Paul F. Jäger

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.

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.

Carsten T. Lüth, Jeremias Traub, Kim-Celine Kahl et al.

Active learning (AL) has the potential to drastically reduce annotation costs in 3D biomedical image segmentation, where expert labeling of volumetric data is both time-consuming and expensive. Yet, existing AL methods are unable to consistently outperform improved random sampling baselines adapted to 3D data, leaving the field without a reliable solution. We introduce Class-stratified Scheduled Power Predictive Entropy (ClaSP PE), a simple and effective query strategy that addresses two key limitations of standard uncertainty-based AL methods: class imbalance and redundancy in early selections. ClaSP PE combines class-stratified querying to ensure coverage of underrepresented structures and log-scale power noising with a decaying schedule to enforce query diversity in early-stage AL and encourage exploitation later. In our evaluation on 24 experimental settings using four 3D biomedical datasets within the comprehensive nnActive benchmark, ClaSP PE is the only method that generally outperforms improved random baselines in terms of both segmentation quality with statistically significant gains, whilst remaining annotation efficient. Furthermore, we explicitly simulate the real-world application by testing our method on four previously unseen datasets without manual adaptation, where all experiment parameters are set according to predefined guidelines. The results confirm that ClaSP PE robustly generalizes to novel tasks without requiring dataset-specific tuning. Within the nnActive framework, we present compelling evidence that an AL method can consistently outperform random baselines adapted to 3D segmentation, in terms of both performance and annotation efficiency in a realistic, close-to-production scenario. Our open-source implementation and clear deployment guidelines make it readily applicable in practice. Code is at https://github.com/MIC-DKFZ/nnActive.

Evangelia Christodoulou, Annika Reinke, Rola Houhou et al.

Medical imaging is spearheading the AI transformation of healthcare. Performance reporting is key to determine which methods should be translated into clinical practice. Frequently, broad conclusions are simply derived from mean performance values. In this paper, we argue that this common practice is often a misleading simplification as it ignores performance variability. Our contribution is threefold. (1) Analyzing all MICCAI segmentation papers (n = 221) published in 2023, we first observe that more than 50% of papers do not assess performance variability at all. Moreover, only one (0.5%) paper reported confidence intervals (CIs) for model performance. (2) To address the reporting bottleneck, we show that the unreported standard deviation (SD) in segmentation papers can be approximated by a second-order polynomial function of the mean Dice similarity coefficient (DSC). Based on external validation data from 56 previous MICCAI challenges, we demonstrate that this approximation can accurately reconstruct the CI of a method using information provided in publications. (3) Finally, we reconstructed 95% CIs around the mean DSC of MICCAI 2023 segmentation papers. The median CI width was 0.03 which is three times larger than the median performance gap between the first and second ranked method. For more than 60% of papers, the mean performance of the second-ranked method was within the CI of the first-ranked method. We conclude that current publications typically do not provide sufficient evidence to support which models could potentially be translated into clinical practice.

Lukas Klein, Carsten T. Lüth, Udo Schlegel et al.

Explainable AI (XAI) is a rapidly growing domain with a myriad of proposed methods as well as metrics aiming to evaluate their efficacy. However, current studies are often of limited scope, examining only a handful of XAI methods and ignoring underlying design parameters for performance, such as the model architecture or the nature of input data. Moreover, they often rely on one or a few metrics and neglect thorough validation, increasing the risk of selection bias and ignoring discrepancies among metrics. These shortcomings leave practitioners confused about which method to choose for their problem. In response, we introduce LATEC, a large-scale benchmark that critically evaluates 17 prominent XAI methods using 20 distinct metrics. We systematically incorporate vital design parameters like varied architectures and diverse input modalities, resulting in 7,560 examined combinations. Through LATEC, we showcase the high risk of conflicting metrics leading to unreliable rankings and consequently propose a more robust evaluation scheme. Further, we comprehensively evaluate various XAI methods to assist practitioners in selecting appropriate methods aligning with their needs. Curiously, the emerging top-performing method, Expected Gradients, is not examined in any relevant related study. LATEC reinforces its role in future XAI research by publicly releasing all 326k saliency maps and 378k metric scores as a (meta-)evaluation dataset. The benchmark is hosted at: https://github.com/IML-DKFZ/latec.

Zdravko Marinov, Paul F. Jäger, Jan Egger et al.

