Characterizing brain mineral deposition in patients with Wilson disease using susceptibility-weighted imaging

Zhou, Xiangxue; Qin, Haolin; Li, Xunhua; Huang, Hongbo; Liang, Yingying; Liang, Xiaoyan; Pu, Xiao‐Yong

doi:10.4103/0028-3886.141221

Cited by 12 publications

(13 citation statements)

References 14 publications

(27 reference statements)

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“…Although a negative correlation between changes in the SWI signal and iron accumulation has been confirmed (Zhang et al, ), the utility of SWI in evaluating copper deposition and associated pathological processes has yet to be established. Abnormal SWI signals in the brain of WD patients were previously thought to reflect both iron and copper deposition (Lee et al, ; Zhou et al, ). But the correlation between copper deposition and CP values should be confirmed by pathological research.…”

Section: Discussionmentioning

confidence: 99%

“…Susceptibility-weighted imaging (SWI) is a sensitive method for detecting metals, particularly iron, that has been used for in vivo assessment of brain metal concentrations (Rossi, Ruottinen, Soimakallio, Elovaara, & Dastidar, 2013). Abnormal SWI signals in the brains of WD patients have been previously reported (Lee et al, 2012;Zhou et al, 2014). However, the characteristics of metal deposition in WD on SWI and the utility of this technique for evaluating copper deposition require further investigation.…”

Section: Introductionmentioning

confidence: 91%

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Injury factors and pathological features of toxic milk mice during different disease stages

Zhou

Chen

et al. 2019

Brain and Behavior

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ObjectiveTo evaluate different injury factors and pathological characteristics of the brain at different disease stages in toxic milk (TX) mice, an animal model of Wilson's disease (WD).MethodsThirty TX mice (10 each at 3, 6 and 12 months old) and 30 age‐matched C57 mice were used in this study. Corrected phase (CP) values were determined from susceptibility‐weighted images. Myelin content was determined by measuring inhibition optical density values of Luxol fast blue‐stained sections. Neurofilament protein 68 kDa (NF68), β‐amyloid precursor protein (β‐APP), and myelin basic protein (MBP) levels, as well as copper and iron content, in brain nuclei of the TX mouse were evaluated. Gene amplification ratios for catalase (CAT), GSH peroxidase (GSH‐PX), nitric oxide synthase (NOS), and superoxide dismutase (SOD) in mouse brain were also determined.ResultsCompared with C57 mice, neuronal cell counts were decreased in 12‐months‐old TX mice (p = .011). Myelin content was decreased in the lenticular nucleus (p = .029), thalamus (p = .030), and brainstem (p = .034) of 6‐months‐old TX mice; decreases in the corresponding nuclei (p = .044, .037, and .032, respectively) were also found in 12‐months‐old TX mice. MBP values were lower in the lenticular nucleus and thalamus (p = .027 and .016, respectively) of 6‐months‐old TX mice and in the corresponding nuclei (p = .24 and .040) of 12‐months‐old TX mice. NF‐68 values were lower in the lenticular nucleus and thalamus (p = .034 and .037, respectively) of 6‐months‐old TX mice and in the corresponding nuclei (p = .006 and .012) of 12‐months‐old TX mice. β‐APP values were higher in the thalamus of 6‐months‐old (p = .037) and 12‐months‐old (p = .012) TX mice. Iron content was higher in the lenticular nucleus, thalamus, and cerebellum (p = .044, .038, and .029, respectively) of 6‐months‐old TX mice and in the corresponding nuclei (p = .017, .024, and .029) of 12‐months‐old TX mice. The NOS gene amplification multiple was higher (p = .039), whereas the SOD1 gene amplification multiple was lower (p = .041) in 12‐months‐old TX mice. There was no correlation between metal content or oxidation index and pathological index.ConclusionsThe pathological characteristics of the brains of TX mice may differ at different ages. Different pathogenic factors, including copper and iron deposition and abnormal oxidative stress, are present at different stages.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Injury factors and pathological features of toxic milk mice during different disease stages

Zhou

Chen

et al. 2019

Brain and Behavior

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“…Copper is the main building block in more than 30 enzymes and has a role in angiogenesis (Mulware, ). Copper also changes between oxidation states, Cu + and Cu 2+ , that generates reactive oxygen species (ROS) (Thomas and Jankovic, ; Ebrahim et al, ; Sian‐Hülsmann et al, ; Zheng and Monnot, ; Mulware, ; Zhou et al, ). Therefore, an increase in copper could lead to excessive ROS formation.…”

