Mauricio Reyes

Jianning Li, Zongwei Zhou, Jiancheng Yang et al.

Prior to the deep learning era, shape was commonly used to describe the objects. Nowadays, state-of-the-art (SOTA) algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from numerous shape-related publications in premier vision conferences as well as the growing popularity of ShapeNet (about 51,300 models) and Princeton ModelNet (127,915 models). For the medical domain, we present a large collection of anatomical shapes (e.g., bones, organs, vessels) and 3D models of surgical instrument, called MedShapeNet, created to facilitate the translation of data-driven vision algorithms to medical applications and to adapt SOTA vision algorithms to medical problems. As a unique feature, we directly model the majority of shapes on the imaging data of real patients. As of today, MedShapeNet includes 23 dataset with more than 100,000 shapes that are paired with annotations (ground truth). Our data is freely accessible via a web interface and a Python application programming interface (API) and can be used for discriminative, reconstructive, and variational benchmarks as well as various applications in virtual, augmented, or mixed reality, and 3D printing. Exemplary, we present use cases in the fields of classification of brain tumors, facial and skull reconstructions, multi-class anatomy completion, education, and 3D printing. In future, we will extend the data and improve the interfaces. The project pages are: https://medshapenet.ikim.nrw/ and https://github.com/Jianningli/medshapenet-feedback

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.

Sarthak Pati, Ujjwal Baid, Brandon Edwards et al.

Although machine learning (ML) has shown promise in numerous domains, there are concerns about generalizability to out-of-sample data. This is currently addressed by centrally sharing ample, and importantly diverse, data from multiple sites. However, such centralization is challenging to scale (or even not feasible) due to various limitations. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here we present findings from the largest FL study to-date, involving data from 71 healthcare institutions across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, utilizing the largest dataset of such patients ever used in the literature (25,256 MRI scans from 6,314 patients). We demonstrate a 33% improvement over a publicly trained model to delineate the surgically targetable tumor, and 23% improvement over the tumor's entire extent. We anticipate our study to: 1) enable more studies in healthcare informed by large and diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further quantitative analyses for glioblastoma via performance optimization of our consensus model for eventual public release, and 3) demonstrate the effectiveness of FL at such scale and task complexity as a paradigm shift for multi-site collaborations, alleviating the need for data sharing.

Moritz Roman Hernandez Petzsche, Ezequiel de la Rosa, Uta Hanning et al.

Magnetic resonance imaging (MRI) is a central modality for stroke imaging. It is used upon patient admission to make treatment decisions such as selecting patients for intravenous thrombolysis or endovascular therapy. MRI is later used in the duration of hospital stay to predict outcome by visualizing infarct core size and location. Furthermore, it may be used to characterize stroke etiology, e.g. differentiation between (cardio)-embolic and non-embolic stroke. Computer based automated medical image processing is increasingly finding its way into clinical routine. Previous iterations of the Ischemic Stroke Lesion Segmentation (ISLES) challenge have aided in the generation of identifying benchmark methods for acute and sub-acute ischemic stroke lesion segmentation. Here we introduce an expert-annotated, multicenter MRI dataset for segmentation of acute to subacute stroke lesions. This dataset comprises 400 multi-vendor MRI cases with high variability in stroke lesion size, quantity and location. It is split into a training dataset of n=250 and a test dataset of n=150. All training data will be made publicly available. The test dataset will be used for model validation only and will not be released to the public. This dataset serves as the foundation of the ISLES 2022 challenge with the goal of finding algorithmic methods to enable the development and benchmarking of robust and accurate segmentation algorithms for ischemic stroke.

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.

Evamaria Olga Riedel, Ezequiel de la Rosa, The Anh Baran et al.

Stroke remains a leading cause of global morbidity and mortality, imposing a heavy socioeconomic burden. Advances in endovascular reperfusion therapy and CT and MR imaging for treatment guidance have significantly improved patient outcomes. Developing machine learning algorithms that can create accurate models of brain function from stroke images for tasks like lesion identification and tissue survival prediction requires large, diverse, and well annotated public datasets. While several high-quality image datasets in stroke exist, they include only single time point data. Data over different time points are essential to accurately identify lesions and predict prognosis. Here, we provide comprehensive longitudinal stroke data, including (sub-)acute CT imaging with angiography and perfusion, follow-up MRI after 2-9 days, and acute and longitudinal clinical data up to a three-month outcome. The dataset also includes vessel occlusion masks from acute CT angiography and delineated infarction masks in follow-up MRI. This multicenter dataset consists of 245 cases and is a solid basis for developing powerful machine-learning algorithms to facilitate clinical decision-making.

Ezequiel de la Rosa, Ruisheng Su, Mauricio Reyes et al.

