Iron deposition and Parkinson disease / 中华行为医学与脑科学杂志

Iron is an essential metal element for human body. It is involved in many important biological metabolic processes. Iron metabolism in the central nervous system has a strict regulatory mechanism. Iron deposition occurs when the homeostasis of iron metabolism is disrupted, leading to an increase in neuronal iron uptake and a decrease in iron discharge. Aging cells develop specific iron deposition, and excessive iron produce reactive oxygen species, which can damage DNA. Highly reactive aldehydes result in irreversible modification of proteins. Stored proteins were stimulated to release iron, which in turn produces more reactive oxygen species, ultimately leading to iron-mediated cell death and neurological dysfunction. The widely used methods for assessing iron deposition include susceptibility weighted imaging and quantitative susceptibility mapping. Abnormally elevated brain iron deposition has been observed in a variety of central nervous system diseases, especially in Parkinson disease. Iron deposition plays an important role in early diagnosis, differential diagnosis, disease evaluation and monitoring and therapeutic effect evaluation of Parkinson disease. This article reviews the research progress of iron deposition in Parkinson disease.

Value of central vein sign and iron deposition to differentiate multiple sclerosis from neuromyelitis optica spectrum disorder / 中华放射学杂志

Objective:To investigate the value of central vein sign (CVS) and iron deposition on quantitative susceptibility imaging (QSM) of 3.0 T MRI in differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disease (NMOSD).Methods:This study was a retrospective study. A total of 54 MS patients and 49 NMOSD patients were enrolled from July 2018 to December 2020 in People′s Hospital of Leshan and the First Affiliated Hospital of Chongqing Medical University. All patients underwent conventional MRI and three-dimensional enhanced T 2*-weighted angiography (3D-ESWAN), and ESWAN-filtered phase and QSM were reconstructed from 3D-ESWAN data. First, brain lesions of MS and NMOSD were screened on proton density (PD)-T 2WI, and then the location of lesions, CVS and nodular/annular iron deposition were observed on phase and QSM images. The χ 2 test was used to compare the differences in intracranial lesion location, CVS and iron deposition between MS and NMOSD patients. Receiver operating characteristic curve and area under the curve (AUC) were used to assess the efficiency of CVS and QSM iron deposition to differentiate MS from NMOSD. Results:A total of 968 MS lesions were observed in 54 MS patients, of which CVSs were found in 354 lesions and 227 CVSs were located around the lateral ventricles, 117 in deep white matter (DWM) and 10 in the cortex/subcortex; 372 lesions showed nodular iron deposition, and 193 lesions ring iron deposition on QSM. Totally 247 brain lesions were observed in 41 of 48 patients with NMOSD, of which CVSs were found in 4 lesions and 1 located around the lateral ventricle, 3 located in the DWM; 3 lesions showed nodular iron deposition on QSM. There were significant differences in cortex/subcortex lesions, CVS and iron deposition between MS and NMOSD patients (χ 2 were 29.33, 115.66 and 258.21, respectively, all P<0.001). The AUC of CVS for differentiating MS from NMOSD was 0.941 (95%CI 0.887-0.994), with a sensitivity of 96.3% and a specificity of 91.8%; the AUC of iron deposition for differentiating MS from NMOSD was 0.969 (95%CI 0.930-1.000), with a sensitivity of 100% and a specificity of 93.9%. Conclusion:CVS and iron deposition on 3.0 T MRI are distinct radiologic features of MS lesions from those of NMOSD lesions, and have certain value in the differential diagnosis.

