Marie Piraud

Titouan Le Breton, Karol Szustakowski, Marie Piraud

We present Flash Cubical, a highly efficient computation of cubical persistence on a V-filtration for 2D and 3D images over $\mathbb{F}_2$. The implementation is built around three core ideas. First, cubical complexes satisfy properties that allow for the computation of persistence of the highest dimension via union-find and duality. Second, pruning of certain edges allows for a fast and efficient implementation of union-find. Third, the use of a lookup table, which exploits the regularity of cubical complexes to pre-compute local information. This avoids the need to compute local information at run time. To the best of our knowledge, this is the most efficient implementation of cubical persistence with a V-filtration, both in terms of time and memory costs. Although the paper focuses on persistence for V-filtration cubical complexes, the underlying ideas generalise naturally to T-filtrations on cubical complexes and suggest promising directions for other complexes.

Florian Kofler, Johannes Wahle, Ivan Ezhov et al.

Machine learning models are typically evaluated by computing similarity with reference annotations and trained by maximizing similarity with such. Especially in the biomedical domain, annotations are subjective and suffer from low inter- and intra-rater reliability. Since annotations only reflect one interpretation of the real world, this can lead to sub-optimal predictions even though the model achieves high similarity scores. Here, the theoretical concept of PGT is introduced. PGT marks the point beyond which an increase in similarity with the \emph{reference annotation} stops translating to better RWMP. Additionally, a quantitative technique to approximate PGT by computing inter- and intra-rater reliability is proposed. Finally, four categories of PGT-aware strategies to evaluate and improve model performance are reviewed.

Florian Kofler, Suprosanna Shit, Ivan Ezhov et al.

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.

Anahita Fathi Kazerooni, Nastaran Khalili, Xinyang Liu et al.

Pediatric central nervous system tumors are the leading cause of cancer-related deaths in children. The five-year survival rate for high-grade glioma in children is less than 20%. The development of new treatments is dependent upon multi-institutional collaborative clinical trials requiring reproducible and accurate centralized response assessment. We present the results of the BraTS-PEDs 2023 challenge, the first Brain Tumor Segmentation (BraTS) challenge focused on pediatric brain tumors. This challenge utilized data acquired from multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. BraTS-PEDs 2023 aimed to evaluate volumetric segmentation algorithms for pediatric brain gliomas from magnetic resonance imaging using standardized quantitative performance evaluation metrics employed across the BraTS 2023 challenges. The top-performing AI approaches for pediatric tumor analysis included ensembles of nnU-Net and Swin UNETR, Auto3DSeg, or nnU-Net with a self-supervised framework. The BraTSPEDs 2023 challenge fostered collaboration between clinicians (neuro-oncologists, neuroradiologists) and AI/imaging scientists, promoting faster data sharing and the development of automated volumetric analysis techniques. These advancements could significantly benefit clinical trials and improve the care of children with brain tumors.

Florian Kofler, Ivan Ezhov, Lucas Fidon et al.

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.

Diana Waldmannstetter, Benedikt Wiestler, Julian Schwarting et al.

Even though simultaneous optimization of similarity metrics is a standard procedure in the field of semantic segmentation, surprisingly, this is much less established for image registration. To help closing this gap in the literature, we investigate in a complex multi-modal 3D setting whether simultaneous optimization of registration metrics, here implemented by means of primitive summation, can benefit image registration. We evaluate two challenging datasets containing collections of pre- to post-operative and pre- to intra-operative MR images of glioma. Employing the proposed optimization, we demonstrate improved registration accuracy in terms of TRE on expert neuroradiologists' landmark annotations.

Diana Waldmannstetter, Ivan Ezhov, Benedikt Wiestler et al.