Accurate estimation of brain infarction (i.e., irreversibly damaged tissue) is critical for guiding treatment decisions in acute ischemic stroke. Reliable infarct prediction informs key clinical interventions, including the need for patient transfer to comprehensive stroke centers, the potential benefit of additional reperfusion attempts during mechanical thrombectomy, decisions regarding secondary neuroprotective treatments, and ultimately, prognosis of clinical outcomes. This work introduces the Ischemic Stroke Lesion Segmentation (ISLES) 2024 challenge, which focuses on the prediction of final infarct volumes from pre-interventional acute stroke imaging and clinical data. ISLES24 provides a comprehensive, multimodal setting where participants can leverage all clinically and practically available data, including full acute CT imaging, sub-acute follow-up MRI, and structured clinical information, across a train set of 150 cases. On the hidden test set of 98 cases, the top-performing model, a multimodal nnU-Net-based architecture, achieved a Dice score of 0.285 (+/- 0.213) and an absolute volume difference of 21.2 (+/- 37.2) mL, underlining the significant challenges posed by this task and the need for further advances in multimodal learning. This work makes two primary contributions: first, we establish a standardized, clinically realistic benchmark for post-treatment infarct prediction, enabling systematic evaluation of multimodal algorithmic strategies on a longitudinal stroke dataset; second, we analyze current methodological limitations and outline key research directions to guide the development of next-generation infarct prediction models.

Haozhe Luo, Shelley Zixin Shu, Ziyu Zhou et al.

Vision--language models (VLMs) show promise for clinical decision support in radiology because they enable joint reasoning over radiological images and clinical text, thereby leveraging complementary clinical information. However, radiological findings are long-tailed in practice, leaving some conditions underrepresented and making zero-shot inference essential. Yet current CLIP-style medical VLMs are sensitive to prompt variations and often lack trustworthy external knowledge at inference time, which hinders reliable clinical deployment. We present \textit{KEPIL}, a prompt-robust framework that integrates curated medical knowledge to stabilize zero-shot generalization. KEPIL comprises: (i) \emph{dynamic prompt enrichment} using ontologies with LLM assistance, (ii) a \emph{semantic-aware contrastive loss} aligning embeddings of equivalent prompt variants via a dual-embedding objective, and (iii) \emph{entity-centric report standardization} to yield ontology-aligned representations. Across seven benchmarks, KEPIL achieves state-of-the-art zero-shot inference performance; under prompt-variation tests, it improves AUC by \(6.37\%\) on \textit{CheXpert} and by \(4.11\%\) on average. These results suggest that structured knowledge and robust prompt design are key to clinically reliable radiology-facing VLMs. Code will be released at https://github.com/Roypic/KEPIL.

Ezequiel de la Rosa, Mauricio Reyes, Sook-Lei Liew et al.

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

Haozhe Luo, Ziyu Zhou, Zixin Shu et al.

Deep neural networks excel in medical imaging but remain prone to biases, leading to fairness gaps across demographic groups. We provide the first systematic exploration of Human-AI alignment and fairness in this domain. Our results show that incorporating human insights consistently reduces fairness gaps and enhances out-of-domain generalization, though excessive alignment can introduce performance trade-offs, emphasizing the need for calibrated strategies. These findings highlight Human-AI alignment as a promising approach for developing fair, robust, and generalizable medical AI systems, striking a balance between expert guidance and automated efficiency. Our code is available at https://github.com/Roypic/Aligner.

Pooya Mohammadi Kazaj, Giovanni Baj, Yazdan Salimi et al.

While numerous architectures for medical image segmentation have been proposed, achieving competitive performance with state-of-the-art models networks such as nnUNet, still leave room for further innovation. In this work, we introduce nnUZoo, an open source benchmarking framework built upon nnUNet, which incorporates various deep learning architectures, including CNNs, Transformers, and Mamba-based models. Using this framework, we provide a fair comparison to demystify performance claims across different medical image segmentation tasks. Additionally, in an effort to enrich the benchmarking, we explored five new architectures based on Mamba and Transformers, collectively named X2Net, and integrated them into nnUZoo for further evaluation. The proposed models combine the features of conventional U2Net, nnUNet, CNN, Transformer, and Mamba layers and architectures, called X2Net (UNETR2Net (UNETR), SwT2Net (SwinTransformer), SS2D2Net (SwinUMamba), Alt1DM2Net (LightUMamba), and MambaND2Net (MambaND)). We extensively evaluate the performance of different models on six diverse medical image segmentation datasets, including microscopy, ultrasound, CT, MRI, and PET, covering various body parts, organs, and labels. We compare their performance, in terms of dice score and computational efficiency, against their baseline models, U2Net, and nnUNet. CNN models like nnUNet and U2Net demonstrated both speed and accuracy, making them effective choices for medical image segmentation tasks. Transformer-based models, while promising for certain imaging modalities, exhibited high computational costs. Proposed Mamba-based X2Net architecture (SS2D2Net) achieved competitive accuracy with no significantly difference from nnUNet and U2Net, while using fewer parameters. However, they required significantly longer training time, highlighting a trade-off between model efficiency and computational cost.

Haozhe Luo, Shelley Zixin Shu, Ziyu Zhou et al.

