Folded concave penalized learning of high-dimensional MRI data in Parkinson’s disease

• Published in: Journal of neuroscience methods 2021-06, Vol.357, p.109157, Article 109157
• Main Authors: Li, Changcheng, Wang, Xue, Du, Guangwei, Chen, Hairong, Brown, Gregory, Lewis, Mechelle M., Yao, Tao, Li, Runze, Huang, Xuemei
• Format: Article
• Language: English
• Subjects: Algorithms; Brain - diagnostic imaging; Diffusion tensor imaging; Folded concave penalized learning; Humans; Logistic regression; Magnetic Resonance Imaging; Parkinson Disease - diagnostic imaging; Parkinson’s disease; Support Vector Machine
• ISSN: 0165-0270; 1872-678X; 1872-678X
• DOI: 10.1016/j.jneumeth.2021.109157

•We introduce fused folded concave penalized method to identify Parkinson’s markers.•We construct markers from high-dimensional voxel level MRI data with small samples.•Proposed method identifies markers more accurately than other penalized approaches.•Proposed method had better classification accuracy/specificity/sensitivity. 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. 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. 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. 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. 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.