Increased iron in the substantia nigra pars compacta identifies patients with early Parkinson’s disease: A 3T and 7T MRI study

Alushaj, Erind; Handfield-Jones, Nicholas; Kuurstra, Alan; Morava, Anisa; Menon, Ravi S.; Owen, Adrian M.; Sharma, Manas; Khan, Ali R.; MacDonald, Penny A.

doi:10.1016/j.nicl.2024.103577

Cited by 4 publications

(3 citation statements)

References 135 publications

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“…The cardinal motor symptoms of PD—bradykinesia, rigidity, and resting tremor—are attributed to the degeneration of dopamine-producing neurons in the substantia nigra (SN) pars compacta (SNc), and the consequent dopamine depletion of the caudal motor subregion of the striatum 9 , 15 – 17 . Iron 10 , 12 , 18 , neuromelanin 19 , 20 , and diffusion 21 MRI measures reveal abnormalities in the SN/SNc and striatum in PD. Few studies, however, present MRI measures that accurately identify PD patients at the individual level.…”

Section: Introductionmentioning

confidence: 96%

“…MRI is lower cost and more available to clinical generalists. MRI has shown promise in distinguishing PD and age-matched healthy control (HC) groups 9 , 10 – 12 and in tracking PD progression 13 , 14 . In this study, we focused on the potential of MRI to investigate the earliest stages of PD to provide diagnostic and progression biomarkers of disease.…”

Section: Introductionmentioning

confidence: 99%

“…By the time that PD is clinically diagnosed, the preponderance of SNc dopaminergic neurons have already degenerated with greater sparing in the ventral tegmental area 10 , 24 . Idiopathic rapid eye movement (REM) sleep behaviour disorder (iRBD) is a sleep disorder in which patients act out their dreams due to failure of normal muscular paralysis during dreaming 25 .…”

Section: Introductionmentioning

confidence: 99%

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Increased mean diffusivity of the caudal motor SNc identifies patients with REM sleep behaviour disorder and Parkinson’s disease

Alushaj,

Hemachandra,

Ganjavi

et al. 2024

npj Parkinsons Dis.

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Idiopathic rapid eye movement sleep behaviour disorder (iRBD)—a Parkinson’s disease (PD) prodrome—might exhibit neural changes similar to those in PD. Substantia nigra pars compacta (SNc) degeneration underlies motor symptoms of PD. In iRBD and early PD (ePD), we measured diffusion MRI (dMRI) in the caudal motor SNc, which overlaps the nigrosome-1—the earliest-degenerating dopaminergic neurons in PD—and in the striatum. Nineteen iRBD, 26 ePD (1.7 ± 0.03 years), and 46 age-matched healthy controls (HCs) were scanned at Western University, and 47 iRBD, 115 ePD (0.9 ± 0.01 years), and 56 HCs were scanned through the Parkinson’s Progression Markers Initiative, using 3T MRI. We segmented the SNc and striatum into subregions using automated probabilistic tractography to the cortex. We measured mean diffusivity (MD) and fractional anisotropy (FA) along white-matter bundles and subregional surfaces. We performed group-level and classification analyses. Increased caudal motor SNc surface MD was the only iRBD-HCs and ePD-HCs difference replicating across datasets (padj < 0.05). No iRBD-ePD differences emerged. Caudal motor SNc surface MD classified patient groups from HCs at the single-subject level with good-to-excellent balanced accuracy in an independent sample (0.91 iRBD and 0.86 iRBD and ePD combined), compared to fair performance for total SNc surface MD (0.72 iRBD and ePD). Caudal motor SNc surface MD correlated significantly with MDS-UPDRS-III scores in ePD patients. Using dMRI and automated segmentation, we detected changes suggesting altered microstructural integrity in iRBD and ePD in the nigrostriatal subregion known to degenerate first in PD. Surface MD of the caudal motor SNc presents a potential measure for inclusion in neuroimaging biomarkers of iRBD and PD.

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Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased mean diffusivity of the caudal motor SNc identifies patients with REM sleep behaviour disorder and Parkinson’s disease

Alushaj,

Hemachandra,

Ganjavi

et al. 2024

npj Parkinsons Dis.

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Prospective motion correction for R2* and susceptibility mapping using spherical navigators

Hewlett,

Oran,

Liu

et al. 2024

Magnetic Resonance in Med

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PurposeTo perform prospective motion correction (PMC) for improved and susceptibility mapping using a purely navigator‐based approach.MethodsSpherical navigators (SNAVs) were combined with an additional FID readout for simultaneous measurement of motion and zeroth‐order field shifts. The resulting FIDSNAVs were interleaved for PMC of a multi‐echo gradient echo sequence with retrospective correction. Experiments were performed on a 3T scanner with a 32‐channel head coil. Performance was assessed in five volunteers with motion prompts derived from real unintentional motion trajectories.ResultsAt short TEs, PMC alone was sufficient to achieve good image quality; at longer TEs, retrospective correction was often just as important for artifact reduction as motion correction. Both PMC and retrospective correction reduced error in and susceptibility maps for all participants. Residual artifacts were observed in the most severe motion case.ConclusionCombining SNAVs with an additional FID readout enables simultaneous motion and field correction with no additional hardware requirements, improving the fidelity of quantitative mapping in the presence of motion.

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Neuroimaging and fluid biomarkers in Parkinson’s disease in an era of targeted interventions

Zarkali,

Thomas,

Zetterberg

et al. 2024

Nat Commun

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A major challenge in Parkinson’s disease is the variability in symptoms and rates of progression, underpinned by heterogeneity of pathological processes. Biomarkers are urgently needed for accurate diagnosis, patient stratification, monitoring disease progression and precise treatment. These were previously lacking, but recently, novel imaging and fluid biomarkers have been developed. Here, we consider new imaging approaches showing sensitivity to brain tissue composition, and examine novel fluid biomarkers showing specificity for pathological processes, including seed amplification assays and extracellular vesicles. We reflect on these biomarkers in the context of new biological staging systems, and on emerging techniques currently in development.

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Increased iron in the substantia nigra pars compacta identifies patients with early Parkinson’s disease: A 3T and 7T MRI study

Cited by 4 publications

References 135 publications

Increased mean diffusivity of the caudal motor SNc identifies patients with REM sleep behaviour disorder and Parkinson’s disease

Increased mean diffusivity of the caudal motor SNc identifies patients with REM sleep behaviour disorder and Parkinson’s disease

Prospective motion correction for R2* and susceptibility mapping using spherical navigators

Neuroimaging and fluid biomarkers in Parkinson’s disease in an era of targeted interventions

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