Vision-language models (VLMs) have recently shown remarkable zero-shot performance in medical image understanding, yet their grounding ability, the extent to which textual concepts align with visual evidence, remains underexplored. In the medical domain, however, reliable grounding is essential for interpretability and clinical adoption. In this work, we present the first systematic benchmark for evaluating cross-modal interpretability in chest X-rays across seven CLIP-style VLM variants. We generate visual explanations using cross-attention and similarity-based localization maps, and quantitatively assess their alignment with radiologist-annotated regions across multiple pathologies. Our analysis reveals that: (1) while all VLM variants demonstrate reasonable localization for large and well-defined pathologies, their performance substantially degrades for small or diffuse lesions; (2) models that are pretrained on chest X-ray-specific datasets exhibit improved alignment compared to those trained on general-domain data. (3) The overall recognition ability and grounding ability of the model are strongly correlated. These findings underscore that current VLMs, despite their strong recognition ability, still fall short in clinically reliable grounding, highlighting the need for targeted interpretability benchmarks before deployment in medical practice. XBench code is available at https://github.com/Roypic/Benchmarkingattention

Alain Jungo, Olivier Scheidegger, Mauricio Reyes et al.

Background and Objective: Deep learning enables tremendous progress in medical image analysis. One driving force of this progress are open-source frameworks like TensorFlow and PyTorch. However, these frameworks rarely address issues specific to the domain of medical image analysis, such as 3-D data handling and distance metrics for evaluation. pymia, an open-source Python package, tries to address these issues by providing flexible data handling and evaluation independent of the deep learning framework. Methods: The pymia package provides data handling and evaluation functionalities. The data handling allows flexible medical image handling in every commonly used format (e.g., 2-D, 2.5-D, and 3-D; full- or patch-wise). Even data beyond images like demographics or clinical reports can easily be integrated into deep learning pipelines. The evaluation allows stand-alone result calculation and reporting, as well as performance monitoring during training using a vast amount of domain-specific metrics for segmentation, reconstruction, and regression. Results: The pymia package is highly flexible, allows for fast prototyping, and reduces the burden of implementing data handling routines and evaluation methods. While data handling and evaluation are independent of the deep learning framework used, they can easily be integrated into TensorFlow and PyTorch pipelines. The developed package was successfully used in a variety of research projects for segmentation, reconstruction, and regression. Conclusions: The pymia package fills the gap of current deep learning frameworks regarding data handling and evaluation in medical image analysis. It is available at https://github.com/rundherum/pymia and can directly be installed from the Python Package Index using pip install pymia.

Miao Kang, Xiaojun Hu, Weilin Huang et al.

We propose a Dual-Stream Pyramid Registration Network (referred as Dual-PRNet) for unsupervised 3D medical image registration. Unlike recent CNN-based registration approaches, such as VoxelMorph, which explores a single-stream encoder-decoder network to compute a registration fields from a pair of 3D volumes, we design a two-stream architecture able to compute multi-scale registration fields from convolutional feature pyramids. Our contributions are two-fold: (i) we design a two-stream 3D encoder-decoder network which computes two convolutional feature pyramids separately for a pair of input volumes, resulting in strong deep representations that are meaningful for deformation estimation; (ii) we propose a pyramid registration module able to predict multi-scale registration fields directly from the decoding feature pyramids. This allows it to refine the registration fields gradually in a coarse-to-fine manner via sequential warping, and enable the model with the capability for handling significant deformations between two volumes, such as large displacements in spatial domain or slice space. The proposed Dual-PRNet is evaluated on two standard benchmarks for brain MRI registration, where it outperforms the state-of-the-art approaches by a large margin, e.g., having improvements over recent VoxelMorph [2] with 0.683->0.778 on the LPBA40, and 0.511->0.631 on the Mindboggle101, in term of average Dice score. Code is available at: https://github.com/kangmiao15/Dual-Stream-PRNet-Plus.

Sanaz Karimijafarbigloo, Armin Khosravi, Alireza Kheyrkhah et al.

Multi-rater medical image segmentation captures the inherent ambiguity of clinical interpretation, where diagnostic boundaries vary across experts and imaging devices. Existing approaches often reduce this diversity to consensus labels or treat rater differences as noise, resulting in overconfident and poorly calibrated models. We propose a harmonized probabilistic framework that disentangles acquisition artifacts from genuine annotator variability through adaptive feature conditioning and frequency-domain personalization. A lightweight Harmonizer Network implicitly models scanner-specific artifacts and performs dynamic feature modulation to standardize latent representations, ensuring that uncertainty reflects anatomy rather than noise. To represent rater-specific styles, we introduce a novel High-Frequency Prompt Modules that operate in the spectral domain to encode annotator-dependent boundary precision and textural sensitivity. These prompts adaptively modulate harmonized features to produce personalized yet anatomically consistent segmentations. Furthermore, a Generalized Energy Distance based regularization aligns the generative distribution with empirical annotation variability, promoting diversity where experts disagree and consensus where they converge. Experiments on LIDC-IDRI and NPC-170 show SOTA aggregated and individualized segmentation, with notable GED reductions and improved Dice scores, especially on noisy cases. Beyond accuracy, the model exhibits clinically meaningful uncertainty. Confidence rises in agreement regions and declines in ambiguous areas, supporting its use as a reliable and interpretable tool for multi-expert clinical workflows.

