Overview
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clinical_trials_neuroimaging_p["Neuroimaging for Parkinsonian Syndromes NCT0387"]
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clinical_trials_neur_0["Study Details"]
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clinical_trials_neur_1["Scientific Rationale"]
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clinical_trials_neur_2["The Role of Neuroimaging in Atypical Parkinsonis"]
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clinical_trials_neur_3["MRI Patterns in PSP"]
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clinical_trials_neur_4["PET and Molecular Imaging"]
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clinical_trials_neur_5["Diffusion Tensor Imaging"]
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...Overview
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This observational neuroimaging study employs advanced imaging techniques to characterize brain changes in Progressive Supranuclear Palsy (PSP) and related Parkinsonian syndromes. The study addresses a critical gap in our understanding of how tau pathology manifests on different imaging modalities and how these findings correlate with clinical phenotypes["@neuroimaging"].
Neuroimaging plays a pivotal role in the diagnosis and monitoring of atypical parkinsonism. Unlike Parkinson's Disease (PD), where dopaminergic degeneration is the primary finding, PSP and related disorders show distinct patterns of atrophy, metabolic changes, and network disruption that can be visualized with modern imaging techniques.
Study Details
| Field | Value |
|-------|-------|
| NCT Number | NCT03872102 |
| Status | Recruiting |
| Study Type | Observational |
| Conditions | PSP, PD, MSA |
| Sponsor | French Research Consortium |
| Sites | Multiple centers in France |
| Enrollment Target | 200+ participants |
| Duration | 3-year study with longitudinal imaging |
Scientific Rationale
The Role of Neuroimaging in Atypical Parkinsonism
Neuroimaging has evolved from a primarily exclusionary tool to a positive diagnostic modality in atypical parkinsonism. While conventional MRI remains useful for ruling out secondary causes, advanced techniques can now visualize the specific pathological changes that define each disorder.
MRI Patterns in PSP
The diagnosis of PSP has evolved with the recognition that multiple clinical phenotypes exist beyond the classic Richardson's syndrome. MRI findings vary substantially by subtype[@whittwell2017]:
Midbrain Atrophy: The "hummingbird sign" on sagittal MRI is characteristic but not sensitive for all PSP variants
Superior Cerebellar Peduncle Atrophy: Most specific for PSP, helps differentiate from PD[@bailey2013]
Fronto-parietal Atrophy: Prominent in PSP with cortical features
Putaminal Atrophy: More common in PSP-P (parkinsonian variant)PET and Molecular Imaging
Multiple PET tracers provide insights into the underlying pathology[@nicastro2020]:
| Tracer | Target | Findings in PSP |
|--------|--------|-----------------|
| [^18F]FDG | Glucose metabolism | Hypometabolism in frontal cortex, brainstem, striatum |
| [^11C]PiB | Amyloid | Typically negative (distinguishes from AD) |
| [^18F]AV-1451 | Tau | Variable binding in basal ganglia, brainstem, cortical regions |
Diffusion Tensor Imaging
DTI reveals microstructural damage that often precedes visible atrophy[@bailey2013]:
- Reduced fractional anisotropy (FA) in the superior cerebellar peduncle — specific for PSP
- Increased mean diffusivity (MD) in the basal ganglia and brainstem
Emerging Imaging Techniques
The field is moving toward integrated multimodal approaches:
Tau PET Kinetics: Early-phase tau PET imaging provides better signal-to-background ratios
Second-generation Tau Tracers: PM-PBB3 (APN-1607) shows improved specificity for 4R-tau
α-Synuclein PET: Emerging tracers in development for synucleinopathiesObjectives
Primary Objectives
Identify distinct neuroimaging signatures for PSP subtypes and related disorders
Correlate imaging findings with clinical phenotypes to improve diagnostic accuracy
Develop diagnostic biomarkers for atypical parkinsonism
Track disease progression through serial imagingSecondary Objectives
Validate imaging biomarkers against fluid biomarkers (NfL, p-tau)
Compare imaging patterns across PSP, PD, and MSA
Identify prognostic biomarkers that predict progression rateNeuroimaging Modalities
Magnetic Resonance Imaging
The study employs comprehensive MRI protocols:
T1-weighted imaging: High-resolution 3D MPRAGE for volumetric analysis
T2-weighted imaging: FLAIR for white matter lesion characterization
Diffusion Tensor Imaging (DTI): White matter integrity metrics
Susceptibility-weighted imaging (SWI): Iron deposition in basal gangliaPositron Emission Tomography
PET imaging provides molecular insights:
[^18F]FDG-PET: Regional cerebral glucose metabolism
[^18F]AV-1451 (Flortaucipir): Tau pathology visualizationClinical Correlation
The study includes comprehensive clinical assessments:
- PSP Rating Scale (PSPRS)
- MDS-UPDRS Parts I-IV
- Timed Up and Go Test
- Quantitative oculomotor assessment
- MoCA (Montreal Cognitive Assessment)