Accurate image registration is pivotal in biomedical image analysis, where selecting suitable registration algorithms demands careful consideration. While numerous algorithms are available, the evaluation metrics to assess their performance have remained relatively static. This study addresses this challenge by introducing a novel evaluation metric termed Landmark Hit Rate (HitR), which focuses on the clinical relevance of image registration accuracy. Unlike traditional metrics such as Target Registration Error, which emphasize subresolution differences, HitR considers whether registration algorithms successfully position landmarks within defined confidence zones. This paradigm shift acknowledges the inherent annotation noise in medical images, allowing for more meaningful assessments. To equip HitR with label-noise-awareness, we propose defining these confidence zones based on an Inter-rater Variance analysis. Consequently, hit rate curves are computed for varying landmark zone sizes, enabling performance measurement for a task-specific level of accuracy. Our approach offers a more realistic and meaningful assessment of image registration algorithms, reflecting their suitability for clinical and biomedical applications.

Florian Kofler, Hendrik Möller, Josef A. Buchner et al.

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.

Florian Kofler, Marcel Rosier, Mehdi Astaraki et al.

The Brain Tumor Segmentation (BraTS) cluster of challenges has significantly advanced brain tumor image analysis by providing large, curated datasets and addressing clinically relevant tasks. However, despite its success and popularity, algorithms and models developed through BraTS have seen limited adoption in both scientific and clinical communities. To accelerate their dissemination, we introduce BraTS orchestrator, an open-source Python package that provides seamless access to state-of-the-art segmentation and synthesis algorithms for diverse brain tumors from the BraTS challenge ecosystem. Available on GitHub (https://github.com/BrainLesion/BraTS), the package features intuitive tutorials designed for users with minimal programming experience, enabling both researchers and clinicians to easily deploy winning BraTS algorithms for inference. By abstracting the complexities of modern deep learning, BraTS orchestrator democratizes access to the specialized knowledge developed within the BraTS community, making these advances readily available to broader neuro-radiology and neuro-oncology audiences.

Francesco Campi, Lucrezia Tondo, Ekin Karabati et al.

Deep learning-based object detectors have achieved impressive performance in microscopy imaging, yet their confidence estimates often lack calibration, limiting their reliability for biomedical applications. In this work, we introduce a new approach to improve model calibration by leveraging multi-rater annotations. We propose to train separate models on the annotations from single experts and aggregate their predictions to emulate consensus. This improves upon label sampling strategies, where models are trained on mixed annotations, and offers a more principled way to capture inter-rater variability. Experiments on a colorectal organoid dataset annotated by two experts demonstrate that our rater-specific ensemble strategy improves calibration performance while maintaining comparable detection accuracy. These findings suggest that explicitly modelling rater disagreement can lead to more trustworthy object detectors in biomedical imaging.

Alicia Durrer, Julia Wolleb, Florentin Bieder et al.

Monitoring diseases that affect the brain's structural integrity requires automated analysis of magnetic resonance (MR) images, e.g., for the evaluation of volumetric changes. However, many of the evaluation tools are optimized for analyzing healthy tissue. To enable the evaluation of scans containing pathological tissue, it is therefore required to restore healthy tissue in the pathological areas. In this work, we explore and extend denoising diffusion models for consistent inpainting of healthy 3D brain tissue. We modify state-of-the-art 2D, pseudo-3D, and 3D methods working in the image space, as well as 3D latent and 3D wavelet diffusion models, and train them to synthesize healthy brain tissue. Our evaluation shows that the pseudo-3D model performs best regarding the structural-similarity index, peak signal-to-noise ratio, and mean squared error. To emphasize the clinical relevance, we fine-tune this model on data containing synthetic MS lesions and evaluate it on a downstream brain tissue segmentation task, whereby it outperforms the established FMRIB Software Library (FSL) lesion-filling method.

Dominic LaBella, Ujjwal Baid, Omaditya Khanna et al.

