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Segmenting 3D blood vessels is a critical yet challenging task in medical image analysis. This is due to significant imaging modality-specific variations in artifacts, vascular patterns and scales, signal-to-noise ratios, and background tissues. These variations, along with domain gaps arising from varying imaging protocols, limit the generalization of existing supervised learning-based methods, requiring tedious voxel-level annotations for each dataset separately. While foundation models promise to alleviate this limitation, they typically fail to generalize to the task of blood vessel segmentation, posing a unique, complex problem. In this work, we present vesselFM, a foundation model designed specifically for the broad task of 3D blood vessel segmentation. Unlike previous models, vesselFM can effortlessly generalize to unseen domains. To achieve zero-shot generalization, we train vesselFM on three heterogeneous data sources: a large, curated annotated dataset, data generated by a domain randomization scheme, and data sampled from a flow matching-based generative model. Extensive evaluations show that vesselFM outperforms state-of-the-art medical image segmentation foundation models across four (pre-)clinically relevant imaging modalities in zero-, one-, and few-shot scenarios, therefore providing a universal solution for 3D blood vessel segmentation.

This paper presents FedPID, our submission to the Federated Tumor Segmentation Challenge 2024 (FETS24). Inspired by FedCostWAvg and FedPIDAvg, our winning contributions to FETS21 and FETS2022, we propose an improved aggregation strategy for federated and collaborative learning. FedCostWAvg is a method that averages results by considering both the number of training samples in each group and how much the cost function decreased in the last round of training. This is similar to how the derivative part of a PID controller works. In FedPIDAvg, we also included the integral part that was missing. Another challenge we faced were vastly differing dataset sizes at each center. We solved this by assuming the sizes follow a Poisson distribution and adjusting the training iterations for each center accordingly. Essentially, this part of the method controls that outliers that require too much training time are less frequently used. Based on these contributions we now adapted FedPIDAvg by changing how the integral part is computed. Instead of integrating the loss function we measure the global drop in cost since the first round.

Blood vessel networks, represented as 3D graphs, help predict disease biomarkers, simulate blood flow, and aid in synthetic image generation, relevant in both clinical and pre-clinical settings. However, generating realistic vessel graphs that correspond to an anatomy of interest is challenging. Previous methods aimed at generating vessel trees mostly in an autoregressive style and could not be applied to vessel graphs with cycles such as capillaries or specific anatomical structures such as the Circle of Willis. Addressing this gap, we introduce the first application of \textit{denoising diffusion models} in 3D vessel graph generation. Our contributions include a novel, two-stage generation method that sequentially denoises node coordinates and edges. We experiment with two real-world vessel datasets, consisting of microscopic capillaries and major cerebral vessels, and demonstrate the generalizability of our method for producing diverse, novel, and anatomically plausible vessel graphs., Comment: Accepted to MICCAI 2024

Cardiac Magnetic Resonance (CMR) imaging serves as the gold-standard for evaluating cardiac morphology and function. Typically, a multi-view CMR stack, covering short-axis (SA) and 2/3/4-chamber long-axis (LA) views, is acquired for a thorough cardiac assessment. However, efficiently streamlining the complex, high-dimensional 3D+T CMR data and distilling compact, coherent representation remains a challenge. In this work, we introduce a whole-heart self-supervised learning framework that utilizes masked imaging modeling to automatically uncover the correlations between spatial and temporal patches throughout the cardiac stacks. This process facilitates the generation of meaningful and well-clustered heart representations without relying on the traditionally required, and often costly, labeled data. The learned heart representation can be directly used for various downstream tasks. Furthermore, our method demonstrates remarkable robustness, ensuring consistent representations even when certain CMR planes are missing/flawed. We train our model on 14,000 unlabeled CMR data from UK BioBank and evaluate it on 1,000 annotated data. The proposed method demonstrates superior performance to baselines in tasks that demand comprehensive 3D+T cardiac information, e.g. cardiac phenotype (ejection fraction and ventricle volume) prediction and multi-plane/multi-frame CMR segmentation, highlighting its effectiveness in extracting comprehensive cardiac features that are both anatomically and pathologically relevant.

Vertebral fracture grading classifies the severity of vertebral fractures, which is a challenging task in medical imaging and has recently attracted Deep Learning (DL) models. Only a few works attempted to make such models human-interpretable despite the need for transparency and trustworthiness in critical use cases like DL-assisted medical diagnosis. Moreover, such models either rely on post-hoc methods or additional annotations. In this work, we propose a novel interpretable-by-design method, ProtoVerse, to find relevant sub-parts of vertebral fractures (prototypes) that reliably explain the model's decision in a human-understandable way. Specifically, we introduce a novel diversity-promoting loss to mitigate prototype repetitions in small datasets with intricate semantics. We have experimented with the VerSe'19 dataset and outperformed the existing prototype-based method. Further, our model provides superior interpretability against the post-hoc method. Importantly, expert radiologists validated the visual interpretability of our results, showing clinical applicability., Comment: Accepted for publication at the Journal of Machine Learning for Biomedical Imaging (MELBA) https://melba-journal.org/2024:015

