Alexandra Golby

Reuben Dorent, Nazim Haouchine, Fryderyk Kögl et al. · harvard

We introduce MHVAE, a deep hierarchical variational auto-encoder (VAE) that synthesizes missing images from various modalities. Extending multi-modal VAEs with a hierarchical latent structure, we introduce a probabilistic formulation for fusing multi-modal images in a common latent representation while having the flexibility to handle incomplete image sets as input. Moreover, adversarial learning is employed to generate sharper images. Extensive experiments are performed on the challenging problem of joint intra-operative ultrasound (iUS) and Magnetic Resonance (MR) synthesis. Our model outperformed multi-modal VAEs, conditional GANs, and the current state-of-the-art unified method (ResViT) for synthesizing missing images, demonstrating the advantage of using a hierarchical latent representation and a principled probabilistic fusion operation. Our code is publicly available \url{https://github.com/ReubenDo/MHVAE}.

Maximilian Fehrentz, Mohammad Farid Azampour, Reuben Dorent et al.

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/.

Hassan Rasheed, Reuben Dorent, Maximilian Fehrentz et al.

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.

Reuben Dorent, Erickson Torio, Nazim Haouchine et al.

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}.

Reuben Dorent, Nazim Haouchine, Alexandra Golby et al.

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.

Kathleen Baur, Xin Xiong, Erickson Torio et al. · harvard

Although Digital Subtraction Angiography (DSA) is the most important imaging for visualizing cerebrovascular anatomy, its interpretation by clinicians remains difficult. This is particularly true when treating arteriovenous malformations (AVMs), where entangled vasculature connecting arteries and veins needs to be carefully identified.The presented method aims to enhance DSA image series by highlighting critical information via automatic classification of vessels using a combination of two learning models: An unsupervised machine learning method based on Independent Component Analysis that decomposes the phases of flow and a convolutional neural network that automatically delineates the vessels in image space. The proposed method was tested on clinical DSA images series and demonstrated efficient differentiation between arteries and veins that provides a viable solution to enhance visualizations for clinical use.

Lasse Hansen, Wiebke Heyer, Christoph Großbröhmer et al.

Medical image registration is critical for clinical applications, and fair benchmarking of different methods is essential for monitoring ongoing progress. To date, the Learn2Reg 2020-2023 challenges have released several complementary datasets and established metrics for evaluations. However, these editions did not capture all aspects of the registration problem, particularly in terms of modality diversity and task complexity. To address these limitations, the 2024 edition introduces three new tasks, including large-scale multi-modal registration and unsupervised inter-subject brain registration, as well as the first microscopy-focused benchmark within Learn2Reg. The new datasets also inspired new method developments, including invertibility constraints, pyramid features, keypoints alignment and instance optimisation.

Reuben Dorent, Laura Rigolo, Colin P. Galvin et al.

Accurate intraoperative image guidance is critical for achieving maximal safe resection in brain tumor surgery, yet neuronavigation systems based on preoperative MRI lose accuracy during the procedure due to brain shift. Aligning post-resection intraoperative ultrasound (iUS) with preoperative MRI can restore spatial accuracy by estimating brain shift deformations, but it remains a challenging problem given the large anatomical and topological changes and substantial modality intensity gap. The ReMIND2Reg 2025 Challenge provides the largest public benchmark for this task, built upon the ReMIND dataset. It offers 99 training cases, 5 validation cases, and 10 private test cases comprising paired 3D ceT1 MRI, T2 MRI, and post-resection 3D iUS volumes. Data are provided without annotations for training, while validation and test performance are evaluated on manually annotated anatomical landmarks. Metrics include target registration error (TRE), robustness to worst-case landmark misalignment (TRE30), and runtime. By establishing a standardized evaluation framework for this clinically critical and technically complex problem, ReMIND2Reg aims to accelerate the development of robust, generalizable, and clinically deployable multimodal registration algorithms for image-guided neurosurgery.

Jie Luo, Guangshen Ma, Sarah Frisken et al.