Section: Resultsmentioning

confidence: 99%

Trace Element Concentration Changes in Brain Tumors: A Review

Cilliers

Muller

Page

2019

The Anatomical Record

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Trace elements have been implicated in cancer, since the levels differ between cancerous and noncancerous tissue, different cancer types, and different malignancy grades. However, few studies have been conducted on trace element concentrations in brain tumors. Thus, this study aims to review the available literature on trace element changes related to brain tumors, and to identify gaps in the literature. A literature search was done on Google Scholar and PubMed from their start date to January 2018, using terms related to trace element concentration and brain tumors. All brain tumor types were included, and articles could be published in any year. From this search, only 11 articles on this topic could be found. Tumors had significantly higher concentrations of arsenic, thorium, lanthanum, lutetium, cerium, and gadolinium compared to control brain samples. Compared to adjacent tissue, tumor tissue indicated increased magnesium, decreased copper, and contradicting results for zinc. Furthermore, the higher the malignancy grade, the lower the calcium, cadmium, iron, phosphorus and sulfur concentration, and the higher the mercury, manganese, lead, and zinc concentrations. In conclusion, altered trace element levels differ amongst different tumor types, as well as malignancy grades. Consequently, it is impossible to compare data from these studies, and available data are still considerably inconclusive. Ideally, future studies should have a sufficient samples size, compare different tumor types, and compare tumors with adjacent healthy tissue as well as with samples from unaffected matched brains.

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“… 29 , 30 Furthermore, SWI technique may indicate mineral deposition in caudate nuclei, globus pallidus, putamen, thalamus, substantia nigra, and red nucleus based on the phase values in WD. 30 – 32 With the introduction of QSM technique, it has been possible to map magnetic susceptibility of brain tissue in vivo . QSM is a post-processing technique that inverts the phase data to magnetic susceptibility maps.…”

Section: Discussionmentioning

confidence: 99%

Magnetic Susceptibility Changes in the Basal Ganglia and Brain Stem of Patients with Wilson’s Disease: Evaluation with Quantitative Susceptibility Mapping

et al. 2018

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Objectives:Wilson’s disease (WD) is characterized with the accumulation of copper in the liver and brain. The objective of this study is to quantitatively measure the susceptibility changes of basal ganglia and brain stem of pediatric patients with neurological WD using quantitative susceptibility mapping (QSM) in comparison to healthy controls.Methods:Eleven patients with neurological WD (mean age 15 ± 3.3 years, range 10–22 years) and 14 age-matched controls were prospectively recruited. Both groups were scanned on a 1.5 Tesla clinical scanner. In addition to T1- and T2-weighted MR images, a 3D multi-echo spoiled gradient echo (GRE) sequence was acquired and QSM images were derived offline. The quantitative measurement of susceptibility of corpus striatum, thalamus of each hemisphere, midbrain, and pons were assessed with the region of interest analysis on the QSM images. The susceptibility values for the patient and control groups were compared using two-sample t-test.Results:One patient with WD had T1 shortening in the bilateral globus pallidus. Another one had hyperintensity in the bilateral putamen, caudate nuclei, and substantia nigra on T2-weighted images. The rest of the patients with WD and all subjects of the control group had no signal abnormalities on conventional MR images. The susceptibility measures of right side of globus pallidus, putamen, thalamus, midbrain, and entire pons were significantly different in patients compared to controls (P < 0.05).Conclusion:QSM method exhibits increased susceptibility differences of basal ganglia and brain stem in patients with WD that have neurologic impairment even if no signal alteration is detected on T1- and T2-weighted MR images.

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Characterizing brain mineral deposition in patients with Wilson disease using susceptibility-weighted imaging

Abstract: There might be abnormal iron metabolism in patients with WD. The decreased CP values might reflect a deposition of both copper and iron. SWI may be more sensitive than the ordinary MRI. The mineral deposition may contribute to the neural symptoms.

Cited by 12 publications

References 14 publications

Injury factors and pathological features of toxic milk mice during different disease stages

Injury factors and pathological features of toxic milk mice during different disease stages

Trace Element Concentration Changes in Brain Tumors: A Review

Magnetic Susceptibility Changes in the Basal Ganglia and Brain Stem of Patients with Wilson’s Disease: Evaluation with Quantitative Susceptibility Mapping

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