Diffusion-weighted MRI (DWI) is essential for stroke diagnosis, treatment decisions, and prognosis. However, image and disease variability hinder the development of generalizable AI algorithms with clinical value. We address this gap by presenting a novel ensemble algorithm derived from the 2022 Ischemic Stroke Lesion Segmentation (ISLES) challenge. ISLES'22 provided 400 patient scans with ischemic stroke from various medical centers, facilitating the development of a wide range of cutting-edge segmentation algorithms by the research community. Through collaboration with leading teams, we combined top-performing algorithms into an ensemble model that overcomes the limitations of individual solutions. Our ensemble model achieved superior ischemic lesion detection and segmentation accuracy on our internal test set compared to individual algorithms. This accuracy generalized well across diverse image and disease variables. Furthermore, the model excelled in extracting clinical biomarkers. Notably, in a Turing-like test, neuroradiologists consistently preferred the algorithm's segmentations over manual expert efforts, highlighting increased comprehensiveness and precision. Validation using a real-world external dataset (N=1686) confirmed the model's generalizability. The algorithm's outputs also demonstrated strong correlations with clinical scores (admission NIHSS and 90-day mRS) on par with or exceeding expert-derived results, underlining its clinical relevance. This study offers two key findings. First, we present an ensemble algorithm (https://github.com/Tabrisrei/ISLES22_Ensemble) that detects and segments ischemic stroke lesions on DWI across diverse scenarios on par with expert (neuro)radiologists. Second, we show the potential for biomedical challenge outputs to extend beyond the challenge's initial objectives, demonstrating their real-world clinical applicability.

Uncertainty in medical image segmentation tasks, especially inter-rater variability, arising from differences in interpretations and annotations by various experts, presents a significant challenge in achieving consistent and reliable image segmentation. This variability not only reflects the inherent complexity and subjective nature of medical image interpretation but also directly impacts the development and evaluation of automated segmentation algorithms. Accurately modeling and quantifying this variability is essential for enhancing the robustness and clinical applicability of these algorithms. We report the set-up and summarize the benchmark results of the Quantification of Uncertainties in Biomedical Image Quantification Challenge (QUBIQ), which was organized in conjunction with International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020 and 2021. The challenge focuses on the uncertainty quantification of medical image segmentation which considers the omnipresence of inter-rater variability in imaging datasets. The large collection of images with multi-rater annotations features various modalities such as MRI and CT; various organs such as the brain, prostate, kidney, and pancreas; and different image dimensions 2D-vs-3D. A total of 24 teams submitted different solutions to the problem, combining various baseline models, Bayesian neural networks, and ensemble model techniques. The obtained results indicate the importance of the ensemble models, as well as the need for further research to develop efficient 3D methods for uncertainty quantification methods in 3D segmentation tasks., Comment: initial technical report

Topological accuracy in medical image segmentation is a highly important property for downstream applications such as network analysis and flow modeling in vessels or cell counting. Recently, significant methodological advancements have brought well-founded concepts from algebraic topology to binary segmentation. However, these approaches have been underexplored in multi-class segmentation scenarios, where topological errors are common. We propose a general loss function for topologically faithful multi-class segmentation extending the recent Betti matching concept, which is based on induced matchings of persistence barcodes. We project the N-class segmentation problem to N single-class segmentation tasks, which allows us to use 1-parameter persistent homology, making training of neural networks computationally feasible. We validate our method on a comprehensive set of four medical datasets with highly variant topological characteristics. Our loss formulation significantly enhances topological correctness in cardiac, cell, artery-vein, and Circle of Willis segmentation.

Direct image-to-graph transformation is a challenging task that involves solving object detection and relationship prediction in a single model. Due to this task's complexity, large training datasets are rare in many domains, making the training of deep-learning methods challenging. This data sparsity necessitates transfer learning strategies akin to the state-of-the-art in general computer vision. In this work, we introduce a set of methods enabling cross-domain and cross-dimension learning for image-to-graph transformers. We propose (1) a regularized edge sampling loss to effectively learn object relations in multiple domains with different numbers of edges, (2) a domain adaptation framework for image-to-graph transformers aligning image- and graph-level features from different domains, and (3) a projection function that allows using 2D data for training 3D transformers. We demonstrate our method's utility in cross-domain and cross-dimension experiments, where we utilize labeled data from 2D road networks for simultaneous learning in vastly different target domains. Our method consistently outperforms standard transfer learning and self-supervised pretraining on challenging benchmarks, such as retinal or whole-brain vessel graph extraction.

The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neuro-vascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited public datasets with annotations on CoW anatomy, especially for CTA. Therefore we organized the TopCoW Challenge in 2023 with the release of an annotated CoW dataset. The TopCoW dataset was the first public dataset with voxel-level annotations for thirteen possible CoW vessel components, enabled by virtual-reality (VR) technology. It was also the first large dataset with paired MRA and CTA from the same patients. TopCoW challenge formalized the CoW characterization problem as a multiclass anatomical segmentation task with an emphasis on topological metrics. We invited submissions worldwide for the CoW segmentation task, which attracted over 140 registered participants from four continents. The top performing teams managed to segment many CoW components to Dice scores around 90%, but with lower scores for communicating arteries and rare variants. There were also topological mistakes for predictions with high Dice scores. Additional topological analysis revealed further areas for improvement in detecting certain CoW components and matching CoW variant topology accurately. TopCoW represented a first attempt at benchmarking the CoW anatomical segmentation task for MRA and CTA, both morphologically and topologically., Comment: 24 pages, 11 figures, 9 tables. Summary Paper for the MICCAI TopCoW 2023 Challenge

This paper introduces panoptica, a versatile and performance-optimized package designed for computing instance-wise segmentation quality metrics from 2D and 3D segmentation maps. panoptica addresses the limitations of existing metrics and provides a modular framework that complements the original intersection over union-based panoptic quality with other metrics, such as the distance metric Average Symmetric Surface Distance. The package is open-source, implemented in Python, and accompanied by comprehensive documentation and tutorials. panoptica employs a three-step metrics computation process to cover diverse use cases. The efficacy of panoptica is demonstrated on various real-world biomedical datasets, where an instance-wise evaluation is instrumental for an accurate representation of the underlying clinical task. Overall, we envision panoptica as a valuable tool facilitating in-depth evaluation of segmentation methods., Comment: 15 pages, 6 figures, 3 tables