We describe the design and results from the BraTS 2023 Intracranial Meningioma Segmentation Challenge. The BraTS Meningioma Challenge differed from prior BraTS Glioma challenges in that it focused on meningiomas, which are typically benign extra-axial tumors with diverse radiologic and anatomical presentation and a propensity for multiplicity. Nine participating teams each developed deep-learning automated segmentation models using image data from the largest multi-institutional systematically expert annotated multilabel multi-sequence meningioma MRI dataset to date, which included 1000 training set cases, 141 validation set cases, and 283 hidden test set cases. Each case included T2, FLAIR, T1, and T1Gd brain MRI sequences with associated tumor compartment labels delineating enhancing tumor, non-enhancing tumor, and surrounding non-enhancing FLAIR hyperintensity. Participant automated segmentation models were evaluated and ranked based on a scoring system evaluating lesion-wise metrics including dice similarity coefficient (DSC) and 95% Hausdorff Distance. The top ranked team had a lesion-wise median dice similarity coefficient (DSC) of 0.976, 0.976, and 0.964 for enhancing tumor, tumor core, and whole tumor, respectively and a corresponding average DSC of 0.899, 0.904, and 0.871, respectively. These results serve as state-of-the-art benchmarks for future pre-operative meningioma automated segmentation algorithms. Additionally, we found that 1286 of 1424 cases (90.3%) had at least 1 compartment voxel abutting the edge of the skull-stripped image edge, which requires further investigation into optimal pre-processing face anonymization steps.

Anahita Fathi Kazerooni, Nastaran Khalili, Xinyang Liu et al.

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs challenge, focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors.

Lisa Barros de Andrade e Sousa, Gregor Miller, Ronan Le Gleut et al.

As machine learning models are increasingly deployed in sensitive application areas, the demand for interpretable and trustworthy decision-making has increased. Random Forests (RF), despite their widespread use and strong performance on tabular data, remain difficult to interpret due to their ensemble nature. We present Forest-Guided Clustering (FGC), a model-specific explainability method that reveals both local and global structure in RFs by grouping instances according to shared decision paths. FGC produces human-interpretable clusters aligned with the model's internal logic and computes cluster-specific and global feature importance scores to derive decision rules underlying RF predictions. FGC accurately recovered latent subclass structure on a benchmark dataset and outperformed classical clustering and post-hoc explanation methods. Applied to an AML transcriptomic dataset, FGC uncovered biologically coherent subpopulations, disentangled disease-relevant signals from confounders, and recovered known and novel gene expression patterns. FGC bridges the gap between performance and interpretability by providing structure-aware insights that go beyond feature-level attribution.

Florian Kofler, Marcel Rosier, Mehdi Astaraki et al.

BrainLesion Suite is a versatile toolkit for building modular brain lesion image analysis pipelines in Python. Following Pythonic principles, BrainLesion Suite is designed to provide a 'brainless' development experience, minimizing cognitive effort and streamlining the creation of complex workflows for clinical and scientific practice. At its core is an adaptable preprocessing module that performs co-registration, atlas registration, and optional skull-stripping and defacing on arbitrary multi-modal input images. BrainLesion Suite leverages algorithms from the BraTS challenge to synthesize missing modalities, inpaint lesions, and generate pathology-specific tumor segmentations. BrainLesion Suite also enables quantifying segmentation model performance, with tools such as panoptica to compute lesion-wise metrics. Although BrainLesion Suite was originally developed for image analysis pipelines of brain lesions such as glioma, metastasis, and multiple sclerosis, it can be adapted for other biomedical image analysis applications. The individual BrainLesion Suite packages and tutorials are accessible on GitHub.

Klemens Flöge, Srisruthi Udayakumar, Johanna Sommer et al.

Recent advances in Artificial Intelligence have enabled multi-modal systems to model and translate diverse information spaces. Extending beyond text and vision, we introduce OneProt, a multi-modal AI for proteins that integrates structural, sequence, text, and binding site data. Using the ImageBind framework, OneProt aligns the latent spaces of protein modality encoders in a lightweight fine-tuning scheme that focuses on pairwise alignment with sequence data rather than requiring full matches. This novel approach comprises a mix of Graph Neural Networks and transformer architectures. It demonstrates strong performance in retrieval tasks and showcases the efficacy of multi-modal systems in Protein Machine Learning through a broad spectrum of downstream baselines, including enzyme function prediction and binding site analysis. Furthermore, OneProt enables the transfer of representational information from specialized encoders to the sequence encoder, enhancing capabilities for distinguishing evolutionarily related and unrelated sequences and exhibiting representational properties where evolutionarily related proteins align in similar directions within the latent space. In addition, we extensively investigate modality ablations to identify the encoders that contribute most to predictive performance, highlighting the significance of the binding site encoder, which has not been used in similar models previously. This work expands the horizons of multi-modal protein models, paving the way for transformative applications in drug discovery, biocatalytic reaction planning, and protein engineering.

