Background: Brain MRI is a promising technique for Parkinson's disease (PD) biomarker development. Its analysis, however, is hindered by the high-dimensional nature of the data, particularly when the sample size is relatively small. New Method: This study introduces a folded concave penalized machine learning scheme with spatial coupling fused penalty (fused FCP) to build biomarkers for PD directly from whole-brain voxel-wise MRI data. The penalized maximum likelihood estimation problem of the model is solved by local linear approximation. Results: The proposed approach is evaluated on synthetic and Parkinson's Progression Marker Initiative (PPMI) data. It achieves good AUC scores, accuracy in classification, and biomarker identification with a relatively small sample size, and the results are robust for different tuning parameter choices. On the PPMI data, the proposed method discovers over 80 % of large regions of interest (ROIs) identified by the voxel-wise method, as well as potential new ROIs. Comparison with Existing Methods: The fused FCP approach is compared with L1, fused-L1, and FCP method using three popular machine learning algorithms, logistic regression, support vector machine, and linear discriminant analysis, as well as the voxel-wise method, on both synthetic and PPMI datasets. The fused FCP method demonstrated better accuracy in separating PD from controls than L1 and fused-L1 methods, and similar performance when compared with FCP method. In addition, the fused FCP method showed better ROI identification. Conclusions: The fused FCP method can be an effective approach for MRI biomarker discovery in PD and other studies using high dimensionality data/low sample sizes.
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