Surface-based Morphological Biomarkers of Subcortical Brain Structures for Tracking and Predicting Anatomical and Functional Hallmarks of Parkinson’s Disease

Last Updated Date: February 24, 2026

Authors: Felix Carbonell, Ph.D., Jean-Philippe Coutu, Simone P. Zehntner, Ph.D., Alex P. Zijdenbos, Ph.D., Barry J. Bedell, M.D., Ph.D., for the Parkinson's Progression Markers Initiative (PPMI).

Key Takeaways

• Surface-based morphological changes in the shape of subcortical structures provides an accurate quantification of atrophy in PD
• Local deformations in the shape of the Thalamus is a more sensitive biomarker than volume for tracking the progression of atrophy in PD
• Morphological change in subcortical structures, such as Thalamus and Midbrain, is an effective biomarker to reduce the sample size requirements for clinical trials
• Local deformations in the shape of the Midbrain is a sensitive biomarker able to predict reduction of Dopamine Transporter (DaT) density in the striatum

Subcortical brain regions, such as the basal ganglia, hippocampus, thalamus, and amygdala, are critical for various cognitive, emotional, and motor functions. Volumetric measurements of such structures have been consistently used as a reliable biomarker to assess atrophy and related neurodegenerative processes. On the other hand, subtle disease-related changes on the shape, cortical folding, or surface deformation of subcortical structures are better detected by applying morphological shape analysis techniques.

In the current study, we applied a morphological surface shape analysis for characterizing the longitudinal patterns of subcortical structures in Parkinson’s disease (PD). For that purpose, we used a local shape metric that is estimated from the nonlinear deformations that measure the spatial displacement of individual outer surface of subcortical regions with respect to a reference anatomical model. We also used this surface-based metric to perform actual out-of-the-sample predictions of other PD biomarkers, such as Dopamine Transporter (DaT) density as measured by DaTscan SPECT imaging.

Our findings revealed that local deformations in the shape of subcortical structures, such as the Thalamus, is a more sensitive biomarker than volume for tracking the longitudinal progression of atrophy in PD. We also derived a novel Statistical ROI (StatROI) measure of surface deformation that, compared to volumes, substantially decreased sample sizes requirement to assess reduction in atrophy. Finally, we also derived predictive models that accurately recovered observed DaTscan measurements, suggesting the possibility to use anatomical 3D T1-weighted MRI data as a surrogate for DaTscan SPECT for eligibility screening in clinical trials of disease-modifying therapeutics.

Presentation Highlights