Diffuse optical modalities such as broadband near-infrared spectroscopy (bNIRS) and hyperspectral imaging (HSI) represent a promising alternative for low-cost, non-invasive, and fast monitoring of functional and structural properties of living tissue. Particularly, the possibility of extracting the molecular composition of the tissue from the optical spectra in real-time deems the spectroscopy techniques as a unique diagnostic tool. However, no established method exists to streamline the inference of the biochemical composition from the optical spectrum for real-time applications such as surgical monitoring. In this paper, we analyse a machine learning technique for fast and accurate inference of changes in the molecular composition of brain tissue. We reconsider and propose modifications to the existing learnable methodology based on the Beer-Lambert law, which analytically connects the spectra with concentrations. We evaluate the method's applicability to linear and non-linear formulations of the Beer-Lambert law. The approach is tested on real data obtained from the bNIRS- and HSI-based optical monitoring of brain tissue. The results demonstrate that the proposed method enables real-time molecular composition inference while maintaining the accuracy of traditional linear and non-linear optimization solvers. Preliminary findings show that Beer-Lambert law-based spectral unmixing allows to contrast brain anatomy semantics such as the vessel tree and tumor area.

The skeleton of a digital image is a compact representation of its topology, geometry, and scale. It has utility in many computer vision applications, such as image description, segmentation, and registration. However, skeletonization has only seen limited use in contemporary deep learning solutions. Most existing skeletonization algorithms are not differentiable, making it impossible to integrate them with gradient-based optimization. Compatible algorithms based on morphological operations and neural networks have been proposed, but their results often deviate from the geometry and topology of the true medial axis. This work introduces the first three-dimensional skeletonization algorithm that is both compatible with gradient-based optimization and preserves an object's topology. Our method is exclusively based on matrix additions and multiplications, convolutional operations, basic non-linear functions, and sampling from a uniform probability distribution, allowing it to be easily implemented in any major deep learning library. In benchmarking experiments, we prove the advantages of our skeletonization algorithm compared to non-differentiable, morphological, and neural-network-based baselines. Finally, we demonstrate the utility of our algorithm by integrating it with two medical image processing applications that use gradient-based optimization: deep-learning-based blood vessel segmentation, and multimodal registration of the mandible in computed tomography and magnetic resonance images., Comment: Accepted at ICCV 2023

Cardiovascular diseases (CVD) can be diagnosed using various diagnostic modalities. The electrocardiogram (ECG) is a cost-effective and widely available diagnostic aid that provides functional information of the heart. However, its ability to classify and spatially localise CVD is limited. In contrast, cardiac magnetic resonance (CMR) imaging provides detailed structural information of the heart and thus enables evidence-based diagnosis of CVD, but long scan times and high costs limit its use in clinical routine. In this work, we present a deep learning strategy for cost-effective and comprehensive cardiac screening solely from ECG. Our approach combines multimodal contrastive learning with masked data modelling to transfer domain-specific information from CMR imaging to ECG representations. In extensive experiments using data from 40,044 UK Biobank subjects, we demonstrate the utility and generalisability of our method for subject-specific risk prediction of CVD and the prediction of cardiac phenotypes using only ECG data. Specifically, our novel multimodal pre-training paradigm improves performance by up to 12.19 % for risk prediction and 27.59 % for phenotype prediction. In a qualitative analysis, we demonstrate that our learned ECG representations incorporate information from CMR image regions of interest. Our entire pipeline is publicly available at https://github.com/oetu/MMCL-ECG-CMR.

In dynamic Magnetic Resonance Imaging (MRI), k-space is typically undersampled due to limited scan time, resulting in aliasing artifacts in the image domain. Hence, dynamic MR reconstruction requires not only modeling spatial frequency components in the x and y directions of k-space but also considering temporal redundancy. Most previous works rely on image-domain regularizers (priors) to conduct MR reconstruction. In contrast, we focus on interpolating the undersampled k-space before obtaining images with Fourier transform. In this work, we connect masked image modeling with k-space interpolation and propose a novel Transformer-based k-space Global Interpolation Network, termed k-GIN. Our k-GIN learns global dependencies among low- and high-frequency components of 2D+t k-space and uses it to interpolate unsampled data. Further, we propose a novel k-space Iterative Refinement Module (k-IRM) to enhance the high-frequency components learning. We evaluate our approach on 92 in-house 2D+t cardiac MR subjects and compare it to MR reconstruction methods with image-domain regularizers. Experiments show that our proposed k-space interpolation method quantitatively and qualitatively outperforms baseline methods. Importantly, the proposed approach achieves substantially higher robustness and generalizability in cases of highly-undersampled MR data. For video presentation, poster, GIF results and code please check our project page: https://jzpeterpan.github.io/k-gin.github.io/.

