Distinct progression pattern of susceptibility MRI in the substantia nigra of Parkinson's patients

Du, Guangwei; Lewis, Mechelle M.; Sica, Christopher T.; He, Lu; Connor, James R.; Kong, Lan; Mailman, Richard B.; Huang, Xuemei

doi:10.1002/mds.27318

Cited by 77 publications

(116 citation statements)

References 40 publications

(99 reference statements)

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“…5–7 The performance of these MRI markers for early PD detection, however, is less promising according to follow-up studies. 11, 17, 18, 32 For example, a meta-analysis of diffusion MRI in PD reported a rather modest effect size for FA, 18 and the performance of R2* in early-stage PD patients is inconsistent between studies. 5, 26 …”

Section: Discussionmentioning

confidence: 99%

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Magnetic resonance T1w/T2w ratio: A parsimonious marker for Parkinson disease

Lewis

Sica

et al. 2018

Annals of Neurology

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Objective: Newer MRI techniques have shown promise in capturing early Parkinson’s disease (PD)-related changes in the substantia nigra pars compacta (SNc), the key pathological loci. Their translational value, however, is hindered by technical complexity and inconsistent results. Methods: A novel yet simple MRI contrast, the T1w/T2w ratio, was used to study 76 PD patients and 70 controls. The T1w/T2w ratio maps were analyzed using both voxel-based and region-of-interest approaches in normalized space. The sensitivity and specificity of the SN T1w/T2w ratio in discriminating between PD and controls also were assessed. In addition, its diagnostic performance was tested in a subgroup of PD patients with disease duration ≤2 years (PDE). A second independent cohort of 73 PD and 49 controls was used for validation. Results: Compared to controls, PD patients showed a higher T1w/T2w ratio in both the right (cluster size=164 mm3, p<0.0001) and left (cluster size=213 mm3, p<0.0001) midbrain that was located ventrolateral to the red nucleus and corresponded to the SNc. The region-of-interest approach confirmed the group difference in the SNc T1w/T2w ratio between PD and controls (p<0.0001). The SNc T1w/T2w ratio had high sensitivity (0.908) and specificity (0.80) to separate PD and controls (AUC=0.926), even for PDE patients (AUC=0.901, sensitivity=0.857, specificity=0.857). These results were validated in the second cohort. Interpretation: The T1w/T2w ratio can detect PD-related changes in the SN and may be used as a novel, parsimonious in vivo biomarker for the disease, particularly early stage patients, with high translational value for clinical practice and research.

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Section: Discussionmentioning

confidence: 99%

“…13–16 In addition, the results from both iron-sensitive and diffusion MRI have not been consistent in detecting early-stage PD-related changes. 5, 17, 18 There is a clear need for practical and sensitive objective markers to detect early PD-related pathophysiological changes.…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance T1w/T2w ratio: A parsimonious marker for Parkinson disease

Lewis

Sica

et al. 2018

Annals of Neurology

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“…Three types of biomarkers were investigated that can investigate iron load, neuromelanin content, and microstructural changes using diffusion imaging in the SN. The findings from these articles use different designs and cut across pathological validation and longitudinal progression of MRI iron‐sensitive markers in the SN, the relationship between neuromelanin changes in the SN and brain stem atrophy in PSP, and diffusion changes in a novel at‐risk cohort …”

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confidence: 63%

“…The investigation of both controls and PD is a critical aspect of the study design, as it helps to rule out the effects of age on the biomarker under question, and without this comparison it is difficult to indicate that the change observed longitudinally is specific to PD. Du and colleagues studied 3 PD subgroups based on disease duration: PD early (<1 year), PD middle (<5 years), and PD late (>5 years). Interestingly, both R2* and QSM were higher in the SN for PD versus controls at baseline, but only the R2* measure changed longitudinally.…”

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confidence: 91%

“…This study is important because it demonstrates for the first time that an MRI marker in the substantia nigra relates directly to the presence of α‐synuclein pathology in the same individuals, and it suggests that R2* and QSM relate to pathology differently. In the study by Du and colleagues, these same imaging parameters, R2* and QSM, were compared longitudinally from baseline to 18‐month follow‐up, in both control subjects and PD. The investigation of both controls and PD is a critical aspect of the study design, as it helps to rule out the effects of age on the biomarker under question, and without this comparison it is difficult to indicate that the change observed longitudinally is specific to PD.…”

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Illuminating basal ganglia and beyond in Parkinson's disease

Vaillancourt

Lehericy

2018

Movement Disorders

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Emerging Neuroimaging Biomarkers Across Disease Stage in Parkinson Disease

et al. 2021

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Imaging biomarkers in Parkinson disease (PD) are increasingly important for monitoring progression in clinical trials and also have the potential to improve clinical care and management. This Review addresses a critical need to make clear the temporal relevance for diagnostic and progression imaging biomarkers to be used by clinicians and researchers over the clinical course of PD. Magnetic resonance imaging (diffusion imaging, neuromelanin-sensitive imaging, iron-sensitive imaging, T1-weighted imaging), positron emission tomography/single-photon emission computed tomography dopaminergic, serotonergic, and cholinergic imaging as well as metabolic and cerebral blood flow network neuroimaging biomarkers in the preclinical, prodromal, early, and moderate to late stages are characterized.OBSERVATIONS If a clinical trial is being carried out in the preclinical and prodromal stages, potentially useful disease-state biomarkers include dopaminergic imaging of the striatum; metabolic imaging; free-water, neuromelanin-sensitive, and iron-sensitive imaging in the substantia nigra; and T1-weighted structural magnetic resonance imaging. Disease-state biomarkers that can distinguish atypical parkinsonisms are metabolic imaging, free-water imaging, and T1-weighted imaging; dopaminergic imaging and other molecular imaging track progression in prodromal patients, whereas other established progression biomarkers need to be evaluated in prodromal cohorts. Progression in early-stage PD can be monitored using dopaminergic imaging in the striatum, metabolic imaging, and free-water and neuromelanin-sensitive imaging in the posterior substantia nigra. Progression in patients with moderate to late-stage PD can be monitored using free-water imaging in the anterior substantia nigra, R2* of substantia nigra, and metabolic imaging. Cortical thickness and gyrification might also be useful markers or predictors of progression. Dopaminergic imaging and free-water imaging detect progression over 1 year, whereas other modalities detect progression over 18 months or longer. The reliability of progression biomarkers varies with disease stage, whereas disease-state biomarkers are relatively consistent in individuals with preclinical, prodromal, early, and moderate to late-stage PD.CONCLUSIONS AND RELEVANCE Imaging biomarkers for various stages of PD are readily available to be used as outcome measures in clinical trials and are potentially useful in multimodal combination with routine clinical assessment. This Review provides a critically important template for considering disease stage when implementing diagnostic and progression biomarkers in both clinical trials and clinical care settings.

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Distinct progression pattern of susceptibility MRI in the substantia nigra of Parkinson's patients

Cited by 77 publications

References 40 publications

Magnetic resonance T1w/T2w ratio: A parsimonious marker for Parkinson disease

Magnetic resonance T1w/T2w ratio: A parsimonious marker for Parkinson disease

Illuminating basal ganglia and beyond in Parkinson's disease

Emerging Neuroimaging Biomarkers Across Disease Stage in Parkinson Disease

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