Spyridon Bakas

Lena Maier-Hein, Annika Reinke, Patrick Godau et al. · utoronto

Increasing evidence shows that flaws in machine learning (ML) algorithm validation are an underestimated global problem. Particularly in automatic biomedical image analysis, chosen performance metrics often do not reflect the domain interest, thus failing to adequately measure scientific progress and hindering translation of ML techniques into practice. To overcome this, our large international expert consortium created Metrics Reloaded, a comprehensive framework guiding researchers in the problem-aware selection of metrics. Following the convergence of ML methodology across application domains, Metrics Reloaded fosters the convergence of validation methodology. The framework was developed in a multi-stage Delphi process and is based on the novel concept of a problem fingerprint - a structured representation of the given problem that captures all aspects that are relevant for metric selection, from the domain interest to the properties of the target structure(s), data set and algorithm output. Based on the problem fingerprint, users are guided through the process of choosing and applying appropriate validation metrics while being made aware of potential pitfalls. Metrics Reloaded targets image analysis problems that can be interpreted as a classification task at image, object or pixel level, namely image-level classification, object detection, semantic segmentation, and instance segmentation tasks. To improve the user experience, we implemented the framework in the Metrics Reloaded online tool, which also provides a point of access to explore weaknesses, strengths and specific recommendations for the most common validation metrics. The broad applicability of our framework across domains is demonstrated by an instantiation for various biological and medical image analysis use cases.

Matthias Eisenmann, Annika Reinke, Vivienn Weru et al. · utoronto

The number of international benchmarking competitions is steadily increasing in various fields of machine learning (ML) research and practice. So far, however, little is known about the common practice as well as bottlenecks faced by the community in tackling the research questions posed. To shed light on the status quo of algorithm development in the specific field of biomedical imaging analysis, we designed an international survey that was issued to all participants of challenges conducted in conjunction with the IEEE ISBI 2021 and MICCAI 2021 conferences (80 competitions in total). The survey covered participants' expertise and working environments, their chosen strategies, as well as algorithm characteristics. A median of 72% challenge participants took part in the survey. According to our results, knowledge exchange was the primary incentive (70%) for participation, while the reception of prize money played only a minor role (16%). While a median of 80 working hours was spent on method development, a large portion of participants stated that they did not have enough time for method development (32%). 25% perceived the infrastructure to be a bottleneck. Overall, 94% of all solutions were deep learning-based. Of these, 84% were based on standard architectures. 43% of the respondents reported that the data samples (e.g., images) were too large to be processed at once. This was most commonly addressed by patch-based training (69%), downsampling (37%), and solving 3D analysis tasks as a series of 2D tasks. K-fold cross-validation on the training set was performed by only 37% of the participants and only 50% of the participants performed ensembling based on multiple identical models (61%) or heterogeneous models (39%). 48% of the respondents applied postprocessing steps.

Annika Reinke, Minu D. Tizabi, Michael Baumgartner et al.

Validation metrics are key for the reliable tracking of scientific progress and for bridging the current chasm between artificial intelligence (AI) research and its translation into practice. However, increasing evidence shows that particularly in image analysis, metrics are often chosen inadequately in relation to the underlying research problem. This could be attributed to a lack of accessibility of metric-related knowledge: While taking into account the individual strengths, weaknesses, and limitations of validation metrics is a critical prerequisite to making educated choices, the relevant knowledge is currently scattered and poorly accessible to individual researchers. Based on a multi-stage Delphi process conducted by a multidisciplinary expert consortium as well as extensive community feedback, the present work provides the first reliable and comprehensive common point of access to information on pitfalls related to validation metrics in image analysis. Focusing on biomedical image analysis but with the potential of transfer to other fields, the addressed pitfalls generalize across application domains and are categorized according to a newly created, domain-agnostic taxonomy. To facilitate comprehension, illustrations and specific examples accompany each pitfall. As a structured body of information accessible to researchers of all levels of expertise, this work enhances global comprehension of a key topic in image analysis validation.

