Background: Plantar pressure image (PPI) recorded in high spatial and temporal resolution is very useful in clinical gait analysis. For functional analysis of PPI, image registration is often performed to maximally correlate source image with a template image. Previous methods estimate the registration parameters by iteratively optimizing different objective functions. These methods are often computational expensive to achieve satisfactory registration accuracy.Research Question: Can we develop a single PPI registration technique that performs more rapidly than previous methods, and that also maintains adequate PPI correspondence as defined by various (dis)similarity metrics?Methods: A cascaded convolutional neural network (CNN) was proposed for the registration of PPIs. Our model was trained to learn a regression from the difference between the template and misaligned images to the registration parameters. The registration performance was evaluated by three different metrics, i.e. the mean squared error (MSE), the exclusive or (XOR), and the mutual information (MI). For comparison, four previous methods were also implemented. These included the principal axes (PA) method, the center of pressure trajectory (COP) method, the MSE method, and the XOR method.Results: Experimental results on a dataset with 71 PPI template-source pairs showed that the proposed CNN-based method could obtain comparable registration accuracy to the MSE and XOR method. With regards to the registration speed, registration durations (mean ± sd in seconds) per image pair were: MSE (30.584 ± 2.171), XOR (24.245 ± 1.596), PA (0.016 ± 0.003), COP (25.614 ± 0.341), and the proposed model (0.054 ± 0.007).Significance: Our findings indicate that the proposed registration approach can achieve high accuracy but less computational time. Thus, it is more practical to utilize our pre-trained CNN-based model to develop near-real time applications for plantar pressure images registration. [ABSTRACT FROM AUTHOR]