As clinical research in Parkinson’s Disease (PD) continues to evolve, neuroimaging has become a cornerstone in trial design, patient selection, and therapeutic evaluation. Across the industry, sponsors and imaging partners are adopting increasingly sophisticated imaging strategies to enhance data quality, regulatory compliance, and scientific insight. Below are key areas where neuroimaging is shaping the future of PD trials.

How are imaging biomarkers used to select and stratify patients in PD trials?

Neuroimaging biomarkers are essential for confirming diagnosis and stratifying participants. Techniques like DaT SPECT imaging assess dopamine transporter density, helping differentiate idiopathic PD from atypical Parkinsonian syndromes. Neuromelanin-sensitive MRI is also gaining traction for visualising degeneration in the substantia nigra.

Centralised radiology reads—performed by expert neuroradiologists—play a pivotal role in screening for differential diagnosis. By consistently reviewing key radiological features, they help rule out other Parkinsonian syndromes, supporting more accurate and confident clinical decision-making. These reads combine visual interpretation with quantitative metrics, supporting consistent and reproducible inclusion criteria across sites.

Which imaging modalities are most effective for monitoring disease progression in PD?

To monitor progression and therapeutic impact, trials increasingly rely on a multi-modal imaging approach:

• Diffusion MRI (DTI, NODDI, Free Water Analysis) for white matter integrity and neuroinflammation.
• Structural MRI for brain atrophy in regions like the striatum and thalamus.
• Arterial Spin Labelling (ASL) for cerebral blood flow.
• PET imaging (FDG, VMAT2, DAT PET ad DaT SPECT) for metabolic and dopaminergic function.

These modalities are analysed cross-sectionally and longitudinally, providing sensitive endpoints for tracking changes over time. The use of quantitative imaging biomarkers is now considered best practice for efficacy assessments.

What systems and workflows ensure consistent imaging data across global trial sites?

Multicentre trials present challenges in maintaining imaging consistency. To address this, sponsors and imaging CROs implement robust frameworks:

• Centralised imaging platforms compliant with GCP and 21 CFR Part 11.
• Site qualification and training to standardise acquisition procedures.
• Imaging charters and reader manuals to define protocols and workflows.
• Automated and manual QC to flag and resolve discrepancies.

These practices ensure imaging data is reliable, reproducible, and suitable for regulatory submission.

How is artificial intelligence enhancing neuroimaging analysis in clinical research?

AI is increasingly used to streamline neuroimaging analysis. AI-driven platforms support:

• Automated volumetric measurements for brain atrophy.
• Quantification of biomarkers like striatal binding ratios (SBR) and standardized uptake value ratios (SUVRs).
• Post-hoc analysis of legacy datasets to uncover new insights.

By reducing manual variability and accelerating data processing, AI contributes to more efficient workflows and higher-quality imaging endpoints.

Why is centralised radiology reading considered essential in PD trial design?

Centralised radiology reading is now standard in PD trials. Key elements include:

• Study-specific training for readers to standardise read outcomes and minimise reader variability.
• Tailored read paradigms (single, dual, consensus, adjudication).
• Rapid turnaround times (typically 3–5 days).
• Discordance resolution workflows to address discrepancies.

These practices minimise delays and ensure imaging assessments are rigorous and aligned with trial objectives.

What are the key challenges in managing multicentre neuroimaging trials for PD?

Multicentre trials are vital for diverse recruitment but introduce operational complexity. Challenges include:

• Variability in equipment and protocols across sites
  • Minimised with robust site setup and qualification process using phantoms and optimised scanner protocols.
• Differences in site experience, especially with PD patients.
  • Resolved through detailed training modules, documentation, user-friendly systems, site support contacts and communication throughout the trial.
• Logistical coordination for scheduling, tracer supply, and data uploads.
• Data harmonisation across formats and systems.

To mitigate these challenges, sponsors use centralised imaging charters, site training, real-time QC systems, and centralised reads to maintain consistency and compliance.

What considerations should imaging sites keep in mind when working with PD patients?

PD patients may have motor symptoms like tremors and rigidity, which affect scan quality. Cognitive issues and fatigue can also impact cooperation.

Best practices include:

• Scheduling scans during optimal medication windows.
• Using motion correction techniques or faster sequences.
• Clear, empathetic communication to reduce anxiety.
• Ensuring physical comfort and accessibility.

Sites should be prepared to adapt protocols for patients with advanced disease or comorbidities.

How is tracer management handled in PD imaging studies?

Tracer management is critical when including SPECT and PET on a trial, to ensure the management and logistics are in place for effective tracer ordering, production, delivery and usage of the radioactive tracers.

Key considerations:

• Tracer supply logistics, including manufacturer contracts, distribution networks and delivery schedules.
• Site readiness, including licensing, staff training and set up of ordering mechanisms.
• Tracer-agnostic analysis pipelines for flexibility in use of multiple tracers where required.
• Regulatory compliance for storage, transport, and disposal.

Effective management ensures timely imaging and reliable biomarker data.

What are the best practices for data collection, anonymisation, and security in PD trials?

Protecting patient data while ensuring scientific utility involves:

• Automated and manual QC to validate datasets.
• Anonymisation workflows to remove personal identifiers.
• Secure data transfer agreements (DTAs) with sponsors and third parties.
• Use of compliant platforms with audit trails and access control.

These measures uphold ethical standards and enable robust analysis.

How should imaging teams handle incidental findings or abnormalities unrelated to PD?

Incidental findings—like tumours or vascular anomalies—are common in neuroimaging, especially in older populations.

Best practices include:

• Centralised radiology reads to identify and classify abnormalities.
• Defined escalation protocols to notify clinical teams.
• Ethical guidelines for informing participants.
• Documentation standards for transparency.

Managing these findings responsibly ensures patient safety and maintains trial integrity.

 

We hope this Q&A guide will help inform you on what you should consider when including imaging in your Parkinson’s disease clinical trial and if you want to find out more, please contact us

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