Christina Bukas, Harshavardhan Subramanian, Fenja See et al.

High-throughput image analysis in the biomedical domain has gained significant attention in recent years, driving advancements in drug discovery, disease prediction, and personalized medicine. Organoids, specifically, are an active area of research, providing excellent models for human organs and their functions. Automating the quantification of organoids in microscopy images would provide an effective solution to overcome substantial manual quantification bottlenecks, particularly in high-throughput image analysis. However, there is a notable lack of open biomedical datasets, in contrast to other domains, such as autonomous driving, and, notably, only few of them have attempted to quantify annotation uncertainty. In this work, we present MultiOrg a comprehensive organoid dataset tailored for object detection tasks with uncertainty quantification. This dataset comprises over 400 high-resolution 2d microscopy images and curated annotations of more than 60,000 organoids. Most importantly, it includes three label sets for the test data, independently annotated by two experts at distinct time points. We additionally provide a benchmark for organoid detection, and make the best model available through an easily installable, interactive plugin for the popular image visualization tool Napari, to perform organoid quantification.

Karol Szustakowski, Luk Frank, Julia Esser et al.

In many biomedical segmentation tasks, the preservation of elongated structure continuity and length is more important than voxel-wise accuracy. We propose two novel loss functions, Negative Centerline Loss and Simplified Topology Loss, that, applied to Convolutional Neural Networks (CNNs), help preserve connectivity of output instances. Moreover, we discuss characteristics of experiment design, such as downscaling and spacing correction, that help obtain continuous segmentation masks. We evaluate our approach on a 3D light-sheet fluorescence microscopy dataset of axon initial segments (AIS), a task prone to discontinuity due to signal dropout. Compared to standard CNNs and existing topology-aware losses, our methods reduce the number of segmentation discontinuities per instance, particularly in regions with missing input signal, resulting in improved instance length calculation in downstream applications. Our findings demonstrate that structural priors embedded in the loss design can significantly enhance the reliability of segmentation for biological applications.

Anahita Fathi Kazerooni, Nastaran Khalili, Xinyang Liu et al.

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20\%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a landmark community benchmark event with a successful history of 12 years of resource creation for the segmentation and analysis of adult glioma. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which represents the first BraTS challenge focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on benchmarking the development of volumentric segmentation algorithms for pediatric brain glioma through standardized quantitative performance evaluation metrics utilized across the BraTS 2023 cluster of challenges. Models gaining knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training data will be evaluated on separate validation and unseen test mpMRI dataof high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors.

Hongwei Bran Li, Gian Marco Conte, Qingqiao Hu et al.

Automated brain tumor segmentation methods have become well-established and reached performance levels offering clear clinical utility. These methods typically rely on four input magnetic resonance imaging (MRI) modalities: T1-weighted images with and without contrast enhancement, T2-weighted images, and FLAIR images. However, some sequences are often missing in clinical practice due to time constraints or image artifacts, such as patient motion. Consequently, the ability to substitute missing modalities and gain segmentation performance is highly desirable and necessary for the broader adoption of these algorithms in the clinical routine. In this work, we present the establishment of the Brain MR Image Synthesis Benchmark (BraSyn) in conjunction with the Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2023. The primary objective of this challenge is to evaluate image synthesis methods that can realistically generate missing MRI modalities when multiple available images are provided. The ultimate aim is to facilitate automated brain tumor segmentation pipelines. The image dataset used in the benchmark is diverse and multi-modal, created through collaboration with various hospitals and research institutions.

Florian Kofler, Felix Meissen, Felix Steinbauer et al.

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.

Dominic LaBella, Maruf Adewole, Michelle Alonso-Basanta et al.

