Combined Application of Quantitative Susceptibility Mapping and Diffusion Kurtosis Imaging Techniques to Investigate the Effect of Iron Deposition on Microstructural Changes in the Brain in Parkinson’s Disease

Yang, Lin; Cheng, Yan; Sun, Yi; Yang, Xuan; Niu, Jianping; Guan, Jitian; Rong, Yunjie; Jia, Yanlong; Zhuang, Zerui; Yan, Gen; Wu, Renhua

doi:10.3389/fnagi.2022.792778

Cited by 6 publications

(3 citation statements)

References 74 publications

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“…A recent systematic review (Ravanfar et al, 2021 ) examining 37 studies provides valuable insight into susceptibility changes in PD. The great majority of these studies reported increased susceptibility in the brains of PD patients, mainly in the SN (30 studies) but also in the red nucleus (seven studies), putamen (Xu et al, 2021 ), globus pallidus (Yang et al, 2022 ), caudate nucleus (Uchida et al, 2019 ), and thalamus (Shahmaei et al, 2019 ). Only a few studies documented cortical increase of susceptibility, mainly in the frontal, parietal, temporal, and insular cortices (Acosta‐Cabronero et al, 2017 ; Thomas et al, 2021 ; Uchida et al, 2019 ; Zhao, Qu, et al, 2022 ), predominantly in patients with longer disease duration (7, 6, and 4 years) and/or cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

Whole brain pattern of iron accumulation in REM sleep behavior disorder

Varga,

Keller,

Robinson

et al. 2024

Human Brain Mapping

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Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole‐brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility‐weighted images were acquired and processed to space standardized QSM. Voxel‐based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family‐wise error‐corrected p‐values <.05. Whole‐brain analysis showed increased susceptibility in the bilateral fronto‐parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto‐parietal cortex involvement than incidental early‐stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.

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Section: Discussionmentioning

confidence: 99%

Whole brain pattern of iron accumulation in REM sleep behavior disorder

Varga,

Keller,

Robinson

et al. 2024

Human Brain Mapping

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“…In addition, these sequences are sensitive to iron deposition but cannot distinguish their boundaries well. Therefore, the dense and reticular zones of the substantia nigra are mostly used to analyze the iron deposition content to judge the degree of neuronal degeneration ( 17 , 18 ).…”

Section: Discussionmentioning

confidence: 99%

Application value of multiparametric MRI for evaluating iron deposition in the substantia nigra in Parkinson's disease

Cao

Huang²,

Tang³

et al. 2023

Front. Neurol.

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ObjectiveThis study aimed to investigate the application value of multi-parametric magnetic resonance imaging (MRI) in the diagnosis of iron deposition in the substantia nigra dense zone in Parkinson's disease (PD) and to evaluate the diagnostic value of the correlation among multi-parametric imaging indicators, clinical stage, and disease duration.Materials and methodsThirty-six patients with clinically confirmed PD and 36 healthy controls were enrolled. The disease course was recorded, and PD severity was graded using the Hoehn–Yahr (H–Y) scale. All subjects underwent magnetic sensitivity weighted imaging (SWI), neuromelanin magnetic resonance imaging (NM-MRI), and a T2*mapping sequence. Based on the fusion of the NM-MRI and SWI amplitude maps, phase maps, and T2*MAPPING value maps, NM-MRI was used to delineate the dense zone of the substantia nigra, which was divided into three sub-regions: upper, middle, and lower. In this way, the amplitude, phase, and R2* values of each sub-region and the average value of the sum of the three sub-regions were obtained simultaneously in the SWI amplitude, phase, and T2*MAPPING maps. The multi-parameter imaging indices were compared between the two groups, and the correlation between them and clinical indices was evaluated in the PD group.ResultsThe upper (amplitude, phase value, R2* value), middle, and lower (amplitude) right substantia nigra compact zones were significantly different between the PD and control groups. The upper (phase value, R2* value) and middle (amplitude) areas of the left substantia nigra compact zone were also significantly different between the two groups (all P < 0.05). The mean values (amplitude, phase value, R2* value) of the right substantia nigra densification zone and the mean values (phase value) of the left substantia nigra densification zone were also significantly different (all P < 0.05). Amplitudes in the middle and lower parts of the right substantia nigra dense zone were negatively correlated with the H–Y grade (middle: r = −0.475, P = 0.003; lower: r = −0.331, P = 0.049). Amplitudes of the middle and lower parts of the dense zone of the left substantia nigra were negatively correlated with the H–Y grade (middle: r = −0.342, P = 0.041; lower: r = −0.399, P = 0.016). The average amplitude of the right substantia nigra compact zone was negatively correlated with the H–Y grade (r = −0.367, P = 0.027). The average R2* value of the compact zone of the left substantia nigra was positively correlated with the H–Y grade (r = 0.345, P = 0.040).ConclusionMultiparametric MRI sequence examination has application value in the evaluation of iron deposition in the dense zone of the substantia nigra in PD. Combined with NM-MRI, fusion analysis is beneficial for accurately locating the substantia nigra compact zone and quantitatively analyzing the iron deposition in different sub-regions. Quantitative iron deposition in the middle and lower parts of the substantia nigra dense zone may become an imaging biological indicator for early diagnosis, severity evaluation, and follow-up evaluation of PD and is thus conducive for clinical diagnosis and treatment evaluation.

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“…Iron deposition significantly increases in the bilateral SN, red nucleus (RN), putamen, and globus pallidus of PD patients. Iron deposition is likely a common mechanism underlying microstructural alterations in the SN and putamen of PD patients (Yang et al 2022 ). The dysfunction of dopaminergic striatal pathways and the loss of cells in the SN pars compacta are intricately linked to the elevated iron content in the SN (Biondetti et al 2021 ).…”

Section: Iron Deposition and Pdmentioning

confidence: 99%

Iron Deposition in Parkinson’s Disease: A Mini-Review

Zeng,

Cai,

Zhang

et al. 2024

Cell Mol Neurobiol

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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. Graphical Abstract 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.

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Combined Application of Quantitative Susceptibility Mapping and Diffusion Kurtosis Imaging Techniques to Investigate the Effect of Iron Deposition on Microstructural Changes in the Brain in Parkinson’s Disease

Cited by 6 publications

References 74 publications

Whole brain pattern of iron accumulation in REM sleep behavior disorder

Whole brain pattern of iron accumulation in REM sleep behavior disorder

Application value of multiparametric MRI for evaluating iron deposition in the substantia nigra in Parkinson's disease

Iron Deposition in Parkinson’s Disease: A Mini-Review

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