Cycle Inverse-Consistent TransMorph: A Balanced Deep Learning Framework for Brain MRI Registration

Image registration is a fundamental task that aligns anatomical structures between images. While CNNs perform well, they lack rotation equivariance - a rotated input does not produce a correspondingly rotated output. This hinders performance by failing to exploit the rotational symmetries inherent in anatomical structures, particularly in brain MRI. In this work, we integrate rotation-equivariant convolutions into deformable brain MRI registration networks. We evaluate this approach by replacing standard encoders with equivariant ones in three baseline architectures, testing on multiple public brain MRI datasets. Our experiments demonstrate that equivariant encoders have three key advantages: 1) They achieve higher registration accuracy while reducing network parameters, confirming the benefit of this anatomical inductive bias. 2) They outperform baselines on rotated input pairs, demonstrating robustness to orientation variations common in clinical practice. 3) They show improved performance with less training data, indicating greater sample efficiency. Our results demonstrate that incorporating geometric priors is a critical step toward building more robust, accurate, and efficient registration models.

Medical image registration benefits significantly from deep learning, yet existing approaches often lack physical explainability and fine-grained deformation control. Motivated by Demons algorithms, we propose a novel DrivenMorph framework that bridges attention mechanisms with variational image registration by incorporating difference modeling as a physically inspired inductive bias. The resulting driving force, computed from local differences in the latent feature space, provides explicit semantic guidance throughout the registration process. It directly drives the registration process through a neural Demons layer that simulates force-displacement interactions to generate smooth and anatomically consistent deformation. Unlike previous methods, our approach not only integrates traditional registration principles with popular deep networks, providing an explainable and efficient solution for learning-based medical image registration, but also separates difference modeling from deformation, improving modularity and explainability. Extensive experiments on multiple 3D brain MRI datasets demonstrate superior performance over state of-the-art learning-based and optimization-based methods. Furthermore, visualizations and statistical analyses confirm that the learned driving force aligns closely with actual deformation patterns, supporting its explanatory value.

Longitudinal MRI enables sensitive measurement of structural brain change for studying aging and neurodegenerative disease. Deformable image registration is a key tool for estimating such change by computing a dense deformation that captures geometric differences between longitudinal scans. However, MRI scanners introduce geometric distortions that vary across acquisition systems and protocols, such as gradient non-linearity (GNL) distortion. Existing registration methods estimate a single field that conflates biological and technical effects, potentially biasing downstream morphometric measurements if distortions remain (partially) uncorrected. We propose $\texttt{DisMorph}$, a registration framework trained entirely on synthetic data that explicitly decomposes longitudinal deformation into technical and anatomical transforms. It predicts two dense deformations, each encoding one effect. During training, a novel generative model synthesizes both effects separately to provide disentanglement supervision, while domain randomization promotes generalization across imaging protocols. We evaluate our method in three complementary settings. On simulated data with known ground truth, our method detects anatomical change more accurately and consistently than conventional registration. On real image pairs that differ only by GNL distortion, our method assigns most geometric change to the distortion field, demonstrating specificity in the absence of anatomical change. On longitudinal Alzheimer's disease (AD) pairs, our method detects anatomical change in AD-related brain structures while identifying residual distortion left after standard correction. By disentangling MRI-induced distortion from biological change in the longitudinal deformation, our method paves the way for more accurate longitudinal morphometry in clinical settings where maintaining acquisition consistency is challenging.