Meningiomas are the most common primary intracranial tumor in adults and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on multiparametric MRI (mpMRI) for diagnosis, treatment planning, and longitudinal treatment monitoring; yet automated, objective, and quantitative tools for non-invasive assessment of meningiomas on mpMRI are lacking. The BraTS meningioma 2023 challenge will provide a community standard and benchmark for state-of-the-art automated intracranial meningioma segmentation models based on the largest expert annotated multilabel meningioma mpMRI dataset to date. Challenge competitors will develop automated segmentation models to predict three distinct meningioma sub-regions on MRI including enhancing tumor, non-enhancing tumor core, and surrounding nonenhancing T2/FLAIR hyperintensity. Models will be evaluated on separate validation and held-out test datasets using standardized metrics utilized across the BraTS 2023 series of challenges including the Dice similarity coefficient and Hausdorff distance. The models developed during the course of this challenge will aid in incorporation of automated meningioma MRI segmentation into clinical practice, which will ultimately improve care of patients with meningioma.

Suprosanna Shit, Ivan Ezhov, Leon Mächler et al.

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.

Christina Bukas, Bailiang Jian, Luis F. Rodriguez Venegas et al.

Symptomatic spinal vertebral compression fractures (VCFs) often require osteoplasty treatment. A cement-like material is injected into the bone to stabilize the fracture, restore the vertebral body height and alleviate pain. Leakage is a common complication and may occur due to too much cement being injected. In this work, we propose an automated patient-specific framework that can allow physicians to calculate an upper bound of cement for the injection and estimate the optimal outcome of osteoplasty. The framework uses the patient CT scan and the fractured vertebra label to build a virtual healthy spine using a high-level approach. Firstly, the fractured spine is segmented with a three-step Convolution Neural Network (CNN) architecture. Next, a per-vertebra rigid registration to a healthy spine atlas restores its curvature. Finally, a GAN-based inpainting approach replaces the fractured vertebra with an estimation of its original shape. Based on this outcome, we then estimate the maximum amount of bone cement for injection. We evaluate our framework by comparing the virtual vertebrae volumes of ten patients to their healthy equivalent and report an average error of 3.88$\pm$7.63\%. The presented pipeline offers a first approach to a personalized automatic high-level framework for planning osteoplasty procedures.

Florian Kofler, Ivan Ezhov, Fabian Isensee et al.

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.

Suprosanna Shit, Abinav Ravi Venkatakrishnan, Ivan Ezhov et al.

Fast and accurate solution of time-dependent partial differential equations (PDEs) is of key interest in many research fields including physics, engineering, and biology. Generally, implicit schemes are preferred over the explicit ones for better stability and correctness. The existing implicit schemes 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 for a class of PDEs, in a data-driven fashion. We attain this objective by modifying an iteration of an existing semi-implicit solver using a deep neural network. Further, we prove theoretically that our approach preserves the correctness and convergence guarantees provided by the existing iterative-solvers. We also demonstrate that our model generalizes to a different parameter setting than the one seen during training and achieves faster convergence compared to the semi-implicit schemes.

Patrick Bilic, Patrick Christ, Hongwei Bran Li et al.

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in \url{http://medicaldecathlon.com/}. In addition, both data and online evaluation are accessible via \url{www.lits-challenge.com}.

Spyridon Bakas, Mauricio Reyes, Andras Jakab et al.

Gliomas are the most common primary brain malignancies, with different degrees of aggressiveness, variable prognosis and various heterogeneous histologic sub-regions, i.e., peritumoral edematous/invaded tissue, necrotic core, active and non-enhancing core. This intrinsic heterogeneity is also portrayed in their radio-phenotype, as their sub-regions are depicted by varying intensity profiles disseminated across multi-parametric magnetic resonance imaging (mpMRI) scans, reflecting varying biological properties. Their heterogeneous shape, extent, and location are some of the factors that make these tumors difficult to resect, and in some cases inoperable. The amount of resected tumor is a factor also considered in longitudinal scans, when evaluating the apparent tumor for potential diagnosis of progression. Furthermore, there is mounting evidence that accurate segmentation of the various tumor sub-regions can offer the basis for quantitative image analysis towards prediction of patient overall survival. This study assesses the state-of-the-art machine learning (ML) methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e., 2012-2018. Specifically, we focus on i) evaluating segmentations of the various glioma sub-regions in pre-operative mpMRI scans, ii) assessing potential tumor progression by virtue of longitudinal growth of tumor sub-regions, beyond use of the RECIST/RANO criteria, and iii) predicting the overall survival from pre-operative mpMRI scans of patients that underwent gross total resection. Finally, we investigate the challenge of identifying the best ML algorithms for each of these tasks, considering that apart from being diverse on each instance of the challenge, the multi-institutional mpMRI BraTS dataset has also been a continuously evolving/growing dataset.

