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Increased iron-deposition in lateral-ventral substantia nigra pars compacta: A promising neuroimaging marker for Parkinson's disease.

ABSTRACT: BACKGROUND:To date there are no validated MRI biomarkers to assist diagnosis of Parkinson's disease (PD). Our aim was to investigate PD related iron changes in the substantia nigra pars compacta (SNpc) as defined by neuromelanin-sensitive MR contrast. METHODS:Thirty-nine PD participants and 33 healthy controls were scanned at 3.0-T using a 16-echo gradient echo sequence to create R2* maps for the evaluation of iron content to find the overlap with a neuromelanin based SNpc mask. The SNpc overlap percentage with the R2* map, and the R2* values in both the whole SNpc and the overlap volume were compared between PD and control groups, and correlated with clinical features for PD participants. Finally, the diagnostic performance of the SNpc overlap percentage was evaluated using ROC analysis. RESULTS:PD related iron changes mostly occur in the lateral-ventral part of the neuromelanin SNpc. The R2* values in the whole SNpc and the SNpc overlap volume, and the SNpc overlap percentage were larger in PD participants than in controls. Furthermore, the SNpc overlap percentage was positively correlated with the disease duration in PD. The SNpc overlap percentage provided excellent diagnostic accuracy for discriminating PD participants from controls (AUC = 0.93), while the R2* values in the whole SNpc or the overlap volume were less effective. CONCLUSION:The overlap between the iron content as determined by R2* mapping and neuromelanin in the substantia nigra pars compacta has the potential to be a neuroimaging biomarker for diagnosing Parkinson's disease.

SUBMITTER: He N

PROVIDER: S-EPMC7479276 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Increased iron-deposition in lateral-ventral substantia nigra pars compacta: A promising neuroimaging marker for Parkinson's disease.

He Naying N Langley Jason J Huddleston Daniel E DE Chen Shengdi S Huang Pei P Ling Huawei H Yan Fuhua F Hu Xiaoping X

NeuroImage. Clinical 20200820

<h4>Background</h4>To date there are no validated MRI biomarkers to assist diagnosis of Parkinson's disease (PD). Our aim was to investigate PD related iron changes in the substantia nigra pars compacta (SNpc) as defined by neuromelanin-sensitive MR contrast.<h4>Methods</h4>Thirty-nine PD participants and 33 healthy controls were scanned at 3.0-T using a 16-echo gradient echo sequence to create R<sub>2</sub>* maps for the evaluation of iron content to find the overlap with a neuromelanin based S ...[more]

PMID: 32889398

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Project description:This article gives a detailed description of a protocol using density gradient centrifugation for the enrichment of neuromelanin granules and synaptosomes from low amounts (?0.15g) of human substantia nigra pars compacta tissue. This has a great advantage compared to already existing methods as it allows for the first time (i) a combined enrichment of neuromelanin granules and synaptosomes and (ii) just minimal amounts of tissue necessary to enable donor specific analysis. Individual specimens were classified as control or diseased according to clinical evaluation and neuropathological examination. For the enrichment of synaptosomes and neuromelanin granules from the same tissue sample density gradient centrifugations using Percoll® and Iodixanol were performed. The purity of resulting fractions was checked by transmission electron microscopy. We were able to establish a reproducible and easy to handle protocol combining two different density gradient centrifugations: using an Iodixanol gradient neuromelanin granules were enriched and in parallel, from the same sample, a fraction of synaptosomes with high purity using a Percoll® gradient was obtained. Our subfractionation strategy will enable a subsequent in depth proteomic characterization of neurodegenerative processes in the substantia nigra pars compacta in patients with Parkinson's disease and dementia with Lewy bodies compared to appropriate controls.Key features of Parkinson's disease are the degeneration of dopaminergic neurons in the substantia nigra pars compacta, an associated loss of the brain pigment neuromelanin and a resulting impairment of the neuronal network. The accumulation of iron binding neuromelanin granules is age- and disease-dependent and disease specific alterations could affect the neuronal iron homeostasis leading to oxidative stress induced cell death. The focus of the described method is the analysis of neuromelanin granules as well as axonal cell-endings of nerve cells (synaptosomes) of individual donors (control and diseased). It is the basis for the identification of disease-relevant changes in the iron homeostasis and the generation of new insight into altered protein compositions or regulations which might lead to disturbed communications between nerve cells resulting in pathogenic processes.

Dataset Information

Increased iron-deposition in lateral-ventral substantia nigra pars compacta: A promising neuroimaging marker for Parkinson's disease.

Publications

Increased iron-deposition in lateral-ventral substantia nigra pars compacta: A promising neuroimaging marker for Parkinson's disease.

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