Amelia Jiménez-Sánchez, Natalia-Rozalia Avlona, Sarah de Boer et al.

Datasets play a critical role in medical imaging research, yet issues such as label quality, shortcuts, and metadata are often overlooked. This lack of attention may harm the generalizability of algorithms and, consequently, negatively impact patient outcomes. While existing medical imaging literature reviews mostly focus on machine learning (ML) methods, with only a few focusing on datasets for specific applications, these reviews remain static -- they are published once and not updated thereafter. This fails to account for emerging evidence, such as biases, shortcuts, and additional annotations that other researchers may contribute after the dataset is published. We refer to these newly discovered findings of datasets as research artifacts. To address this gap, we propose a living review that continuously tracks public datasets and their associated research artifacts across multiple medical imaging applications. Our approach includes a framework for the living review to monitor data documentation artifacts, and an SQL database to visualize the citation relationships between research artifact and dataset. Lastly, we discuss key considerations for creating medical imaging datasets, review best practices for data annotation, discuss the significance of shortcuts and demographic diversity, and emphasize the importance of managing datasets throughout their entire lifecycle. Our demo is publicly available at http://inthepicture.itu.dk/.

Seyed Amir Ahmad Safavi-Naini, Elahe Meftah, Josh Mohess et al.

The competency of any intelligent agent is bounded by its formal account of the world in which it operates. Clinical AI lacks such an account. Existing frameworks address evaluation, regulation, or system design in isolation, without a shared model of the clinical world to connect them. We introduce the Clinical World Model, a framework that formalizes care as a tripartite interaction among Patient, Provider, and Ecosystem. To formalize how any agent, whether human or artificial, transforms information into clinical action, we develop parallel decision-making architectures for providers, patients, and AI agents, grounded in validated principles of clinical cognition. The Clinical AI Skill-Mix operationalizes competency through eight dimensions. Five define the clinical competency space (condition, phase, care setting, provider role, and task) and three specify how AI engages human reasoning (assigned authority, agent facing, and anchoring layer). The combinatorial product of these dimensions yields a space of billions of distinct competency coordinates. A central structural implication is that validation within one coordinate provides minimal evidence for performance in another, rendering the competency space irreducible. The framework supplies a common grammar through which clinical AI can be specified, evaluated, and bounded across stakeholders. By making this structure explicit, the Clinical World Model reframes the field's central question from whether AI works to in which competency coordinates reliability has been demonstrated, and for whom.

Shelley Zixin Shu, Haozhe Luo, Alexander Poellinger et al.

Transformer-based deep learning models have demonstrated exceptional performance in medical imaging by leveraging attention mechanisms for feature representation and interpretability. However, these models are prone to learning spurious correlations, leading to biases and limited generalization. While human-AI attention alignment can mitigate these issues, it often depends on costly manual supervision. In this work, we propose a Hybrid Explanation-Guided Learning (H-EGL) framework that combines self-supervised and human-guided constraints to enhance attention alignment and improve generalization. The self-supervised component of H-EGL leverages class-distinctive attention without relying on restrictive priors, promoting robustness and flexibility. We validate our approach on chest X-ray classification using the Vision Transformer (ViT), where H-EGL outperforms two state-of-the-art Explanation-Guided Learning (EGL) methods, demonstrating superior classification accuracy and generalization capability. Additionally, it produces attention maps that are better aligned with human expertise.

Haozhe Luo, Aurélie Pahud de Mortanges, Oana Inel et al.

The interpretability of deep learning is crucial for evaluating the reliability of medical imaging models and reducing the risks of inaccurate patient recommendations. This study addresses the "human out of the loop" and "trustworthiness" issues in medical image analysis by integrating medical professionals into the interpretability process. We propose a disease-weighted attention map refinement network (DWARF) that leverages expert feedback to enhance model relevance and accuracy. Our method employs cyclic training to iteratively improve diagnostic performance, generating precise and interpretable feature maps. Experimental results demonstrate significant improvements in interpretability and diagnostic accuracy across multiple medical imaging datasets. This approach fosters effective collaboration between AI systems and healthcare professionals, ultimately aiming to improve patient outcomes

Jean Pablo Vieira de Mello, Thiago M. Paixão, Rodrigo Berriel et al.