Recent trends in Video Instance Segmentation (VIS) have seen a growing reliance on online methods to model complex and lengthy video sequences. However, the degradation of representation and noise accumulation of the online methods, especially during occlusion and abrupt changes, pose substantial challenges. Transformer-based query propagation provides promising directions at the cost of quadratic memory attention. However, they are susceptible to the degradation of instance features due to the above-mentioned challenges and suffer from cascading effects. The detection and rectification of such errors remain largely underexplored. To this end, we introduce \textbf{GRAtt-VIS}, \textbf{G}ated \textbf{R}esidual \textbf{Att}ention for \textbf{V}ideo \textbf{I}nstance \textbf{S}egmentation. Firstly, we leverage a Gumbel-Softmax-based gate to detect possible errors in the current frame. Next, based on the gate activation, we rectify degraded features from its past representation. Such a residual configuration alleviates the need for dedicated memory and provides a continuous stream of relevant instance features. Secondly, we propose a novel inter-instance interaction using gate activation as a mask for self-attention. This masking strategy dynamically restricts the unrepresentative instance queries in the self-attention and preserves vital information for long-term tracking. We refer to this novel combination of Gated Residual Connection and Masked Self-Attention as \textbf{GRAtt} block, which can easily be integrated into the existing propagation-based framework. Further, GRAtt blocks significantly reduce the attention overhead and simplify dynamic temporal modeling. GRAtt-VIS achieves state-of-the-art performance on YouTube-VIS and the highly challenging OVIS dataset, significantly improving over previous methods. Code is available at \url{https://github.com/Tanveer81/GRAttVIS}., Comment: 14 pages, 5 tables, 9 figures

A myriad of algorithms for the automatic analysis of brain MR images is available to support clinicians in their decision-making. For brain tumor patients, the image acquisition time series typically starts with an already pathological scan. This poses problems, as many algorithms are designed to analyze healthy brains and provide no guarantee for images featuring lesions. Examples include, but are not limited to, algorithms for brain anatomy parcellation, tissue segmentation, and brain extraction. To solve this dilemma, we introduce the BraTS inpainting challenge. Here, the participants explore inpainting techniques to synthesize healthy brain scans from lesioned ones. The following manuscript contains the task formulation, dataset, and submission procedure. Later, it will be updated to summarize the findings of the challenge. The challenge is organized as part of the ASNR-BraTS MICCAI challenge., Comment: 14 pages, 6 figures

This paper presents FedPIDAvg, the winning submission to the Federated Tumor Segmentation Challenge 2022 (FETS22). Inspired by FedCostWAvg, our winning contribution to FETS21, we contribute an improved aggregation strategy for federated and collaborative learning. FedCostWAvg is a weighted averaging method that not only considers the number of training samples of each cluster but also the size of the drop of the respective cost function in the last federated round. This can be interpreted as the derivative part of a PID controller (proportional-integral-derivative controller). In FedPIDAvg, we further add the missing integral term. Another key challenge was the vastly varying size of data samples per center. We addressed this by modeling the data center sizes as following a Poisson distribution and choosing the training iterations per center accordingly. Our method outperformed all other submissions.

Clinical routine and retrospective cohorts commonly include multi-parametric Magnetic Resonance Imaging; however, they are mostly acquired in different anisotropic 2D views due to signal-to-noise-ratio and scan-time constraints. Thus acquired views suffer from poor out-of-plane resolution and affect downstream volumetric image analysis that typically requires isotropic 3D scans. Combining different views of multi-contrast scans into high-resolution isotropic 3D scans is challenging due to the lack of a large training cohort, which calls for a subject-specific framework. This work proposes a novel solution to this problem leveraging Implicit Neural Representations (INR). Our proposed INR jointly learns two different contrasts of complementary views in a continuous spatial function and benefits from exchanging anatomical information between them. Trained within minutes on a single commodity GPU, our model provides realistic super-resolution across different pairs of contrasts in our experiments with three datasets. Using Mutual Information (MI) as a metric, we find that our model converges to an optimum MI amongst sequences, achieving anatomically faithful reconstruction. Code is available at: https://github.com/jqmcginnis/multi_contrast_inr/

Hyperspectral imaging (HSI) is an optical technique that processes the electromagnetic spectrum at a multitude of monochromatic, adjacent frequency bands. The wide-bandwidth spectral signature of a target object's reflectance allows fingerprinting its physical, biochemical, and physiological properties. HSI has been applied for various applications, such as remote sensing and biological tissue analysis. Recently, HSI was also used to differentiate between healthy and pathological tissue under operative conditions in a surgery room on patients diagnosed with brain tumors. In this article, we perform a statistical analysis of the brain tumor patients' HSI scans from the HELICoiD dataset with the aim of identifying the correlation between reflectance spectra and absorption spectra of tissue chromophores. By using the principal component analysis (PCA), we determine the most relevant spectral features for intra- and inter-tissue class differentiation. Furthermore, we demonstrate that such spectral features are correlated with the spectra of cytochrome, i.e., the chromophore highly involved in (hyper) metabolic processes. Identifying such fingerprints of chromophores in reflectance spectra is a key step for automated molecular profiling and, eventually, expert-free biomarker discovery.

Quantifying the perceptual similarity of two images is a long-standing problem in low-level computer vision. The natural image domain commonly relies on supervised learning, e.g., a pre-trained VGG, to obtain a latent representation. However, due to domain shift, pre-trained models from the natural image domain might not apply to other image domains, such as medical imaging. Notably, in medical imaging, evaluating the perceptual similarity is exclusively performed by specialists trained extensively in diverse medical fields. Thus, medical imaging remains devoid of task-specific, objective perceptual measures. This work answers the question: Is it necessary to rely on supervised learning to obtain an effective representation that could measure perceptual similarity, or is self-supervision sufficient? To understand whether recent contrastive self-supervised representation (CSR) may come to the rescue, we start with natural images and systematically evaluate CSR as a metric across numerous contemporary architectures and tasks and compare them with existing methods. We find that in the natural image domain, CSR behaves on par with the supervised one on several perceptual tests as a metric, and in the medical domain, CSR better quantifies perceptual similarity concerning the experts' ratings. We also demonstrate that CSR can significantly improve image quality in two image synthesis tasks. Finally, our extensive results suggest that perceptuality is an emergent property of CSR, which can be adapted to many image domains without requiring annotations., Comment: under review

