  The majority of current research in deep learning based image registration
addresses inter-patient brain registration with moderate deformation
magnitudes. The recent Learn2Reg medical registration benchmark has
demonstrated that single-scale U-Net architectures, such as VoxelMorph that
directly employ a spatial transformer loss, often do not generalise well beyond
the cranial vault and fall short of state-of-the-art performance for abdominal
or intra-patient lung registration. Here, we propose two straightforward steps
that greatly reduce this gap in accuracy. First, we employ keypoint
self-supervision with a novel network head that predicts a discretised heatmap
and robustly reduces large deformations for better robustness. Second, we
replace multiple learned fine-tuning steps by a single instance optimisation
with hand-crafted features and the Adam optimiser. Different to other related
work, including FlowNet or PDD-Net, our approach does not require a fully
discretised architecture with correlation layer. Our ablation study
demonstrates the importance of keypoints in both self-supervised and
unsupervised (using only a MIND metric) settings. On a multi-centric
inspiration-exhale lung CT dataset, including very challenging COPD scans, our
method outperforms VoxelMorph by improving nonlinear alignment by 77% compared
to 19% - reaching target registration errors of 2 mm that outperform all but
one learning methods published to date. Extending the method to semantic
features sets new stat-of-the-art performance on inter-subject abdominal CT
registration.