Sanyukta Adap, Ujjwal Baid, Spyridon Bakas

Glioblastoma (GBM) is the most common aggressive, fast-growing brain tumor, with a grim prognosis. Despite clinical diagnostic advancements, there have not been any substantial improvements to patient prognosis. Histopathological assessment of excised tumors is the first line of clinical diagnostic routine. We hypothesize that automated, robust, and accurate identification of distinct histological sub-regions within GBM could contribute to morphologically understanding this disease at scale. In this study, we designed a four-step deep learning approach to classify six (6) histopathological regions and quantitatively evaluated it on the BraTS-Path 2024 challenge dataset, which includes digitized Hematoxylin \& Eosin (H\&E) stained GBM tissue sections annotated for six distinct regions. We used the challenge's publicly available training dataset to develop and evaluate the effectiveness of several variants of EfficientNet architectures (i.e., B0, B1, B2, B3, B4). EfficientNet-B1 and EfficientNet-B4 achieved the best performance, achieving an F1 score of 0.98 in a 5-fold cross-validation configuration using the BraTS-Path training set. The quantitative performance evaluation of our proposed approach with EfficientNet-B1 on the BraTS-Path hold-out validation data and the final hidden testing data yielded F1 scores of 0.546 and 0.517, respectively, for the associated 6-class classification task. The difference in the performance on training, validation, and testing data highlights the challenge of developing models that generalize well to new data, which is crucial for clinical applications. The source code of the proposed approach can be found at the GitHub repository of Indiana University Division of Computational Pathology: https://github.com/IUCompPath/brats-path-2024-enet.

Matthias Eisenmann, Annika Reinke, Vivienn Weru et al.

International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multi-center study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and postprocessing (66%). The "typical" lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work.

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.

Zahra Riahi Samani, Drew Parker, Hamed Akbari et al.

In malignant primary brain tumors, cancer cells infiltrate into the peritumoral brain structures which results in inevitable recurrence. Quantitative assessment of infiltrative heterogeneity in the peritumoral region, the area where biopsy or resection can be hazardous, is important for clinical decision making. Previous work on characterizing the infiltrative heterogeneity in the peritumoral region used various imaging modalities, but information of extracellular free water movement restriction has been limitedly explored. Here, we derive a unique set of Artificial Intelligence (AI)-based markers capturing the heterogeneity of tumor infiltration, by characterizing free water movement restriction in the peritumoral region using Diffusion Tensor Imaging (DTI)-based free water volume fraction maps. A novel voxel-wise deep learning-based peritumoral microenvironment index (PMI) is first extracted by leveraging the widely different water diffusivity properties of glioblastomas and brain metastases as regions with and without infiltrations in the peritumoral tissue. Descriptive characteristics of locoregional hubs of uniformly high PMI values are extracted as AI-based markers to capture distinct aspects of infiltrative heterogeneity. The proposed markers are applied to two clinical use cases on an independent population of 275 adult-type diffuse gliomas (CNS WHO grade 4), analyzing the duration of survival among Isocitrate-Dehydrogenase 1 (IDH1)-wildtypes and the differences with IDH1-mutants. Our findings provide a panel of markers as surrogates of infiltration that captures unique insight about underlying biology of peritumoral microstructural heterogeneity, establishing them as biomarkers of prognosis pertaining to survival and molecular stratification, with potential applicability in clinical decision making.

Ramya Muthukrishnan, Angelina Heyler, Keshava Katti et al.

In this study, we automate quantitative mammographic breast density estimation with neural networks and show that this tool is a strong use case for federated learning on multi-institutional datasets. Our dataset included bilateral CC-view and MLO-view mammographic images from two separate institutions. Two U-Nets were separately trained on algorithm-generated labels to perform segmentation of the breast and dense tissue from these images and subsequently calculate breast percent density (PD). The networks were trained with federated learning and compared to three non-federated baselines, one trained on each single-institution dataset and one trained on the aggregated multi-institution dataset. We demonstrate that training on multi-institution datasets is critical to algorithm generalizability. We further show that federated learning on multi-institutional datasets improves model generalization to unseen data at nearly the same level as centralized training on multi-institutional datasets, indicating that federated learning can be applied to our method to improve algorithm generalizability while maintaining patient privacy.

Bhakti Baheti, Sunny Rai, Shubham Innani et al.