Interactive segmentation is a crucial research area in medical image analysis aiming to boost the efficiency of costly annotations by incorporating human feedback. This feedback takes the form of clicks, scribbles, or masks and allows for iterative refinement of the model output so as to efficiently guide the system towards the desired behavior. In recent years, deep learning-based approaches have propelled results to a new level causing a rapid growth in the field with 121 methods proposed in the medical imaging domain alone. In this review, we provide a structured overview of this emerging field featuring a comprehensive taxonomy, a systematic review of existing methods, and an in-depth analysis of current practices. Based on these contributions, we discuss the challenges and opportunities in the field. For instance, we find that there is a severe lack of comparison across methods which needs to be tackled by standardized baselines and benchmarks.

Lukas Klein, Mennatallah El-Assady, Paul F. Jäger

Explainable AI (XAI) is a necessity in safety-critical systems such as in clinical diagnostics due to a high risk for fatal decisions. Currently, however, XAI resembles a loose collection of methods rather than a well-defined process. In this work, we elaborate on conceptual similarities between the largest subgroup of XAI, interpretable machine learning (IML), and classical statistics. Based on these similarities, we present a formalization of IML along the lines of a statistical process. Adopting this statistical view allows us to interpret machine learning models and IML methods as sophisticated statistical tools. Based on this interpretation, we infer three key questions, which we identify as crucial for the success and adoption of IML in safety-critical settings. By formulating these questions, we further aim to spark a discussion about what distinguishes IML from classical statistics and what our perspective implies for the future of the field.

Tassilo Wald, Constantin Ulrich, Stanislav Lukyanenko et al.

Self-Supervised Learning (SSL) presents an exciting opportunity to unlock the potential of vast, untapped clinical datasets, for various downstream applications that suffer from the scarcity of labeled data. While SSL has revolutionized fields like natural language processing and computer vision, its adoption in 3D medical image computing has been limited by three key pitfalls: Small pre-training dataset sizes, architectures inadequate for 3D medical image analysis, and insufficient evaluation practices. In this paper, we address these issues by i) leveraging a large-scale dataset of 39k 3D brain MRI volumes and ii) using a Residual Encoder U-Net architecture within the state-of-the-art nnU-Net framework. iii) A robust development framework, incorporating 5 development and 8 testing brain MRI segmentation datasets, allowed performance-driven design decisions to optimize the simple concept of Masked Auto Encoders (MAEs) for 3D CNNs. The resulting model not only surpasses previous SSL methods but also outperforms the strong nnU-Net baseline by an average of approximately 3 Dice points setting a new state-of-the-art. Our code and models are made available here.

Stefan Denner, David Zimmerer, Dimitrios Bounias et al.

Content-based image retrieval (CBIR) has the potential to significantly improve diagnostic aid and medical research in radiology. However, current CBIR systems face limitations due to their specialization to certain pathologies, limiting their utility. On the other hand, several vision foundation models have been shown to produce general-purpose visual features. Therefore, in this work, we propose using vision foundation models as powerful and versatile off-the-shelf feature extractors for content-based image retrieval. Our contributions include: (1) benchmarking a diverse set of vision foundation models on an extensive dataset comprising 1.6 million 2D radiological images across four modalities and 161 pathologies; (2) identifying weakly-supervised models, particularly BiomedCLIP, as highly effective, achieving a achieving a P@1 of up to 0.594 (P@3: 0.590, P@5: 0.588, P@10: 0.583), comparable to specialized CBIR systems but without additional training; (3) conducting an in-depth analysis of the impact of index size on retrieval performance; (4) evaluating the quality of embedding spaces generated by different models; and (5) investigating specific challenges associated with retrieving anatomical versus pathological structures. Despite these challenges, our research underscores the vast potential of foundation models for CBIR in radiology, proposing a shift towards versatile, general-purpose medical image retrieval systems that do not require specific tuning. Our code, dataset splits and embeddings are publicly available under https://github.com/MIC-DKFZ/foundation-models-for-cbmir.

Fabian Isensee, Paul F. Jäger, Simon A. A. Kohl et al.

Biomedical imaging is a driver of scientific discovery and core component of medical care, currently stimulated by the field of deep learning. While semantic segmentation algorithms enable 3D image analysis and quantification in many applications, the design of respective specialised solutions is non-trivial and highly dependent on dataset properties and hardware conditions. We propose nnU-Net, a deep learning framework that condenses the current domain knowledge and autonomously takes the key decisions required to transfer a basic architecture to different datasets and segmentation tasks. Without manual tuning, nnU-Net surpasses most specialised deep learning pipelines in 19 public international competitions and sets a new state of the art in the majority of the 49 tasks. The results demonstrate a vast hidden potential in the systematic adaptation of deep learning methods to different datasets. We make nnU-Net publicly available as an open-source tool that can effectively be used out-of-the-box, rendering state of the art segmentation accessible to non-experts and catalyzing scientific progress as a framework for automated method design.