Image segmentation is a largely researched field where neural networks find vast applications in many facets of technology. Some of the most popular approaches to train segmentation networks employ loss functions optimizing pixel-overlap, an objective that is insufficient for many segmentation tasks. In recent years, their limitations fueled a growing interest in topology-aware methods, which aim to recover the correct topology of the segmented structures. However, so far, none of the existing approaches achieve a spatially correct matching between the topological features of ground truth and prediction. In this work, we propose the first topologically and feature-wise accurate metric and loss function for supervised image segmentation, which we term Betti matching. We show how induced matchings guarantee the spatially correct matching between barcodes in a segmentation setting. Furthermore, we propose an efficient algorithm to compute the Betti matching of images. We show that the Betti matching error is an interpretable metric to evaluate the topological correctness of segmentations, which is more sensitive than the well-established Betti number error. Moreover, the differentiability of the Betti matching loss enables its use as a loss function. It improves the topological performance of segmentation networks across six diverse datasets while preserving the volumetric performance. Our code is available in https://github.com/nstucki/Betti-matching.

Recent transformer-based offline video instance segmentation (VIS) approaches achieve encouraging results and significantly outperform online approaches. However, their reliance on the whole video and the immense computational complexity caused by full Spatio-temporal attention limit them in real-life applications such as processing lengthy videos. In this paper, we propose a single-stage transformer-based efficient online VIS framework named InstanceFormer, which is especially suitable for long and challenging videos. We propose three novel components to model short-term and long-term dependency and temporal coherence. First, we propagate the representation, location, and semantic information of prior instances to model short-term changes. Second, we propose a novel memory cross-attention in the decoder, which allows the network to look into earlier instances within a certain temporal window. Finally, we employ a temporal contrastive loss to impose coherence in the representation of an instance across all frames. Memory attention and temporal coherence are particularly beneficial to long-range dependency modeling, including challenging scenarios like occlusion. The proposed InstanceFormer outperforms previous online benchmark methods by a large margin across multiple datasets. Most importantly, InstanceFormer surpasses offline approaches for challenging and long datasets such as YouTube-VIS-2021 and OVIS. Code is available at https://github.com/rajatkoner08/InstanceFormer.

Detection Transformers represent end-to-end object detection approaches based on a Transformer encoder-decoder architecture, exploiting the attention mechanism for global relation modeling. Although Detection Transformers deliver results on par with or even superior to their highly optimized CNN-based counterparts operating on 2D natural images, their success is closely coupled to access to a vast amount of training data. This, however, restricts the feasibility of employing Detection Transformers in the medical domain, as access to annotated data is typically limited. To tackle this issue and facilitate the advent of medical Detection Transformers, we propose a novel Detection Transformer for 3D anatomical structure detection, dubbed Focused Decoder. Focused Decoder leverages information from an anatomical region atlas to simultaneously deploy query anchors and restrict the cross-attention's field of view to regions of interest, which allows for a precise focus on relevant anatomical structures. We evaluate our proposed approach on two publicly available CT datasets and demonstrate that Focused Decoder not only provides strong detection results and thus alleviates the need for a vast amount of annotated data but also exhibits exceptional and highly intuitive explainability of results via attention weights. Our code is available at https://github.com/bwittmann/transoar., Comment: Accepted for publication at the Journal of Machine Learning for Biomedical Imaging (MELBA) https://melba-journal.org/2023:003

Human ratings are abstract representations of segmentation quality. To approximate human quality ratings on scarce expert data, we train surrogate quality estimation models. We evaluate on a complex multi-class segmentation problem, specifically glioma segmentation, following the BraTS annotation protocol. The training data features quality ratings from 15 expert neuroradiologists on a scale ranging from 1 to 6 stars for various computer-generated and manual 3D annotations. Even though the networks operate on 2D images and with scarce training data, we can approximate segmentation quality within a margin of error comparable to human intra-rater reliability. Segmentation quality prediction has broad applications. While an understanding of segmentation quality is imperative for successful clinical translation of automatic segmentation quality algorithms, it can play an essential role in training new segmentation models. Due to the split-second inference times, it can be directly applied within a loss function or as a fully-automatic dataset curation mechanism in a federated learning setting., Comment: 10 pages, 5 figures

Deep convolutional neural networks (CNN) have proven to be remarkably effective in semantic segmentation tasks. Most popular loss functions were introduced targeting improved volumetric scores, such as the Dice coefficient (DSC). By design, DSC can tackle class imbalance, however, it does not recognize instance imbalance within a class. As a result, a large foreground instance can dominate minor instances and still produce a satisfactory DSC. Nevertheless, detecting tiny instances is crucial for many applications, such as disease monitoring. For example, it is imperative to locate and surveil small-scale lesions in the follow-up of multiple sclerosis patients. We propose a novel family of loss functions, \emph{blob loss}, primarily aimed at maximizing instance-level detection metrics, such as F1 score and sensitivity. \emph{Blob loss} is designed for semantic segmentation problems where detecting multiple instances matters. We extensively evaluate a DSC-based \emph{blob loss} in five complex 3D semantic segmentation tasks featuring pronounced instance heterogeneity in terms of texture and morphology. Compared to soft Dice loss, we achieve 5% improvement for MS lesions, 3% improvement for liver tumor, and an average 2% improvement for microscopy segmentation tasks considering F1 score., Comment: 23 pages, 7 figures // corrected one mistake where it said beta instead of alpha in the text