Value of magnetic resonance imaging in assessment of iron deposition among patients with hepatic alveolar echinococcosis: a preliminary evaluation / 中国血吸虫病防治杂志

Objective To assess the value of MRI combined with serum ferritin analysis in measurement of hepatic iron deposition among patients with hepatic alveolar echinococcosis. Methods A total of 96 patients with definitive diagnosis of hepatic alveolar echinococcosis and 30 healthy volunteers were enrolled and underwent routine 1.5T MR scanning, and all laboratory examination data were captured. The liver-to-muscle signal intensity ratio, serum ferritin level and liver functions were analyzed. Results The liver-to-muscle signal intensity ratio was (1.95 ± 0.57) in patients with hepatic alveolar echinococcosis and (2.22 ± 0.28) in healthy volunteers (t = 2.022, P < 0.05), and the liver-to-muscle signal intensity ratio was negatively associated the serum ferritin level in patients with hepatic alveolar echinococcosis (rs = –0.446, P < 0.01). Conclusions Abnormal iron deposition is detected in the liver of patients with hepatic alveolar echinococcosis, and serum ferritin level may be helpful for the identification of abnormal iron deposition in the liver of patients with hepatic alveolar echinococcosis. The liver-to-muscle signal intensity ratio measured by MRI may be a non-invasive approached used to assess the hepatic iron deposition in patients with hepatic alveolar echinococcosis.

The application value of mDIXON?Quant sequence in the quantification of liver and pancreatic iron deposition in blood transfusion?dependent diseases / 中华放射学杂志

Objective To explore the clinical value of mDIXON?Quant sequence in the quantitative evaluation of transfusion dependent patients with liver and pancreas iron deposition. Method Prospective collection of 34 transfusion dependent patients from December 2016 to May 2018 in Tianjin First Central Hospital who had not undergone iron chelation therapy was conducted in this study. According to the volume of blood transfusion,the subjects were divided into small amount of blood transfusion group (23 cases with blood transfusion of 2 000 to 5 000 ml within 3 years) and massive blood transfusion group (11 cases with blood transfusion of greater than 5 000 ml within 3 years). All patients underwent MR examinations using a Philips Ingenia 3.0 T MR scanner with multi?echo 3D?fast field echo (FFE) and 3D mDIXON?Quant protocols. For 3D multi?echo FFE images, the R2*(R2*=1/T2*) of liver and pancreas were calculated voxel by voxel. For mDIXON?Quant images,the dR2*(d R2*=1/dT2*),which was different from the R2*with 3D multi?echo FFE,was calculated within liver and pancreas voxel by voxel. Pearson correlation was performed to investigate the relationship between the R2*value and dR2*value of liver and pancreas in each group,and between the R2*(and dR2*) of liver and pancreas with the volume of blood transfusion. A paired ttest was used to compare the values of R2* and dR2* in the same patient. Results For small amount of blood transfusion group: liver and pancreas R2* and dR2* values were significantly correlated with the correlation coefficients of 0.993 and 0.962 respectively. There was no correlation between the value of liver and pancreas and the amount of blood transfusion (P>0.05). There was no significant difference in R2*and dR2*values in liver and pancreas (P>0.05). For massive blood transfusion group:when T2*was smaller than 1.8 ms, the SNR of T2*maps was lower than that of dT2*maps, and the noise seriously affects the T2*measurements. When T2*was greater than 1.8 ms:liver and pancreas R2*and dR2*values were significantly correlated with the correlation coefficients of 0.991 and 0.989 respectively. Liver R2* and dR2* value were correlated with the volume of blood transfusion with the correlation coefficients of 0.527 and 0.639 respectively. Pancreas R2* and dR2* value were correlated with the volume of blood transfusion with the correlation coefficients of 0.590 and 0.602 respectively. There was statistical difference in R2*value of liver and dR2*value in paired t test (P<0.05),but there was no significant difference in R2*value of pancreas and dR2* value of pancreas (P>0.05). Conclusions Both multi?echo 3D FFE and mDIXON?Quant sequences can be applied for the evaluation of organ iron deposition.The mDIXON?quant sequence has advantages in heavy liver and pancreatic iron quantification

The value of MR T2* in evaluation of liver iron overload related to long term blood transfusion / 实用放射学杂志

