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Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson's disease.
Brain. 2020 09 01; 143(9):2757-2770.B

Abstract

This study aimed to investigate the spatiotemporal changes in neuromelanin-sensitive MRI signal in the substantia nigra and their relation to clinical scores of disease severity in patients with early or progressing Parkinson's disease and patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) exempt of Parkinsonian signs compared to healthy control subjects. Longitudinal T1-weighted anatomical and neuromelanin-sensitive MRI was performed in two cohorts, including patients with iRBD, patients with early or progressing Parkinson's disease, and control subjects. Based on the aligned substantia nigra segmentations using a study-specific brain anatomical template, parametric maps of the probability of a voxel belonging to the substantia nigra were calculated for patients with various degrees of disease severity and controls. For each voxel in the substantia nigra, probability map of controls, correlations between signal-to-noise ratios on neuromelanin-sensitive MRI in patients with iRBD and Parkinson's disease and clinical scores of motor disability, cognition and mood/behaviour were calculated. Our results showed that in patients, compared to the healthy control subjects, the volume of the substantia nigra was progressively reduced for increasing disease severity. The neuromelanin signal changes appeared to start in the posterolateral motor areas of the substantia nigra and then progressed to more medial areas of this region. The ratio between the volume of the substantia nigra in patients with Parkinson's disease relative to the controls was best fitted by a mono-exponential decay. Based on this model, the pre-symptomatic phase of the disease started at 5.3 years before disease diagnosis, and 23.1% of the substantia nigra volume was lost at the time of diagnosis, which was in line with previous findings using post-mortem histology of the human substantia nigra and radiotracer studies of the human striatum. Voxel-wise patterns of correlation between neuromelanin-sensitive MRI signal-to-noise ratio and motor, cognitive and mood/behavioural clinical scores were localized in distinct regions of the substantia nigra. This localization reflected the functional organization of the nigrostriatal system observed in histological and electrophysiological studies in non-human primates (motor, cognitive and mood/behavioural domains). In conclusion, neuromelanin-sensitive MRI enabled us to assess voxel-wise modifications of substantia nigra's morphology in vivo in humans, including healthy controls, patients with iRBD and patients with Parkinson's disease, and identify their correlation with nigral function across all motor, cognitive and behavioural domains. This insight could help assess disease progression in drug trials of disease modification.

Authors+Show Affiliations

Institut du Cerveau - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France. ICM, Centre de NeuroImagerie de Recherche - CENIR, Paris, France. ICM, Team "Movement Investigations and Therapeutics" (MOV'IT), Paris, France.Institut du Cerveau - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France. ICM, Centre de NeuroImagerie de Recherche - CENIR, Paris, France. ICM, Team "Movement Investigations and Therapeutics" (MOV'IT), Paris, France.Institut du Cerveau - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France. ICM, Centre de NeuroImagerie de Recherche - CENIR, Paris, France.Institut du Cerveau - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France. National Institute of Health and Medical Research - INSERM, Clinical Investigation Centre, Pitié-Salpêtrière Hospital, Paris, France.Institut du Cerveau - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France. ICM, Team "Movement Investigations and Therapeutics" (MOV'IT), Paris, France. Department of Neuroradiology, Pitié-Salpêtrière Hospital, Public Assistance - Paris Hospitals (AP-HP), Paris, France.Institut du Cerveau - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France. ICM, Centre de NeuroImagerie de Recherche - CENIR, Paris, France.Institut du Cerveau - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France. ICM, Team "Movement Investigations and Therapeutics" (MOV'IT), Paris, France. Department of Neurology, Pitié-Salpêtrière Hospital, Public Assistance - Paris Hospitals (AP-HP), Paris, France.Biogen Inc., Cambridge, MA, USA.Institut du Cerveau - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France.No affiliation info availableInstitut du Cerveau - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France. National Institute of Health and Medical Research - INSERM, Clinical Investigation Centre, Pitié-Salpêtrière Hospital, Paris, France. Department of Neurology, Pitié-Salpêtrière Hospital, Public Assistance - Paris Hospitals (AP-HP), Paris, France.Institut du Cerveau - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France. ICM, Team "Movement Investigations and Therapeutics" (MOV'IT), Paris, France. Department of Neurology, Pitié-Salpêtrière Hospital, Public Assistance - Paris Hospitals (AP-HP), Paris, France.Institut du Cerveau - ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France. ICM, Centre de NeuroImagerie de Recherche - CENIR, Paris, France. ICM, Team "Movement Investigations and Therapeutics" (MOV'IT), Paris, France. Department of Neuroradiology, Pitié-Salpêtrière Hospital, Public Assistance - Paris Hospitals (AP-HP), Paris, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32856056

