Fast and Accurate Monomodal 3D High Resolution Deep Registration of Drosophila Larval Brain Volumes
Authors: Daniel Reisenbüchler, Yousef Sadegheih, Michael Dittrich, Pratibha Kumari, Muhammad Usman, Dorit Merhof
Abstract
The larval stage of Drosophila melanogaster is a compact model system for neuroscience whose genetic toolkit allows fluorescent markers to be expressed in defined neural populations, and comparing the resulting expression patterns across animals requires every brain to be registered into a shared anatomical reference space. Existing pipelines for this task are predominantly based on classical registration methods, which perform a new optimization for each volume, often require per-case parameter tuning, and can take minutes per brain, limiting their use as a routine preprocessing step. We present a trained deep registration pipeline that deformably aligns a larval brain to a reference template in a single forward pass at high spatial resolution, on volumes that hold several times more voxels than those learned 3D registration is normally reported on, together with the preprocessing and anatomy-anchored evaluation pipeline required to apply it. Against eleven classical and seven further learned baselines on a held-out collection acquired with different acquisition and quality strata, the proposed pipeline is the most accurate, improving on the strongest classical baseline by 23 percentage points of anatomical landmark-local mutual information. It registers a volume one to two orders of magnitude faster than the classical deformable pipelines, and it retains more of its accuracy than any other method as acquisition quality degrades. The network, its trained weights and the full pipeline are released as the open-source deep larval brain registration framework: https://github.com/agentdr1/deep-larval-brain-reg
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.
Deformable medical image registration aligns anatomical structures across images but remains computationally dense at 3D resolution. Spiking neural networks (SNNs) offer sparse event-driven computation, yet have not been systematically studied for deformable medical image registration. We introduce SpikeReg, a spiking U-Net for 3D brain MRI registration. SpikeReg is initialized from an analog ANN registration teacher, converted by layer-wise weight transfer and activation-percentile threshold calibration, and fine-tuned with a surrogate-gradient objective combining local cross-correlation, diffusion regularization, and spike-rate sparsity. On the OASIS Learn2Reg validation split (19 image pairs), SpikeReg reaches Dice 0.7474±0.032, with no significant paired Dice difference from the ANN teacher (0.7480±0.037, p=0.67), at a 12.8% mean spike rate and a 55.5× projected arithmetic-energy reduction under an event-sparse SynOps/MAC proxy relative to the dense-ANN baseline. We additionally report two negative findings: displacement distillation from the ANN teacher hurts performance, and ANN teachers trained with a label-Dice loss fail to transfer through rate-code conversion. Together these results show that dense geometric prediction can be performed under sparse event-driven computation, opening a path toward neuromorphic medical image registration.
Ali Mikaeili Barzili, Behzad Moshiri, Hamid Azadegan +1
3D/2D registration serves as a cornerstone technique in surgical navigation. Traditional iterative optimization algorithms suffer from low efficiency and high failure rates in intraoperative settings. Deep learning-based methods reformulate registration from iterative optimization to a regression problem that maps image appearance features to spatial pose, typically achieving improved real-time performance and accuracy. However, such learnable methods are confined to memory-driven retrieval of specific pose features rather than understanding the task of image alignment itself, which limits their generalization in complex scenarios. We propose LayersReg, a pioneering regression paradigm that endows the model with 3D anatomical awareness and searches for the correct pose in a progressive, layer-by-layer manner. Inspired by the iterative pose-searching optimization criterion of classical registration, LayersReg searches for correlations between the moving and fixed images in feature space, capturing the trend of pixel flow and thereby converging iteratively toward the correct spatial pose transformation. We further design a coupling of node-wise regression with the progressive registration framework to enhance the model's perception of spatial pose changes. Experimental results demonstrate that under large offsets and multimodality conditions, LayersReg achieves high accuracy on both X-ray/CT registration (0.68°, 1.41 mm) and slice localization (0.73°, 1.55 mm) tasks, outperforming existing state-of-the-art methods while meeting the intraoperative demands for precision and real-time capability.