Objective To investigate the value of MR T2* in evaluation of liver iron overload caused by long term blood transfusion.Methods Thirty one patients with long term blood transfusion were collected.Both serum ferritin(SF)and CRP levels were measured and the adjusted serum ferritin(ASF)concentration was calculated.MRI of the maximum cross-sectional liver was performed using a 1.5T scanner (Siemens Avanto).The T2* value of the liver was measured,and the correlation analysis was carried out.Twenty one normal volunteers served as controls.The transfusion group was divided into iron overload group and non overload group,and differences between groups were analyzed.Results The correlation coefficient in 31 patients between liver T2* value and SF,ASF and blood transfusion volume was-0.695,-0.728 and -0.657 respectively,and the difference was statistically significant(P<0.05).The correlation coefficient between SF and blood transfusion volume was 0.518,and the difference was statistically significant(P<0.05).There was difference in T 2* value between three groups.Conclusion MR T2* has some practical value in the evaluation of liver iron overload in patients with long term blood transfusion.

Reduction of iron deposition by verbascoside in HO-1 overexpression rats astrocytes / 中国药学杂志

OBJECTIVE: To investigate the effect of verbascoside on iron deposition of astrocyte cell overexpressing heme oxygenase-1 gene, and to seek new drug in treating Alzheimer's disease. METHODS: Primary cultured astrocyte cells of rats were cultured and purified in vitro. With gene recombination and transfer techniques, transfect HO-1 gene into primary cultured astrocyte cells. HO-1 transfected astrocyte were then treated by different concentrations of verbascoside. Proliferation of cell was measured by CCK-8 assay and expression of HO-1 protein was analyzed by Western blotting. Iron deposition was also visualized by Perl's Prussian blue stain. RESULTS: Immunofluorescence staining showed that most of the cells were GFAP-postitive and the purity was over 95%. The expression of HO-1 protein was increased in HO-1 injury model of astrocyte. Treatment of verbascoside with variable concentration caused the decrease of HO-1 protein expression more or less and reduction of iron deposition in transfected cells(20 μmol·L-1 reducing 47.69%, 40 μmol·L-1 reducing 51.63%). CONCLUSION: Verbascoside could enhance astrocyte cell resistance against injury induced by overexpression of heme oxygenase-1 gene.

The research of age-related iron deposition in the brain using T2 * value / 实用放射学杂志

Objective To analyze quantitatively the iron deposition in deep brain gray nucleus and frontal white matter in healthy population and to explore its correlation with age using ESWAN with 3.0 Tesla scanner.Methods 157 healthy subjects (age 20 to 85)had been manned with routine sequences and ESWAN sequences.The subjects were divided into 6 groups according to their ages:Group A (age 20-29),Group B (age 30-39),Group C (age 40-49),Group D (age 50-59),Group E (age 60-69)and Group F (age ≥70).T2 ?value was measured in both sides of the frontal white matter,red nucleus,substantia nigra pars reticulate,substantia nigra pars compacta,putamen,globus pallidus,head of caudate nucleus and thalamus,and the correlations between the T2 ? value and age were also analyzed.Results The T2 ? value of globus pallidus and substantia nigra pars reticulata were the lowest.The highest T2 ?value was observed in the frontal white matter.The difference of T2 ? value among some age groups had statistical significance in red nucleus putamen,globus pallidus,head of caudate nucleus and thalamus (P <0.05).Obvious negative correlations between age and T2 ? value was shown in red nucleus (r=-0.258),substantia nigra pars reticulate (r=-0.229),substantia nigra pars compacta (r=-0.231), putamen(r=-0.584),globus pallidus (r=-0.320),and head of caudate nucleus (r=-0.437,P <0.001),while positive correlation was displayed in thalamus (r=0.31 9),frontal white matter (r=0.161,P <0.05 ).Conclusion ESWAN can clearly display the morphology of cerebral nuclei,evaluate the brain iron content accurately and present the age-related iron concentration changes.

