Deep learning for differentiating Progressive Supranuclear Palsy from Corticobasal Degeneration using T1w-MRI
Author Block: R. Juglan1, A. Robasco1, Z. I. Carrero1, H. H. Kitzler1, D. Truhn2, J. Kather1; 1Dresden/DE, 2Aachen/DE
Purpose: Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD) are rare neurodegenerative disorders that present with overlapping clinical phenotypes, yet differ in underlying neuropathology. Accurate differentiation remains challenging with conventional MRI assessment. We investigated whether a brain MRI foundation model can enable automated and interpretable classification of PSP versus CBD.
Methods or Background: A self-supervised foundation model pre-trained on 42,000 UK Biobank T1-weighted MRIs was used as a feature extractor. A linear classification layer was trained on the 4RTNI cohort to separate PSP and CBD. Model performance was evaluated on a held-out test set with independent subjects using AUROC, AUPRC, and threshold-based diagnostic metrics. Interpretability was assessed with Grad-CAM heatmaps and atlas-based regional quantification. Longitudinal analyses examined prediction score trajectories and t-SNE embeddings across baseline, 6-month, and 12-month follow-up scans.
Results or Findings: In classifying PSP from CBD, the model achieved an AUROC of 0.78 (95% CI: 0.67–0.88) and AUPRC of 0.73 (95% CI: 0.58–0.87). At the optimal threshold determined by Youden’s J (0.53), the model achieved an accuracy of 0.75 with sensitivity of 0.78, specificity of 0.72, and F1 score of 0.75. With time progression, discrimination between the two diseases improved with AUROC increasing from 0.68 at baseline to 0.81 at 1-year follow-up, along with greater divergence in the embedding space. Grad-CAM localized highest attention to atlas-derived midbrain and thalamic structures, consistent with PSP pathology.
Conclusion: A lightweight linear classifier built on a foundation model distinguished PSP from CBD with good accuracy. Model-derived attention maps aligned with known disease-specific neuroanatomical patterns, supporting the potential of MRI foundation models to aid stratification in rare neurodegenerative syndromes.
Limitations: The limitation of the study is that it was restricted to a single cohort.
Funding for this study: Funding was provided by the the European Union EU’s Horizon Europe research and innovation programme (ODELIA, 101057091; GENIAL, 101096312), German Cancer Aid DKH (DECADE, 70115166), the German Federal Ministry of Research, Technology and Space BMFTR (PEARL, 01KD2104C; CAMINO, 01EO2101; TRANSFORM LIVER, 031L0312A; TANGERINE, 01KT2302 through ERA-NET Transcan; Come2Data, 16DKZ2044A; DEEP-HCC, 031L0315A; DECIPHER-M, 01KD2420A; NextBIG, 01ZU2402A), the German Research Foundation DFG (CRC/TR 412, 535081457; SFB 1709/1 2025, 533056198), the German Academic Exchange Service DAAD (SECAI, 57616814), the German Federal Joint Committee G-BA (TransplantKI, 01VSF21048), the European Research Council ERC (NADIR, 101114631), the National Institutes of Health NIH (EPICO, R01 CA263318) and the National Institute for Health and Care Research NIHR (Leeds Biomedical Research Centre, NIHR203331).
This work is partly supported by BMBF (Federal Ministry of Education and Research) in DAAD project 57616814 (SECAI, School of Embedded Composite AI, https://secai.org/) as part of the program Konrad Zuse Schools of Excellence in Artificial Intelligence.
This research has been conducted using the UK Biobank Resource under Application Number 92261. Data used in the preparation of this abstract were obtained from the 4-Repeat Neuroimaging Initiative (4RTNI) database and the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) (http://4rtni-ftldni.ini.usc.edu/).
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: The overall analysis was approved by the Ethics board at University Hospital Carl Gustav Carus, Dresden, Germany. This study adhered to the tenets of the Declaration of Helsinki.