Xiaobin Hu, Hongwei Li, Yu Zhao et al.

For many segmentation tasks, especially for the biomedical image, the topological prior is vital information which is useful to exploit. The containment/nesting is a typical inter-class geometric relationship. In the MICCAI Brain tumor segmentation challenge, with its three hierarchically nested classes 'whole tumor', 'tumor core', 'active tumor', the nested classes relationship is introduced into the 3D-residual-Unet architecture. The network comprises a context aggregation pathway and a localization pathway, which encodes increasingly abstract representation of the input as going deeper into the network, and then recombines these representations with shallower features to precisely localize the interest domain via a localization path. The nested-class-prior is combined by proposing the multi-class activation function and its corresponding loss function. The model is trained on the training dataset of Brats2018, and 20% of the dataset is regarded as the validation dataset to determine parameters. When the parameters are fixed, we retrain the model on the whole training dataset. The performance achieved on the validation leaderboard is 86%, 77% and 72% Dice scores for the whole tumor, enhancing tumor and tumor core classes without relying on ensembles or complicated post-processing steps. Based on the same start-of-the-art network architecture, the accuracy of nested-class (enhancing tumor) is reasonably improved from 69% to 72% compared with the traditional Softmax-based method which blind to topological prior.

Marie Piraud, Anjany Sekuboyina, Bjoern H. Menze

For many biological image segmentation tasks, including topological knowledge, such as the nesting of classes, can greatly improve results. However, most `out-of-the-box' CNN models are still blind to such prior information. In this paper, we propose a novel approach to encode this information, through a multi-level activation layer and three compatible losses. We benchmark all of them on nuclei segmentation in bright-field microscopy cell images from the 2018 Data Science Bowl challenge, offering an exemplary segmentation task with cells and nested subcellular structures. Our scheme greatly speeds up learning, and outperforms standard multi-class classification with soft-max activation and a previously proposed method stemming from it, improving the Dice score significantly (p-values<0.007). Our approach is conceptually simple, easy to implement and can be integrated in any CNN architecture. It can be generalized to a higher number of classes, with or without further relations of containment.

Giles Tetteh, Velizar Efremov, Nils D. Forkert et al.

We present DeepVesselNet, an architecture tailored to the challenges faced when extracting vessel networks or trees and corresponding features in 3-D angiographic volumes using deep learning. We discuss the problems of low execution speed and high memory requirements associated with full 3-D convolutional networks, high-class imbalance arising from the low percentage of vessel voxels, and unavailability of accurately annotated training data - and offer solutions as the building blocks of DeepVesselNet. First, we formulate 2-D orthogonal cross-hair filters which make use of 3-D context information at a reduced computational burden. Second, we introduce a class balancing cross-entropy loss function with false positive rate correction to handle the high-class imbalance and high false positive rate problems associated with existing loss functions. Finally, we generate synthetic dataset using a computational angiogenesis model capable of generating vascular trees under physiological constraints on local network structure and topology and use these data for transfer learning. DeepVesselNet is optimized for segmenting and analyzing vessels, and we test the performance on a range of angiographic volumes including clinical MRA data of the human brain, as well as X-ray tomographic microscopy scans of the rat brain. Our experiments show that, by replacing 3-D filters with cross-hair filters in our network, we achieve over 23% improvement in speed, lower memory footprint, lower network complexity which prevents overfitting and comparable accuracy (with a Cox-Wilcoxon paired sample significance test p-value of 0.07 when compared to full 3-D filters). Our class balancing metric is crucial for training the network and transfer learning with synthetic data is an efficient, robust, and very generalizable approach leading to a network that excels in a variety of angiography segmentation tasks.