Glioblastoma is the most common and aggressive malignant adult tumor of the central nervous system, with a grim prognosis and heterogeneous morphologic and molecular profiles. Since adopting the current standard-of-care treatment 18 years ago, no substantial prognostic improvement has been noticed. Accurate prediction of patient overall survival (OS) from histopathology whole slide images (WSI) integrated with clinical data using advanced computational methods could optimize clinical decision-making and patient management. Here, we focus on identifying prognostically relevant glioblastoma characteristics from H&E stained WSI & clinical data relating to OS. The exact approach for WSI capitalizes on the comprehensive curation of apparent artifactual content and an interpretability mechanism via a weakly supervised attention-based multiple-instance learning algorithm that further utilizes clustering to constrain the search space. The automatically placed patterns of high diagnostic value classify each WSI as representative of short or long-survivors. Further assessment of the prognostic relevance of the associated clinical patient data is performed both in isolation and in an integrated manner, using XGBoost and SHapley Additive exPlanations (SHAP). Identifying tumor morphological & clinical patterns associated with short and long OS will enable the clinical neuropathologist to provide additional relevant prognostic information to the treating team and suggest avenues of biological investigation for understanding and potentially treating glioblastoma.

Suhang You, Sanyukta Adap, Siddhesh Thakur et al.

Time to biochemical recurrence in prostate cancer is essential for prognostic monitoring of the progression of patients after prostatectomy, which assesses the efficacy of the surgery. In this work, we proposed to leverage multiple instance learning through a two-stage ``thinking fast \& slow'' strategy for the time to recurrence (TTR) prediction. The first (``thinking fast'') stage finds the most relevant WSI area for biochemical recurrence and the second (``thinking slow'') stage leverages higher resolution patches to predict TTR. Our approach reveals a mean C-index ($Ci$) of 0.733 ($θ=0.059$) on our internal validation and $Ci=0.603$ on the LEOPARD challenge validation set. Post hoc attention visualization shows that the most attentive area contributes to the TTR prediction.

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.

Sarthak Pati, Szymon Mazurek, Spyridon Bakas

Generative Artificial Intelligence (GenAI) is a field of AI that creates new data samples from existing ones. It utilizing deep learning to overcome the scarcity and regulatory constraints of healthcare data by generating new data points that integrate seamlessly with original datasets. This paper explores the background and motivation for GenAI, and introduces the Generally Nuanced Deep Learning Framework for Synthesis (GaNDLF-Synth) to address a significant gap in the literature and move towards democratizing the implementation and assessment of image synthesis tasks in healthcare. GaNDLF-Synth describes a unified abstraction for various synthesis algorithms, including autoencoders, generative adversarial networks, and diffusion models. Leveraging the GANDLF-core framework, it supports diverse data modalities and distributed computing, ensuring scalability and reproducibility through extensive unit testing. The aim of GaNDLF-Synth is to lower the entry barrier for GenAI, and make it more accessible and extensible by the wider scientific community.

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.

Raghav Mehta, Angelos Filos, Ujjwal Baid et al.

Deep learning (DL) models have provided state-of-the-art performance in various medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder translating DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties could enable clinical review of the most uncertain regions, thereby building trust and paving the way toward clinical translation. Several uncertainty estimation methods have recently been introduced for DL medical image segmentation tasks. Developing scores to evaluate and compare the performance of uncertainty measures will assist the end-user in making more informed decisions. In this study, we explore and evaluate a score developed during the BraTS 2019 and BraTS 2020 task on uncertainty quantification (QU-BraTS) and designed to assess and rank uncertainty estimates for brain tumor multi-compartment segmentation. This score (1) rewards uncertainty estimates that produce high confidence in correct assertions and those that assign low confidence levels at incorrect assertions, and (2) penalizes uncertainty measures that lead to a higher percentage of under-confident correct assertions. We further benchmark the segmentation uncertainties generated by 14 independent participating teams of QU-BraTS 2020, all of which also participated in the main BraTS segmentation task. Overall, our findings confirm the importance and complementary value that uncertainty estimates provide to segmentation algorithms, highlighting the need for uncertainty quantification in medical image analyses. Finally, in favor of transparency and reproducibility, our evaluation code is made publicly available at: https://github.com/RagMeh11/QU-BraTS.

G Anthony Reina, Alexey Gruzdev, Patrick Foley et al.

