A Systematic Review on Data-Driven Brain Deformation Modeling for Image-Guided Neurosurgery

Accurate compensation of brain deformation is a critical challenge for reliable image-guided neurosurgery, as surgical manipulation and tumor resection induce tissue motion that misaligns preoperative planning images with intraoperative anatomy and longitudinal studies. In this systematic review, we synthesize recent AI-driven approaches developed between January 2020 and April 2025 for modeling and correcting brain deformation. A comprehensive literature search was conducted in PubMed, IEEE Xplore, Scopus, and Web of Science, with predefined inclusion and exclusion criteria focused on computational methods applied to brain deformation compensation for neurosurgical imaging, resulting in 41 studies meeting these criteria. 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 addressing missing correspondences, and hybrid models that integrate biomechanical priors. We also examine dataset utilization, reported evaluation metrics, validation protocols, and how uncertainty and generalization have been assessed across studies. While AI-based deformation models demonstrate promising performance and computational efficiency, current approaches exhibit limitations in out-of-distribution robustness, standardized benchmarking, interpretability, and readiness for clinical deployment. Our review highlights these gaps and outlines opportunities for future research aimed at achieving more robust, generalizable, and clinically translatable deformation compensation solutions for neurosurgical guidance. By organizing recent advances and critically evaluating evaluation practices, this work provides a comprehensive foundation for researchers and clinicians engaged in developing and applying AI-based brain deformation methods.

Connecting Jensen-Shannon and Kullback-Leibler Divergences: A New Bound for Representation Learning

Mutual Information (MI) is a fundamental measure of statistical dependence widely used in representation learning. While direct optimization of MI via its definition as a Kullback-Leibler divergence (KLD) is often intractable, many recent methods have instead maximized alternative dependence measures, most notably, the Jensen-Shannon divergence (JSD) between joint and product of marginal distributions via discriminative losses. However, the connection between these surrogate objectives and MI remains poorly understood. In this work, we bridge this gap by deriving a new, tight, and tractable lower bound on KLD as a function of JSD in the general case. By specializing this bound to joint and marginal distributions, we demonstrate that maximizing the JSD-based information increases a guaranteed lower bound on mutual information. Furthermore, we revisit the practical implementation of JSD-based objectives and observe that minimizing the cross-entropy loss of a binary classifier trained to distinguish joint from marginal pairs recovers a known variational lower bound on the JSD. Extensive experiments demonstrate that our lower bound is tight when applied to MI estimation. We compared our lower bound to state-of-the-art neural estimators of variational lower bound across a range of established reference scenarios. Our lower bound estimator consistently provides a stable, low-variance estimate of a tight lower bound on MI. We also demonstrate its practical usefulness in the context of the Information Bottleneck framework. Taken together, our results provide new theoretical justifications and strong empirical evidence for using discriminative learning in MI-based representation learning.

Unsupervised anomaly detection using Bayesian flow networks: application to brain FDG PET in the context of Alzheimer's disease

Unsupervised anomaly detection (UAD) plays a crucial role in neuroimaging for identifying deviations from healthy subject data and thus facilitating the diagnosis of neurological disorders. In this work, we focus on Bayesian flow networks (BFNs), a novel class of generative models, which have not yet been applied to medical imaging or anomaly detection. BFNs combine the strength of diffusion frameworks and Bayesian inference. We introduce AnoBFN, an extension of BFNs for UAD, designed to: i) perform conditional image generation under high levels of spatially correlated noise, and ii) preserve subject specificity by incorporating a recursive feedback from the input image throughout the generative process. We evaluate AnoBFN on the challenging task of Alzheimer's disease-related anomaly detection in FDG PET images. Our approach outperforms other state-of-the-art methods based on VAEs (beta-VAE), GANs (f-AnoGAN), and diffusion models (AnoDDPM), demonstrating its effectiveness at detecting anomalies while reducing false positive rates.

