Abstract

In this work we propose FlowReg, a deep learning-based framework that performs unsupervised image registration for neuroimaging applications. The system is composed of two architectures that are trained sequentially: FlowReg-A which affinely corrects for gross differences between moving and fixed volumes in 3D followed by FlowReg-O which performs pixel-wise deformations on a slice-by-slice basis for fine tuning in 2D. FlowReg-A warps the moving volume using gross global parameters to align rotation, scale, shear, and translation to the fixed volume. A correlation loss that encourages global alignment between the moving and the fixed volumes is employed to regress the affine parameters. The deformable network FlowReg-O operates on 2D image slices and is based on the optical flow CNN network that is adapted to neuroimaging with three loss components. The photometric loss minimizes pixel intensity differences, the smoothness loss encourages similar magnitudes between neighbouring vectors, and a correlation loss that is used to maintain the intensity similarity between fixed and moving image slices. The proposed method is compared to four open source registration techniques ANTs, Demons, SE, and Voxelmorph for FLAIR MRI applications. In total, 4643 FLAIR MR imaging volumes (approximately 255,000 image slices) are used from dementia and vascular disease cohorts, acquired from over 60 international centres with varying acquisition parameters. To quantitatively assess the performance of the registration tools, a battery of novel validation metrics are proposed that focus on the structural integrity of tissues, spatial alignment, and intensity similarity. Experimental results show FlowReg (FlowReg-A+O) performs better than iterative-based registration algorithms for intensity and spatial alignment metrics with a Pixelwise Agreement (PWA) of 0.65, correlation coefficient (R) of 0.80, and Mutual Information (MI) of 0.29. Among the deep learning frameworks evaluated, FlowReg-A or FlowReg-A+O provided the highest performance over all but one of the metrics. Results show that FlowReg is able to obtain high intensity and spatial similarity between the moving and the fixed volumes while maintaining the shape and structure of anatomy and pathology.