Federated learning (FL) is a computational paradigm that enables organizations to collaborate on machine learning (ML) projects without sharing sensitive data, such as, patient records, financial data, or classified secrets. Open Federated Learning (OpenFL https://github.com/intel/openfl) is an open-source framework for training ML algorithms using the data-private collaborative learning paradigm of FL. OpenFL works with training pipelines built with both TensorFlow and PyTorch, and can be easily extended to other ML and deep learning frameworks. Here, we summarize the motivation and development characteristics of OpenFL, with the intention of facilitating its application to existing ML model training in a production environment. Finally, we describe the first use of the OpenFL framework to train consensus ML models in a consortium of international healthcare organizations, as well as how it facilitates the first computational competition on FL.

Ahmed Hosny, Michael Schwier, Christoph Berger et al.

Recent advances in artificial intelligence research have led to a profusion of studies that apply deep learning to problems in image analysis and natural language processing among others. Additionally, the availability of open-source computational frameworks has lowered the barriers to implementing state-of-the-art methods across multiple domains. Albeit leading to major performance breakthroughs in some tasks, effective dissemination of deep learning algorithms remains challenging, inhibiting reproducibility and benchmarking studies, impeding further validation, and ultimately hindering their effectiveness in the cumulative scientific progress. In developing a platform for sharing research outputs, we present ModelHub.AI (www.modelhub.ai), a community-driven container-based software engine and platform for the structured dissemination of deep learning models. For contributors, the engine controls data flow throughout the inference cycle, while the contributor-facing standard template exposes model-specific functions including inference, as well as pre- and post-processing. Python and RESTful Application programming interfaces (APIs) enable users to interact with models hosted on ModelHub.AI and allows both researchers and developers to utilize models out-of-the-box. ModelHub.AI is domain-, data-, and framework-agnostic, catering to different workflows and contributors' preferences.

Amber L. Simpson, Michela Antonelli, Spyridon Bakas et al.

Semantic segmentation of medical images aims to associate a pixel with a label in a medical image without human initialization. The success of semantic segmentation algorithms is contingent on the availability of high-quality imaging data with corresponding labels provided by experts. We sought to create a large collection of annotated medical image datasets of various clinically relevant anatomies available under open source license to facilitate the development of semantic segmentation algorithms. Such a resource would allow: 1) objective assessment of general-purpose segmentation methods through comprehensive benchmarking and 2) open and free access to medical image data for any researcher interested in the problem domain. Through a multi-institutional effort, we generated a large, curated dataset representative of several highly variable segmentation tasks that was used in a crowd-sourced challenge - the Medical Segmentation Decathlon held during the 2018 Medical Image Computing and Computer Aided Interventions Conference in Granada, Spain. Here, we describe these ten labeled image datasets so that these data may be effectively reused by the research community.

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.

Spyridon Bakas, Siddhesh P. Thakur, Shahriar Faghani et al.

Glioblastoma is the most common primary adult brain tumor, with a grim prognosis - median survival of 12-18 months following treatment, and 4 months otherwise. Glioblastoma is widely infiltrative in the cerebral hemispheres and well-defined by heterogeneous molecular and micro-environmental histopathologic profiles, which pose a major obstacle in treatment. Correctly diagnosing these tumors and assessing their heterogeneity is crucial for choosing the precise treatment and potentially enhancing patient survival rates. In the gold-standard histopathology-based approach to tumor diagnosis, detecting various morpho-pathological features of distinct histology throughout digitized tissue sections is crucial. Such "features" include the presence of cellular tumor, geographic necrosis, pseudopalisading necrosis, areas abundant in microvascular proliferation, infiltration into the cortex, wide extension in subcortical white matter, leptomeningeal infiltration, regions dense with macrophages, and the presence of perivascular or scattered lymphocytes. With these features in mind and building upon the main aim of the BraTS Cluster of Challenges https://www.synapse.org/brats2024, the goal of the BraTS-Path challenge is to provide a systematically prepared comprehensive dataset and a benchmarking environment to develop and fairly compare deep-learning models capable of identifying tumor sub-regions of distinct histologic profile. These models aim to further our understanding of the disease and assist in the diagnosis and grading of conditions in a consistent manner.

Raisa Amiruddin, Nikolay Y. Yordanov, Nazanin Maleki et al.