crossMoDA Challenge: Evolution of Cross-Modality Domain Adaptation Techniques for Vestibular Schwannoma and Cochlea Segmentation from 2021 to 2023

The cross-Modality Domain Adaptation (crossMoDA) challenge series, initiated in 2021 in conjunction with the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI), focuses on unsupervised cross-modality segmentation, learning from contrast-enhanced T1 (ceT1) and transferring to T2 MRI. The task is an extreme example of domain shift chosen to serve as a meaningful and illustrative benchmark. From a clinical application perspective, it aims to automate Vestibular Schwannoma (VS) and cochlea segmentation on T2 scans for more cost-effective VS management. Over time, the challenge objectives have evolved to enhance its clinical relevance. The challenge evolved from using single-institutional data and basic segmentation in 2021 to incorporating multi-institutional data and Koos grading in 2022, and by 2023, it included heterogeneous routine data and sub-segmentation of intra- and extra-meatal tumour components. In this work, we report the findings of the 2022 and 2023 editions and perform a retrospective analysis of the challenge progression over the years. The observations from the successive challenge contributions indicate that the number of outliers decreases with an expanding dataset. This is notable since the diversity of scanning protocols of the datasets concurrently increased. The winning approach of the 2023 edition reduced the number of outliers on the 2021 and 2022 testing data, demonstrating how increased data heterogeneity can enhance segmentation performance even on homogeneous data. However, the cochlea Dice score declined in 2023, likely due to the added complexity from tumour sub-annotations affecting overall segmentation performance. While progress is still needed for clinically acceptable VS segmentation, the plateauing performance suggests that a more challenging cross-modal task may better serve future benchmarking.

Beyond the LUMIR challenge: The pathway to foundational registration models

Medical image challenges have played a transformative role in advancing the field, catalyzing algorithmic innovation and establishing new performance standards across diverse clinical applications. Image registration, a foundational task in neuroimaging pipelines, has similarly benefited from the Learn2Reg initiative. Building on this foundation, we introduce the Large-scale Unsupervised Brain MRI Image Registration (LUMIR) challenge, a next-generation benchmark designed to assess and advance unsupervised brain MRI registration. Distinct from prior challenges that leveraged anatomical label maps for supervision, LUMIR removes this dependency by providing over 4,000 preprocessed T1-weighted brain MRIs for training without any label maps, encouraging biologically plausible deformation modeling through self-supervision. In addition to evaluating performance on 590 held-out test subjects, LUMIR introduces a rigorous suite of zero-shot generalization tasks, spanning out-of-domain imaging modalities (e.g., FLAIR, T2-weighted, T2*-weighted), disease populations (e.g., Alzheimer's disease), acquisition protocols (e.g., 9.4T MRI), and species (e.g., macaque brains). A total of 1,158 subjects and over 4,000 image pairs were included for evaluation. Performance was assessed using both segmentation-based metrics (Dice coefficient, 95th percentile Hausdorff distance) and landmark-based registration accuracy (target registration error). Across both in-domain and zero-shot tasks, deep learning-based methods consistently achieved state-of-the-art accuracy while producing anatomically plausible deformation fields. The top-performing deep learning-based models demonstrated diffeomorphic properties and inverse consistency, outperforming several leading optimization-based methods, and showing strong robustness to most domain shifts, the exception being a drop in performance on out-of-domain contrasts.

Unified Cross-Modal Image Synthesis with Hierarchical Mixture of Product-of-Experts

We propose a deep mixture of multimodal hierarchical variational auto-encoders called MMHVAE that synthesizes missing images from observed images in different modalities. MMHVAE's design focuses on tackling four challenges: (i) creating a complex latent representation of multimodal data to generate high-resolution images; (ii) encouraging the variational distributions to estimate the missing information needed for cross-modal image synthesis; (iii) learning to fuse multimodal information in the context of missing data; (iv) leveraging dataset-level information to handle incomplete data sets at training time. Extensive experiments are performed on the challenging problem of pre-operative brain multi-parametric magnetic resonance and intra-operative ultrasound imaging.

