Neuromelanin and T2*-MRI for the assessment of genetically at-risk, prodromal, and symptomatic Parkinson’s disease

Bashat, Dafna Ben; Thaler, Avner; Shacham, Hedva Lerman; Even-Sapir, Einat; Hutchison, Matthew; Evans, Karleyton C.; Orr-Urterger, Avi; Cedarbaum, Jesse M.; Droby, Amgad; Giladi, Nir; Mirelman, Anat; Artzi, Moran

doi:10.1038/s41531-022-00405-9

Cited by 10 publications

(15 citation statements)

References 59 publications

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“…Du Guangwei et al also mentioned in the study that during the 18 months follow-up, the substantia nigra pars compacta R2 * showed a faster increase in PD compared with controls. Through ROC curve analysis, we found that the average value of R2 * in the right substantia nigra compact zone has higher diagnostic energy efficiency, in line with previous results ( 2 , 20 , 22 ).…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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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“…The findings indicated genotype-specific differences in NM-based radiomic features only. Specifically, significant differences in the left and NM-SN skewness radiomic feature between sPD were observed, possibly indicating greater dopaminergic loss in the LRRK2 -PD group [ 26 ].…”

Section: Imaging Studies Findings In Genetic Forms and Prodromal Phas...mentioning

confidence: 99%

Imaging Markers in Genetic Forms of Parkinson’s Disease

2023

Self Cite

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Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by motor symptoms such as bradykinesia, rigidity, and resting tremor. While the majority of PD cases are sporadic, approximately 15–20% of cases have a genetic component. Advances in neuroimaging techniques have provided valuable insights into the pathophysiology of PD, including the different genetic forms of the disease. This literature review aims to summarize the current state of knowledge regarding neuroimaging findings in genetic PD, focusing on the most prevalent known genetic forms: mutations in the GBA1, LRRK2, and Parkin genes. In this review, we will highlight the contributions of various neuroimaging modalities, including positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI), in elucidating the underlying pathophysiological mechanisms and potentially identifying candidate biomarkers for genetic forms of PD.

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“…Another study reported significantly lower T2*‐based contrast in the left red nucleus in patients with GBA‐PD compared with those having iPD. However, no significant differences in the neuromelanin signal in the substantia nigra were found between GBA‐PD and iPD groups 9 . Collectively, these findings motivated us to investigate white matter (WM) alterations.…”

Section: Introductionmentioning

confidence: 99%

“…However, no significant differences in the neuromelanin signal in the substantia nigra were found between GBA-PD and iPD groups. 9 Collectively, these findings motivated us to investigate white matter (WM) alterations. WM microstructure abnormalities have been widely observed using diffusion tensor imaging (DTI) in patients with iPD.…”

Section: Introductionmentioning

confidence: 99%

Fiber‐Specific White Matter Alterations in Parkinson's Disease Patients with GBA Gene Mutations

Andica,

Kamagata,

Uchida

et al. 2023

Movement Disorders

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BackgroundPatients with Parkinson's disease (PD) carrying GBA gene mutations (GBA‐PD) have a more aggressive disease course than those with idiopathic PD (iPD).ObjectiveThe objective of this study was to investigate fiber‐specific white matter (WM) differences in nonmedicated patients with early‐stage GBA‐PD and iPD using fixel‐based analysis, a novel technique to assess tract‐specific WM microstructural and macrostructural features comprehensively.MethodsFixel‐based metrics, including microstructural fiber density (FD), macrostructural fiber‐bundle cross section (FC), and a combination of FD and FC (FDC), were compared among 30 healthy control subjects, 16 patients with GBA‐PD, and 35 patients with iPD. Associations between FDC and clinical evaluations were also explored using multiple linear regression analyses.ResultsPatients with GBA‐PD showed significantly lower FD in the fornix and superior longitudinal fasciculus than healthy control subjects, and lower FC in the corticospinal tract (CST) and lower FDC in the CST, middle cerebellar peduncle, and striatal‐thalamo‐cortical pathways than patients with iPD. Contrarily, patients with iPD showed significantly higher FC and FDC in the CST and striatal‐thalamo‐cortical pathways than healthy control subjects. In addition, lower FDC in patients with GBA‐PD was associated with reduced glucocerebrosidase enzyme activity, lower cerebrospinal fluid total α‐synuclein levels, lower Montreal Cognitive Assessment scores, lower striatal binding ratio, and higher Unified Parkinson's Disease Rating Scale Part III scores.ConclusionsWe report reduced fiber‐specific WM density and bundle cross‐sectional size in patients with GBA‐PD, suggesting neurodegeneration linked to glucocerebrosidase deficiency, α‐synuclein accumulation, and poorer cognition and motor functions. Conversely, patients with iPD showed increased fiber bundle size, likely because of WM reorganization. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Neuromelanin and T2*-MRI for the assessment of genetically at-risk, prodromal, and symptomatic Parkinson’s disease

Cited by 10 publications

References 59 publications

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

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

Imaging Markers in Genetic Forms of Parkinson’s Disease

Fiber‐Specific White Matter Alterations in Parkinson's Disease Patients with GBA Gene Mutations

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