Maximilian Zenk, David Zimmerer, Fabian Isensee et al.

Semantic segmentation is an essential component of medical image analysis research, with recent deep learning algorithms offering out-of-the-box applicability across diverse datasets. Despite these advancements, segmentation failures remain a significant concern for real-world clinical applications, necessitating reliable detection mechanisms. This paper introduces a comprehensive benchmarking framework aimed at evaluating failure detection methodologies within medical image segmentation. Through our analysis, we identify the strengths and limitations of current failure detection metrics, advocating for the risk-coverage analysis as a holistic evaluation approach. Utilizing a collective dataset comprising five public 3D medical image collections, we assess the efficacy of various failure detection strategies under realistic test-time distribution shifts. Our findings highlight the importance of pixel confidence aggregation and we observe superior performance of the pairwise Dice score (Roy et al., 2019) between ensemble predictions, positioning it as a simple and robust baseline for failure detection in medical image segmentation. To promote ongoing research, we make the benchmarking framework available to the community.

Jens Petersen, Fabian Isensee, Gregor Köhler et al.

The ability to estimate how a tumor might evolve in the future could have tremendous clinical benefits, from improved treatment decisions to better dose distribution in radiation therapy. Recent work has approached the glioma growth modeling problem via deep learning and variational inference, thus learning growth dynamics entirely from a real patient data distribution. So far, this approach was constrained to predefined image acquisition intervals and sequences of fixed length, which limits its applicability in more realistic scenarios. We overcome these limitations by extending Neural Processes, a class of conditional generative models for stochastic time series, with a hierarchical multi-scale representation encoding including a spatio-temporal attention mechanism. The result is a learned growth model that can be conditioned on an arbitrary number of observations, and that can produce a distribution of temporally consistent growth trajectories on a continuous time axis. On a dataset of 379 patients, the approach successfully captures both global and finer-grained variations in the images, exhibiting superior performance compared to other learned growth models.

Jens Petersen, Gregor Köhler, David Zimmerer et al.

Neural Processes (NPs) are a family of conditional generative models that are able to model a distribution over functions, in a way that allows them to perform predictions at test time conditioned on a number of context points. A recent addition to this family, Convolutional Conditional Neural Processes (ConvCNP), have shown remarkable improvement in performance over prior art, but we find that they sometimes struggle to generalize when applied to time series data. In particular, they are not robust to distribution shifts and fail to extrapolate observed patterns into the future. By incorporating a Gaussian Process into the model, we are able to remedy this and at the same time improve performance within distribution. As an added benefit, the Gaussian Process reintroduces the possibility to sample from the model, a key feature of other members in the NP family.

Peter M. Full, Fabian Isensee, Paul F. Jäger et al.

Cardiac magnetic resonance imaging (cMRI) is an integral part of diagnosis in many heart related diseases. Recently, deep neural networks have demonstrated successful automatic segmentation, thus alleviating the burden of time-consuming manual contouring of cardiac structures. Moreover, frameworks such as nnU-Net provide entirely automatic model configuration to unseen datasets enabling out-of-the-box application even by non-experts. However, current studies commonly neglect the clinically realistic scenario, in which a trained network is applied to data from a different domain such as deviating scanners or imaging protocols. This potentially leads to unexpected performance drops of deep learning models in real life applications. In this work, we systematically study challenges and opportunities of domain transfer across images from multiple clinical centres and scanner vendors. In order to maintain out-of-the-box usability, we build upon a fixed U-Net architecture configured by the nnU-net framework to investigate various data augmentation techniques and batch normalization layers as an easy-to-customize pipeline component and provide general guidelines on how to improve domain generalizability abilities in existing deep learning methods. Our proposed method ranked first at the Multi-Centre, Multi-Vendor & Multi-Disease Cardiac Image Segmentation Challenge (M&Ms).

Jens Petersen, Paul F. Jäger, Fabian Isensee et al.

Existing approaches to modeling the dynamics of brain tumor growth, specifically glioma, employ biologically inspired models of cell diffusion, using image data to estimate the associated parameters. In this work, we propose an alternative approach based on recent advances in probabilistic segmentation and representation learning that implicitly learns growth dynamics directly from data without an underlying explicit model. We present evidence that our approach is able to learn a distribution of plausible future tumor appearances conditioned on past observations of the same tumor.