High-quality reference standard image data creation by neuroradiology experts for automated clinical tools can be a powerful tool for neuroradiology & artificial intelligence education. We developed a multimodal educational approach for students and trainees during the MICCAI Brain Tumor Segmentation Lighthouse Challenge 2025, a landmark initiative to develop accurate brain tumor segmentation algorithms. Fifty-six medical students & radiology trainees volunteered to annotate brain tumor MR images for the BraTS challenges of 2023 & 2024, guided by faculty-led didactics on neuropathology MRI. Among the 56 annotators, 14 select volunteers were then paired with neuroradiology faculty for guided one-on-one annotation sessions for BraTS 2025. Lectures on neuroanatomy, pathology & AI, journal clubs & data scientist-led workshops were organized online. Annotators & audience members completed surveys on their perceived knowledge before & after annotations & lectures respectively. Fourteen coordinators, each paired with a neuroradiologist, completed the data annotation process, averaging 1322.9+/-760.7 hours per dataset per pair and 1200 segmentations in total. On a scale of 1-10, annotation coordinators reported significant increase in familiarity with image segmentation software pre- and post-annotation, moving from initial average of 6+/-2.9 to final average of 8.9+/-1.1, and significant increase in familiarity with brain tumor features pre- and post-annotation, moving from initial average of 6.2+/-2.4 to final average of 8.1+/-1.2. We demonstrate an innovative offering for providing neuroradiology & AI education through an image segmentation challenge to enhance understanding of algorithm development, reinforce the concept of data reference standard, and diversify opportunities for AI-driven image analysis among future physicians.

Suhang You, Carla Pitarch-Abaigar, Sanket Kachole et al.

Almost 30% of prostate cancer (PCa) patients undergoing radical prostatectomy (RP) experience biochemical recurrence (BCR), characterized by increased prostate specific antigen (PSA) and associated with increased mortality. Accurate early prediction of BCR, at the time of RP, would contribute to prompt adaptive clinical decision-making and improved patient outcomes. In this work, we propose prostate cancer BCR prediction via fused multi-modal embeddings (PROFUSEme), which learns cross-modal interactions of clinical, radiology, and pathology data, following an intermediate fusion configuration in combination with Cox Proportional Hazard regressors. Quantitative evaluation of our proposed approach reveals superior performance, when compared with late fusion configurations, yielding a mean C-index of 0.861 ($σ=0.112$) on the internal 5-fold nested cross-validation framework, and a C-index of 0.7107 on the hold out data of CHIMERA 2025 challenge validation leaderboard.

Jong Sung Park, Juhyung Ha, Siddhesh Thakur et al.

While many skull stripping algorithms have been developed for multi-modal and multi-species cases, there is still a lack of a fundamentally generalizable approach. We present PUMBA(PUrely synthetic Multimodal/species invariant Brain extrAction), a strategy to train a model for brain extraction with no real brain images or labels. Our results show that even without any real images or anatomical priors, the model achieves comparable accuracy in multi-modal, multi-species and pathological cases. This work presents a new direction of research for any generalizable medical image segmentation task.

Hongwei Bran Li, Fernando Navarro, Ivan Ezhov et al.

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.

Maruf Adewole, Jeffrey D. Rudie, Anu Gbadamosi et al.

Gliomas are the most common type of primary brain tumors. Although gliomas are relatively rare, they are among the deadliest types of cancer, with a survival rate of less than 2 years after diagnosis. Gliomas are challenging to diagnose, hard to treat and inherently resistant to conventional therapy. Years of extensive research to improve diagnosis and treatment of gliomas have decreased mortality rates across the Global North, while chances of survival among individuals in low- and middle-income countries (LMICs) remain unchanged and are significantly worse in Sub-Saharan Africa (SSA) populations. Long-term survival with glioma is associated with the identification of appropriate pathological features on brain MRI and confirmation by histopathology. Since 2012, the Brain Tumor Segmentation (BraTS) Challenge have evaluated state-of-the-art machine learning methods to detect, characterize, and classify gliomas. However, it is unclear if the state-of-the-art methods can be widely implemented in SSA given the extensive use of lower-quality MRI technology, which produces poor image contrast and resolution and more importantly, the propensity for late presentation of disease at advanced stages as well as the unique characteristics of gliomas in SSA (i.e., suspected higher rates of gliomatosis cerebri). Thus, the BraTS-Africa Challenge provides a unique opportunity to include brain MRI glioma cases from SSA in global efforts through the BraTS Challenge to develop and evaluate computer-aided-diagnostic (CAD) methods for the detection and characterization of glioma in resource-limited settings, where the potential for CAD tools to transform healthcare are more likely.

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.

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.

Ujjwal Baid, Sarthak Pati, Tahsin M. Kurc et al.