The analysis of Magnetic Resonance Imaging (MRI) sequences enables clinical professionals to monitor the progression of a brain tumor. As the interest for automatizing brain volume MRI analysis increases, it becomes convenient to have each sequence well identified. However, the unstandardized naming of MRI sequences makes their identification difficult for automated systems, as well as makes it difficult for researches to generate or use datasets for machine learning research. In the face of that, we propose a system for identifying types of brain MRI sequences based on deep learning. By training a Convolutional Neural Network (CNN) based on 18-layer ResNet architecture, our system can classify a volumetric brain MRI as a FLAIR, T1, T1c or T2 sequence, or whether it does not belong to any of these classes. The network was evaluated on publicly available datasets comprising both, pre-processed (BraTS dataset) and non-pre-processed (TCGA-GBM dataset), image types with diverse acquisition protocols, requiring only a few slices of the volume for training. Our system can classify among sequence types with an accuracy of 96.81%.

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.

Adriano Pinto, Sérgio Pereira, Raphael Meier et al.

Predicting the final ischaemic stroke lesion provides crucial information regarding the volume of salvageable hypoperfused tissue, which helps physicians in the difficult decision-making process of treatment planning and intervention. Treatment selection is influenced by clinical diagnosis, which requires delineating the stroke lesion, as well as characterising cerebral blood flow dynamics using neuroimaging acquisitions. Nonetheless, predicting the final stroke lesion is an intricate task, due to the variability in lesion size, shape, location and the underlying cerebral haemodynamic processes that occur after the ischaemic stroke takes place. Moreover, since elapsed time between stroke and treatment is related to the loss of brain tissue, assessing and predicting the final stroke lesion needs to be performed in a short period of time, which makes the task even more complex. Therefore, there is a need for automatic methods that predict the final stroke lesion and support physicians in the treatment decision process. We propose a fully automatic deep learning method based on unsupervised and supervised learning to predict the final stroke lesion after 90 days. Our aim is to predict the final stroke lesion location and extent, taking into account the underlying cerebral blood flow dynamics that can influence the prediction. To achieve this, we propose a two-branch Restricted Boltzmann Machine, which provides specialized data-driven features from different sets of standard parametric Magnetic Resonance Imaging maps. These data-driven feature maps are then combined with the parametric Magnetic Resonance Imaging maps, and fed to a Convolutional and Recurrent Neural Network architecture. We evaluated our proposal on the publicly available ISLES 2017 testing dataset, reaching a Dice score of 0.38, Hausdorff Distance of 29.21 mm, and Average Symmetric Surface Distance of 5.52 mm.

Fabian Balsiger, Alain Jungo, Olivier Scheidegger et al.

Magnetic resonance fingerprinting (MRF) enables fast and multiparametric MR imaging. Despite fast acquisition, the state-of-the-art reconstruction of MRF based on dictionary matching is slow and lacks scalability. To overcome these limitations, neural network (NN) approaches estimating MR parameters from fingerprints have been proposed recently. Here, we revisit NN-based MRF reconstruction to jointly learn the forward process from MR parameters to fingerprints and the backward process from fingerprints to MR parameters by leveraging invertible neural networks (INNs). As a proof-of-concept, we perform various experiments showing the benefit of learning the forward process, i.e., the Bloch simulations, for improved MR parameter estimation. The benefit especially accentuates when MR parameter estimation is difficult due to MR physical restrictions. Therefore, INNs might be a feasible alternative to the current solely backward-based NNs for MRF reconstruction.

Fabian Balsiger, Alain Jungo, Olivier Scheidegger et al.

Magnetic resonance fingerprinting (MRF) provides a unique concept for simultaneous and fast acquisition of multiple quantitative MR parameters. Despite acquisition efficiency, adoption of MRF into the clinics is hindered by its dictionary matching-based reconstruction, which is computationally demanding and lacks scalability. Here, we propose a convolutional neural network-based reconstruction, which enables both accurate and fast reconstruction of parametric maps, and is adaptable based on the needs of spatial regularization and the capacity for the reconstruction. We evaluated the method using MRF T1-FF, an MRF sequence for T1 relaxation time of water (T1H2O) and fat fraction (FF) mapping. We demonstrate the method's performance on a highly heterogeneous dataset consisting of 164 patients with various neuromuscular diseases imaged at thighs and legs. We empirically show the benefit of incorporating spatial regularization during the reconstruction and demonstrate that the method learns meaningful features from MR physics perspective. Further, we investigate the ability of the method to handle highly heterogeneous morphometric variations and its generalization to anatomical regions unseen during training. The obtained results outperform the state-of-the-art in deep learning-based MRF reconstruction. The method achieved normalized root mean squared errors of 0.048 $\pm$ 0.011 for T1H2O maps and 0.027 $\pm$ 0.004 for FF maps when compared to the dictionary matching in a test set of 50 patients. Coupled with fast MRF sequences, the proposed method has the potential of enabling multiparametric MR imaging in clinically feasible time.

