\texttt{DisMorph}: learning to disentangle technical distortions from true biological change
Authors: Jingru Fu, Kathleen E. Larson, Douglas N. Greve, Bruce Fischl, Malte Hoffmann
Organizations: Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, USA · Department of Radiology, Massachusetts General Hospital, Boston, USA · Department of Radiology, Harvard Medical School, Boston, USA
Abstract
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 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.
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.
Accurate compensation of brain deformation is critical for reliable image-guided neurosurgery. Surgical manipulation and tumor resection induce tissue motion, causing preoperative planning images to become misaligned with the intraoperative anatomy. In this systematic review, we examine data-driven methods developed between 2020 and 2025 for brain deformation registration and modeling, with a particular focus on learning-based approaches. A comprehensive literature search was conducted in PubMed, IEEE Xplore, Scopus, and Web of Science using predefined inclusion and exclusion criteria for computational methods addressing brain deformation in neurosurgical imaging, resulting in 46 eligible studies. We provide a unified analysis of methodological strategies, including deep learning-based image registration, direct deformation field regression, synthesis-driven multimodal alignment, resection-aware architectures for handling missing correspondences, and hybrid models integrating biomechanical priors. We also examine dataset utilization, evaluation metrics, validation protocols, and the assessment of uncertainty and generalization across studies. While learning-based methods demonstrate promising accuracy and computational efficiency, current approaches remain limited by out-of-distribution robustness, standardized benchmarking, interpretability, and readiness for clinical deployment. Our review highlights these gaps and outlines future directions toward more robust, generalizable, and clinically translatable solutions for neurosurgical guidance. By organizing recent advances and critically assessing evaluation practices, this work provides a comprehensive reference for researchers and clinicians working on data-driven registration and modeling of brain deformation.
Tiago Assis, Colin P. Galvin, Joshua P. Castillo +12
Accurate longitudinal analysis of brain MRI is often hindered by evolving lesions, which bias automated neuroimaging pipelines. While deep generative models have shown promise in inpainting these lesions, most existing methods operate cross-sectionally or lack 3D anatomical continuity. We present a novel pseudo-3D longitudinal inpainting framework based on Denoising Diffusion Probabilistic Models (DDPM). Our approach utilizes multi-channel conditioning to incorporate longitudinal context from distinct visits (t_1, t_2) and extends Region-Aware Diffusion (RAD) to the medical domain, focusing the generative process on pathological regions without altering surrounding healthy tissue. We evaluated our model against state-of-the-art baselines on longitudinal brain MRI from 93 patients. Our model significantly outperforms the leading baseline (FastSurfer-LIT) in terms of perceptual fidelity, reducing the Learned Perceptual Image Patch Similarity (LPIPS) distance from 0.07 to 0.03 while effectively eliminating inter-slice discontinuities. Furthermore, our model demonstrates high longitudinal stability with a Temporal Fidelity Index of 1.024, closely approaching the ideal value of 1.0 and substantially narrowing the gap compared to LIT's TFI of 1.22. Notably, the RAD mechanism provides a substantial gain in efficiency; our framework achieves an average processing time of 2.53 min per volume, representing approximately 10x speedup over the 24.30 min required by LIT. By leveraging longitudinal priors and region-specific denoising, our framework provides a highly reliable and efficient preprocessing step for the study of progressive neurodegenerative diseases. A derivative dataset consisting of 93 pre-processed scans used for testing will be available upon request after acceptance. Code will be released upon acceptance.
Zahra Karimaghaloo, Dumitru Fetco, Haz-Edine Assemlal +2