Automated differentiation for parkinsonism using clinical structural MRI: A multicenter study

Multimodal research-grade magnetic resonance imaging (MRI) scans show potential for differentiating Parkinson’s disease (PD) from multiple system atrophy (MSA), but clinical translation is limited by cost, acquisition time, and processing burden. Here, we developed a T1-weighted structural MRI-based machine learning model to differentiate Parkinsonism and generalized it to routine anisotropic 2D clinical MRI. Using a multicenter cohort of 969 participants, we employed a hierarchical discovery–verification–translation framework.

While a multimodal benchmark model achieved an area under the receiver operating characteristic curve (AUROC) of 0.98, our streamlined unimodal T1-Top20 model achieved an AUROC of 0.93 for multiclass discrimination (healthy controls, PD, MSA). For PD vs MSA, the frozen T1-Top20 model achieved a pooled AUROC of 0.88 in the external research-grade cohort (n = 227) and identified 19 of 25 who phenoconverted from idiopathic rapid eye movement sleep behavior disorder (iRBD) to PD. Importantly, the generalized model achieved a pooled AUROC of 0.84 in the clinical-MRI cohort (2D T1, n = 303), supporting its potential for clinical translation.

We thank the participants and their families and the investigators and staff at the five participating clinical centers for their contributions to data acquisition and clinical assessment. Large-scale image preprocessing was partly performed on the Siyuan-1 cluster supported by the Center for High Performance Computing at Shanghai Jiao Tong University. Data used in the preparation of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org/data).

For up-to-date information on the study, visit www.ppmi-info.org. PPMI–a public-private partnership–is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including AbbVie, AcureX Therapeutics, Allergan, Amathus Therapeutics, Avid Radiopharmaceuticals, Bial Biotech, Biogen, BioLegend, Bristol Myers Squibb, Celgene, Dacapo Brainscience, Denali, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Diagnostics, Neurocrine Biosciences, Pfizer, Piramal Imaging, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Vanqua Bio, Verily Life Science, Voyager Therapeutics, and Golub Capital.The study was supported by the National Natural Science Foundation of China (82471504, 32271148, 82230040, 82341251), the Shanghai Clinical Cohort Program—Parkinson’s Disease (SHDC2025CCS043), the Shanghai Research Doctor Program (SHDC2023CRT014), the Shanghai Health Commission Research Program (202440091) and the Shanghai Jiao Tong University STAR Program (20220103), the Shanghai Jiao Tong University Medical Engineering Cross Research Funds (YG2024ZD27), the Natural Science Foundation of Shanghai (24ZR1448600).

The funders had no role in the study design, data collection, data analysis, data interpretation, preparation of the manuscript, or decision to submit the manuscript. These authors contributed equally: Liche Zhou, Chengzhe Wang, Xue Zhu, Dongling Zhang. Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Liche Zhou, Xue Zhu, Sijia Huang & Jun Liu Department of Neurology, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China Chengzhe Wang, Jinfeng Wu, Ailian Du & Jie Wang Department of Neurology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China Shanghai Key Laboratory of Emotions and Affective Disorders, Songjiang Research Institute, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Radiology, Clinical Neuroscience Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Clinical Neuroscience Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China Department of Neurology and Clinical Research of Neurological Diseases, The Second Affiliated Hospital of Soochow University, Suzhou, China Xiaoyu Cheng, Jinru Zhang, Chengjie Mao & Chunfeng Liu Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China Department of Neurology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China Correspondence to Ailian Du, Jun Liu or Jie Wang.

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