Nonlinearity-aware based dimensionality reduction and over-sampling for AD/MCI classification from MRI measures

Alzheimer's disease (AD) has been not only a substantial financial burden to the health care system but also an emotional burden to patients and their families. Making accurate diagnosis of AD based on brain magnetic resonance imaging (MRI) is becoming more and more critical and emphasized at the earliest stages. However, the high dimensionality and imbalanced data issues are two major challenges in the study of computer aided AD diagnosis. The greatest limitations of existing dimensionality reduction and over-sampling methods are that they assume a linear relationship between the MRI features (predictor) and the disease status (response). To better capture the complicated but more flexible relationship, we propose a multi-kernel based dimensionality reduction and over-sampling approaches. We combined Marginal Fisher Analysis with l(2,1)-norm based multi-kernel learning (MKMFA) to achieve the sparsity of region-of-interest (ROI), which leads to simultaneously selecting a subset of the relevant brain regions and learning a dimensionality transformation. Meanwhile, a multi-kernel over-sampling (MKOS) was developed to generate synthetic instances in the optimal kernel space induced by MKMFA, so as to compensate for the class imbalanced distribution. We comprehensively evaluate the proposed models for the diagnostic classification (binary class and multi-class classification) including all subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. The experimental results not only demonstrate the proposed method has superior performance over multiple comparable methods, but also identifies relevant imaging biomarkers that are consistent with prior medical knowledge.