Neuroimaging in Parkinson’s Disease

Nigrostriatal dopaminergic denervation is a critical pathological event in Parkinson’s Disease (PD) and related disorders. Degeneration of presynaptic neurons leads to reduced density of dopamine transporters in the striatum, the progression of which leads to development of motor deficits and other clinical features.

DaTscan SPECT permits the in vivo assessment of striatal dopamine transporter (DAT) availability, which is the most widely utilized imaging biomarker for clinical trials in PD. Emerging evidence suggests that a pattern of reduced volume in the striatum and altered morphometry throughout the brain may inform the likelihood of progressive reduction in DaTscan binding. These morphometric changes may be driven by disruptions in white matter integrity yielding impaired structural connectivity within and between functional brain networks.

In this webinar, we will discuss how the integration of biomarkers across neuroimaging modalities can improve the characterization of PD disease state and help to predict whether a PD patient will reliably progress over the time frame of a clinical trial. Evidence of therapeutic efficacy will be most robust in those patients with reliable disease progression and the identification of such patients presents an enrichment opportunity requiring fewer study subjects to meet a primary endpoint.

We will present findings from the open source Parkinson’s Progression Markers Initiative database, which suggests that baseline volumetric MRI and diffusion tensor imaging (DTI) can meaningfully inform the longitudinal progression of DaTscan uptake in PD patients. Our work identified a pattern of morphometric and diffusivity features associated with progressive decline in DAT availability, suggesting that structural changes in the brain may reflect an orthogonal feature associated with an accelerated disease trajectory.

The webinar will also explore the performance of different image processing pipelines (i.e., FreeSurfer versus SPM), analytic endpoints (anisotropy, diffusivity and free water fraction) and anatomic localization (regional versus voxelwise) to determine which combination is most sensitive in predicting disease progression. Together, these findings help encourage the use of MRI to augment the diagnostic utility of DaTscan SPECT and provide a unique set of imaging markers, which could yield their own evidence of therapeutic benefit.

Speaker

David Scott, PhD, Scientific Director, Bioclinica

David Scott is a Scientific Director at Bioclinica. His aim is to facilitate drug development through standardized measurement of the neural correlates of neurodegenerative and other centrally mediated diseases. As a student at Johns Hopkins University and the University of Michigan, he employed multi-modal imaging approaches including dynamic PET and functional MRI to study the neurobiology of placebo analgesia. At Omneuron, he developed real-time fMRI applications aimed at treating chronic pain, depression and addiction.

Since joining Bioclinica in 2012, Scott’s focus has been to enable MRI and molecular imaging solutions geared toward safety, eligibility and therapeutic efficacy endpoints. He works with Bioclinica’s staff radiologists, physicists, software engineers and operational specialists on the design, execution, analysis and interpretation of imaging clinical trials in the neuroscience therapeutic area. His motivation is to effectively translate advanced neuroimaging tools from the lab to the clinic so that therapeutic benefit can be delivered to patients around the world.

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