Alain Jungo, Mauricio Reyes

Despite the recent improvements in overall accuracy, deep learning systems still exhibit low levels of robustness. Detecting possible failures is critical for a successful clinical integration of these systems, where each data point corresponds to an individual patient. Uncertainty measures are a promising direction to improve failure detection since they provide a measure of a system's confidence. Although many uncertainty estimation methods have been proposed for deep learning, little is known on their benefits and current challenges for medical image segmentation. Therefore, we report results of evaluating common voxel-wise uncertainty measures with respect to their reliability, and limitations on two medical image segmentation datasets. Results show that current uncertainty methods perform similarly and although they are well-calibrated at the dataset level, they tend to be miscalibrated at subject-level. Therefore, the reliability of uncertainty estimates is compromised, highlighting the importance of developing subject-wise uncertainty estimations. Additionally, among the benchmarked methods, we found auxiliary networks to be a valid alternative to common uncertainty methods since they can be applied to any previously trained segmentation model.

Fabian Balsiger, Yannick Soom, Olivier Scheidegger et al.

Volumetric image segmentation with convolutional neural networks (CNNs) encounters several challenges, which are specific to medical images. Among these challenges are large volumes of interest, high class imbalances, and difficulties in learning shape representations. To tackle these challenges, we propose to improve over traditional CNN-based volumetric image segmentation through point-wise classification of point clouds. The sparsity of point clouds allows processing of entire image volumes, balancing highly imbalanced segmentation problems, and explicitly learning an anatomical shape. We build upon PointCNN, a neural network proposed to process point clouds, and propose here to jointly encode shape and volumetric information within the point cloud in a compact and computationally effective manner. We demonstrate how this approach can then be used to refine CNN-based segmentation, which yields significantly improved results in our experiments on the difficult task of peripheral nerve segmentation from magnetic resonance neurography images. By synthetic experiments, we further show the capability of our approach in learning an explicit anatomical shape representation.

Behzad Bozorgtabar, Dwarikanath Mahapatra, Hendrik von Teng et al.

Training robust deep learning (DL) systems for disease detection from medical images is challenging due to limited images covering different disease types and severity. The problem is especially acute, where there is a severe class imbalance. We propose an active learning (AL) framework to select most informative samples for training our model using a Bayesian neural network. Informative samples are then used within a novel class aware generative adversarial network (CAGAN) to generate realistic chest xray images for data augmentation by transferring characteristics from one class label to another. Experiments show our proposed AL framework is able to achieve state-of-the-art performance by using about $35\%$ of the full dataset, thus saving significant time and effort over conventional methods.

Richard McKinley, Lorenz Grunder, Rik Wepfer et al.

The detection of new or enlarged white-matter lesions in multiple sclerosis is a vital task in the monitoring of patients undergoing disease-modifying treatment for multiple sclerosis. However, the definition of 'new or enlarged' is not fixed, and it is known that lesion-counting is highly subjective, with high degree of inter- and intra-rater variability. Automated methods for lesion quantification hold the potential to make the detection of new and enlarged lesions consistent and repeatable. However, the majority of lesion segmentation algorithms are not evaluated for their ability to separate progressive from stable patients, despite this being a pressing clinical use-case. In this paper we show that change in volumetric measurements of lesion load alone is not a good method for performing this separation, even for highly performing segmentation methods. Instead, we propose a method for identifying lesion changes of high certainty, and establish on a dataset of longitudinal multiple sclerosis cases that this method is able to separate progressive from stable timepoints with a very high level of discrimination (AUC = 0.99), while changes in lesion volume are much less able to perform this separation (AUC = 0.71). Validation of the method on a second external dataset confirms that the method is able to generalize beyond the setting in which it was trained, achieving an accuracy of 83% in separating stable and progressive timepoints. Both lesion volume and count have previously been shown to be strong predictors of disease course across a population. However, we demonstrate that for individual patients, changes in these measures are not an adequate means of establishing no evidence of disease activity. Meanwhile, directly detecting tissue which changes, with high confidence, from non-lesion to lesion is a feasible methodology for identifying radiologically active patients.

Richard McKinley, Michael Rebsamen, Raphael Meier et al.

In applications of supervised learning applied to medical image segmentation, the need for large amounts of labeled data typically goes unquestioned. In particular, in the case of brain anatomy segmentation, hundreds or thousands of weakly-labeled volumes are often used as training data. In this paper, we first observe that for many brain structures, a small number of training examples, (n=9), weakly labeled using Freesurfer 6.0, plus simple data augmentation, suffice as training data to achieve high performance, achieving an overall mean Dice coefficient of $0.84 \pm 0.12$ compared to Freesurfer over 28 brain structures in T1-weighted images of $\approx 4000$ 9-10 year-olds from the Adolescent Brain Cognitive Development study. We then examine two varieties of heteroscedastic network as a method for improving classification results. An existing proposal by Kendall and Gal, which uses Monte-Carlo inference to learn to predict the variance of each prediction, yields an overall mean Dice of $0.85 \pm 0.14$ and showed statistically significant improvements over 25 brain structures. Meanwhile a novel heteroscedastic network which directly learns the probability that an example has been mislabeled yielded an overall mean Dice of $0.87 \pm 0.11$ and showed statistically significant improvements over all but one of the brain structures considered. The loss function associated to this network can be interpreted as performing a form of learned label smoothing, where labels are only smoothed where they are judged to be uncertain.