With the increasing availability of new image registration approaches, an unbiased evaluation is becoming more needed so that clinicians can choose the most suitable approaches for their applications. Current evaluations typically use landmarks in manually annotated datasets. As a result, the quality of annotations is crucial for unbiased comparisons. Even though most data providers claim to have quality control over their datasets, an objective third-party screening can be reassuring for intended users. In this study, we use the variogram to screen the manually annotated landmarks in two datasets used to benchmark registration in image-guided neurosurgeries. The variogram provides an intuitive 2D representation of the spatial characteristics of annotated landmarks. Using variograms, we identified potentially problematic cases and had them examined by experienced radiologists. We found that (1) a small number of annotations may have fiducial localization errors; (2) the landmark distribution for some cases is not ideal to offer fair comparisons. If unresolved, both findings could incur bias in registration evaluation.

Jie Luo, Sarah Frisken, Duo Wang et al.

In image-guided neurosurgery, current commercial systems usually provide only rigid registration, partly because it is harder to predict, validate and understand non-rigid registration error. For instance, when surgeons see a discrepancy in aligned image features, they may not be able to distinguish between registration error and actual tissue deformation caused by tumor resection. In this case, the spatial distribution of registration error could help them make more informed decisions, e.g., ignoring the registration where the estimated error is high. However, error estimates are difficult to acquire. Probabilistic image registration (PIR) methods provide measures of registration uncertainty, which could be a surrogate for assessing the registration error. It is intuitive and believed by many clinicians that high uncertainty indicates a large error. However, the monotonic association between uncertainty and error has not been examined in image registration literature. In this pilot study, we attempt to address this fundamental problem by looking at one PIR method, the Gaussian process (GP) registration. We systematically investigate the relation between GP uncertainty and error based on clinical data and show empirically that there is a weak-to-moderate positive monotonic correlation between point-wise GP registration uncertainty and non-rigid registration error.

Jie Luo, Matt Toews, Ines Machado et al.

A reliable Ultrasound (US)-to-US registration method to compensate for brain shift would substantially improve Image-Guided Neurological Surgery. Developing such a registration method is very challenging, due to factors such as missing correspondence in images, the complexity of brain pathology and the demand for fast computation. We propose a novel feature-driven active framework. Here, landmarks and their displacement are first estimated from a pair of US images using corresponding local image features. Subsequently, a Gaussian Process (GP) model is used to interpolate a dense deformation field from the sparse landmarks. Kernels of the GP are estimated by using variograms and a discrete grid search method. If necessary, the user can actively add new landmarks based on the image context and visualization of the uncertainty measure provided by the GP to further improve the result. We retrospectively demonstrate our registration framework as a robust and accurate brain shift compensation solution on clinical data acquired during neurosurgery.

Jie Luo, Alireza Sedghi, Karteek Popuri et al.

Estimating the uncertainty in (probabilistic) image registration enables, e.g., surgeons to assess the operative risk based on the trustworthiness of the registered image data. If surgeons receive inaccurately calculated registration uncertainty and misplace unwarranted confidence in the alignment solutions, severe consequences may result. For probabilistic image registration (PIR), the predominant way to quantify the registration uncertainty is using summary statistics of the distribution of transformation parameters. The majority of existing research focuses on trying out different summary statistics as well as a means to exploit them. Distinctively, in this paper, we study two rarely examined topics: (1) whether those summary statistics of the transformation distribution most informatively represent the registration uncertainty; (2) Does utilizing the registration uncertainty always be beneficial. We show that there are two types of uncertainties: the transformation uncertainty, Ut, and label uncertainty Ul. The conventional way of using Ut to quantify Ul is inappropriate and can be misleading. By a real data experiment, we also share a potentially critical finding that making use of the registration uncertainty may not always be an improvement.

Jan Egger, Tina Kapur, Andriy Fedorov et al.

Volumetric change in glioblastoma multiforme (GBM) over time is a critical factor in treatment decisions. Typically, the tumor volume is computed on a slice-by-slice basis using MRI scans obtained at regular intervals. (3D)Slicer - a free platform for biomedical research - provides an alternative to this manual slice-by-slice segmentation process, which is significantly faster and requires less user interaction. In this study, 4 physicians segmented GBMs in 10 patients, once using the competitive region-growing based GrowCut segmentation module of Slicer, and once purely by drawing boundaries completely manually on a slice-by-slice basis. Furthermore, we provide a variability analysis for three physicians for 12 GBMs. The time required for GrowCut segmentation was on an average 61% of the time required for a pure manual segmentation. A comparison of Slicer-based segmentation with manual slice-by-slice segmentation resulted in a Dice Similarity Coefficient of 88.43 +/- 5.23% and a Hausdorff Distance of 2.32 +/- 5.23 mm.