Solving the inverse problem is the key step in evaluating the capacity of a physical model to describe real phenomena. In medical image computing, it aligns with the classical theme of image-based model personalization. Traditionally, a solution to the problem is obtained by performing either sampling or variational inference based methods. Both approaches aim to identify a set of free physical model parameters that results in a simulation best matching an empirical observation. When applied to brain tumor modeling, one of the instances of image-based model personalization in medical image computing, the overarching drawback of the methods is the time complexity for finding such a set. In a clinical setting with limited time between imaging and diagnosis or even intervention, this time complexity may prove critical. As the history of quantitative science is the history of compression, we align in this paper with the historical tendency and propose a method compressing complex traditional strategies for solving an inverse problem into a simple database query task. We evaluated different ways of performing the database query task assessing the trade-off between accuracy and execution time. On the exemplary task of brain tumor growth modeling, we prove that the proposed method achieves one order speed-up compared to existing approaches for solving the inverse problem. The resulting compute time offers critical means for relying on more complex and, hence, realistic models, for integrating image preprocessing and inverse modeling even deeper, or for implementing the current model into a clinical workflow.

A comprehensive representation of an image requires understanding objects and their mutual relationship, especially in image-to-graph generation, e.g., road network extraction, blood-vessel network extraction, or scene graph generation. Traditionally, image-to-graph generation is addressed with a two-stage approach consisting of object detection followed by a separate relation prediction, which prevents simultaneous object-relation interaction. This work proposes a unified one-stage transformer-based framework, namely Relationformer, that jointly predicts objects and their relations. We leverage direct set-based object prediction and incorporate the interaction among the objects to learn an object-relation representation jointly. In addition to existing [obj]-tokens, we propose a novel learnable token, namely [rln]-token. Together with [obj]-tokens, [rln]-token exploits local and global semantic reasoning in an image through a series of mutual associations. In combination with the pair-wise [obj]-token, the [rln]-token contributes to a computationally efficient relation prediction. We achieve state-of-the-art performance on multiple, diverse and multi-domain datasets that demonstrate our approach's effectiveness and generalizability.

Automatic localization and segmentation of organs-at-risk (OAR) in CT are essential pre-processing steps in medical image analysis tasks, such as radiation therapy planning. For instance, the segmentation of OAR surrounding tumors enables the maximization of radiation to the tumor area without compromising the healthy tissues. However, the current medical workflow requires manual delineation of OAR, which is prone to errors and is annotator-dependent. In this work, we aim to introduce a unified 3D pipeline for OAR localization-segmentation rather than novel localization or segmentation architectures. To the best of our knowledge, our proposed framework fully enables the exploitation of 3D context information inherent in medical imaging. In the first step, a 3D multi-variate regression network predicts organs' centroids and bounding boxes. Secondly, 3D organ-specific segmentation networks are leveraged to generate a multi-organ segmentation map. Our method achieved an overall Dice score of $0.9260\pm 0.18 \%$ on the VISCERAL dataset containing CT scans with varying fields of view and multiple organs.

Brain tumor segmentation from multiple Magnetic Resonance Imaging (MRI) modalities is a challenging task in medical image computation. The main challenges lie in the generalizability to a variety of scanners and imaging protocols. In this paper, we explore strategies to increase model robustness without increasing inference time. Towards this aim, we explore finding a robust ensemble from models trained using different losses, optimizers, and train-validation data split. Importantly, we explore the inclusion of a transformer in the bottleneck of the U-Net architecture. While we find transformer in the bottleneck performs slightly worse than the baseline U-Net in average, the generalized Wasserstein Dice loss consistently produces superior results. Further, we adopt an efficient test time augmentation strategy for faster and robust inference. Our final ensemble of seven 3D U-Nets with test-time augmentation produces an average dice score of 89.4% and an average Hausdorff 95% distance of 10.0 mm when evaluated on the BraTS 2021 testing dataset. Our code and trained models are publicly available at https://github.com/LucasFidon/TRABIT_BraTS2021., Comment: BraTS 2021 challenge

We propose a simple new aggregation strategy for federated learning that won the MICCAI Federated Tumor Segmentation Challenge 2021 (FETS), the first ever challenge on Federated Learning in the Machine Learning community. Our method addresses the problem of how to aggregate multiple models that were trained on different data sets. Conceptually, we propose a new way to choose the weights when averaging the different models, thereby extending the current state of the art (FedAvg). Empirical validation demonstrates that our approach reaches a notable improvement in segmentation performance compared to FedAvg.

Current treatment planning of patients diagnosed with a brain tumor, such as glioma, could significantly benefit by accessing the spatial distribution of tumor cell concentration. Existing diagnostic modalities, e.g. magnetic resonance imaging (MRI), contrast sufficiently well areas of high cell density. In gliomas, however, they do not portray areas of low cell concentration, which can often serve as a source for the secondary appearance of the tumor after treatment. To estimate tumor cell densities beyond the visible boundaries of the lesion, numerical simulations of tumor growth could complement imaging information by providing estimates of full spatial distributions of tumor cells. Over recent years a corpus of literature on medical image-based tumor modeling was published. It includes different mathematical formalisms describing the forward tumor growth model. Alongside, various parametric inference schemes were developed to perform an efficient tumor model personalization, i.e. solving the inverse problem. However, the unifying drawback of all existing approaches is the time complexity of the model personalization which prohibits a potential integration of the modeling into clinical settings. In this work, we introduce a deep learning based methodology for inferring the patient-specific spatial distribution of brain tumors from T1Gd and FLAIR MRI medical scans. Coined as Learn-Morph-Infer the method achieves real-time performance in the order of minutes on widely available hardware and the compute time is stable across tumor models of different complexity, such as reaction-diffusion and reaction-advection-diffusion models. We believe the proposed inverse solution approach not only bridges the way for clinical translation of brain tumor personalization but can also be adopted to other scientific and engineering domains.