We evaluate the performance of federated learning (FL) in developing deep learning models for analysis of digitized tissue sections. A classification application was considered as the example use case, on quantifiying the distribution of tumor infiltrating lymphocytes within whole slide images (WSIs). A deep learning classification model was trained using 50*50 square micron patches extracted from the WSIs. We simulated a FL environment in which a dataset, generated from WSIs of cancer from numerous anatomical sites available by The Cancer Genome Atlas repository, is partitioned in 8 different nodes. Our results show that the model trained with the federated training approach achieves similar performance, both quantitatively and qualitatively, to that of a model trained with all the training data pooled at a centralized location. Our study shows that FL has tremendous potential for enabling development of more robust and accurate models for histopathology image analysis without having to collect large and diverse training data at a single location.

Reuben Dorent, Aaron Kujawa, Marina Ivory et al.

Domain Adaptation (DA) has recently raised strong interests in the medical imaging community. While a large variety of DA techniques has been proposed for image segmentation, most of these techniques have been validated either on private datasets or on small publicly available datasets. Moreover, these datasets mostly addressed single-class problems. To tackle these limitations, the Cross-Modality Domain Adaptation (crossMoDA) challenge was organised in conjunction with the 24th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2021). CrossMoDA is the first large and multi-class benchmark for unsupervised cross-modality DA. The challenge's goal is to segment two key brain structures involved in the follow-up and treatment planning of vestibular schwannoma (VS): the VS and the cochleas. Currently, the diagnosis and surveillance in patients with VS are performed using contrast-enhanced T1 (ceT1) MRI. However, there is growing interest in using non-contrast sequences such as high-resolution T2 (hrT2) MRI. Therefore, we created an unsupervised cross-modality segmentation benchmark. The training set provides annotated ceT1 (N=105) and unpaired non-annotated hrT2 (N=105). The aim was to automatically perform unilateral VS and bilateral cochlea segmentation on hrT2 as provided in the testing set (N=137). A total of 16 teams submitted their algorithm for the evaluation phase. The level of performance reached by the top-performing teams is strikingly high (best median Dice - VS:88.4%; Cochleas:85.7%) and close to full supervision (median Dice - VS:92.5%; Cochleas:87.7%). All top-performing methods made use of an image-to-image translation approach to transform the source-domain images into pseudo-target-domain images. A segmentation network was then trained using these generated images and the manual annotations provided for the source image.

Bhakti Baheti, Satrajit Chakrabarty, Hamed Akbari et al.

Registration of longitudinal brain MRI scans containing pathologies is challenging due to dramatic changes in tissue appearance. Although there has been progress in developing general-purpose medical image registration techniques, they have not yet attained the requisite precision and reliability for this task, highlighting its inherent complexity. Here we describe the Brain Tumor Sequence Registration (BraTS-Reg) challenge, as the first public benchmark environment for deformable registration algorithms focusing on estimating correspondences between pre-operative and follow-up scans of the same patient diagnosed with a diffuse brain glioma. The BraTS-Reg data comprise de-identified multi-institutional multi-parametric MRI (mpMRI) scans, curated for size and resolution according to a canonical anatomical template, and divided into training, validation, and testing sets. Clinical experts annotated ground truth (GT) landmark points of anatomical locations distinct across the temporal domain. Quantitative evaluation and ranking were based on the Median Euclidean Error (MEE), Robustness, and the determinant of the Jacobian of the displacement field. The top-ranked methodologies yielded similar performance across all evaluation metrics and shared several methodological commonalities, including pre-alignment, deep neural networks, inverse consistency analysis, and test-time instance optimization per-case basis as a post-processing step. The top-ranked method attained the MEE at or below that of the inter-rater variability for approximately 60% of the evaluated landmarks, underscoring the scope for further accuracy and robustness improvements, especially relative to human experts. The aim of BraTS-Reg is to continue to serve as an active resource for research, with the data and online evaluation tools accessible at https://bratsreg.github.io/.

Evan Calabrese, Javier E. Villanueva-Meyer, Jeffrey D. Rudie et al.