Richard McKinley, Rik Wepfer, Fabian Aschwanden et al.

Segmentation of white matter lesions and deep grey matter structures is an important task in the quantification of magnetic resonance imaging in multiple sclerosis. In this paper we explore segmentation solutions based on convolutional neural networks (CNNs) for providing fast, reliable segmentations of lesions and grey-matter structures in multi-modal MR imaging, and the performance of these methods when applied to out-of-centre data. We trained two state-of-the-art fully convolutional CNN architectures on the 2016 MSSEG training dataset, which was annotated by seven independent human raters: a reference implementation of a 3D Unet, and a more recently proposed 3D-to-2D architecture (DeepSCAN). We then retrained those methods on a larger dataset from a single centre, with and without labels for other brain structures. We quantified changes in performance owing to dataset shift, and changes in performance by adding the additional brain-structure labels. We also compared performance with freely available reference methods. Both fully-convolutional CNN methods substantially outperform other approaches in the literature when trained and evaluated in cross-validation on the MSSEG dataset, showing agreement with human raters in the range of human inter-rater variability. Both architectures showed drops in performance when trained on single-centre data and tested on the MSSEG dataset. When trained with the addition of weak anatomical labels derived from Freesurfer, the performance of the 3D Unet degraded, while the performance of the DeepSCAN net improved. Overall, the DeepSCAN network predicting both lesion and anatomical labels was the best-performing network examined.

Yannick Suter, Alain Jungo, Michael Rebsamen et al.

Deep learning for regression tasks on medical imaging data has shown promising results. However, compared to other approaches, their power is strongly linked to the dataset size. In this study, we evaluate 3D-convolutional neural networks (CNNs) and classical regression methods with hand-crafted features for survival time regression of patients with high grade brain tumors. The tested CNNs for regression showed promising but unstable results. The best performing deep learning approach reached an accuracy of 51.5% on held-out samples of the training set. All tested deep learning experiments were outperformed by a Support Vector Classifier (SVC) using 30 radiomic features. The investigated features included intensity, shape, location and deep features. The submitted method to the BraTS 2018 survival prediction challenge is an ensemble of SVCs, which reached a cross-validated accuracy of 72.2% on the BraTS 2018 training set, 57.1% on the validation set, and 42.9% on the testing set. The results suggest that more training data is necessary for a stable performance of a CNN model for direct regression from magnetic resonance images, and that non-imaging clinical patient information is crucial along with imaging information.

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.

Sergio Pereira, Raphael Meier, Victor Alves et al.

Glioblastoma Multiforme is a high grade, very aggressive, brain tumor, with patients having a poor prognosis. Lower grade gliomas are less aggressive, but they can evolve into higher grade tumors over time. Patient management and treatment can vary considerably with tumor grade, ranging from tumor resection followed by a combined radio- and chemotherapy to a "wait and see" approach. Hence, tumor grading is important for adequate treatment planning and monitoring. The gold standard for tumor grading relies on histopathological diagnosis of biopsy specimens. However, this procedure is invasive, time consuming, and prone to sampling error. Given these disadvantages, automatic tumor grading from widely used MRI protocols would be clinically important, as a way to expedite treatment planning and assessment of tumor evolution. In this paper, we propose to use Convolutional Neural Networks for predicting tumor grade directly from imaging data. In this way, we overcome the need for expert annotations of regions of interest. We evaluate two prediction approaches: from the whole brain, and from an automatically defined tumor region. Finally, we employ interpretability methodologies as a quality assurance stage to check if the method is using image regions indicative of tumor grade for classification.

Fabian Balsiger, Amaresha Shridhar Konar, Shivaprasad Chikop et al.

Magnetic resonance fingerprinting (MRF) quantifies multiple nuclear magnetic resonance parameters in a single and fast acquisition. Standard MRF reconstructs parametric maps using dictionary matching, which lacks scalability due to computational inefficiency. We propose to perform MRF map reconstruction using a spatiotemporal convolutional neural network, which exploits the relationship between neighboring MRF signal evolutions to replace the dictionary matching. We evaluate our method on multiparametric brain scans and compare it to three recent MRF reconstruction approaches. Our method achieves state-of-the-art reconstruction accuracy and yields qualitatively more appealing maps compared to other reconstruction methods. In addition, the reconstruction time is significantly reduced compared to a dictionary-based approach.

Dwarikanath Mahapatra, Behzad Bozorgtabar, Jean-Philippe Thiran et al.

Training robust deep learning (DL) systems for medical image classification or segmentation is challenging due to limited images covering different disease types and severity. We propose an active learning (AL) framework to select most informative samples and add to the training data. We use conditional generative adversarial networks (cGANs) to generate realistic chest xray images with different disease characteristics by conditioning its generation on a real image sample. Informative samples to add to the training set are identified using a Bayesian neural network. Experiments show our proposed AL framework is able to achieve state of the art performance by using about 35% of the full dataset, thus saving significant time and effort over conventional methods.

