In recent years, the rapid development of artificial intelligence has promoted the widespread application of convolutional neural networks (CNNs) in neuroimaging analysis. Although three-dimensional (3D) CNNs can utilize the spatial information in 3D volumes, there are still some challenges related to high-dimensional features and potential overfitting issues. To overcome these problems, patch-based CNNs have been used, which are beneficial for model generalization. However, it is unclear how the choice of a patchwise sampling strategy affects the performance of the Alzheimer's Disease (AD) classification. To this end, the present work investigates the impact of a patchwise sampling strategy for 3D CNN based AD classification. A 3D framework cascaded by two-stage subnetworks was used for AD classification. The patch-level subnetworks learned feature representations from local image patches, and the subject-level subnetwork combined discriminative feature representations from all patch-level subnetworks to generate a classification score at the subject level. Experiments were conducted to determine the effect of patch partitioning methods, the effect of patch size, and interactions between patch size and training set size for AD classification. With the same data size and identical network structure, the 3D CNN model trained with 48 × 48 × 48 cubic image patches showed the best performance in AD classification (ACC = 89.6%). The model trained with hippocampus-centered, region of interest (ROI)-based image patches showed suboptimal performance. If the pathological features are concentrated only in some regions affected by the disease, the empirically predefined ROI patches might be the right choice. The better performance of cubic image patches compared with cuboidal image patches is likely related to the pathological distribution of AD. The image patch size and training sample size together have a complex influence on the performance of the classification. The size of the image patches should be determined based on the size of the training sample to compensate for noisy labels and the problem of the curse of dimensionality. The conclusions of the present study can serve as a reference for the researchers who wish to develop a superior 3D patch-based CNN model with an appropriate patch sampling strategy.
Keywords: Alzheimer’s Disease; convolutional neural networks; deep learning; image patch; neuroimaging.