Intraoperative Registration by Cross-Modal Inverse Neural Rendering

We present in this paper a novel approach for 3D/2D intraoperative registration during neurosurgery via cross-modal inverse neural rendering. Our approach separates implicit neural representation into two components, handling anatomical structure preoperatively and appearance intraoperatively. This disentanglement is achieved by controlling a Neural Radiance Field's appearance with a multi-style hypernetwork. Once trained, the implicit neural representation serves as a differentiable rendering engine, which can be used to estimate the surgical camera pose by minimizing the dissimilarity between its rendered images and the target intraoperative image. We tested our method on retrospective patients' data from clinical cases, showing that our method outperforms state-of-the-art while meeting current clinical standards for registration. Code and additional resources can be found at https://maxfehrentz.github.io/style-ngp/.

Learning to Match 2D Keypoints Across Preoperative MR and Intraoperative Ultrasound

We propose in this paper a texture-invariant 2D keypoints descriptor specifically designed for matching preoperative Magnetic Resonance (MR) images with intraoperative Ultrasound (US) images. We introduce a matching-by-synthesis strategy, where intraoperative US images are synthesized from MR images accounting for multiple MR modalities and intraoperative US variability. We build our training set by enforcing keypoints localization over all images then train a patient-specific descriptor network that learns texture-invariant discriminant features in a supervised contrastive manner, leading to robust keypoints descriptors. Our experiments on real cases with ground truth show the effectiveness of the proposed approach, outperforming the state-of-the-art methods and achieving 80.35% matching precision on average.

LNQ 2023 challenge: Benchmark of weakly-supervised techniques for mediastinal lymph node quantification

Accurate assessment of lymph node size in 3D CT scans is crucial for cancer staging, therapeutic management, and monitoring treatment response. Existing state-of-the-art segmentation frameworks in medical imaging often rely on fully annotated datasets. However, for lymph node segmentation, these datasets are typically small due to the extensive time and expertise required to annotate the numerous lymph nodes in 3D CT scans. Weakly-supervised learning, which leverages incomplete or noisy annotations, has recently gained interest in the medical imaging community as a potential solution. Despite the variety of weakly-supervised techniques proposed, most have been validated only on private datasets or small publicly available datasets. To address this limitation, the Mediastinal Lymph Node Quantification (LNQ) challenge was organized in conjunction with the 26th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2023). This challenge aimed to advance weakly-supervised segmentation methods by providing a new, partially annotated dataset and a robust evaluation framework. A total of 16 teams from 5 countries submitted predictions to the validation leaderboard, and 6 teams from 3 countries participated in the evaluation phase. The results highlighted both the potential and the current limitations of weakly-supervised approaches. On one hand, weakly-supervised approaches obtained relatively good performance with a median Dice score of $61.0\%$. On the other hand, top-ranked teams, with a median Dice score exceeding $70\%$, boosted their performance by leveraging smaller but fully annotated datasets to combine weak supervision and full supervision. This highlights both the promise of weakly-supervised methods and the ongoing need for high-quality, fully annotated data to achieve higher segmentation performance.

Patient-Specific Real-Time Segmentation in Trackerless Brain Ultrasound

Intraoperative ultrasound (iUS) imaging has the potential to improve surgical outcomes in brain surgery. However, its interpretation is challenging, even for expert neurosurgeons. In this work, we designed the first patient-specific framework that performs brain tumor segmentation in trackerless iUS. To disambiguate ultrasound imaging and adapt to the neurosurgeon's surgical objective, a patient-specific real-time network is trained using synthetic ultrasound data generated by simulating virtual iUS sweep acquisitions in pre-operative MR data. Extensive experiments performed in real ultrasound data demonstrate the effectiveness of the proposed approach, allowing for adapting to the surgeon's definition of surgical targets and outperforming non-patient-specific models, neurosurgeon experts, and high-end tracking systems. Our code is available at: \url{https://github.com/ReubenDo/MHVAE-Seg}.