Adriano Pinto, Sergio Pereira, Raphael Meier et al.

Stroke is the second most common cause of death in developed countries, where rapid clinical intervention can have a major impact on a patient's life. To perform the revascularization procedure, the decision making of physicians considers its risks and benefits based on multi-modal MRI and clinical experience. Therefore, automatic prediction of the ischemic stroke lesion outcome has the potential to assist the physician towards a better stroke assessment and information about tissue outcome. Typically, automatic methods consider the information of the standard kinetic models of diffusion and perfusion MRI (e.g. Tmax, TTP, MTT, rCBF, rCBV) to perform lesion outcome prediction. In this work, we propose a deep learning method to fuse this information with an automated data selection of the raw 4D PWI image information, followed by a data-driven deep-learning modeling of the underlying blood flow hemodynamics. We demonstrate the ability of the proposed approach to improve prediction of tissue at risk before therapy, as compared to only using the standard clinical perfusion maps, hence suggesting on the potential benefits of the proposed data-driven raw perfusion data modelling approach.

Alain Jungo, Raphael Meier, Ekin Ermis et al.

Uncertainty estimates of modern neuronal networks provide additional information next to the computed predictions and are thus expected to improve the understanding of the underlying model. Reliable uncertainties are particularly interesting for safety-critical computer-assisted applications in medicine, e.g., neurosurgical interventions and radiotherapy planning. We propose an uncertainty-driven sanity check for the identification of segmentation results that need particular expert review. Our method uses a fully-convolutional neural network and computes uncertainty estimates by the principle of Monte Carlo dropout. We evaluate the performance of the proposed method on a clinical dataset with 30 postoperative brain tumor images. The method can segment the highly inhomogeneous resection cavities accurately (Dice coefficients 0.792 $\pm$ 0.154). Furthermore, the proposed sanity check is able to detect the worst segmentation and three out of the four outliers. The results highlight the potential of using the additional information from the model's parameter uncertainty to validate the segmentation performance of a deep learning model.

Alain Jungo, Raphael Meier, Ekin Ermis et al.

Uncertainty estimation methods are expected to improve the understanding and quality of computer-assisted methods used in medical applications (e.g., neurosurgical interventions, radiotherapy planning), where automated medical image segmentation is crucial. In supervised machine learning, a common practice to generate ground truth label data is to merge observer annotations. However, as many medical image tasks show a high inter-observer variability resulting from factors such as image quality, different levels of user expertise and domain knowledge, little is known as to how inter-observer variability and commonly used fusion methods affect the estimation of uncertainty of automated image segmentation. In this paper we analyze the effect of common image label fusion techniques on uncertainty estimation, and propose to learn the uncertainty among observers. The results highlight the negative effect of fusion methods applied in deep learning, to obtain reliable estimates of segmentation uncertainty. Additionally, we show that the learned observers' uncertainty can be combined with current standard Monte Carlo dropout Bayesian neural networks to characterize uncertainty of model's parameters.

Raphael Meier, Urspeter Knecht, Alain Jungo et al.

This paper proposes a novel approach for uncertainty quantification in dense Conditional Random Fields (CRFs). The presented approach, called Perturb-and-MPM, enables efficient, approximate sampling from dense multi-label CRFs via random perturbations. An analytic error analysis was performed which identified the main cause of approximation error as well as showed that the error is bounded. Spatial uncertainty maps can be derived from the Perturb-and-MPM model, which can be used to visualize uncertainty in image segmentation results. The method is validated on synthetic and clinical Magnetic Resonance Imaging data. The effectiveness of the approach is demonstrated on the challenging problem of segmenting the tumor core in glioblastoma. We found that areas of high uncertainty correspond well to wrongly segmented image regions. Furthermore, we demonstrate the potential use of uncertainty maps to refine imaging biomarkers in the case of extent of resection and residual tumor volume in brain tumor patients.

Stefan Bauer, Lutz-P. Nolte, Mauricio Reyes

Skull-stripping separates the skull region of the head from the soft brain tissues. In many cases of brain image analysis, this is an essential preprocessing step in order to improve the final result. This is true for both registration and segmentation tasks. In fact, skull-stripping of magnetic resonance images (MRI) is a well-studied problem with numerous publications in recent years. Many different algorithms have been proposed, a summary and comparison of which can be found in [Fennema-Notestine, 2006]. Despite the abundance of approaches, we discovered that the algorithms which had been suggested so far, perform poorly when dealing with tumor-bearing brain images. This is mostly due to additional difficulties in separating the brain from the skull in this case, especially when the lesion is located very close to the skull border. Additionally, images acquired according to standard clinical protocols, often exhibit anisotropic resolution and only partial coverage, which further complicates the task. Therefore, we developed a method which is dedicated to skull-stripping for clinically acquired tumor-bearing brain images.