3.0T MR Susceptibility-weighted Imaging for Substantia Nigra Pars Compacta in Primary Parkinson’s Disease / 昆明医科大学学报

Objective To evaluate the application of measurement of T2*value,width of substantia nigra pars compacta (SNc) and the ratio of the width to the midbrain diameter in diagnosing Parkinson disease (PD) in early stage with susceptibility weighted imaging ( SWI) by 3T MR. Methods 59 patients with early stage idiopathic PD patients and 59 healthy controls,ranging in same ages and gender,had been scanned with routine sequences and SWI sequences by 3T MR. T2*value,width and the ratio of the width to the midbrain diameter of SNc were measured. The results of measurement were analyzed and compared. Results (1) The T2*values, width and the ratio of the width to the midbrain diameter was decreased in homolateral side SNc of symptoms of subjects with PD compared with the healthy controls ( 0.05) . Conclusion Measurement of T2*value, width and the ratio of the width to the midbrain diameter of SNc with SWI is reliable to diagnose PD.

Using susceptibility-weighted images to quantify iron deposition in Alzheimer’s disease / 实用放射学杂志

Objective To quantify iron deposition in Alzheimer’s disease (AD),amnestic mild cognitive impairment (aMCI), and normal old people using susceptibility weighted imaging (SWI).Methods Sixty participants (22 aMCI,20 AD,18 normal con-trols)underwent conventional magnetic resonance imaging sequences and SWI using axial/oblique coronal sequences.Phase images were used to calculate bilateral iron deposition in 1 8 regions of interest (ROI)of every participant.The radian angle values were cal-culated and compared between the three groups.Results The radian angle value difference was significant between the aMCI and control groups in the left (L)-hippocampus,L-head of the caudate nucleus,R/L-lenticular nucleus ROIs.The radian angle value difference was significant between the AD and aMCI groups in the R/L-cerebellar hemisphere,R/L-hippocampus,R-red nucleus, R/L-thalamus and splenium of corpus callosum ROIs.Pearson correlation coefficients of the mini-mental state examination (MMSE)scores and many ROIs were significant.Conclusion Iron depositions in the hippocampus,head of the caudate nucleus,len-ticular nucleus and thalamus are significantly different between individuals with aMCI,AD and controls.Using SWI to quantify the iron deposition is a useful tool in detecting aMCI and AD.

Investigation on Positive Correlation of Increased Brain Iron Deposition with Cog,nitive Imp*airment in Alzheimer Disease by Using Quantitative MR R2 Mapping / 华中科技大学学报（医学）（英德文版）

Brain iron deposition has been proposed to play an important role in the pathophysiology of Alzheimer disease (AD).The aim of this study was to investigate the correlation of brain iron accumulation with the severity of cognitive impairment in patients with AD by using quantitative MR relaxation rate R2' measurements.Fifteen patients with AD,15 age- and sex-matched healthy controls,and 30 healthy volunteers underwent 1.5T MR multi-echo T2 mapping and T2* mapping for the measurement of transverse relaxation rate R2'(R2'=R2*-R2).We statistically analyzed the R2' and iron concentrations of bilateral hippocampus (HP),parietal cortex (PC),frontal white matter (FWM),putamen (PU),caudate nucleus (CN),thalamus (TH),red nucleus (RN),substantia nigra (SN),and dentate nucleus (DN)of the cerebellum for the correlation with the severity of dementia.Two-tailed t-test,Student-Newman-Keuls test (ANOVA) and linear correlation test were used for statistical analysis.In 30 healthy volunteers,the R2' values of bilateral SN,RN,PU,CN,globus pallidus (GP),TH,and FWM were measured.The correlation with the postmortem iron concentration in normal adults was analyzed in order to establish a formula on the relationship between regional R2' and brain iron concentration.The iron concentration of regions of interest (ROI) in AD patients and controls was calculated by this formula and its correlation with the severity of AD was analyzed.Regional R2' was positively correlated with regional brain iron concentration in normal adults (r=0.977,P＜0.01).Iron concentrations in bilateral HP,PC,PU,CN,and DN of patients with AD were significantly higher than those of the controls (P＜0.05); Moreover,the brain iron concentrations,especially in parietal cortex and hippocampus at the early stage of AD,were positively correlated with the severity of patients' cognitive impairment (P＜0.05).The higher the R2' and iron concentrations were,the more severe the cognitive impairment was.Regional R2' and iron concentration in parietal cortex and hippocampus were positively correlated with the severity of AD patients' cognitive impairment,indicating that it may be used as a biomarker to evaluate the progression of AD.