANAD, and 1 into the diagnosis of AREP. Brain imaging revealed cerebellar atrophy, iron deposition in bilateral globus pallidus, and substantia nigra in three cases. Conclusions: Four novel pathogenic variants were discovered and the pathogenic variant spectrum of the PLA2G6 gene was expanded. [ABSTRACT FROM AUTHOR]

Purpose: To explore the feasibility of susceptibility-weighted imaging (SWI) for evaluating renal iron overload. Methods: Twenty-eight rabbits were randomly assigned into control (n = 14) and iron (n = 14) group. In the 0th week, the study group was injected with iron dextran. Both groups underwent SWI examination at the 0th, 8th, and 12th week. The signal intensity (SI) of cortex and medulla was assessed. Angle radian value (ARV) calculated with phase image was taken as the quantitative value for cortical and medullary iron deposition. After the 12th week, the left kidneys of rabbits were removed for pathology. The difference in the ARV among three groups was analyzed using Kruskal-Wallis test. The difference of the iron content between two groups was analyzed through independent sample t-test. Results: In the iron group: at the 12th week, eight rabbits were found to have decreased SI of only cortex, and the other six rabbits had decreased SI of cortex and medulla by the same degree; the ARV of cortex at the 8th and 12th week was significantly higher than that of the 0th week (P < 0.05); the ARV of the six rabbits' medulla at the 12th week was significantly higher than that of the 0th week, 8th week, and the other eight rabbits at the 12th week (P < 0.05); at the 12th week, eight rabbits (iron group) were found to have many irons only deposit in the cortex, and the others were found to have many irons deposit in both cortex and medulla; the iron content of cortex and six rabbits' medulla in the iron group was significantly higher than that of the control (P < 0.05). Conclusion: The ARV of SWI can be used to quantitatively assess the excess iron deposition in the kidneys. Excessive iron deposition mainly occurs in the cortex or medulla and causes their SWI SI to decrease. [ABSTRACT FROM AUTHOR]