This paper describes our method for our participation in the FeTA challenge2021 (team name: TRABIT). The performance of convolutional neural networks for medical image segmentation is thought to correlate positively with the number of training data. The FeTA challenge does not restrict participants to using only the provided training data but also allows for using other publicly available sources. Yet, open access fetal brain data remains limited. An advantageous strategy could thus be to expand the training data to cover broader perinatal brain imaging sources. Perinatal brain MRIs, other than the FeTA challenge data, that are currently publicly available, span normal and pathological fetal atlases as well as neonatal scans. However, perinatal brain MRIs segmented in different datasets typically come with different annotation protocols. This makes it challenging to combine those datasets to train a deep neural network. We recently proposed a family of loss functions, the label-set loss functions, for partially supervised learning. Label-set loss functions allow to train deep neural networks with partially segmented images, i.e. segmentations in which some classes may be grouped into super-classes. We propose to use label-set loss functions to improve the segmentation performance of a state-of-the-art deep learning pipeline for multi-class fetal brain segmentation by merging several publicly available datasets. To promote generalisability, our approach does not introduce any additional hyper-parameters tuning., Comment: Accepted as a poster at the MICCAI 2021 Perinatal, Preterm and Paediatric Image Analysis (PIPPI) workshop

Fast and accurate solutions of time-dependent partial differential equations (PDEs) are of pivotal interest to many research fields, including physics, engineering, and biology. Generally, implicit/semi-implicit schemes are preferred over explicit ones to improve stability and correctness. However, existing semi-implicit methods are usually iterative and employ a general-purpose solver, which may be sub-optimal for a specific class of PDEs. In this paper, we propose a neural solver to learn an optimal iterative scheme in a data-driven fashion for any class of PDEs. Specifically, we modify a single iteration of a semi-implicit solver using a deep neural network. We provide theoretical guarantees for the correctness and convergence of neural solvers analogous to conventional iterative solvers. In addition to the commonly used Dirichlet boundary condition, we adopt a diffuse domain approach to incorporate a diverse type of boundary conditions, e.g., Neumann. We show that the proposed neural solver can go beyond linear PDEs and applies to a class of non-linear PDEs, where the non-linear component is non-stiff. We demonstrate the efficacy of our method on 2D and 3D scenarios. To this end, we show how our model generalizes to parameter settings, which are different from training; and achieves faster convergence than semi-implicit schemes.

Biological neural networks define the brain function and intelligence of humans and other mammals, and form ultra-large, spatial, structured graphs. Their neuronal organization is closely interconnected with the spatial organization of the brain's microvasculature, which supplies oxygen to the neurons and builds a complementary spatial graph. This vasculature (or the vessel structure) plays an important role in neuroscience; for example, the organization of (and changes to) vessel structure can represent early signs of various pathologies, e.g. Alzheimer's disease or stroke. Recently, advances in tissue clearing have enabled whole brain imaging and segmentation of the entirety of the mouse brain's vasculature. Building on these advances in imaging, we are presenting an extendable dataset of whole-brain vessel graphs based on specific imaging protocols. Specifically, we extract vascular graphs using a refined graph extraction scheme leveraging the volume rendering engine Voreen and provide them in an accessible and adaptable form through the OGB and PyTorch Geometric dataloaders. Moreover, we benchmark numerous state-of-the-art graph learning algorithms on the biologically relevant tasks of vessel prediction and vessel classification using the introduced vessel graph dataset. Our work paves a path towards advancing graph learning research into the field of neuroscience. Complementarily, the presented dataset raises challenging graph learning research questions for the machine learning community, in terms of incorporating biological priors into learning algorithms, or in scaling these algorithms to handle sparse,spatial graphs with millions of nodes and edges. All datasets and code are available for download at https://github.com/jocpae/VesselGraph ., Comment: Thirty-fifth Conference on Neural Information Processing Systems Datasets and Benchmarks Track

Self-supervision has demonstrated to be an effective learning strategy when training target tasks on small annotated data-sets. While current research focuses on creating novel pretext tasks to learn meaningful and reusable representations for the target task, these efforts obtain marginal performance gains compared to fully-supervised learning. Meanwhile, little attention has been given to study the robustness of networks trained in a self-supervised manner. In this work, we demonstrate that networks trained via self-supervised learning have superior robustness and generalizability compared to fully-supervised learning in the context of medical imaging. Our experiments on pneumonia detection in X-rays and multi-organ segmentation in CT yield consistent results exposing the hidden benefits of self-supervision for learning robust feature representations.

Novel multimodal imaging methods are capable of generating extensive, super high resolution datasets for preclinical research. Yet, a massive lack of annotations prevents the broad use of deep learning to analyze such data. So far, existing generative models fail to mitigate this problem because of frequent labeling errors. In this paper, we introduce a novel generative method which leverages real anatomical information to generate realistic image-label pairs of tumours. We construct a dual-pathway generator, for the anatomical image and label, trained in a cycle-consistent setup, constrained by an independent, pretrained segmentor. The generated images yield significant quantitative improvement compared to existing methods. To validate the quality of synthesis, we train segmentation networks on a dataset augmented with the synthetic data, substantially improving the segmentation over baseline.