Here we present the University of California San Francisco Preoperative Diffuse Glioma MRI (UCSF-PDGM) dataset. The UCSF-PDGM dataset includes 500 subjects with histopathologically-proven diffuse gliomas who were imaged with a standardized 3 Tesla preoperative brain tumor MRI protocol featuring predominantly 3D imaging, as well as advanced diffusion and perfusion imaging techniques. The dataset also includes isocitrate dehydrogenase (IDH) mutation status for all cases and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation status for World Health Organization (WHO) grade III and IV gliomas. The UCSF-PDGM has been made publicly available in the hopes that researchers around the world will use these data to continue to push the boundaries of AI applications for diffuse gliomas.

Michela Antonelli, Annika Reinke, Spyridon Bakas et al.

International challenges have become the de facto standard for comparative assessment of image analysis algorithms given a specific task. Segmentation is so far the most widely investigated medical image processing task, but the various segmentation challenges have typically been organized in isolation, such that algorithm development was driven by the need to tackle a single specific clinical problem. We hypothesized that a method capable of performing well on multiple tasks will generalize well to a previously unseen task and potentially outperform a custom-designed solution. To investigate the hypothesis, we organized the Medical Segmentation Decathlon (MSD) - a biomedical image analysis challenge, in which algorithms compete in a multitude of both tasks and modalities. The underlying data set was designed to explore the axis of difficulties typically encountered when dealing with medical images, such as small data sets, unbalanced labels, multi-site data and small objects. The MSD challenge confirmed that algorithms with a consistent good performance on a set of tasks preserved their good average performance on a different set of previously unseen tasks. Moreover, by monitoring the MSD winner for two years, we found that this algorithm continued generalizing well to a wide range of other clinical problems, further confirming our hypothesis. Three main conclusions can be drawn from this study: (1) state-of-the-art image segmentation algorithms are mature, accurate, and generalize well when retrained on unseen tasks; (2) consistent algorithmic performance across multiple tasks is a strong surrogate of algorithmic generalizability; (3) the training of accurate AI segmentation models is now commoditized to non AI experts.

Sarthak Pati, Ujjwal Baid, Maximilian Zenk et al.

This manuscript describes the first challenge on Federated Learning, namely the Federated Tumor Segmentation (FeTS) challenge 2021. International challenges have become the standard for validation of biomedical image analysis methods. However, the actual performance of participating (even the winning) algorithms on "real-world" clinical data often remains unclear, as the data included in challenges are usually acquired in very controlled settings at few institutions. The seemingly obvious solution of just collecting increasingly more data from more institutions in such challenges does not scale well due to privacy and ownership hurdles. Towards alleviating these concerns, we are proposing the FeTS challenge 2021 to cater towards both the development and the evaluation of models for the segmentation of intrinsically heterogeneous (in appearance, shape, and histology) brain tumors, namely gliomas. Specifically, the FeTS 2021 challenge uses clinically acquired, multi-institutional magnetic resonance imaging (MRI) scans from the BraTS 2020 challenge, as well as from various remote independent institutions included in the collaborative network of a real-world federation (https://www.fets.ai/). The goals of the FeTS challenge are directly represented by the two included tasks: 1) the identification of the optimal weight aggregation approach towards the training of a consensus model that has gained knowledge via federated learning from multiple geographically distinct institutions, while their data are always retained within each institution, and 2) the federated evaluation of the generalizability of brain tumor segmentation models "in the wild", i.e. on data from institutional distributions that were not part of the training datasets.

Annika Reinke, Minu D. Tizabi, Carole H. Sudre et al.

While the importance of automatic image analysis is continuously increasing, recent meta-research revealed major flaws with respect to algorithm validation. Performance metrics are particularly key for meaningful, objective, and transparent performance assessment and validation of the used automatic algorithms, but relatively little attention has been given to the practical pitfalls when using specific metrics for a given image analysis task. These are typically related to (1) the disregard of inherent metric properties, such as the behaviour in the presence of class imbalance or small target structures, (2) the disregard of inherent data set properties, such as the non-independence of the test cases, and (3) the disregard of the actual biomedical domain interest that the metrics should reflect. This living dynamically document has the purpose to illustrate important limitations of performance metrics commonly applied in the field of image analysis. In this context, it focuses on biomedical image analysis problems that can be phrased as image-level classification, semantic segmentation, instance segmentation, or object detection task. The current version is based on a Delphi process on metrics conducted by an international consortium of image analysis experts from more than 60 institutions worldwide.

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.

Xu Han, Zhengyang Shen, Zhenlin Xu et al.

