Architectural and Regularization Components in Deep Learning Medical Image Registration: Systematic Ablation Study

Deep learning registration methods routinely stack two kinds of enhancement on a base network: architectural additions such as affine pre-alignment stages, and training-objective additions such as regularization losses. Papers tend to adopt both at once, so it is unclear which is doing the work. I ran a controlled ablation to separate them. Using the OASIS brain MRI dataset (394 training subjects, 20 test subjects), I trained four variants of the same registration pipeline: a baseline 3D U-Net with basic similarity losses, the same U-Net with a full regularization suite, an affine-plus-deformable architecture with basic losses, and the affine architecture with the full suite. I evaluated registration accuracy (MSE, NCC, SSIM), deformation quality (Jacobian determinant preservation, displacement statistics, an anatomical plausibility score), and computational cost. Regularization alone accounted for most of the gain: a 21.3% relative gain on the MSE-improvement metric (1.78% to 2.16%, P<.001) and a 21.8% relative gain in NCC improvement, while cutting maximum deformation from 53.1 to 0.51 units, a 99.0% reduction, at essentially no computational cost (-0.06% inference time). The combined model produced the largest accuracy gain, 25.8% (1.78% to 2.24%), and raised anatomical plausibility from 0.596 to 0.930, at a moderate +9.8% inference-time cost. Gradient correlation rose from 0.742 at baseline to 0.980 for the fully enhanced model. All enhanced variants reached sub-voxel accuracy under plausible deformation constraints. Regularization losses are the primary driver in this setting, delivering the accuracy gains and almost all of the deformation control for free at inference time, while the affine architecture adds a smaller complementary benefit at acceptable cost. The 99% reduction in unrealistic deformations addresses a known barrier to clinical deployment.