Citation

Biondetti, Emma, et al. "Spatiotemporal Changes in Substantia Nigra Neuromelanin Content in Parkinson's Disease." Brain : a Journal of Neurology, vol. 143, no. 9, 2020, pp. 2757-2770.
Biondetti E, Gaurav R, Yahia-Cherif L, et al. Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson's disease. Brain. 2020;143(9):2757-2770.
Biondetti, E., Gaurav, R., Yahia-Cherif, L., Mangone, G., Pyatigorskaya, N., Valabrègue, R., Ewenczyk, C., Hutchison, M., François, C., Arnulf, ., Corvol, J. C., Vidailhet, M., & Lehéricy, S. (2020). Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson's disease. Brain : a Journal of Neurology, 143(9), 2757-2770. https://doi.org/10.1093/brain/awaa216
Biondetti E, et al. Spatiotemporal Changes in Substantia Nigra Neuromelanin Content in Parkinson's Disease. Brain. 2020 09 1;143(9):2757-2770. PubMed PMID: 32856056.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson's disease. AU - Biondetti,Emma, AU - Gaurav,Rahul, AU - Yahia-Cherif,Lydia, AU - Mangone,Graziella, AU - Pyatigorskaya,Nadya, AU - Valabrègue,Romain, AU - Ewenczyk,Claire, AU - Hutchison,Matthew, AU - François,Chantal, AU - Arnulf,Isabelle, AU - Corvol,Jean-Christophe, AU - Vidailhet,Marie, AU - Lehéricy,Stéphane, PY - 2020/02/25/received PY - 2020/04/11/revised PY - 2020/05/08/accepted PY - 2020/8/29/pubmed PY - 2021/2/17/medline PY - 2020/8/29/entrez KW - MRI KW - neuromelanin KW - parkinsonism KW - rapid eye movement sleep behaviour disorder KW - substantia nigra SP - 2757 EP - 2770 JF - Brain : a journal of neurology JO - Brain VL - 143 IS - 9 N2 - This study aimed to investigate the spatiotemporal changes in neuromelanin-sensitive MRI signal in the substantia nigra and their relation to clinical scores of disease severity in patients with early or progressing Parkinson's disease and patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) exempt of Parkinsonian signs compared to healthy control subjects. Longitudinal T1-weighted anatomical and neuromelanin-sensitive MRI was performed in two cohorts, including patients with iRBD, patients with early or progressing Parkinson's disease, and control subjects. Based on the aligned substantia nigra segmentations using a study-specific brain anatomical template, parametric maps of the probability of a voxel belonging to the substantia nigra were calculated for patients with various degrees of disease severity and controls. For each voxel in the substantia nigra, probability map of controls, correlations between signal-to-noise ratios on neuromelanin-sensitive MRI in patients with iRBD and Parkinson's disease and clinical scores of motor disability, cognition and mood/behaviour were calculated. Our results showed that in patients, compared to the healthy control subjects, the volume of the substantia nigra was progressively reduced for increasing disease severity. The neuromelanin signal changes appeared to start in the posterolateral motor areas of the substantia nigra and then progressed to more medial areas of this region. The ratio between the volume of the substantia nigra in patients with Parkinson's disease relative to the controls was best fitted by a mono-exponential decay. Based on this model, the pre-symptomatic phase of the disease started at 5.3 years before disease diagnosis, and 23.1% of the substantia nigra volume was lost at the time of diagnosis, which was in line with previous findings using post-mortem histology of the human substantia nigra and radiotracer studies of the human striatum. Voxel-wise patterns of correlation between neuromelanin-sensitive MRI signal-to-noise ratio and motor, cognitive and mood/behavioural clinical scores were localized in distinct regions of the substantia nigra. This localization reflected the functional organization of the nigrostriatal system observed in histological and electrophysiological studies in non-human primates (motor, cognitive and mood/behavioural domains). In conclusion, neuromelanin-sensitive MRI enabled us to assess voxel-wise modifications of substantia nigra's morphology in vivo in humans, including healthy controls, patients with iRBD and patients with Parkinson's disease, and identify their correlation with nigral function across all motor, cognitive and behavioural domains. This insight could help assess disease progression in drug trials of disease modification. SN - 1460-2156 UR - https://www.unboundmedicine.com/medline/citation/32856056/Spatiotemporal_changes_in_substantia_nigra_neuromelanin_content_in_Parkinson's_disease_ L2 - https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awaa216 DB - PRIME DP - Unbound Medicine ER -