Registration of images with pathologies is challenging due to tissue appearance changes and missing correspondences caused by the pathologies. Moreover, mass effects as observed for brain tumors may displace tissue, creating larger deformations over time than what is observed in a healthy brain. Deep learning models have successfully been applied to image registration to offer dramatic speed up and to use surrogate information (e.g., segmentations) during training. However, existing approaches focus on learning registration models using images from healthy patients. They are therefore not designed for the registration of images with strong pathologies for example in the context of brain tumors, and traumatic brain injuries. In this work, we explore a deep learning approach to register images with brain tumors to an atlas. Our model learns an appearance mapping from images with tumors to the atlas, while simultaneously predicting the transformation to atlas space. Using separate decoders, the network disentangles the tumor mass effect from the reconstruction of quasi-normal images. Results on both synthetic and real brain tumor scans show that our approach outperforms cost function masking for registration to the atlas and that reconstructed quasi-normal images can be used for better longitudinal registrations.

Ludovic Venet, Sarthak Pati, Paul Yushkevich et al.

Variously stained histology slices are routinely used by pathologists to assess extracted tissue samples from various anatomical sites and determine the presence or extent of a disease. Evaluation of sequential slides is expected to enable a better understanding of the spatial arrangement and growth patterns of cells and vessels. In this paper we present a practical two-step approach based on diffeomorphic registration to align digitized sequential histopathology stained slides to each other, starting with an initial affine step followed by the estimation of a detailed deformation field.

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}.

Adrià Casamitjana, Marcel Catà, Irina Sánchez et al.

In this work we approach the brain tumor segmentation problem with a cascade of two CNNs inspired in the V-Net architecture \cite{VNet}, reformulating residual connections and making use of ROI masks to constrain the networks to train only on relevant voxels. This architecture allows dense training on problems with highly skewed class distributions, such as brain tumor segmentation, by focusing training only on the vecinity of the tumor area. We report results on BraTS2017 Training and Validation sets.

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.

Micah J Sheller, G Anthony Reina, Brandon Edwards et al.

Deep learning models for semantic segmentation of images require large amounts of data. In the medical imaging domain, acquiring sufficient data is a significant challenge. Labeling medical image data requires expert knowledge. Collaboration between institutions could address this challenge, but sharing medical data to a centralized location faces various legal, privacy, technical, and data-ownership challenges, especially among international institutions. In this study, we introduce the first use of federated learning for multi-institutional collaboration, enabling deep learning modeling without sharing patient data. Our quantitative results demonstrate that the performance of federated semantic segmentation models (Dice=0.852) on multimodal brain scans is similar to that of models trained by sharing data (Dice=0.862). We compare federated learning with two alternative collaborative learning methods and find that they fail to match the performance of federated learning.

Xu Han, Roland Kwitt, Stephen Aylward et al.

Brain extraction from images is a common pre-processing step. Many approaches exist, but they are frequently only designed to perform brain extraction from images without strong pathologies. Extracting the brain from images with strong pathologies, for example, the presence of a tumor or of a traumatic brain injury, is challenging. In such cases, tissue appearance may deviate from normal tissue and violates algorithmic assumptions for these approaches; hence, the brain may not be correctly extracted. This paper proposes a brain extraction approach which can explicitly account for pathologies by jointly modeling normal tissue and pathologies. Specifically, our model uses a three-part image decomposition: (1) normal tissue appearance is captured by principal component analysis, (2) pathologies are captured via a total variation term, and (3) non-brain tissue is captured by a sparse term. Decomposition and image registration steps are alternated to allow statistical modeling in a fixed atlas space. As a beneficial side effect, the model allows for the identification of potential pathologies and the reconstruction of a quasi-normal image in atlas space. We demonstrate the effectiveness of our method on four datasets: the IBSR and LPBA40 datasets which show normal images, the BRATS dataset containing images with brain tumors and a dataset containing clinical TBI images. We compare the performance with other popular models: ROBEX, BEaST, MASS, BET, BSE and a recently proposed deep learning approach. Our model performs better than these competing methods on all four datasets. Specifically, our model achieves the best median (97.11) and mean (96.88) Dice scores over all datasets. The two best performing competitors, ROBEX and MASS, achieve scores of 96.23/95.62 and 96.67/94.25 respectively. Hence, our approach is an effective method for high quality brain extraction on a wide variety of images.