Metrics optimized in complex machine learning tasks are often selected in an ad-hoc manner. It is unknown how they align with human expert perception. We explore the correlations between established quantitative segmentation quality metrics and qualitative evaluations by professionally trained human raters. Therefore, we conduct psychophysical experiments for two complex biomedical semantic segmentation problems. We discover that current standard metrics and loss functions correlate only moderately with the segmentation quality assessment of experts. Importantly, this effect is particularly pronounced for clinically relevant structures, such as the enhancing tumor compartment of glioma in brain magnetic resonance and grey matter in ultrasound imaging. It is often unclear how to optimize abstract metrics, such as human expert perception, in convolutional neural network (CNN) training. To cope with this challenge, we propose a novel strategy employing techniques of classical statistics to create complementary compound loss functions to better approximate human expert perception. Across all rating experiments, human experts consistently scored computer-generated segmentations better than the human-curated reference labels. Our results, therefore, strongly question many current practices in medical image segmentation and provide meaningful cues for future research., Comment: Accepted for publication at the Journal of Machine Learning for Biomedical Imaging (MELBA) https://melba-journal.org/2023:002

The MICCAI conference has encountered tremendous growth over the last years in terms of the size of the community, as well as the number of contributions and their technical success. With this growth, however, come new challenges for the community. Methods are more difficult to reproduce and the ever-increasing number of paper submissions to the MICCAI conference poses new questions regarding the selection process and the diversity of topics. To exchange, discuss, and find novel and creative solutions to these challenges, a new format of a hackathon was initiated as a satellite event at the MICCAI 2020 conference: The MICCAI Hackathon. The first edition of the MICCAI Hackathon covered the topics reproducibility, diversity, and selection of MICCAI papers. In the manner of a small think-tank, participants collaborated to find solutions to these challenges. In this report, we summarize the insights from the MICCAI Hackathon into immediate and long-term measures to address these challenges. The proposed measures can be seen as starting points and guidelines for discussions and actions to possibly improve the MICCAI conference with regards to reproducibility, diversity, and selection of papers., Comment: Revision of discussion; update e-mail address of one author

It is critical to quantitatively analyse the developing human fetal brain in order to fully understand neurodevelopment in both normal fetuses and those with congenital disorders. To facilitate this analysis, automatic multi-tissue fetal brain segmentation algorithms are needed, which in turn requires open databases of segmented fetal brains. Here we introduce a publicly available database of 50 manually segmented pathological and non-pathological fetal magnetic resonance brain volume reconstructions across a range of gestational ages (20 to 33 weeks) into 7 different tissue categories (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, deep grey matter, brainstem/spinal cord). In addition, we quantitatively evaluate the accuracy of several automatic multi-tissue segmentation algorithms of the developing human fetal brain. Four research groups participated, submitting a total of 10 algorithms, demonstrating the benefits the database for the development of automatic algorithms., Comment: This is a preprint of an article published in Nature Scientific Data. The final authenticated version is available online at: https://doi.org/10.1038/s41597-021-00946-3

Designing of a cranial implant needs a 3D understanding of the complete skull shape. Thus, taking a 2D approach is sub-optimal, since a 2D model lacks a holistic 3D view of both the defective and healthy skulls. Further, loading the whole 3D skull shapes at its original image resolution is not feasible in commonly available GPUs. To mitigate these issues, we propose a fully convolutional network composed of two subnetworks. The first subnetwork is designed to complete the shape of the downsampled defective skull. The second subnetwork upsamples the reconstructed shape slice-wise. We train the 3D and 2D networks together end-to-end, with a hierarchical loss function. Our proposed solution accurately predicts a high-resolution 3D implant in the challenge test case in terms of dice-score and the Hausdorff distance.

Modeling of brain tumor dynamics has the potential to advance therapeutic planning. Current modeling approaches resort to numerical solvers that simulate the tumor progression according to a given differential equation. Using highly-efficient numerical solvers, a single forward simulation takes up to a few minutes of compute. At the same time, clinical applications of tumor modeling often imply solving an inverse problem, requiring up to tens of thousands forward model evaluations when used for a Bayesian model personalization via sampling. This results in a total inference time prohibitively expensive for clinical translation. While recent data-driven approaches become capable of emulating physics simulation, they tend to fail in generalizing over the variability of the boundary conditions imposed by the patient-specific anatomy. In this paper, we propose a learnable surrogate for simulating tumor growth which maps the biophysical model parameters directly to simulation outputs, i.e. the local tumor cell densities, whilst respecting patient geometry. We test the neural solver on Bayesian tumor model personalization for a cohort of glioma patients. Bayesian inference using the proposed surrogate yields estimates analogous to those obtained by solving the forward model with a regular numerical solver. The near-real-time computation cost renders the proposed method suitable for clinical settings. The code is available at https://github.com/IvanEz/tumor-surrogate.

In the last two decades, neuroscience has produced intriguing evidence for a central role of the claustrum in mammalian forebrain structure and function. However, relatively few in vivo studies of the claustrum exist in humans. A reason for this may be the delicate and sheet-like structure of the claustrum lying between the insular cortex and the putamen, which makes it not amenable to conventional segmentation methods. Recently, Deep Learning (DL) based approaches have been successfully introduced for automated segmentation of complex, subcortical brain structures. In the following, we present a multi-view DL-based approach to segment the claustrum in T1-weighted MRI scans. We trained and evaluated the proposed method in 181 individuals, using bilateral manual claustrum annotations by an expert neuroradiologist as the reference standard. Cross-validation experiments yielded median volumetric similarity, robust Hausdorff distance, and Dice score of 93.3%, 1.41mm, and 71.8%, respectively, representing equal or superior segmentation performance compared to human intra-rater reliability. The leave-one-scanner-out evaluation showed good transferability of the algorithm to images from unseen scanners at slightly inferior performance. Furthermore, we found that DL-based claustrum segmentation benefits from multi-view information and requires a sample size of around 75 MRI scans in the training set. We conclude that the developed algorithm allows for robust automated claustrum segmentation and thus yields considerable potential for facilitating MRI-based research of the human claustrum. The software and models of our method are made publicly available., Comment: final version