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Aims To develop an automatic method of classification for parkinsonian variant of multiple system atrophy (MSA‐P) and Idiopathic Parkinson's disease (IPD) in early to moderately advanced stages based on multimodal striatal alterations and identify the striatal neuromarkers for distinction. Methods 77 IPD and 75 MSA‐P patients underwent 3.0 T multimodal MRI comprising susceptibility‐weighted imaging, resting‐state functional magnetic resonance imaging, T1‐weighted imaging, and diffusion tensor imaging. Iron‐radiomic features, volumes, functional and diffusion scalars of bilateral 10 striatal subregions were calculated and provided to the support vector machine for classification Results A combination of iron‐radiomic features, function, diffusion, and volumetric measures optimally distinguished IPD and MSA‐P in the testing dataset (accuracy 0.911 and area under the receiver operating characteristic curves [AUC] 0.927). The diagnostic performance further improved when incorporating clinical variables into the multimodal model (accuracy 0.934 and AUC 0.953). The most crucial factor for classification was the functional activity of the left dorsolateral putamen. Conclusion The machine learning algorithm applied to multimodal striatal dysfunction depicted dorsal striatum and supervening prefrontal lobe and cerebellar dysfunction through the frontostriatal and cerebello‐striatal connections and facilitated accurate classification between IPD and MSA‐P. The dorsolateral putamen was the most valuable neuromarker for the classification.

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