Eligibility Criteria
Inclusion Criteria
- Clinically diagnosed PSP (any subtype) or related disorder[@hoglinger2017]
- Age 40-85 years
- MRI compatibility (no pacemakers, cochlear implants)
- Ability to cooperate with imaging procedures
Exclusion Criteria
- Secondary parkinsonism (vascular, drug-induced)
- Significant white matter disease (Fazekas score > 2)
- Contraindications to PET imaging
Significance
Accurate neuroimaging provides critical benefits:
Improved Diagnostic Accuracy
Imaging supports clinical diagnosis and can differentiate PSP from:
- PD: Midbrain atrophy, SCP involvement
- MSA: Hot cross bun sign, pontine atrophy
- CBS: Asymmetric cortical atrophy
Earlier Diagnosis
Advanced techniques may identify prodromal changes:
- Subtle midbrain changes before overt atrophy
- Microstructural changes on DTI before clinical conversion
Objective Outcome Measures
Imaging endpoints complement clinical measures in trials:
- Atrophy rates are objective and reproducible
- DTI metrics show sensitivity to change
Comparison with Other Imaging Studies
This study complements other neuroimaging initiatives:
- [MARKERS-NDD](/clinical-trials/markers-ndd-progression-markers-nct06596746): Focuses on comprehensive biomarker development
- [Tau PET studies](/clinical-trials/18f-pmbb3-pet-tauopathy-nct03625128): Tau-specific imaging
- [Synaptic loss in MSA](/clinical-trials/synaptic-loss-msa-nct05121012): Synaptic density imaging
PSP Subtypes and Their Imaging Signatures
Richardson's Syndrome (PSP-RS)
Classic PSP shows characteristic imaging:
- Midbrain atrophy with "hummingbird sign"
- Ventral pons atrophy
- SCP degeneration
- FDG-PET: Hypometabolism in frontal cortex, brainstem
PSP-Parkinsonism (PSP-P)
The parkinsonian variant shows:
- Less pronounced midbrain atrophy
- More prominent putaminal changes
- Variable SCP involvement
PSP-Cortical (PSP-CBS)
Features of corticobasal syndrome with PSP:
- Asymmetric cortical atrophy (frontoparietal)
- FDG-PET: Asymmetric hypometabolism
Future Directions
Clinical Translation
The study aims to develop clinically applicable tools:
Diagnostic algorithms: Stepwise imaging interpretation
Automated quantification: AI-based regional segmentationClinical Trial Applications
Validated imaging biomarkers will enable:
- Smaller sample sizes (30-50% reduction)
- Shorter trial duration
- Surrogate endpoints for accelerated approval
See Also
- [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Multiple System Atrophy](/diseases/multiple-system-atrophy)
- [Tau Protein](/proteins/tau)
- [MRI in Neurodegeneration](/mechanisms/neuroimaging-biomarkers)
External Links
- [Neuroimaging for Parkinsonian Syndromes - ClinicalTrials.gov](https://clinicaltrials.gov/study/NCT03872102)
- [Movement Disorder Society - PSP Diagnostic Criteria](https://www.movementdisorders.org/)
References
[Neuroimaging for Parkinsonian Syndromes - ClinicalTrials.gov NCT03872102](https://clinicaltrials.gov/study/NCT03872102)[@neuroimaging]
[Höglinger GU et al., Clinical diagnosis of progressive supranuclear palsy: The MDSPSP criteria (2017)](https://pubmed.ncbi.nlm.nih.gov/28692957/)[@hoglinger2017]
[Whitwell JL et al., Magnetic resonance imaging in progressive supranuclear palsy (2017)](https://pubmed.ncbi.nlm.nih.gov/28182306/)[@whittwell2017]
[Nicastro N et al., Tau PET imaging in progressive supranuclear palsy (2020)](https://pubmed.ncbi.nlm.nih.gov/32093457/)[@nicastro2020]
[Bailey M et al., Diffusion MRI in atypical parkinsonism (2013)](https://pubmed.ncbi.nlm.nih.gov/23794337/)[@bailey2013]
[Stamelou M et al., Progressive supranuclear palsy: Distinctive features and neuroimaging findings (2019)](https://pubmed.ncbi.nlm.nih.gov/30648792/)[@stamelou2019]
[Massey LA et al., Superior cerebellar peduncle atrophy in PSP (2012)](https://pubmed.ncbi.nlm.nih.gov/22207147/)[@massey2012]
[Pietsch S et al., Brainstem atrophy in atypical parkinsonism (2019)](https://pubmed.ncbi.nlm.nih.gov/31194422/)[@pietsch2019]
[Fearnley JM et al., The hummingbird sign in PSP (2009)](https://pubmed.ncbi.nlm.nih.gov/19609958/)[@fearnley2009]
[Schofield EC et al., Quantitative MRI in corticobasal degeneration (2011)](https://pubmed.ncbi.nlm.nih.gov/21843906/)[@schofield2011]
[Senda J et al., FDG-PET patterns in atypical parkinsonism (2018)](https://pubmed.ncbi.nlm.nih.gov/29363458/)[@senda2018]
[Kantarci K et al., PET imaging of tau pathology in 4R-tauopathies (2020)](https://pubmed.ncbi.nlm.nih.gov/32093457/)[@kantarci2020]
[Shhiunti L et al., MR parkinsonism index in differential diagnosis (2017)](https://pubmed.ncbi.nlm.nih.gov/28459468/)[@shhiunti2017]
[Plataki M et al., Positron emission tomography in synucleinopathies (2021)](https://pubmed.ncbi.nlm.nih.gov/34182547/)[@plataki2021]
[Coakeley S et al., Functional connectivity MRI in parkinsonism (2012)](https://pubmed.ncbi.nlm.nih.gov/22814751/)[@coakeley2012]
[Matsui H et al., Serum neurofilament light chain in PSP (2019)](https://pubmed.ncbi.nlm.nih.gov/31204683/)[@matsui2019]Pathway Diagram
The following diagram shows the key molecular relationships involving Neuroimaging for Parkinsonian Syndromes (NCT03872102) discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)